On this page
Quick Reference
Overview and Recommendations
Background
- •Define deep vein thrombosis as the presence of a thrombus in the deep veins, which are surrounded by muscle and carry the majority of venous return, as opposed to superficial veins. DVT and are considered two manifestations of the same disease process, VTE, sharing the same risk factors and management principles.
- •Classify DVT by anatomical location into proximal and distal (isolated calf) variants. Proximal DVT involves the popliteal, femoral, or iliac veins and carries a much higher risk of PE and PTS, whereas distal DVT is confined to the calf veins (posterior tibial, anterior tibial, and peroneal) and has a lower, though non-zero, risk of propagation.
- •Understand the etiologic distinction between provoked and unprovoked DVT to guide the duration of therapy. Provoked DVT occurs in the setting of transient risk factors like major surgery, trauma, or immobilization, while unprovoked DVT occurs without an obvious trigger and suggests a higher baseline risk of recurrence.
- •Recognize the role of Virchow’s Triad—venous stasis, endothelial injury, and hypercoagulability—in the pathogenesis of clot formation. Common triggers include malignancy, pregnancy, hormonal therapy, and inherited thrombophilias such as Factor V Leiden.
- •Identify life-threatening variants such as phlegmasia cerulea dolens, which is characterized by massive venous occlusion leading to limb cyanosis and potential arterial compromise. This is a surgical emergency that requires aggressive intervention to prevent gangrene and limb loss.
Evaluation
- •Suspect DVT in any patient presenting with unilateral leg pain, swelling, warmth, or erythema. While these signs are non-specific, the presence of a 'heavy' sensation in the limb or pain that worsens with weight-bearing should increase clinical suspicion.
- •Perform a focused physical examination comparing the affected limb to the contralateral side. Measure the calf circumference 10 cm below the tibial tuberosity; a difference of >3 cm is a significant predictor of DVT.
- •Assess for pitting edema and the presence of prominent, non-varicose collateral superficial veins. Palpate along the course of the deep veins to identify localized tenderness, particularly in the popliteal fossa or along the medial thigh.
- •Calculate the Wells Score for DVT to categorize the patient’s pre-test probability as low (0 points), moderate (1-2 points), or high (≥3 points). This score includes factors such as active cancer, recent immobilization, and the absence of a more likely alternative diagnosis.
- •Order a high-sensitivity D-dimer test for patients with a low or moderate pre-test probability. A negative D-dimer (<500 ng/mL or age-adjusted threshold) effectively rules out DVT in these groups without the need for imaging.
- •Apply age-adjusted D-dimer thresholds for patients over 50 years old to improve specificity. The formula is age × 10 µg/L (e.g., a 70-year-old has a cutoff of 700 µg/L).
- •Obtain a compression ultrasonography (CUS) as the first-line imaging study for patients with a high Wells score or a positive D-dimer. The diagnostic hallmark is the non-compressibility of a venous segment under the ultrasound probe.
- •Utilize whole-leg ultrasound if there is high suspicion of distal (calf) DVT, though many protocols focus on proximal CUS (groin to popliteal) due to the higher clinical significance of proximal clots.
- •Consider CT or MR venography for suspected DVT in atypical locations, such as the iliac veins, vena cava, or upper extremities, especially when CUS is inconclusive or technically limited by body habitus.
- •Rule out common mimics such as , ruptured Baker’s cyst (popliteal cyst), muscle tear (e.g., 'tennis leg'), or lymphedema. Cellulitis typically presents with higher fever and more diffuse erythema, while a ruptured cyst often shows a 'crescent sign' of bruising near the malleolus.
- •Screen for underlying malignancy in patients with a first-time unprovoked DVT. This should generally be limited to age-appropriate cancer screening (e.g., colonoscopy, mammography) rather than extensive 'fishing' with whole-body CT scans unless symptoms suggest a specific primary site.
Management
- •Initiate anticoagulation immediately upon diagnostic confirmation, or even prior to imaging if suspicion is high and the bleeding risk is low. The primary goal is to prevent thrombus propagation and embolization.
- •Administer direct oral anticoagulants (DOACs) as first-line therapy for most non-pregnant patients. Apixaban is dosed at 10 mg BID for 7 days followed by 5 mg BID; Rivaroxaban is dosed at 15 mg BID for 21 days followed by 20 mg daily.
- •Utilize Low-Molecular-Weight Heparin (LMWH), such as Enoxaparin 1 mg/kg every 12 hours, as the preferred agent for patients with active malignancy or those who are pregnant. LMWH is also used as a bridge for patients starting Warfarin.
- •Prescribe Warfarin for patients with severe renal failure (CrCl <15 mL/min) or (APS). Target an International Normalized Ratio (INR) of 2.0–3.0, maintaining LMWH bridging until the INR is therapeutic for at least 24 hours.
- •Treat provoked DVT (e.g., post-surgery) for a fixed duration of 3 months. Extending therapy beyond 3 months in these cases increases bleeding risk without significantly reducing recurrence.
- •Consider indefinite anticoagulation for patients with unprovoked DVT or persistent risk factors like active cancer, provided the bleeding risk is acceptable. Re-evaluate the risk-benefit ratio annually.
- •Avoid the routine use of Inferior Vena Cava (IVC) filters. These should be reserved strictly for patients with proven acute proximal DVT who have an absolute contraindication to anticoagulation (e.g., active intracranial hemorrhage).
- •Refer patients with phlegmasia cerulea dolens or massive iliofemoral DVT with impending limb ischemia for catheter-directed thrombolysis or surgical thrombectomy. These interventions are not indicated for routine DVT.
- •Encourage early ambulation as soon as therapeutic anticoagulation is achieved. Bed rest does not reduce the risk of PE and may actually promote further stasis and clot propagation.
- •Prescribe graduated compression stockings (30–40 mmHg) for symptomatic relief of edema, though they are no longer routinely recommended solely for the prevention of post-thrombotic syndrome based on recent trial data.
- •Monitor for treatment-related bleeding. Educate patients on signs of hemorrhage and the importance of medication adherence. For patients on DOACs, routine coagulation monitoring (PT/INR) is not required.
- •Manage isolated distal (calf) DVT with either 3 months of anticoagulation or serial ultrasound monitoring over 2 weeks. Anticoagulation is preferred if the patient is severely symptomatic or has high-risk features for propagation.
- •Evaluate for May-Thurner Syndrome in young patients, particularly women, presenting with left-sided iliofemoral DVT. This involves compression of the left common iliac vein by the right common iliac artery and may require stenting after initial anticoagulation.
Board Review — High Yield
- •Wells Score — A score of ≥3 indicates high probability; <2 with a negative D-dimer rules out DVT.
- •Age-adjusted D-dimer — Use (Age x 10) ng/mL for patients >50 years to reduce false positives.
- •Phlegmasia cerulea dolens — Massive venous congestion causing a cyanotic, painful, swollen limb; high risk of gangrene.
- •May-Thurner Syndrome — Compression of the left common iliac vein by the right common iliac artery; suspect in young females with left-leg DVT.
- •Paget-Schroetter Syndrome — Upper extremity DVT caused by repetitive overhead activity (effort thrombosis).
- •Post-thrombotic Syndrome (PTS) — Chronic complication featuring edema, skin hyperpigmentation, and ulcers due to venous valve damage.
- •Trousseau Syndrome — Migratory superficial thrombophlebitis associated with visceral malignancy (especially pancreatic cancer).
- •Factor V Leiden — The most common inherited thrombophilia; caused by resistance to activated protein C.
Deep Dive — Evidence Details
Definition, Synonyms, and Classification of Deep Vein Thrombosis
- ▸DVT is classified as proximal if it involves the popliteal vein or higher, which carries a significantly higher risk of pulmonary embolism compared to distal (calf) DVT [3].
- ▸The distinction between provoked and unprovoked DVT is the primary determinant for the duration of anticoagulation therapy [3].
- ▸Phlegmasia cerulea dolens represents the 'nadir' or peak clinical severity of DVT, characterized by total venous occlusion and potential limb-threatening ischemia [7].
Deep vein thrombosis (DVT) is defined as the formation of a blood clot (thrombus) within the deep venous system, most commonly occurring in the lower extremities, which results in partial or total occlusion of venous blood flow and carries a significant risk of pulmonary embolism (PE) [3]D. DVT and PE are collectively referred to under the umbrella term venous thromboembolism (VTE), representing two manifestations of the same underlying pathological process [3]D. The clinical significance of DVT lies in its potential for acute life-threatening complications and long-term morbidity, such as chronic and post-thrombotic syndrome (PTS) [1].
Synonyms and Alternate Nomenclature
In clinical practice and medical literature, DVT may be referred to by several synonyms depending on the context of the vessel involved or the underlying etiology. Common alternate names include:
- Deep Venous Thrombosis: An interchangeable term for DVT.
- Venous Thrombosis (VT): A broader term that may include both superficial and deep systems [13]D.
- Phlebothrombosis: A term emphasizing the formation of a clot without primary inflammation of the vein wall.
- Thrombophlebitis: Often used when the thrombus is associated with significant inflammation, though this more frequently refers to the superficial system.
- Portal Vein Thrombosis (PVT): A specific variant involving the portal venous system, often categorized separately due to its unique association with cirrhosis or non-cirrhotic [5]D[6]D.
- Lemierre's Syndrome: A specific form of septic internal jugular vein thrombosis typically caused by anaerobic oropharyngeal infections [9]C.
Temporal Phases and Stages of DVT
Understanding the temporal evolution of a thrombus is critical for determining the urgency of intervention and the duration of anticoagulation. While terms like "nadir" and "plateau" are more common in neurological literature, they are applied here to describe the clinical trajectory of venous obstruction and recovery [11]D.
- Prodromal Phase: The initial period of hypercoagulability or endothelial injury where a thrombus begins to form. Symptoms are often absent or minimal, consisting of vague limb heaviness or mild aching.
- Progressive Phase: The stage of active thrombus propagation. Without intervention, the clot may extend proximally (e.g., from the calf to the popliteal or femoral veins), increasing the risk of embolization [3]D.
- Nadir (Peak Severity): The point of maximal venous outflow obstruction and inflammatory response. In severe cases, this manifests as phlegmasia cerulea dolens, where massive edema compromises arterial inflow [7]D.
- Plateau Phase: A period of stabilization where the thrombus is no longer actively extending, typically achieved within 24 to 48 hours of initiating therapeutic anticoagulation [3]D.
- Recovery and Recanalization: The chronic phase where the body's endogenous fibrinolytic system begins to break down the clot. This phase determines the development of chronic venous disorders; incomplete recanalization or valvular damage leads to PTS [1].
Anatomic and Etiologic Classification
DVT is classified primarily by its location and the presence of provoking factors, as these variables dictate the risk of recurrence and the intensity of [3]D.
Anatomic Classification: Proximal vs. Distal
The distinction between proximal and distal DVT is the most important anatomic division. Proximal DVT involves the popliteal, femoral, or iliac veins. It is clinically more significant because it is more strongly associated with PE and long-term PTS [3]D. Distal (Isolated Calf) DVT is confined to the infrapopliteal veins (posterior tibial, anterior tibial, and peroneal veins). While the risk of PE is lower in distal DVT, approximately 15% to 25% of untreated calf thrombi will propagate proximally [3]D.
Etiologic Classification: Provoked vs. Unprovoked
- Provoked DVT: Occurs in the presence of a known, identifiable risk factor. These are further divided into transient factors (e.g., surgery, trauma, or immobilization) and persistent factors (e.g., active malignancy) [3]D.
- Unprovoked (Idiopathic) DVT: Occurs in the absence of obvious environmental or clinical triggers. Patients with unprovoked DVT have a significantly higher risk of recurrence and often require extended or indefinite anticoagulation [3]D[13]D.
Specialized Variants and Nomenclature
Certain anatomical locations require specialized classification systems due to their unique clinical implications.
Portal Vein Thrombosis (PVT)
PVT is classified based on the presence of underlying liver disease. Cirrhotic PVT is a common complication of end-stage liver disease, whereas Non-cirrhotic PVT may occur as a primary vascular disorder or due to porto-sinusoidal vascular disease (PSVD) [6]D[14]D. Chronic PVT often leads to cavernous transformation, where a network of collateral vessels (portal cavernoma) forms to bypass the obstructed segment [5]D[8]D.
Upper Extremity DVT
Often associated with central venous catheters or anatomical abnormalities (e.g., Paget-Schroetter syndrome). Specific cases may be complicated by infection, such as axillary abscesses leading to localized venous thrombosis [10]C.
Classification Protocol: Staging the Thrombus
Step 1 → Identify Anatomical Extent: Use duplex ultrasound to determine if the thrombus is proximal (popliteal and above) or isolated distal (calf only) [3]D. Step 2 → Assess Provocation Status: Evaluate for transient risk factors (surgery within 3 months, immobilization >3 days) or persistent factors (cancer) to classify as provoked or unprovoked [3]D. Step 3 → Determine Clinical Severity: Screen for signs of phlegmasia (massive swelling, cyanosis) which indicates a surgical or interventional emergency [7]D. Step 4 → Evaluate for Chronic Sequelae: In follow-up, use the VEIN-TERM consensus to classify any resulting chronic venous disorders or PTS [1].
| Variant | Key Distinguishing Feature | Clinical Implication |
|---|---|---|
| Proximal DVT | Involves popliteal, femoral, or iliac veins | High risk of PE; requires mandatory anticoagulation [3]D |
| Distal DVT | Confined to infrapopliteal (calf) veins | Lower PE risk; may be managed with serial imaging or anticoagulation [3]D |
| Phlegmasia Alba Dolens | 'Milk leg'; massive edema with preserved arterial flow | Early stage of limb-threatening venous occlusion |
| Phlegmasia Cerulea Dolens | Cyanotic limb with compromised arterial inflow | Surgical emergency; high risk of gangrene and amputation [7]D |
| Portal Vein Thrombosis | Thrombus in the portal vein or its branches | Associated with cirrhosis, PSVD, and portal hypertension [6]D[14]D |
| Category | Definition | Examples |
|---|---|---|
| Transient Provoked | Temporary risk factor present within 3 months | Major surgery, trauma, pregnancy, oral contraceptives [3]D |
| Persistent Provoked | Ongoing risk factor that remains present | Active malignancy, chronic inflammatory states [3]D |
| Unprovoked | No identifiable environmental or clinical trigger | Genetic thrombophilia (e.g., Factor V Leiden), idiopathic [13]D |
Epidemiology and Risk Factors
- ▸The in-hospital incidence of DVT in high-risk trauma populations, such as those with tibial plateau fractures, can reach **25.7%** despite prophylaxis.
- ▸Pediatric patients with inflammatory bowel disease (IBD) face a significantly elevated risk of VTE, necessitating vigilance in this younger demographic.
- ▸Iron deficiency anemia is a potent and specific risk factor for cerebral venous thrombosis, particularly in women, where it is present in over **10%** of cases.
The of (DVT) is characterized by a complex interplay between transient triggers and persistent biological predispositions. While the general population incidence is well-documented, specific high-risk cohorts—particularly those undergoing major orthopedic surgery or managing systemic inflammatory conditions—exhibit significantly higher rates of venous thromboembolism (VTE). For instance, in patients hospitalized with tibial plateau fractures, the cumulative in-hospital incidence of DVT reaches 25.7% despite routine thromboprophylaxis [34]D. Similarly, patients undergoing esophagectomy for cancer demonstrate a VTE prevalence of 10.3% by the time of hospital discharge [31]D.
Demographic Distribution and Temporal Trends
Age remains a primary non-modifiable risk factor, with the highest burden observed in surgical patients aged 75 years and older [42]D. However, recent data highlights an increasing recognition of VTE in pediatric populations. Children and teenagers with (IBD) face a significantly elevated risk of VTE compared to their healthy peers, a trend that mirrors the adult IBD population [17].
Sex-based differences are often mediated by hormonal exposures. Sex hormone therapy—including , hormone replacement therapy (HRT), and gender-affirming hormone therapy—alters hemostasis and vascular reactivity, thereby increasing thrombotic risk [27]D. In the context of (CVT), a specific demographic predilection is noted: 96.9% of CVT cases associated with iron deficiency anemia (IDA) occur in women [37]D.
Persistent and Systemic Risk Factors
Systemic inflammation and metabolic dysfunction are increasingly recognized as potent drivers of venous thrombosis. The triglyceride-glucose-systemic inflammation index (TyG-SII), a marker of combined insulin resistance and systemic inflammation, has been identified as a significant predictor of DVT in patients with fresh fractures [21]. This relationship is likely driven by the prothrombotic environment created by chronic inflammatory states.
- Malignancy: Active cancer is a major persistent risk factor. Patients with esophageal cancer [31]D or breast cancer undergoing chemotherapy via totally implantable venous access devices (TIVADs) are at high risk, with TIVAD-related thrombosis occurring in 11.2% of patients [26]. Furthermore, modern oncologic treatments such as immune checkpoint inhibitors (ICIs) have been linked to increased thrombotic adverse events in real-world pharmacovigilance studies [28]D.
- Inflammatory Bowel Disease (IBD): Both Crohn's disease and ulcerative colitis increase VTE risk, even in pediatric patients [17].
- Chronic Liver Disease: Patients with cirrhosis are paradoxically at risk for portal vein thrombosis (PVT), a common sequela of the disease [30]D.
Transient and Procedural Risk Factors
Surgery and trauma represent the most common transient triggers for DVT. The risk is particularly acute in the 90-day perioperative window.
- Orthopedic Surgery: Total hip arthroplasty (THA) and anterior cruciate ligament reconstruction (ACLR) are high-risk procedures. Interestingly, routine thromboprophylaxis may not fully eliminate the risk of symptomatic VTE following ACLR [19].
- Trauma: Lower extremity fractures, especially tibial plateau fractures, carry a high thrombotic burden due to direct vascular injury and prolonged immobilization [34]D.
- Prior Stroke: A history of stroke significantly increases complications following THA. The risk is highest when the interval between the stroke and surgery is less than 6 months [24].
Biological Mechanisms of Risk
Recent research into the molecular basis of DVT has identified serine-threonine kinase 10 (STK10) as a critical regulator. Platelet-specific deletion of STK10 has been shown to impair DVT formation by reducing platelet-neutrophil interactions and the formation of neutrophil extracellular traps (NETs) [39]D. This suggests that the interaction between the innate immune system and the coagulation cascade (immunothrombosis) is a fundamental driver of DVT in high-risk patients.
Anemia also serves as a critical, often overlooked, risk factor. Anemia is prevalent in 27% of patients with CVT and is associated with poorer functional outcomes [43]D. Specifically, moderate to severe iron deficiency anemia is found in 10.4% of CVT cases, suggesting that altered blood rheology and compensatory thrombocytosis in IDA may promote venous stasis and clot formation [37]D.
Risk Factor Summary Table
| Risk Factor | Association/Impact | Evidence Level |
|---|---|---|
| Tibial Plateau Fracture | 25.7% in-hospital incidence [34]D | 5 |
| IBD (Pediatric) | Increased RR for VTE [17] | 2a |
| TIVAD (Breast Cancer) | 11.2% prevalence [26] | 2b |
| Age ≥ 75 years | Major surgical risk factor [42]D | 5 |
| Iron Deficiency Anemia | Found in 10.4% of CVT cases [37]D | 5 |
| Stroke < 6 months prior | Increased THA complications [24] | 2b |
| Sex Hormone Therapy | Altered hemostasis/increased risk [27]D | 5 |
| Population | Incidence/Prevalence | Reference |
|---|---|---|
| Tibial Plateau Fracture (In-hospital) | 25.7% | [34]D |
| Breast Cancer (TIVAD-related) | 11.2% | [26] |
| Esophageal Cancer (Pre-discharge) | 10.3% | [31]D |
| Cerebral Venous Thrombosis (with Anemia) | 27.0% | [43]D |
Etiology and Triggering Factors
- ▸DVT etiology is governed by Virchow's Triad: venous stasis, endothelial injury, and hypercoagulability.
- ▸Pregnancy increases VTE risk up to 60-fold in the postpartum period compared to the non-pregnant state.
- ▸Venous valve pockets are the primary sites of thrombus initiation due to localized hypoxia and flow disturbances.
The development of deep vein thrombosis (DVT) is fundamentally driven by the convergence of three pathophysiological conditions known as Virchow's Triad: venous stasis, endothelial injury, and hypercoagulability [45]D[55]D[70]D. While the triad provides a conceptual framework, the initiation of a thrombus often requires a complex interplay between inherited genetic predispositions and acquired environmental triggers [56]D[61]C. Modern understanding has expanded this model to include the critical role of platelets in thrombus initiation and the specific vulnerability of venous valve pockets to hypoxia and flow disturbances [46]D[71]D[73]D.
The Pathophysiological Framework: Virchow's Triad
Venous thrombosis occurs when the delicate balance between pro-coagulant and anti-coagulant factors is disrupted [55]D.
- Venous Stasis: Reduced blood flow velocity allows for the accumulation of activated clotting factors and prevents their clearance by the liver [58]D. Stasis is most pronounced in the venous valve pockets (VVP), where locally disturbed microenvironments and recirculating flow patterns create a nidus for thrombus formation [64]D[73]D.
- Endothelial Injury: Damage to the vessel wall exposes the subendothelial matrix, triggering platelet adhesion and the extrinsic coagulation pathway [46]D[58]D. This may result from direct trauma, surgical intervention, or the presence of indwelling devices like [48]D[50]D.
- Hypercoagulability: This refers to an altered state of blood composition that favors coagulation. It can be systemic, such as in malignancy or pregnancy, or localized, driven by cytokine release and inflammatory processes [47]D[52]D[53]D.
Acquired and Environmental Triggers
Medical and Surgical Factors
Major surgery and trauma are potent triggers due to the combination of direct vascular injury and prolonged immobilization [50]D[56]D. In burn patients, the systemic inflammatory response fulfills all three criteria of Virchow's triad, with the risk increasing alongside the total body surface area (%TBSA) affected [54]D[66]D. Critically ill patients, particularly those in the ICU, face elevated risks due to the necessity of (CVCs) and peripherally inserted central catheters (PICCs) [48]D[68]D. In neurological ICU settings, the incidence of symptomatic PICC-related large vein thrombosis has been documented at 8.4% [68]D.
Malignancy and Therapy-Induced Thrombosis
Cancer induces a prothrombotic state through the release of procoagulants and direct compression of vessels by tumors [47]D[58]D. This risk is further exacerbated by oncological treatments. For instance, in breast cancer patients, the rate of thrombosis with tamoxifen is approximately 0.9%, while adjuvant chemotherapy increases this rate to 3% to 8% [51]D. The risk is notably higher in post-menopausal women and those receiving combination therapy [51]D.
Pregnancy and Hormonal Factors
Pregnancy induces a physiological hypercoagulable state to mitigate the risk of hemorrhage during delivery [52]D. The risk of VTE increases four- to five-fold during pregnancy and surges up to 60-fold in the postpartum period [52]D. The incidence ranges from 0.5 to 2.0 per 1000 pregnancies, peaking in the third trimester [52]D. Exogenous hormones, including and hormone replacement therapy, also contribute significantly to the hypercoagulable pillar of the triad [56]D.
Infectious and Inflammatory Triggers
has emerged as a unique trigger, characterized by a distinctive hypercoagulability and endothelial damage [53]D. In critically ill COVID-19 patients, prone positioning has been identified as a potential risk factor for DVT development [63]D. Other inflammatory states, such as those seen in psychiatric disorders (psychosis, depression, or ), can trigger VTE through associated physical inactivity and systemic stress [72]D.
Environmental and Disaster-Related Factors
Natural disasters, such as major earthquakes, lead to a documented increase in VTE, with DVT incidence ranging from 10% to 30% in evacuation shelters [45]D. This is primarily due to hemodynamic stasis from prolonged sitting in cramped conditions and dehydration-induced hypercoagulability [45]D. Similarly, long-distance travel is a well-recognized trigger, though the absolute risk depends on individual baseline factors [59]D.
Genetic and Inherited Predispositions
provide the background upon which acquired triggers act. Key genetic factors include:
- Factor V Leiden: Causes resistance to activated protein C [56]D.
- Non-O Blood Group: Associated with higher levels of von Willebrand factor and Factor VIII [56]D.
- Prothrombin G20210A Mutation: Leads to hyperprothrombinemia [56]D.
- Endothelial Cell Protein C Receptor (EPCR) Gene Polymorphisms: Emerging evidence suggests these mutations may impair the natural anticoagulant pathway, increasing recurrence risk [61]C.
Anatomical and Site-Specific Etiologies
Specific anatomical considerations can localize thrombosis to unusual sites. In patients with , portal vein thrombosis (PVT) is common due to altered hepatic blood flow and systemic prothrombotic shifts [57]D[69]D. In pediatric populations, the primary driver of upper extremity DVT is the presence of central lines, accounting for 92% to 100% of secondary cases [67]D. Emerging research also highlights venous valve hypoxia; when blood flow is stagnant, the valve pockets become hypoxic, triggering the endothelium to express procoagulant molecules [71]D.
| Cause | Category | Frequency/Risk | Associated Subtype | Key Reference |
|---|---|---|---|---|
| Major Surgery/Trauma | Acquired | High (varies by type) | Postoperative DVT | [50]D[56]D[62]D |
| Cancer (General) | Acquired | Variable | Cancer-associated thrombosis | [47]D[58]D |
| Tamoxifen Therapy | Drug-induced | ~0.9% | Breast cancer-related | [51]D |
| Adjuvant Chemotherapy | Drug-induced | 3% - 8% | Breast cancer-related | [51]D |
| Pregnancy | Physiological | 0.5 - 2.0 per 1000 | Pregnancy-related VTE | [52]D |
| Postpartum Period | Physiological | 60x baseline risk | Postpartum VTE | [52]D |
| Central Venous Catheter | Mechanical | Primary pediatric risk | Catheter-associated DVT | [48]D[67]D[68]D |
| Major Earthquakes | Environmental | 10% - 30% | Disaster-associated VTE | [45]D |
| COVID-19 Infection | Infectious | High in critical care | COVID-associated coagulopathy | [53]D[63]D |
| Factor V Leiden | Genetic | Variable | Inherited thrombophilia | [56]D[61]C |
| Non-O Blood Group | Genetic | Variable | Inherited predisposition | [56]D |
| Major Burns | Trauma | High (correlates with %TBSA) | Burn-associated VTE | [54]D[66]D |
| Long-distance Travel | Lifestyle | Low absolute risk | Travel-related thrombosis | [59]D |
Pathophysiology
- ▸DVT is increasingly recognized as an inflammatory process (immunothrombosis) where Neutrophil Extracellular Traps (NETs) and platelet mTOR signaling provide the scaffold for fibrin deposition.
- ▸Virchow's Triad remains the foundational framework, with venous stasis, endothelial injury, and hypercoagulability interacting to trigger the molecular cascade.
- ▸Thrombus resolution is a macrophage-dependent process regulated by TGF-β and HIF-1α; failure of this process leads to Post-Thrombotic Syndrome (PTS).
The development of deep vein thrombosis (DVT) is traditionally explained by Virchow's Triad, which includes venous stasis, endothelial injury, and hypercoagulability [45]D[46]D[61]C[82]D. Modern understanding has expanded this model to include immunothrombosis, a complex interplay between the innate immune system and the coagulation cascade [74][78]D[83]D[94]D.
Virchow's Triad and Initial Triggers
Venous stasis is a primary driver of DVT, occurring in conditions of prolonged immobility such as lower limb paralysis following [78]D, spinal trauma [75], or long-haul travel [92]D. In unique environments like spaceflight, weightlessness-induced venous stasis can even lead to neck-vein thrombosis [81]D. Stasis leads to local hypoxia, which triggers metabolic reprogramming in endothelial cells and leukocytes, shifting toward glycolysis and activating inflammatory pathways [88]D.
Endothelial injury can be direct, as seen in orthopedic surgery [76] or intravenous device placement [82]D, or indirect, mediated by systemic inflammation. In , SARS-CoV-2 causes direct endothelial injury and a pro-inflammatory cytokine milieu, promoting systemic thrombosis [74][91]. Hypercoagulability may be inherited, such as through Endothelial Cell Protein C Receptor (EPCR) gene polymorphisms [61]C or Antithrombin Resistance (ATR) caused by prothrombin mutations (e.g., FII R596L) [97]D. It can also be acquired, as seen in pregnancy, where a physiological hemostatic shift occurs to mitigate delivery-related hemorrhage [52]D, or in cancer, where treatments like immunotherapy and hormone modulators increase thrombotic risk [80]D.
Molecular Mechanism of Thrombus Formation
The transition from a healthy vessel to a thrombotic state follows a specific molecular sequence:
- Step 1: Endothelial Activation and Hypoxia: Venous stasis or injury induces hypoxia, leading to the expression of adhesion molecules and the activation of Toll-like receptors (TLRs) and inflammasomes [83]D[85]D[88]D.
- Step 2: Leukocyte Recruitment and Immunothrombosis: Neutrophils are recruited to the vessel wall and release Neutrophil Extracellular Traps (NETs). These NETs, characterized by citrullinated histone H3 (H3cit), provide a scaffold for thrombus growth [77][78]D.
- Step 3: Platelet Activation and mTOR Signaling: Platelets interact with NETs and the activated endothelium. mTOR (mechanistic target of rapamycin) signaling in platelets is a critical regulator of sterile immunothrombosis and thrombus stabilization [94]D. Platelet dysfunction and altered aggregation further exacerbate the hemostatic imbalance [87]D.
- Step 4: Coagulation Cascade Amplification: The scaffold formed by NETs and platelets concentrates coagulation factors. In some patients, deficiencies in endogenous anticoagulants like Endothelial cell-specific molecule-1 (ESM1), which normally activates thrombin inhibitors, accelerate occlusion [96]D.
- Step 5: Thrombus Propagation and Fibrinolysis Resistance: In conditions like Long COVID or sepsis, blood may clot into amyloid microclots (fibrinaloid microclots) that are highly resistant to natural fibrinolysis [93]D.
Thrombus Resolution and Post-Thrombotic Syndrome
Natural resolution of a thrombus is a multifaceted process involving the TGF-β (transforming growth factor-β) family, which regulates vein wall remodeling and thrombus contraction [89]D. Macrophages play a dual role; a shift from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages is essential for efficient resolution [95]D. This process is often linked to HIF-1α signaling, which coordinates the response to the hypoxic environment within the clot [95]D.
Failure of resolution leads to Post-Thrombotic Syndrome (PTS). Persistent inflammation and high levels of NET markers like H3cit measured three months after the initial event are strongly associated with the development of PTS [77]. In some cases, such as severe chest trauma, localized inflammation and occult vascular injury can lead to "de novo" pulmonary embolism even in the absence of a detectable lower extremity DVT [98]D.
| Mediator/Factor | Mechanism/Target | Clinical Significance |
|---|---|---|
| Citrullinated Histone H3 (H3cit) | Marker of Neutrophil Extracellular Traps (NETs) | High levels predict Post-Thrombotic Syndrome (PTS) [77] |
| mTOR | Regulator of platelet signaling and stabilization | Essential for sterile immunothrombosis [94]D |
| ESM1 | Endogenous anticoagulant; activates thrombin inhibitors | Elevated in VTE; deficiency promotes thrombosis [96]D |
| TGF-β Family | Regulates fibrinolysis and vein wall remodeling | Key driver of natural thrombus resolution [89]D |
| HIF-1α | Coordinates macrophage response to hypoxia | Linked to M1/M2 macrophage balance in resolution [95]D |
| FII R596L Mutation | Reduces prothrombin affinity for Antithrombin | Causes congenital Antithrombin Resistance (ATR) [97]D |
Clinical Features
- ▸Physical examination findings like Homan's sign are unreliable; diagnosis must rely on validated clinical prediction rules like the Wells Score.
- ▸For patients over 50 years of age, the D-dimer threshold should be age-adjusted (age × 10 µg/L) to safely rule out DVT while minimizing over-imaging.
- ▸Obesity (BMI ≥30 kg/m²) significantly increases DVT risk and may alter the diagnostic utility of standard D-dimer cutoffs.
The clinical presentation of (DVT) is notoriously variable, often described as a "hidden" condition due to its non-specific signs that frequently overlap with other musculoskeletal or vascular pathologies [107][122]D. A clinician must maintain a high index of suspicion, particularly in patients with known risk factors such as recent orthopedic surgery [100][110], obesity [104][105], or malignancy [126]D. The diagnostic process begins with a structured history and physical examination to determine the pre-test probability, which then dictates the necessity of further imaging or laboratory testing [122]D[125]D.
Presenting Symptoms
Patients typically present with unilateral limb complaints that develop over hours to days. The most common symptom is calf pain or tenderness, often described as a dull ache or "cramping" sensation that worsens with weight-bearing [122]D. Swelling is the most reliable clinical sign, usually occurring distal to the site of the thrombus. In lower extremity DVT, this may involve the entire leg (iliofemoral DVT) or be localized to the calf (femoropopliteal or isolated calf DVT) [112].
In specific populations, symptoms may be more subtle. For instance, elderly patients may present with vague discomfort that is easily attributed to existing comorbidities like or ( ) [111][123]D. In children, chronic limb pain following a DVT may indicate the development of (PTS), which can occur with or without visible physical findings of chronic [101].
Physical Examination Findings
The physical examination should be systematic, comparing the affected limb to the contralateral side to identify subtle asymmetries.
- Inspection: Observe for unilateral edema, erythema, and prominent superficial collateral veins. In severe cases, the limb may appear cyanotic (phlegmasia cerulea dolens) or pale and waxy (phlegmasia alba dolens) due to massive venous obstruction and secondary arterial compromise [122]D.
- Palpation: Assess for localized tenderness along the distribution of the deep venous system. Increased skin temperature (warmth) is common but non-specific. Pitting edema should be documented by applying firm pressure over the medial malleolus or pretibial area for at least 5 seconds.
- Circumferential Measurements: Measure the calf circumference 10 cm below the tibial tuberosity. A difference of >3 cm between limbs is a significant predictor of DVT and is a core component of the Wells score [112][122]D.
- Maneuvers: While historically taught, Homan's sign (pain in the calf upon forced dorsiflexion of the foot) is neither sensitive nor specific and is no longer recommended as a primary diagnostic tool [122]D.
Clinical Prediction Rules
Because physical signs alone are unreliable, validated scoring systems like the Wells Score are essential to categorize patients into low, moderate, or high-probability groups. This stratification determines the utility of a D-dimer test versus immediate imaging [112][122]D.
| Clinical Feature | Points |
|---|---|
| Active cancer (treatment within 6 months or palliative) | +1 |
| Paralysis, paresis, or recent plaster immobilization of the lower extremity | +1 |
| Recently bedridden >3 days or major surgery within 12 weeks | +1 |
| Localized tenderness along the distribution of the deep venous system | +1 |
| Entire leg swollen | +1 |
| Calf swelling >3 cm compared to asymptomatic leg | +1 |
| Pitting edema confined to the symptomatic leg | +1 |
| Collateral superficial veins (non-varicose) | +1 |
| Previously documented DVT | +1 |
| Alternative diagnosis at least as likely as DVT | -2 |
Interpretation: 0 = Low probability; 1-2 = Moderate probability; ≥3 = High probability [112][122]D.
Step-by-Step Clinical Assessment Protocol
Step 1 → Identify Risk Factors: Screen for recent surgery (especially hip/knee arthroplasty [113][118]D), prolonged immobility, obesity (BMI ≥30 kg/m²) [105][117]D, or use of combined hormonal contraceptives [108]. Step 2 → Perform Targeted Exam: Measure calf circumferences and assess for pitting edema and localized tenderness [122]D. Step 3 → Calculate Wells Score: Determine pre-test probability to guide the next diagnostic step [112]. Step 4 → Apply Age-Adjusted Thresholds: For patients >50 years, use the age-adjusted D-dimer cutoff (age × 10 µg/L) to increase diagnostic specificity and reduce unnecessary imaging [102].
Phenotypic Variants
| Variant | Key Features | Frequency/Context |
|---|---|---|
| Upper Extremity DVT | Swelling and pain in the arm; often associated with central venous catheters or strenuous activity (Paget-Schroetter syndrome) [120]D. | 5-10% of all DVT cases |
| Pediatric DVT | Often secondary to central lines; high risk of PTS-related chronic pain [101][109]. | Rare; increasing in tertiary care |
| Pregnancy/Postpartum DVT | Increased risk due to hypercoagulability and venous stasis; often involves the left iliac vein due to May-Thurner anatomy [106][107]. | 1 in 1000 pregnancies |
| Obesity-Associated DVT | Higher baseline D-dimer levels may complicate diagnosis; increased risk in bariatric and cosmetic surgery populations [105][121]D[126]D. | Common in high-BMI cohorts |
Red Flags
Certain findings necessitate urgent intervention to prevent limb loss or fatal (PE):
- Respiratory Distress: Sudden onset dyspnea, tachypnea, or pleuritic chest pain suggests PE [106][109].
- Phlegmasia Cerulea Dolens: Massive edema, cyanosis, and severe pain indicating near-total venous occlusion; requires emergent vascular consultation [122]D.
- Neurological Deficit: While rare in isolated DVT, sudden weakness or sensory loss in the setting of suspected venous thrombosis may indicate (CVT), particularly in pregnant or postpartum patients [107][108].
Atypical Presentations
Clinicians should be wary of "masked" DVT. In patients with large uterine fibroids, pelvic venous stasis can lead to DVT without typical distal triggers [79]D. Furthermore, in the elderly, the prevalence of DVT is significantly higher (17.10%), yet symptoms are often attributed to general frailty or chronic venous insufficiency [111][115]D. In patients with COPD, an acute exacerbation may actually be triggered by an occult PE secondary to an asymptomatic DVT [123]D.
| Clinical Feature | Points |
|---|---|
| Active cancer | +1 |
| Paralysis or recent immobilization | +1 |
| Recent major surgery (<12 weeks) | +1 |
| Localized tenderness | +1 |
| Entire leg swollen | +1 |
| Calf swelling >3 cm (measured 10cm below tuberosity) | +1 |
| Pitting edema (symptomatic leg only) | +1 |
| Collateral superficial veins | +1 |
| Previous DVT | +1 |
| Alternative diagnosis as likely as DVT | -2 |
| Variant | Key Features | Context |
|---|---|---|
| Upper Extremity | Arm swelling, catheter-related | Central lines, Paget-Schroetter |
| Pediatric | Chronic pain, PTS risk | Central venous access |
| Pregnancy-related | Left-sided predominance | Hypercoagulability of pregnancy |
| Phlegmasia | Cyanosis, limb-threatening ischemia | Massive iliofemoral occlusion |
Diagnosis and Workup
- ▸D-dimer testing is highly sensitive for ruling out DVT in low-risk patients, but clinicians must account for the lack of assay standardization [140].
- ▸Compression ultrasonography (CUS) remains the primary imaging modality for limb DVT, while CT/MR venography is required for central sites like the portal or cerebral veins [128, 138].
- ▸In patients with autoimmune conditions like APS, severe thrombocytopenia (< 50 G/L) is a critical finding that complicates the diagnostic and therapeutic landscape [129].
The diagnosis of deep vein thrombosis (DVT) requires a multi-modal approach that integrates clinical risk assessment, laboratory biomarkers, and vascular imaging. Because clinical symptoms such as right thigh pain or acute dyspnea are non-specific and can mimic conditions ranging from to primary vascular-derived sarcoma, a structured diagnostic algorithm is essential to avoid both over-treatment and missed diagnoses [130]C[132]C.
Diagnostic Criteria
Formal diagnosis relies on the objective demonstration of an intraluminal thrombus. Clinical suspicion is the primary driver for workup, particularly in patients with established risk factors such as recent orthopedic surgery (e.g., total hip or knee arthroplasty), a history of stroke within the preceding 6 to 30 months, or high body mass index (BMI) [24][42]D[113][114]D.
- Required Features: Objective evidence of venous obstruction via imaging (e.g., non-compressibility on ultrasound) or direct visualization during interventional procedures [26][134]D.
- Supportive Features: Elevated D-dimer levels, presence of Virchow’s triad components (stasis, hypercoagulability, endothelial injury), and clinical scores indicating high pre-test probability [140]D[141]D.
- Exclusion Criteria: Alternative diagnoses confirmed by imaging or laboratory studies, such as Nocardia saintgeorgesii infection mimicking pulmonary embolism (PE) or malignancy-associated symptoms [132]C.
Laboratory Tests
Laboratory workup serves two roles: excluding DVT in low-risk patients and identifying underlying hypercoagulable states.
- D-dimer Testing: This is the most critical initial laboratory test. However, clinicians must note that D-dimer reporting lacks global standardization across different assays, which can limit comparability [140]D. It is highly sensitive but poorly specific; a negative result in a low-probability patient effectively rules out DVT.
- Coagulation and Inflammatory Indices: In specific populations, such as those with tibial plateau fractures, models incorporating coagulation and nutritional-immune indices (e.g., albumin, lymphocyte counts) have been developed to predict preoperative DVT [141]D.
- Antiphospholipid Syndrome (APS) Screening: In patients with recurrent thrombosis or unexplained thrombocytopenia, screening for APS is vital. Severe thrombocytopenia (< 50 G/L) in APS patients is associated with unique challenges and increased risk [129].
- Metagenomic Next-Generation Sequencing (mNGS): While not routine, mNGS can be a decisive diagnostic tool when infectious mimics (e.g., ) are suspected in immunocompetent hosts presenting with concurrent PE or DVT-like symptoms [132]C.
Imaging
Imaging is the definitive step in the diagnostic workup. The choice of modality depends on the suspected location of the thrombus.
- Compression Ultrasonography (CUS): The modality of choice for lower limb DVT. It involves assessing the compressibility of veins; a non-compressible segment indicates a thrombus [26][141]D. Routine color Doppler is often performed before removing totally implantable venous access devices (TIVADs) to detect asymptomatic [26].
- CT and MR Venography: These are preferred for central or atypical sites. MR venography is highly effective for diagnosing cerebral venous thrombosis (CVT) and assessing full recanalization [128]. CT venography is often used to evaluate portal vein tumor thrombus (PVTT) in patients with advanced hepatocellular carcinoma [138]D[41]D.
- Optical Coherence Tomography Angiography (OCTA): In cases of (RVO), OCTA is used to distinguish between "congestive" and "compensatory" microvascular phenotypes and to identify non-perfusion areas (NPAs) [137]D[139]D.
- Invasive Angiography: Historically the gold standard, it is now reserved for interventional salvage or when aspiration biopsy is needed to differentiate a thrombus from a primary vascular sarcoma [130]C[134]D.
Diagnostic Algorithm
The following protocol should be used for suspected lower extremity DVT:
- Step 1: Clinical Risk Stratification: Utilize validated tools (e.g., LASSO-based models or Wells score) to determine pre-test probability [42]D[141]D.
- Step 2: D-dimer Testing: If the patient is at low or moderate risk, order a D-dimer. If the result is below the threshold, DVT is excluded [140]D.
- Step 3: Vascular Imaging: If the D-dimer is positive or the patient is at high clinical risk, proceed directly to CUS [26][141]D.
- Step 4: Extended Workup: If imaging is negative but suspicion remains high, repeat CUS in 5-7 days. For central symptoms (e.g., Budd-Chiari or CVT), proceed to CT/MR venography [128][134]D.
Diagnostic Test Comparison
| Test | Finding | Timing | Sensitivity | Specificity |
|---|---|---|---|---|
| D-dimer | Elevated fibrin degradation products | Acute phase | High (>95%) | Low |
| CUS | Non-compressible venous segment | Immediate | High for proximal | High |
| CT Venography | Intraluminal filling defect | Immediate | High for central | High |
| OCTA | Vessel diameter index (VDI) changes | Chronic/Subacute | High for RVO [137]D | High |
| mNGS | Pathogen identification | When mimics suspected | High [132]C | High |
Differential Diagnosis of Deep Vein Thrombosis
- ▸Vascular leiomyosarcoma should be suspected if an apparent DVT fails to respond to anticoagulation or shows interval growth on imaging [155, 161].
- ▸Cellulitis and DVT frequently coexist; age is a primary risk factor for this dual pathology [158].
- ▸Tennis leg (gastrocnemius tear) is the most common musculoskeletal mimic and is distinguished by the location of fluid collections on ultrasound [153].
The clinical presentation of deep vein thrombosis (DVT) is notoriously non-specific, often overlapping with a wide array of infectious, musculoskeletal, and neoplastic conditions. Because the sequelae of DVT—including and chronic venous —carry significant morbidity, clinicians must systematically exclude mimics while maintaining a high index of suspicion for concurrent pathologies [144]D. In many cases, conditions like or Charcot neuroarthropathy may not only mimic DVT but also serve as pro-inflammatory triggers for its development [154]D[158]D.
Infectious and Inflammatory Mimics
Cellulitis is the most frequent clinical mimic of DVT, characterized by erythema, warmth, and edema. However, the relationship is complex; the pro-inflammatory state induced by lower limb cellulitis significantly increases the risk of secondary DVT [158]D. Age is a critical risk factor, with older patients exhibiting a higher prevalence of concurrent DVT during cellulitis episodes [158]D.
Charcot Neuroarthropathy (CN), particularly in its acute phase, presents with a red, hot, swollen foot that is frequently misdiagnosed as DVT or cellulitis [154]D. This inflammatory condition affects patients with , often secondary to diabetes, and involves a cascade of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 that drive bone resorption [154]D. Early identification is vital, as the 5-year mortality rate for CN is as high as 29.0% [147]D.
In the upper body, must be considered when internal jugular vein thrombosis occurs following acute pharyngitis or oropharyngeal infection [143]C[150]C. This condition, often associated with Streptococcus constellatus or Fusobacterium necrophorum, can lead to septic pulmonary emboli and pulmonary artery pseudoaneurysms [150]C[167]C.
Musculoskeletal and Soft Tissue Disorders
Tennis Leg refers to an acute rupture or strain of the posterior calf muscles, most commonly the medial of the gastrocnemius at the distal myotendinous junction [153]D. While it presents with sudden-onset pain and swelling similar to DVT, ultrasound can differentiate the two by identifying fluid collections between the gastrocnemius and soleus muscles rather than intraluminal thrombus [153]D.
Ruptured Baker’s Cyst ( ) can cause acute calf pain and swelling that mimics DVT. Similarly, Diabetic Myonecrosis is a rare but serious complication in patients with end-stage kidney disease (ESKD) that presents with ischemic muscle necrosis, often requiring MRI for differentiation from DVT or cellulitis [164]C.
Neoplastic and Rare Vascular Mimics
Primary Vascular Leiomyosarcoma (VLMS) is a rare, aggressive smooth muscle tumor that is frequently misdiagnosed as chronic DVT [148][155]C. A key clinical red flag is the persistence or progression of symptoms despite therapeutic anticoagulation [155]C[161]C. On imaging, VLMS often appears as an intensely FDG-avid intraluminal mass on PET/CT or shows peripheral enhancement on MRI, unlike the non-enhancing nature of a standard thrombus [161]C.
Intravascular Fasciitis (IVF) is a benign myofibroblastic proliferation that can mimic DVT, even in the setting of anatomical predispositions like May-Thurner Syndrome [157]C. Definitive diagnosis requires histopathology showing USP6 rearrangement via FISH [157]C.
Diagnostic Algorithm for Differentiation
Step 1: Clinical Risk Assessment
Evaluate for risk factors of DVT (immobilization, malignancy) versus mimics (diabetes for Charcot, recent infection for Lemierre, or trauma for Tennis Leg) [147]D[153]D[158]D.
Step 2: Initial Imaging (Duplex Ultrasound)
Assess for venous compressibility. If a mass is non-compressible but shows internal vascularity or atypical morphology, consider vascular tumors [148][155]C.
Step 3: Advanced Imaging for Atypical Cases
If symptoms persist despite anticoagulation, order Contrast-Enhanced CT or MRI. Look for "ring enhancement" or interval growth, which suggests leiomyosarcoma or organizing thrombus rather than acute DVT [155]C[156]C[163]C.
Step 4: Laboratory and Systemic Workup
In cases of suspected Lemierre syndrome, obtain blood cultures [150]C. For suspected Charcot, focus on inflammatory markers and metabolic balance [154]D.
Comparative Features of DVT and Mimics
| Condition | Key Differentiating Feature | Preferred Imaging | Clinical Context |
|---|---|---|---|
| Deep Vein Thrombosis | Non-compressible vein; no internal flow | Duplex Ultrasound | Post-op, immobility, cancer [144]D |
| Cellulitis | Diffuse erythema; skin warmth | Clinical / Ultrasound | Bacterial entry site; fever [158]D |
| Tennis Leg | Fluid at gastrocnemius-soleus interface | Ultrasound / MRI | Sudden "pop" during exercise [153]D |
| Leiomyosarcoma | Intraluminal mass growth on anticoagulation | MRI / PET-CT | Chronic, progressive swelling [155]C[161]C |
| Charcot Foot | Neuropathic joint destruction; midfoot collapse | X-ray / MRI | Diabetic with neuropathy [147]D[154]D |
| Lymphedema | Non-pitting edema; Stemmer sign | Clinical / Lymphoscintigraphy | Post-lymph node dissection [145]D |
| Feature | DVT | Cellulitis | Tennis Leg | Charcot Foot |
|---|---|---|---|---|
| Onset | Subacute | Acute/Subacute | Sudden/Traumatic | Subacute |
| Primary Site | Deep veins | Dermis/Soft tissue | Medial gastrocnemius | Midfoot/Ankle |
| Erythema | Possible (mild) | Intense/Diffuse | Rare | Intense |
| Imaging Finding | Intraluminal thrombus | Soft tissue edema | Myotendinous tear | Bone fragmentation |
| Key Risk Factor | Stasis/Hypercoagulability | Skin break | Athletics | Diabetes/Neuropathy |
Special Populations
- ▸Pregnancy increases VTE risk 4-5 fold, peaking at a 60-fold increase in the postpartum period, with LMWH as the preferred treatment.
- ▸Extended anticoagulation for cancer-associated thrombosis can be managed with reduced-dose apixaban (2.5 mg BID) to balance efficacy and bleeding risk.
- ▸Antiphospholipid syndrome (APS) presents a dual challenge of high thrombotic risk and potential severe thrombocytopenia (<50 G/L).
of deep vein thrombosis (DVT) requires significant modification in specific patient cohorts due to altered physiology, unique risk profiles, and varying safety profiles of standard anticoagulants. Clinicians must balance the high risk of recurrence in populations like cancer patients against the increased bleeding risks in the elderly or those with autoimmune-mediated thrombocytopenia [129][173].
Pregnancy and Postpartum
Pregnancy induces a maternal hemostatic shift, characterized by increased coagulation factors, reduced fibrinolysis, and venous stasis, which serves to mitigate hemorrhage risk at delivery but increases VTE risk four- to five-fold [52]D. This risk peaks in the immediate postpartum period, where it can reach 60-fold compared to the non-pregnant state [52]D. Cesarean deliveries further escalate this risk, with a 4-fold relative risk increase compared to vaginal delivery [178]D.
- Diagnostic Considerations: Vascular ultrasound remains the primary diagnostic tool [178]D. While most patients exhibit some pelvic vein thrombosis post-cesarean, only 2.6 to 4.3 per 1000 develop clinically relevant VTE [178]D. Rare presentations, such as ovarian vein thrombosis (OVT), may be suspected intraoperatively during cesarean section if bilateral pelvic venous distension is noted [175]C.
- Treatment Modifications: Low-molecular-weight heparin (LMWH) is the preferred agent due to its safety profile regarding fetal teratogenicity. In high-risk parturients undergoing cesarean section, enoxaparin sodium prophylaxis significantly reduces the incidence of lower extremity DVT [177].
- Safety: LMWH and warfarin are generally considered safe for breastfeeding as they do not significantly enter breast milk, though direct oral anticoagulants (DOACs) are typically avoided due to lack of safety data.
(CAT)
Malignancy is a potent driver of VTE, with specific cancers like pancreatic ductal adenocarcinoma (PDAC) exhibiting exceptionally high rates [172]. The pathophysiology involves a thrombo-inflammatory niche where neutrophil extracellular traps (NETs) facilitate thrombus formation [189]D.
- Diagnostic Considerations: In patients with (RCC) or hepatocellular carcinoma (HCC), clinicians must distinguish between bland thrombus and tumor thrombus (TT), which involves direct vascular invasion by malignant cells [171][174]. Presurgical molecular therapy (PMT) with tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) may be used to downstage TT height before surgery [171].
- Treatment Modifications: DOACs are effective for primary prevention in non-bedridden cancer patients undergoing chemotherapy [179]. For extended treatment (beyond 6 months), apixaban 2.5 mg BID has been shown to be non-inferior to apixaban 5 mg BID for preventing recurrence while reducing clinically relevant bleeding [173].
- Drug-Induced Risks: JAK inhibitors (e.g., for rheumatoid arthritis) are associated with an increased risk of malignancies (RR = 1.53) and major adverse cardiovascular events [170]. Systemic TKIs are also linked to rare but serious retinal vein occlusions (RVO) [186]D.
Elderly and Surgical Considerations
Elderly patients often present with multiple comorbidities and are at higher risk for complications from both the thrombosis and its treatment. In surgical settings, specific positioning can influence risk; for example, the Z-shaped supine position in robot-assisted radical prostatectomy (RARP) is being studied to reduce position-related complications compared to the standard steep Trendelenburg position [176].
- Modified Thresholds: The mean age for TKI-related RVO is 75.9 years, suggesting a need for heightened ophthalmic monitoring in older oncology patients [186]D.
- Surgical Timing: After major sellar region tumor surgeries (e.g., pituitary adenomas), there is a critical shift phase of heightened DVT risk, often linked to perioperative neuroendocrine disturbances [180].
Immunocompromised and Autoimmune
Patients with (APS) or those on (ICIs) present unique challenges. APS is frequently associated with systemic lupus erythematosus and can manifest with severe thrombocytopenia (<50 G/L in 13% of cases), which complicates the use of standard anticoagulation [129].
- Diagnostic Challenges: In immunocompetent or immunocompromised hosts, infections like Nocardia saintgeorgesii can mimic lung cancer on imaging and present with concurrent pulmonary embolism, requiring metagenomic next-generation sequencing (mNGS) for definitive diagnosis [132]C.
- ICI-Related Risks: Pharmacovigilance data indicates that ICIs are associated with significant thrombotic adverse events, necessitating close monitoring during immunotherapy [28]D.
Pediatrics
Pediatric DVT is rare and typically secondary to identifiable triggers such as totally implantable venous access devices (TIVADs) or underlying autoimmune conditions like APS [26][129].
- Diagnostic Considerations: Isolated cortical venous thrombosis (ICoVT) is a rare type of cerebral venous thrombosis (CVT) that can mimic brain tumors on imaging, presenting with headache or progressive limb weakness [156]C[182]D.
- Management: While standard protocols often mirror adult LMWH use, doses must be strictly age- and weight-adjusted. In cases of diffuse mesenteric venous ischemia related to myeloproliferative disorders, early catheter-directed portal vein thrombolysis may be considered [181]C.
| Population | Key Risk Factor | Preferred Management | Clinical Nuance |
|---|---|---|---|
| Pregnancy | Maternal hemostatic shift [52]D | LMWH (Enoxaparin) [177] | Risk is 4x higher after C-section [178]D |
| Cancer (CAT) | Thrombo-inflammatory niche [189]D | Apixaban 2.5 or 5 mg BID [173] | DOACs effective for primary prevention [179] |
| APS | Autoimmune hypercoagulability [129] | Anticoagulation + Platelet monitoring | 13% have platelets <50 G/L [129] |
| Elderly | TKI therapy [186]D | Standard anticoagulation | Risk of retinal vein occlusion with TKIs [186]D |
References
- [1]
Eklof B, Perrin M, Delis KT et al.. “Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document.” Journal of vascular surgery (2009). PMID: 19216970 ↗
L1cGUIDELINECited in: Definition, Synonyms, and Classification - [2]
Sun CR, Liu MY, Ni QH et al.. “Clinical Guidelines on Compression Therapy in Venous Diseases.” Annals of vascular surgery (2025). PMID: 39032593 ↗
L1cGUIDELINECited in: Definition, Synonyms, and Classification - [3]
Stevens SM, Woller SC, Baumann Kreuziger L et al.. “Antithrombotic Therapy for VTE Disease: Compendium and Review of CHEST Guidelines 2012-2021.” Chest (2024). PMID: 38458430 ↗
L5REVIEW_NARRATIVECited in: Definition, Synonyms, and Classification - [4]
Bayraktar Y. “Portal ductopathy: clinical importance and nomenclature.” World journal of gastroenterology (2011). PMID: 21472098 ↗
L5REVIEW_NARRATIVECited in: Definition, Synonyms, and Classification - [5]
Kumar A, Sharma P, Arora A. “Review article: portal vein obstruction--epidemiology, pathogenesis, natural history, prognosis and treatment.” Alimentary pharmacology & therapeutics (2015). PMID: 25475582 ↗
L5REVIEW_NARRATIVECited in: Definition, Synonyms, and Classification - [6]
Shenoy A, Davis JPE. “Contemporary management of portal vein thromboses in patients with and without cirrhosis.” Current opinion in gastroenterology (2025). PMID: 39998941 ↗
L5REVIEW_NARRATIVECited in: Definition, Synonyms, and Classification - [7]
Bayraktar Y, Harmanci O. “Etiology and consequences of thrombosis in abdominal vessels.” World journal of gastroenterology (2006). PMID: 16534866 ↗
L5REVIEW_NARRATIVECited in: Definition, Synonyms, and Classification - [8]
Harmanci O, Bayraktar Y. “Portal hypertension due to portal venous thrombosis: etiology, clinical outcomes.” World journal of gastroenterology (2007). PMID: 17552000 ↗
L5REVIEW_NARRATIVECited in: Definition, Synonyms, and Classification - [9]
Yamagishi T, Hikone M, Sugiyama K et al.. “Purpura fulminans with Lemierre's syndrome caused by Gemella bergeri and Eikenella corrodens: a case report.” BMC infectious diseases (2018). PMID: 30340466 ↗
L4CASE_REPORTCited in: Definition, Synonyms, and Classification - [10]
Kahn F, Linder A, Petersson AC et al.. “Axillary abscess complicated by venous thrombosis: identification of Streptococcus pyogenes by 16S PCR.” Journal of clinical microbiology (2010). PMID: 20592151 ↗
L4CASE_REPORTCited in: Definition, Synonyms, and Classification - [11]
Kupfer M, Kucer BT, Kupfer H et al.. “Persons With Chronic Spinal Cord Injuries in the Emergency Department: a Review of a Unique Population.” The Journal of emergency medicine (2018). PMID: 29807681 ↗
L5REVIEW_NARRATIVECited in: Definition, Synonyms, and Classification - [12]
Comarmond C, Mirault T, Biard L et al.. “Takayasu Arteritis and Pregnancy.” Arthritis & rheumatology (Hoboken, N.J.) (2015). PMID: 26315109 ↗
L5OTHERCited in: Definition, Synonyms, and Classification - [13]
de Haan HG, van Hylckama Vlieg A, van der Gaag KJ et al.. “Male-specific risk of first and recurrent venous thrombosis: a phylogenetic analysis of the Y chromosome.” Journal of thrombosis and haemostasis : JTH (2016). PMID: 27495181 ↗
L5OTHERCited in: Definition, Synonyms, and Classification - [14]
Zhang X, Durham KM, Garza AA et al.. “Portal vein thrombosis, hepatic decompensation, and survival in patients with porto-sinusoidal vascular disease and portal hypertension.” Journal of gastroenterology (2023). PMID: 36692825 ↗
L5OTHERCited in: Definition, Synonyms, and Classification - [15]
Munk MR, Kashani AH, Tadayoni R et al.. “Recommendations for OCT Angiography Reporting in Retinal Vascular Disease: A Delphi Approach by International Experts.” Ophthalmology. Retina (2022). PMID: 35202889 ↗
L5OTHERCited in: Definition, Synonyms, and Classification - [16]
Bayona Molano MDP, Brackett W, Mena P et al.. “Complex filter removal using forceps from combined transfemoral and transjugular approach unhooking the filter apex using forceps and dual access: Two case reports.” Journal of cardiac surgery (2022). PMID: 35819367 ↗
L4CASE_REPORTCited in: Definition, Synonyms, and Classification - [17]
Shen Y, Jiang Y, Wang Y et al.. “Increased risk of venous thromboembolism in children and teenagers with inflammatory bowel disease: a systematic review and meta-analysis.” PeerJ (2026). PMID: 41940394 ↗
L2aSR_OBSCited in: Epidemiology and Risk Factors - [18]
Wen X, Wu H, He Y et al.. “Efficacy and safety of cyanoacrylate ablation vs endovenous radiofrequency ablation for varicose veins in chronic great saphenous vein insufficiency: A systematic review and meta-analysis.” Journal of vascular surgery. Venous and lymphatic disorders (2026). PMID: 41866115 ↗
L2aSR_OBSCited in: Epidemiology and Risk Factors - [19]
Das S, Simunovic N, Di Maria F et al.. “Prophylaxis does not prevent symptomatic venous thromboembolism following anterior cruciate ligament surgery: a systematic review and meta-analysis.” Journal of ISAKOS : joint disorders & orthopaedic sports medicine (2026). PMID: 41850529 ↗
L2aSR_OBSCited in: Epidemiology and Risk Factors - [20]
Gong M, Kong J, Gu J et al.. “Who benefits from a filter? Developing clinical prediction models for thrombus dislodgement in hospitalized patients with deep vein thrombosis: A multicenter retrospective study.” European journal of radiology (2026). PMID: 41946015 ↗
L2bCOHORTCited in: Epidemiology and Risk Factors, Diagnosis and Workup - [21]
Chen H, Chen K, Xie X et al.. “Association between triglyceride glucose- systemic immune inflammation index and deep venous thrombosis in fresh fracture patient: a real-world retrospective study.” Frontiers in endocrinology (2026). PMID: 41907552 ↗
L2bCOHORTCited in: Epidemiology and Risk Factors - [22]
Kou R, Mallick R, Brown C et al.. “Anticoagulation management and outcomes in patients with cancer-associated small venous thromboembolism: a retrospective cohort study.” Journal of thrombosis and haemostasis : JTH (2026). PMID: 41791657 ↗
L2bCOHORTCited in: Epidemiology and Risk Factors - [23]
Wardak YH, Chung YE, Maingard J et al.. “Quality of life following endovascular treatment of proximal lower limb DVT: A systematic review and meta-analysis.” Journal of vascular and interventional radiology : JVIR (2026). PMID: 41905683 ↗
L2aSR_OBSCited in: Epidemiology and Risk Factors - [24]
Botolin P, Robles R, Keshishian C et al.. “Impact of Stroke History and Interval on Outcomes of Total Hip Arthroplasty: A Retrospective Cohort Study.” Orthopedics (2026). PMID: 41885516 ↗
L2bCOHORTCited in: Epidemiology and Risk Factors, Diagnosis and Workup - [25]
Zhai Y, Cao X, Zheng S et al.. “[Comparative observation of analgesic efficacy between liposomal bupivacaine and "cocktail" therapy following artificial intelligence-assisted direct anterior approach total hip arthroplasty: A prospective randomized controlled study].” Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery (2026). PMID: 41981425 ↗
L1bRCTCited in: Epidemiology and Risk Factors, History and Physical Examination, Diagnosis and Workup - [26]
Li Y, Wang S, Zhao X. “Risk factors for TIVAD-related venous thrombosis in Chinese breast cancer patients undergoing chemotherapy: A single-center retrospective study.” Medicine (2026). PMID: 41861226 ↗
L2bCOHORTCited in: Epidemiology and Risk Factors, Diagnosis and Workup, Special Populations - [27]
Skeith L, Bates SM. “Sex Hormone Influences on Venous Thrombotic and Cardiovascular Risk.” The New England journal of medicine (2026). PMID: 41985134 ↗
L5REVIEW_NARRATIVECited in: Epidemiology and Risk Factors - [28]
Hou J, Mu G, Zhang Z et al.. “Hematological toxicities and thrombosis risk associated with immune checkpoint inhibitors: a pharmacovigilance study from 2014 to 2024.” Cancer immunology, immunotherapy : CII (2026). PMID: 41984243 ↗
L5OTHERCited in: Epidemiology and Risk Factors, Special Populations - [29]
Mansour M, Asi AR, Massalha E et al.. “Residual Perfusion Defects after Acute Pulmonary Embolism: Prevalence, Determinants, and Clinical Impact.” The American journal of medicine (2026). PMID: 41941949 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [30]
Gonzalez HC, Gordon SC, Trudeau S et al.. “Impact of Disease-Specific Treatment and Non-Selective Beta Blockers on Risk of PVT in Cirrhotic Patients With HCV or PBC.” Liver international : official journal of the International Association for the Study of the Liver (2026). PMID: 41933920 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [31]
Jones GD, Raja S, Ahmad U et al.. “Prospectively Screening for Venous Thromboembolism in Patients with Esophagectomy for Cancer Improves Survival: The Complexity of Simplicity.” The Journal of thoracic and cardiovascular surgery (2026). PMID: 41932434 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [32]
Sohail A, Powers MT, Suarez T et al.. “Direct Oral Anticoagulants Are Associated With Less Bleeding Risk Than Warfarin in Patients Undergoing Liver Resections.” The Journal of surgical research (2026). PMID: 41921475 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [33]
Yang L, Zhang Z, Li C et al.. “Effect of different durations of compression therapy on quality of life and recurrence after thermal ablation for varicose veins: a protocol for a prospective, multicenter, randomized controlled trial.” Frontiers in medicine (2026). PMID: 41907264 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [34]
Yang S, Li G, Li Y et al.. “In-hospital deep vein thrombosis after tibial plateau fractures: incidence, laterality/anatomy, and risk factors in a multicenter retrospective cohort of 3366 patients.” Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology (2026). PMID: 41886203 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [35]
Horton CE, Wi MS, Sayegh M et al.. “Short-term outcomes of ultrasound-assisted catheter-directed thrombolysis and mechanical thrombectomy in management of intermediate-risk pulmonary embolism.” Journal of vascular surgery. Venous and lymphatic disorders (2026). PMID: 41866114 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [36]
Mao J, Qin L, Gao M et al.. “Perioperative management of colorectal surgical patients receiving a direct oral anticoagulant: a scoping review, particular emphasis on procedure-specific risks, and pharmacogenomics.” Frontiers in cardiovascular medicine (2026). PMID: 41835471 ↗
L5REVIEW_NARRATIVECited in: Epidemiology and Risk Factors - [37]
Doukhi D, Aghetti A, Siguret V et al.. “Specific Features of Cerebral Venous Thrombosis Associated With Iron Deficiency Anemia.” Journal of the American Heart Association (2026). PMID: 41804921 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [38]
Doiron JE, Corpodean F, Kachmar M et al.. “Prevalence of early marginal ulcer in sleeve to bypass conversions: an analysis of the 2020-2022 MBSAQIP.” Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery (2026). PMID: 41791958 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [39]
Fu P, Li Y, Wang C et al.. “Deletion of platelet STK10 impairs deep vein thrombus formation.” Journal of thrombosis and haemostasis : JTH (2026). PMID: 41791658 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [40]
Daghlas I, Perez-Alcantara M, Gill D. “Direct Oral Anticoagulant Protein Targets and Risk of Cerebral Venous Thrombosis: A Mendelian Randomization Study.” Neurology (2026). PMID: 41785432 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [41]
Wu S, Qiu F, Zhang F et al.. “Hepatic arterial infusion chemotherapy combined with apatinib plus camrelizumab for advanced hepatocellular carcinoma with type Vp4 portal vein tumor thrombosis: a multicenter propensity score-matching analysis.” Frontiers in immunology (2026). PMID: 41782861 ↗
L5OTHERCited in: Epidemiology and Risk Factors, Diagnosis and Workup, Special Populations - [42]
Ye H, Li J, Du L et al.. “Development and validation of a deep vein thrombosis risk assessment tool for surgical patients aged 75 years and older.” BMC geriatrics (2026). PMID: 41782093 ↗
L5OTHERCited in: Epidemiology and Risk Factors, Diagnosis and Workup - [43]
Sobih NM, Vellema J, van de Munckhof A et al.. “Impact of anaemia severity on functional outcome in patients with cerebral venous thrombosis: a DOAC-CVT substudy.” European stroke journal (2026). PMID: 41758562 ↗
L5OTHERCited in: Epidemiology and Risk Factors - [44]
Ke X, Liu Y, Chen X et al.. “Association between preoperative anemia and postoperative delirium in elderly patients undergoing total hip arthroplasty with combined spinal-epidural anesthesia: A retrospective cohort study.” Journal of anesthesia and translational medicine (2025). PMID: 41929925 ↗
L2bCOHORTCited in: Epidemiology and Risk Factors - [45]
Kamada K, Fukaya E, Iwata E et al.. “Disaster-associated venous thromboembolism countermeasures in Japan: Insights from past major earthquakes.” Journal of vascular surgery. Venous and lymphatic disorders (2026). PMID: 40935330 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors, Pathophysiology - [46]
Liu S, Shen Y, Chen J et al.. “The critical role of platelets in venous thromboembolism: Pathogenesis, clinical status, and emerging therapeutic strategies.” Blood reviews (2025). PMID: 40382294 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors, Pathophysiology - [47]
Muscat-Baron L, Borg AL, Attard LM et al.. “Cancer-Associated Abdominal Vein Thrombosis.” Cancers (2023). PMID: 37958466 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [48]
Johnson RR, Faustino EVS. “Central venous catheter-associated deep vein thrombosis in critically ill pediatric patients: risk factors, prevention, and treatment.” Current opinion in pediatrics (2022). PMID: 35634701 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [49]
Hembrom AA, Srivastava S, Garg I et al.. “MicroRNAs in venous thrombo-embolism.” Clinica chimica acta; international journal of clinical chemistry (2020). PMID: 32017924 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [50]
Caprini JA. “Risk assessment as a guide for the prevention of the many faces of venous thromboembolism.” American journal of surgery (2010). PMID: 20103082 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [51]
Levine MN. “Adjuvant therapy and thrombosis: how to avoid the problem?” Breast (Edinburgh, Scotland) (2007). PMID: 17720502 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [52]
Didembourg M, Morimont L, De Gottal E et al.. “The maternal hemostatic shift: Understanding VTE risk in pregnancy and postpartum.” Thrombosis research (2026). PMID: 41352199 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors, Pathophysiology, Special Populations - [53]
Mehta JL, Calcaterra G, Bassareo PP. “COVID-19, thromboembolic risk, and Virchow's triad: Lesson from the past.” Clinical cardiology (2020). PMID: 33176009 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [54]
Liu A, Minasian RA, Maniago E et al.. “Venous Thromboembolism Chemoprophylaxis in Burn Patients: A Literature Review and Single-Institution Experience.” Journal of burn care & research : official publication of the American Burn Association (2021). PMID: 32842151 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [55]
Stone J, Hangge P, Albadawi H et al.. “Deep vein thrombosis: pathogenesis, diagnosis, and medical management.” Cardiovascular diagnosis and therapy (2017). PMID: 29399531 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [56]
Byrnes JR, Wolberg AS. “New findings on venous thrombogenesis.” Hamostaseologie (2017). PMID: 27878206 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [57]
Congly SE, Lee SS. “Portal vein thrombosis: should anticoagulation be used?” Current gastroenterology reports (2013). PMID: 23314804 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [58]
López JA, Chen J. “Pathophysiology of venous thrombosis.” Thrombosis research (2009). PMID: 19303501 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [59]
Haas P, Landgraf H. “Studies on travel-related thrombosis.” VASA. Zeitschrift fur Gefasskrankheiten (2008). PMID: 19003739 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [60]
Merli GJ. “Pathophysiology of venous thrombosis, thrombophilia, and the diagnosis of deep vein thrombosis-pulmonary embolism in the elderly.” Clinics in geriatric medicine (2006). PMID: 16377468 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [61]
Savulescu-Fiedler I, Siliste RN, Homentcovschi C et al.. “The role of endothelial cell protein C receptor gene polymorphism in venous thromboembolic disease: a case report and literature review.” Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (2025). PMID: 40643034 ↗
L4CASE_REPORTCited in: Etiology and Triggering Factors, Pathophysiology - [62]
Sasson I, Sorin V, Ziv-Baran T et al.. “Unexpected early pulmonary thrombi in war injured patients.” European radiology (2026). PMID: 40833493 ↗
L5OTHERCited in: Etiology and Triggering Factors - [63]
Gebhard CE, Zellweger N, Gebhard C et al.. “Prone Positioning as a Potential Risk Factor for Deep Vein Thrombosis in COVID-19 Patients: A Hypothesis Generating Observation.” Journal of clinical medicine (2021). PMID: 35011843 ↗
L5OTHERCited in: Etiology and Triggering Factors - [64]
Rajeeva Pandian NK, Walther BK, Suresh R et al.. “Microengineered Human Vein-Chip Recreates Venous Valve Architecture and Its Contribution to Thrombosis.” Small (Weinheim an der Bergstrasse, Germany) (2020). PMID: 33205630 ↗
L5OTHERCited in: Etiology and Triggering Factors - [65]
Lurie JM, Png CYM, Subramaniam S et al.. “Virchow's triad in "silent" deep vein thrombosis.” Journal of vascular surgery. Venous and lymphatic disorders (2019). PMID: 31078515 ↗
L5OTHERCited in: Etiology and Triggering Factors - [66]
Alturki N, Alkahtani M, Daghistani M et al.. “Incidence and risk factors for deep vein thrombosis among pediatric burn patients.” Burns : journal of the International Society for Burn Injuries (2019). PMID: 31018912 ↗
L5OTHERCited in: Etiology and Triggering Factors - [67]
Avila ML, Duan L, Cipolla A et al.. “Postthrombotic syndrome following upper extremity deep vein thrombosis in children.” Blood (2014). PMID: 24957144 ↗
L5OTHERCited in: Etiology and Triggering Factors - [68]
Wilson TJ, Brown DL, Meurer WJ et al.. “Risk factors associated with peripherally inserted central venous catheter-related large vein thrombosis in neurological intensive care patients.” Intensive care medicine (2012). PMID: 22113818 ↗
L5OTHERCited in: Etiology and Triggering Factors - [69]
Bittencourt PL, Couto CA, Ribeiro DD. “Portal vein thrombosis and budd-Chiari syndrome.” Clinics in liver disease (2009). PMID: 19150317 ↗
L5OTHERCited in: Etiology and Triggering Factors - [70]
Bagot CN, Arya R. “Virchow and his triad: a question of attribution.” British journal of haematology (2008). PMID: 18783400 ↗
L5OTHERCited in: Etiology and Triggering Factors - [71]
Shaydakov ME, Diaz JA, Eklöf B et al.. “Venous valve hypoxia as a possible mechanism of deep vein thrombosis: a scoping review.” International angiology : a journal of the International Union of Angiology (2024). PMID: 38864688 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [72]
Sapota-Zaręba K, Nasierowski T. “The risk of pulmonary embolism in the context of various clinical situations and management in psychiatric patients.” Psychiatria polska (2023). PMID: 38345121 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [73]
Malone PC, Agutter PS. “The aetiology of deep venous thrombosis.” QJM : monthly journal of the Association of Physicians (2006). PMID: 16905749 ↗
L5REVIEW_NARRATIVECited in: Etiology and Triggering Factors - [74]
Stojanovic M, Djuric M, Nenadic I et al.. “Vascular Complications of Long COVID-From Endothelial Dysfunction to Systemic Thrombosis: A Systematic Review.” International journal of molecular sciences (2025). PMID: 41516301 ↗
L2aSR_OBSCited in: Pathophysiology - [75]
Gandhi SD, Mohanty S, von Riegen H et al.. “Efficacy and Safety of Chemical Venous Thromboembolism Prophylaxis in Spine Trauma Patients: A Systematic Review and Meta-analysis Comparing Anticoagulant Types.” Clinical spine surgery (2026). PMID: 40071770 ↗
L2aSR_OBSCited in: Pathophysiology - [76]
Shi H, Zhao Y, Shi X et al.. “Effects of traditional Chinese medicine decoctions on coagulation and deep vein thrombosis after total hip arthroplasty: Network meta-analysis.” Explore (New York, N.Y.) (2026). PMID: 41232428 ↗
L2aSR_OBSCited in: Pathophysiology - [77]
Krupa-Zabiegała J, Michel PS, Stępień K et al.. “Higher citrullinated histone H3 is associated with postthrombotic syndrome: a cohort study.” Journal of thrombosis and haemostasis : JTH (2026). PMID: 41192568 ↗
L2bCOHORTCited in: Pathophysiology - [78]
Peng J, Long S, Feng L. “Deep Vein Thrombosis Prevention in Acute Ischemic Stroke Patients with Lower Limb Paralysis: A Narrative Review.” Journal of clinical medicine (2026). PMID: 41899016 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [79]
Sparić R, Stojković M, Šarac M et al.. “Venous Thromboembolism Associated with Uterine Fibroids: A Review of Reported Cases.” Journal of clinical medicine (2026). PMID: 41598382 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology, History and Physical Examination - [80]
Albasanz-García P, Ward MP, Norris LA. “Mechanisms of anticancer treatment-induced arterial and venous thrombosis.” Journal of thrombosis and haemostasis : JTH (2026). PMID: 41203043 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [81]
Limper U, Jordan J. “Neck-vein thrombosis during spaceflight.” British journal of clinical pharmacology (2026). PMID: 41035389 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [82]
Piazza G, Krishnathasan D, Hamade N et al.. “Superficial Vein Thrombosis: A Review.” JAMA (2025). PMID: 40952730 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [83]
Dhar R, Dos Passos RR, Gower RM et al.. “Toward targeting of inflammasome signaling in venous thrombosis.” Journal of thrombosis and haemostasis : JTH (2025). PMID: 40946806 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [84]
Galanaud JP, Laroche JP, Righini M. “The history and historical treatments of deep vein thrombosis: toward the era of new anticoagulants.” Journal of thrombosis and haemostasis : JTH (2025). PMID: 40714194 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [85]
Shao W, Wang Z, Wu J et al.. “Targeting toll-like receptors: unveiling potential therapeutic strategies for deep vein thrombosis.” Frontiers in immunology (2025). PMID: 40510367 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [86]
Byun JH, Jung J, Woo J. “Clonal hematopoiesis and thromboembolic diseases: a review.” Journal of thrombosis and haemostasis : JTH (2025). PMID: 40499722 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [87]
Badulescu OV, Ciocoiu M, Vladeanu MC et al.. “The Role of Platelet Dysfunctions in the Pathogenesis of the Hemostatic-Coagulant System Imbalances.” International journal of molecular sciences (2025). PMID: 40141398 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [88]
Budnik I, Kumskova M, Chauhan AK. “Metabolic pathways in deep vein thrombosis: a new frontier for therapeutic intervention.” Blood (2025). PMID: 40132161 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [89]
Davis J, Maranto M, Kennedy J et al.. “Transforming Growth Factors in Venous Thrombus Formation and Resolution.” Arteriosclerosis, thrombosis, and vascular biology (2025). PMID: 40109257 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [90]
Cox C, Roberts LN. “Basics of diagnosis and treatment of venous thromboembolism.” Journal of thrombosis and haemostasis : JTH (2025). PMID: 39938684 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [91]
Secades D, Dufner Krieger S, Hidalgo Ramos RA et al.. “Incidence of Deep Vein Thrombosis in Patients With COVID-19: A Systematic Review.” Cureus (2025). PMID: 40861621 ↗
L2aSR_OBSCited in: Pathophysiology - [92]
Papadakis E, Gavriilaki E, Kotsiou N et al.. “Fright of Long-Haul Flights: Focus on Travel-Associated Thrombosis.” Seminars in thrombosis and hemostasis (2025). PMID: 40015328 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [93]
Kell DB, Pretorius E. “The Proteome Content of Blood Clots Observed Under Different Conditions: Successful Role in Predicting Clot Amyloid(ogenicity).” Molecules (Basel, Switzerland) (2025). PMID: 39942772 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology - [94]
Denorme F, Portier I, Castro H et al.. “Platelet mTOR Is a Regulator of Sterile Immunothrombosis.” Arteriosclerosis, thrombosis, and vascular biology (2026). PMID: 41783929 ↗
L5OTHERCited in: Pathophysiology - [95]
Shen YJ, Nie ZY, Zhang JQ et al.. “Cyanidin-3-O-glucoside promotes late-stage venous thrombus resolution in mice, accompanied by reduced macrophage M1-associated inflammation and attenuated HIF-1α-linked signaling.” Food & function (2026). PMID: 41734240 ↗
L5OTHERCited in: Pathophysiology - [96]
Chen C, Ge X, Fu D et al.. “Endothelial Cell-Specific Molecule-1 (ESM1): An Endogenous Anticoagulant and Protective Factor in Venous Thrombosis.” Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2026). PMID: 41517829 ↗
L5OTHERCited in: Pathophysiology - [97]
Suzuki N, Suzuki A, Tamura S et al.. “Antithrombotic Therapy on Antithrombin Resistance in a Mouse Model.” Arteriosclerosis, thrombosis, and vascular biology (2026). PMID: 41503699 ↗
L5OTHERCited in: Pathophysiology - [98]
Wongweerakit O, Sangthong B, Akaraborworn O et al.. “De novo pulmonary embolism following chest trauma: fact or fiction?” European journal of trauma and emergency surgery : official publication of the European Trauma Society (2025). PMID: 41410754 ↗
L5OTHERCited in: Pathophysiology - [99]
Noda H, Yutani C, Takahashi S et al.. “Morphological Visualization of Thrombi During Catheter-Directed Fibrinolytic Therapy for Pulmonary Thromboembolism.” The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (2026). PMID: 41292114 ↗
L5OTHERCited in: Pathophysiology - [100]
Shi TL, Yang ZB, Zhang YQ et al.. “Vibration-stimulation device-assisted enhanced recovery after lower limb fracture surgery: A randomized controlled trial.” International orthopaedics (2026). PMID: 41413326 ↗
L1bRCTCited in: History and Physical Examination - [101]
Betensky M, Mosha M, Ashour D et al.. “Postthrombotic syndrome-related chronic limb pain in children: findings from the Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) trial.” Journal of thrombosis and haemostasis : JTH (2026). PMID: 41407160 ↗
L1bRCTCited in: History and Physical Examination - [102]
Le Gal G, Robert-Ebadi H, Thiruganasambandamoorthy V et al.. “Age-Adjusted D-Dimer Cutoff Levels to Rule Out Deep Vein Thrombosis.” JAMA (2026). PMID: 41490105 ↗
L2bTRIAL_NONRANDOMCited in: History and Physical Examination - [103]
Kang T, Han S, Lu YL et al.. “Artificial intelligence risk stratification from dynamic digital subtraction angiography radiomics predicts pulmonary embolism and associates with clinical outcomes in deep vein thrombosis: A retrospective cohort study.” Journal of vascular surgery. Venous and lymphatic disorders (2026). PMID: 41638306 ↗
L2bCOHORTCited in: History and Physical Examination - [104]
Simard C, Le Gal G, Lazo-Langner A et al.. “Association Between Bariatric Surgery and the Long-Term Risk for Venous Thromboembolism: A Population-Based Matched Cohort Study.” American journal of hematology (2026). PMID: 41588795 ↗
L2bCOHORTCited in: History and Physical Examination - [105]
Klimitz FJ, Knoedler S, Fabi A et al.. “Weighing the Risk: The Impact of Obesity on 30-Day Complications After Cosmetic Abdominoplasty-An Observational Cohort Study of 1,778 Cases.” Aesthetic plastic surgery (2026). PMID: 41201611 ↗
L2bCOHORTCited in: History and Physical Examination - [106]
Ye Y, Mahati S, Aihemaiti W et al.. “A postpartum-adapted algorithm for safe management of suspected pulmonary embolism: a retrospective cohort study.” American journal of obstetrics and gynecology (2026). PMID: 41183725 ↗
L2bCOHORTCited in: History and Physical Examination - [107]
. “[Guidelines for the management of cerebral venous thrombosis during pregnancy and the puerperium (2025 edition)].” Zhonghua yi xue za zhi (2025). PMID: 41145272 ↗
L1cGUIDELINECited in: History and Physical Examination - [108]
Abbattista M, Truma A, Martinelli I et al.. “The risk of cerebral vein thrombosis associated with different types of combined hormonal contraceptives: a case-control study.” Journal of thrombosis and haemostasis : JTH (2025). PMID: 40617503 ↗
L3bCASE_CONTROLCited in: History and Physical Examination - [109]
Li S, Wang M, Xu Y. “Predictors of pulmonary infarction in pediatric pulmonary embolism: A retrospective cohort study.” Thrombosis research (2025). PMID: 41086550 ↗
L2bCOHORTCited in: History and Physical Examination - [110]
Ajrawat P, Price B, Gooch D et al.. “Assessing Postoperative Pain in Patients Who Underwent Total Knee Arthroplasty Using an Automated Self-Logging Patient-Reported Outcome Measure Collection Device: Retrospective Cohort Study.” JMIR human factors (2025). PMID: 40638842 ↗
L2bCOHORTCited in: History and Physical Examination - [111]
Ren Y, Liu R. “Prevalence and risk factors of deep vein thrombosis in elderly: a systematic review and meta-analysis.” Open medicine (Warsaw, Poland) (2026). PMID: 41726136 ↗
L2aSR_OBSCited in: History and Physical Examination - [112]
Kargar-Soleimanabad S, Najafi S, Ahmadi M et al.. “Diagnostic value of the wells score for lower extremity deep vein thrombosis in hospitalized patients: A case-control study.” Phlebology (2026). PMID: 41489509 ↗
L3bCASE_CONTROLCited in: History and Physical Examination - [113]
Zhao Y, Zhou T, Fang Q et al.. “Short-term outcomes after hybrid unicompartmental knee arthroplasty: A retrospective cohort study with minimum 3-year follow-up.” Medicine (2026). PMID: 41861224 ↗
L2bCOHORTCited in: History and Physical Examination, Diagnosis and Workup - [114]
Benseler A, Gien LT, Swift B et al.. “Association of body mass index and length of stay in patients undergoing minimally invasive surgery for uterine cancer: a National Surgical Quality Improvement Program (NSQIP) study.” International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (2026). PMID: 41774951 ↗
L5OTHERCited in: History and Physical Examination, Diagnosis and Workup, Special Populations - [115]
Kulachote N, Phoophiboon P, Chanplakorn P et al.. “Risk Factors for Preoperative DVT in Elderly Patients with Hip Fractures.” Journal of clinical medicine (2026). PMID: 41753171 ↗
L5OTHERCited in: History and Physical Examination - [116]
Fu C, Chen J, Shen Z et al.. “Plasma Protein Mediation of the Association Between Blood Pressure and Retinal Vascular Occlusion.” Translational vision science & technology (2025). PMID: 41324311 ↗
L5OTHERCited in: History and Physical Examination - [117]
Smadi Z, Lingam S, Muwalla R et al.. “Weight on the fixation: the influence of body mass index on lower extremity fracture fixation outcomes.” Injury (2025). PMID: 41197500 ↗
L5OTHERCited in: History and Physical Examination - [118]
Xu JJ, Johnson MC, Lama G et al.. “The Effect of Body Mass Index on the Efficacy of Semaglutide Use at the Time of Total Knee Arthroplasty.” The Journal of arthroplasty (2026). PMID: 41072554 ↗
L5OTHERCited in: History and Physical Examination - [119]
Akar B, Oztürkmen Y, Balioglu MB et al.. “The Effect of Obesity on Simultaneous Bilateral Knee Arthroplasty Surgery.” Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews (2025). PMID: 40981512 ↗
L5OTHERCited in: History and Physical Examination - [120]
Hoedemakers T, van Hattum ES, Petri BJ et al.. “Upper extremity post-thrombotic syndrome score: consensus results from an international Delphi study.” Journal of thrombosis and haemostasis : JTH (2025). PMID: 40973017 ↗
L5OTHERCited in: History and Physical Examination - [121]
O'Connor B, Meister K, Fellner A et al.. “Analyzing the Adequacy of BMI-Tiered Enoxaparin Dosing for Venous Thromboembolism Prophylaxis in the Bariatric Surgery Population Based on Anti-Factor Xa Assay Data.” Obesity surgery (2025). PMID: 40615759 ↗
L5OTHERCited in: History and Physical Examination - [122]
Canas A, Epstein J, Chen T et al.. “Diagnosis of Venous Thromboembolism.” The Medical clinics of North America (2025). PMID: 40500082 ↗
L5REVIEW_NARRATIVECited in: History and Physical Examination - [123]
Jin C, Hu Y, Liu F. “Clinical characteristics, clinical laboratories, and risk factors of elderly patients with chronic obstructive pulmonary disease complicated with pulmonary embolism.” Frontiers in medicine (2025). PMID: 40438367 ↗
L5OTHERCited in: History and Physical Examination - [124]
Kumar S, Nasef H, Yates Z et al.. “Association of Body Mass Index With Severe Sepsis Outcomes in Critically-Ill Severely Injured Adult Trauma Patients: A National Analysis.” The Journal of surgical research (2025). PMID: 40378666 ↗
L5OTHERCited in: History and Physical Examination - [125]
Cherkaoui M, Al-Attabi M, Salimi S et al.. “Proximal venous ultrasound with risk stratification safely excludes deep venous thrombosis in emergency department routine care: an observational study.” Scandinavian journal of trauma, resuscitation and emergency medicine (2025). PMID: 40369661 ↗
L5OTHERCited in: History and Physical Examination - [126]
Masuda Y, Konishi T, Yakushijin Y et al.. “Impact of body mass index on D-dimer diagnostic utility for deep vein thrombosis in patients with cancer: a single-center retrospective analysis.” International journal of clinical oncology (2025). PMID: 40355784 ↗
L5OTHERCited in: History and Physical Examination - [127]
Daher M, Liu J, Smith N et al.. “Short-term outcomes of outpatient total joint arthroplasty in morbidly obese patients.” European journal of orthopaedic surgery & traumatology : orthopedie traumatologie (2025). PMID: 40349255 ↗
L5OTHERCited in: History and Physical Examination - [128]
Waseem MH, Abideen ZU, Rissardo JP et al.. “Comparing Efficacy and Safety of Different Anticoagulants in Cerebral Venous Thrombosis: A Systematic Review and Network Meta-Analysis.” Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis (2026). PMID: 41773593 ↗
L2aSR_OBSCited in: Diagnosis and Workup - [129]
Schmidt C, Papo M, Taïeb D et al.. “Severe thrombocytopenia in antiphospholipid syndrome: a retrospective study of 432 patients.” RMD open (2026). PMID: 41956709 ↗
L2bCOHORTCited in: Diagnosis and Workup, Special Populations - [130]
Huang J, Lin P, Wang L et al.. “Case Report: Primary vascular sarcoma presenting as massive pulmonary embolism salvaged by veno-arterial extracorporeal membrane oxygenation and interventional therapy.” Frontiers in cardiovascular medicine (2026). PMID: 41940087 ↗
L4CASE_REPORTCited in: Diagnosis and Workup - [131]
Mo R, Yu S, Xu H et al.. “Upadacitinib in refractory ulcerative colitis patients with high thromboembolic risk: two case reports.” Frontiers in immunology (2026). PMID: 41853288 ↗
L4CASE_REPORTCited in: Diagnosis and Workup - [132]
Hu H, Cai D, Li J et al.. “Pulmonary infection by Nocardia saintgeorgesii mimicking lung cancer with concurrent pulmonary embolism in an immunocompetent host: a case highlighting the diagnostic role of mNGS.” Frontiers in cellular and infection microbiology (2026). PMID: 41822328 ↗
L4CASE_REPORTCited in: Diagnosis and Workup, Differential Diagnosis, Special Populations - [133]
Xu C, Annapureddy H, Carson L et al.. “Impact of a factor Xa inhibitor (apixaban) on SIV pathogenesis and response to antiretroviral therapy.” JCI insight (2026). PMID: 41948932 ↗
L5OTHERCited in: Diagnosis and Workup - [134]
Mukund A, Thakur V, Jindal A et al.. “Long-Term Efficacy and Outcomes of Endovascular Interventions in Budd-Chiari Syndrome-A Real World Analysis.” Liver international : official journal of the International Association for the Study of the Liver (2026). PMID: 41947698 ↗
L5OTHERCited in: Diagnosis and Workup - [135]
Terao R, Fujino R, Hayashi K et al.. “Role of Autotaxin in the Pathogenesis of Retina Ischemia and Its Therapeutic Implications.” International journal of molecular sciences (2026). PMID: 41898636 ↗
L5OTHERCited in: Diagnosis and Workup - [136]
Deng Y, Liu Y, Li X et al.. “Delayed anti-vascular endothelial growth factor therapy in patients with type 2 diabetes mellitus and branch retinal vein occlusion-associated macular edema negatively affects visual outcomes.” Frontiers in endocrinology (2026). PMID: 41884213 ↗
L5OTHERCited in: Diagnosis and Workup - [137]
Zhan J, Qiao D, Sun G et al.. “Geometric Decomposition of OCT Angiography in RVO: Unmasking Congestive Versus Compensatory Phenotypes and Deep Retina-Choroid Coupling.” Translational vision science & technology (2026). PMID: 41873904 ↗
L5OTHERCited in: Diagnosis and Workup - [138]
Jia J, Ning C, Wang Q et al.. “Stereotactic body radiotherapy plus lenvatinib and sintilimab with and without transarterial embolization for advanced hepatocellular carcinoma with portal vein tumor thrombus: a dual-center, propensity score-matched retrospective analysis.” Frontiers in immunology (2026). PMID: 41859127 ↗
L5OTHERCited in: Diagnosis and Workup, Special Populations - [139]
Iby J, Kreminger J, Stino H et al.. “Retinal Characteristics in Eyes With Retinal Vein Occlusion Using Widefield Swept-Source Optical Coherence Tomography Angiography.” Investigative ophthalmology & visual science (2026). PMID: 41854209 ↗
L5OTHERCited in: Diagnosis and Workup - [140]
Hofstetter RV, Marx CE, Kraaijpoel N et al.. “Reporting of D-dimer testing in venous thromboembolism diagnostic management studies: a scoping review.” Journal of thrombosis and haemostasis : JTH (2026). PMID: 41839295 ↗
L5REVIEW_NARRATIVECited in: Diagnosis and Workup - [141]
Cun D, Li J, He P et al.. “Preoperative deep vein thrombosis in tibial plateau fractures: development and internal validation of an interpretable multivariable machine-learning diagnostic model.” Frontiers in medicine (2026). PMID: 41767515 ↗
L5OTHERCited in: Diagnosis and Workup - [142]
Wu CL, Lu JW, Ho YJ et al.. “Deep Immunophenotyping Reveals a Resilient Tph-ABC Axis in Difficult-to-treat Rheumatoid Arthritis: A Case Report of JAK Inhibitor Failure Complicated by Herpes Zoster and Thrombosis.” In vivo (Athens, Greece) (2026). PMID: 41760293 ↗
L4CASE_REPORTCited in: Diagnosis and Workup - [143]
Ezeh UC, Tesema N, Hasnie S et al.. “Isolated external jugular thrombophlebitis secondary to acute pharyngitis: a case report and a review of the literature.” Italian journal of pediatrics (2024). PMID: 39285285 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [144]
Knight GM, Desai KR. “Team-based approach to deep venous disease: A multidisciplinary approach to the multifaceted problem of thrombotic lower extremity venous disease.” Seminars in vascular surgery (2025). PMID: 41386912 ↗
L5REVIEW_NARRATIVECited in: Differential Diagnosis - [145]
Phuyal D, Abbas F, Darras O et al.. “Evaluating the Safety of Immediate Lymphatic Reconstruction With Implant-Based Breast Reconstruction: Eight-Year Institutional Review.” Microsurgery (2025). PMID: 40956145 ↗
L5REVIEW_NARRATIVECited in: Differential Diagnosis - [146]
Hassanzadeh S, Lakhman Y, Sadowski EA et al.. “Abdominopelvic complications of gynecologic malignancy: Essentials for radiologists.” European journal of radiology (2025). PMID: 40753689 ↗
L5REVIEW_NARRATIVECited in: Differential Diagnosis - [147]
Hurst M, Shin L. “Charcot neuroarthropathy: Surgical and conservative treatment approaches.” Seminars in vascular surgery (2025). PMID: 40086925 ↗
L5REVIEW_NARRATIVECited in: Differential Diagnosis - [148]
Wen X, Wu Z. “A retrospective study on the diagnostic value of ultrasonography for primary vascular leiomyosarcoma misdiagnosed as deep vein thrombosis.” Phlebology (2026). PMID: 40454675 ↗
L2bCOHORTCited in: Differential Diagnosis - [149]
Mitchell S, Rojas OG, Mathavan A et al.. “A 36-Year-Old Man With Hemoptysis and Fevers.” Chest (2026). PMID: 41672657 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [150]
Lesage L, Barral PA, Chew A et al.. “Streptococcus constellatus-associated Lemierre syndrome complicated by pulmonary artery pseudoaneurysm in an 11-year-old girl.” Pediatric radiology (2026). PMID: 41511544 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [151]
Ossuna M, Hamamoto Filho PT, Zanini MA. “Spontaneous thrombosis of drainage vein in cavernoma-associated developmental venous anomaly.” Neuroradiology (2025). PMID: 41065868 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [152]
DSouza R, Kuruvilla Thomas S, Patharateeranart K et al.. “Pseudo hepatic vein thrombosis in a newborn with infracardiac total anomalous pulmonary venous connection.” Pediatric radiology (2024). PMID: 39485501 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [153]
Godoy IRB, Cantarelli Rodrigues T, Alharfi M et al.. “Imaging in the diagnosis and characterization of tennis leg.” Skeletal radiology (2026). PMID: 41981329 ↗
L5REVIEW_NARRATIVECited in: Differential Diagnosis - [154]
Embaby O, Bin Asmadi A, Binte Asmadi A et al.. “PATHOGENESIS OF ACUTE DIABETIC CHARCOT ARTHROPATHY IN THE FOOT AND ANKLE: A COMPREHENSIVE LITERATURE REVIEW.” Orthopedic reviews (2025). PMID: 40969400 ↗
L5REVIEW_NARRATIVECited in: Differential Diagnosis - [155]
Jang E, Moon KY, Park SC et al.. “Primary leiomyosarcoma originating from the deep femoral vein initially presenting as chronic deep vein thrombosis: A case report and review of literature.” Medicine (2026). PMID: 41961719 ↗
L4CASE_REPORTCited in: Differential Diagnosis, Special Populations - [156]
Cheng L, Li L. “Tumor-like cortical venous thrombosis: Case report and literature review.” Medicine (2026). PMID: 41766497 ↗
L4CASE_REPORTCited in: Differential Diagnosis, Special Populations - [157]
Ak S, Thomas-Ogunniyi J, Takei H. “Intravascular Fasciitis Mimicking Deep Vein Thrombosis with Pulmonary Embolism in May-Thurner Syndrome: First Reported Case with Literature Review.” Annals of clinical and laboratory science (2025). PMID: 40962462 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [158]
Teshima R, Saito-Sasaki N, Sawada Y. “Age as a key risk factor for deep vein thrombosis in patients with lower limb cellulitis.” Frontiers in medicine (2025). PMID: 40620438 ↗
L5OTHERCited in: Differential Diagnosis - [159]
Cleary CM, Orosco E, Gallagher J et al.. “Continuation of anticoagulation through ambulatory phlebectomy does not impact postoperative bleeding risk.” Journal of vascular surgery. Venous and lymphatic disorders (2025). PMID: 39890080 ↗
L5OTHERCited in: Differential Diagnosis - [160]
Awashra A, Salameh AA, Milhem F et al.. “Right atrial thrombus mimicking cardiac myxoma: surgical and postoperative management.” Journal of cardiothoracic surgery (2025). PMID: 41422031 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [161]
Phillips I, Chen J, Milhem M et al.. “Vascular Leiomyosarcoma Masquerading as Chronic Deep Venous Thrombosis.” Clinical nuclear medicine (2026). PMID: 41380714 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [162]
Romano A, Kaisari E, Belkoniene M et al.. “A case of paracentral acute middle maculopathy and retinal vein occlusion: idiopathic occlusive retinal vasculitis or incomplete Behçet's disease?” BMC ophthalmology (2025). PMID: 41088010 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [163]
Bass R, Mitta P, Burgan C et al.. “Intravascular organizing thrombus in the forearm: a unique imaging presentation.” Skeletal radiology (2026). PMID: 41068310 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [164]
Tse JD, Laller S, Kharait S. “Case Report: Steroids for diabetic myonecrosis in ESKD: an unconventional treatment with unexpected success.” Frontiers in nephrology (2025). PMID: 40963896 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [165]
Al-Akhali ES, Alshoabi SA, Muslem HF et al.. “Multisystemic Tuberculosis Masquerading as Aggressive Cardiac Tumor Causing Budd-Chiari Syndrome Disseminated to the Brain Resulting in Death of a Six-Year-Old Boy.” Pathogens (Basel, Switzerland) (2025). PMID: 40872282 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [166]
Okumura M, Sakuta K, Gomi T et al.. “Atypical intracerebral hemorrhage and internal jugular vein thrombosis in meningovascular neurosyphilis.” Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (2025). PMID: 40633667 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [167]
Erb BM, Jeffrey JH, Reed DS et al.. “MRSA Cellulitis with Orbital and Retinal Abscesses Resulting in Lemierre Syndrome Following Eyebrow Piercing.” Ophthalmic plastic and reconstructive surgery (Unknown). PMID: 39718131 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [168]
Reich T, Blum B, Zimmerli L. “[The slightly different neck pain].” Praxis (2026). PMID: 41784513 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [169]
Gietzelt C, Wiedemann J, Lappas A et al.. “[Thrombosis of the superior ophthalmic vein-A case series and review of the literature].” Die Ophthalmologie (2024). PMID: 39266751 ↗
L4CASE_REPORTCited in: Differential Diagnosis - [170]
Duan H, Jiang C, Zhang B et al.. “Risk of Malignancies and Major Adverse Cardiovascular Events Related to JAK Inhibitors in Rheumatoid Arthritis: A Meta-Analysis.” Clinical pharmacology and therapeutics (2026). PMID: 41427516 ↗
L2aSR_OBSCited in: Special Populations - [171]
Chen K, Zhuo L, Liu Z et al.. “Presurgical molecular therapy for renal cell carcinoma with venous tumor thrombus: a systematic review and meta-analysis.” Frontiers in immunology (2025). PMID: 41394875 ↗
L2aSR_OBSCited in: Special Populations - [172]
Willems RAL, van Diepen AE, Dekker EN et al.. “Thromboembolic Events During Perioperative Therapy for Resectable and Borderline Resectable Pancreatic Cancer in the PREOPANC-2 Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026). PMID: 41610374 ↗
L1bRCTCited in: Special Populations - [173]
Mahé I, Chapelle C, Girard P et al.. “Predictors of clinically relevant bleeding during extended anticoagulation for cancer-associated venous thromboembolism (API-CAT): a post-hoc analysis of a randomised, non-inferiority trial.” The Lancet. Haematology (2026). PMID: 41365312 ↗
L1bRCTCited in: Special Populations - [174]
Mo N, Hu K, Zeng Z et al.. “Stereotactic body radiation therapy combined with cadonilimab and lenvatinib in the treatment of hepatocellular carcinoma with Vp3 or Vp4 portal vein tumor thrombus: a prospective, multicenter, single-arm, phase II clinical trial.” Frontiers in immunology (2025). PMID: 41293180 ↗
L2bTRIAL_NONRANDOMCited in: Special Populations - [175]
Tong CX, Ma R, Meng T. “Left ovarian vein thrombosis suspected during cesarean section and confirmed postoperatively: a case report and review of the literature.” BMC pregnancy and childbirth (2026). PMID: 41688956 ↗
L4CASE_REPORTCited in: Special Populations - [176]
Yaqian Y, Chuanliang Z, Guowei Z et al.. “Efficacy of Z-shaped supine position in robot-assisted radical prostatectomy: study protocol for a randomized controlled trial.” Trials (2026). PMID: 41588472 ↗
L2bTRIAL_NONRANDOMCited in: Special Populations - [177]
Jian H, Cui X, Dou Y et al.. “Adoption of plasma D-dimer testing, color Doppler ultrasound, and enoxaparin sodium in predicting and preventing lower extremity deep vein thrombosis in high-risk parturients undergoing cesarean section.” Medicine (2025). PMID: 41398758 ↗
L1bRCTCited in: Special Populations - [178]
Federspiel JJ, Rodger MA, Hoffman MR et al.. “Postoperative venous thromboembolism following cesarean delivery: prevalence, pathophysiology, diagnosis, treatment, and prevention.” American journal of obstetrics and gynecology (2026). PMID: 41485833 ↗
L5REVIEW_NARRATIVECited in: Special Populations - [179]
Ma J, Ke X, Zhu D. “The effect of anticoagulants on preventing venous thromboembolism in cancer patients: A systematic review and meta-analysis.” The National medical journal of India (2025). PMID: 41645951 ↗
L2aSR_OBSCited in: Special Populations - [180]
Wardhana DPW, Soetomo CT, Satyarsa ABS et al.. “Critical shift phase in deep vein thrombosis development after major sellar region tumor surgeries: a systematic review.” Annals of medicine (2025). PMID: 41392925 ↗
L2aSR_OBSCited in: Special Populations - [181]
Chiu YC, Chang WC, Chiu YC. “Early catheter-directed portal vein thrombolysis in myeloproliferative disorder-related diffuse mesenteric venous ischemia: A case report.” World journal of gastroenterology (2026). PMID: 41640868 ↗
L4CASE_REPORTCited in: Special Populations - [182]
Darby A, Bocchicchio M, Tabatabai R. “Cerebral Venous Thrombosis.” Emergency medicine clinics of North America (2026). PMID: 41260855 ↗
L5REVIEW_NARRATIVECited in: Special Populations - [183]
Guo B, Yerken S, Luo C et al.. “Liver resection versus transarterial chemoembolization plus PD-1 inhibitors and lenvatinib for hepatocellular carcinoma with portal vein tumour thrombus.” BJS open (2025). PMID: 41871372 ↗
L5OTHERCited in: Special Populations - [184]
Wang L, Feng JK, Zhou B et al.. “Optimal duration of adjuvant targeted-immunotherapy in patients with initially unresectable hepatocellular carcinoma with portal vein tumor thrombus following successful conversion therapy.” The oncologist (2026). PMID: 41723827 ↗
L5OTHERCited in: Special Populations - [185]
Xie R, Lu M, Wu J et al.. “Renal Pelvic Urothelial Carcinoma With Venous Tumor Thrombus: Prognosis and Reconsideration of TNM Staging.” Clinical genitourinary cancer (2026). PMID: 41680068 ↗
L5OTHERCited in: Special Populations - [186]
Mohan N, Srivastava SK, Duphare C et al.. “Risk of retinal vein occlusions in patients taking systemic tyrosine kinase inhibitors.” Eye (London, England) (2026). PMID: 41652018 ↗
L5OTHERCited in: Special Populations - [187]
Kurita D, Miyamoto S, Saito Y et al.. “Prevalence of Subclinical Internal Jugular Vein Thrombosis After Microvascular Head and Neck Reconstruction.” Microsurgery (2026). PMID: 41575013 ↗
L5OTHERCited in: Special Populations - [188]
Zhou B, Ma Z, Wang L et al.. “Real-world outcomes of stereotactic body radiotherapy plus sintilimab and bevacizumab for hepatocellular carcinoma with portal vein tumor thrombus.” The oncologist (2026). PMID: 41495001 ↗
L5OTHERCited in: Special Populations - [189]
Cui S, Wang D, Lyu S et al.. “Organ-specific role of neutrophil extracellular traps in shaping the postoperative thrombo-inflammatory niche in pancreatic ductal adenocarcinoma: a multi-model machine learning and mechanistic study.” Frontiers in immunology (2025). PMID: 41445740 ↗
L5OTHERCited in: Special Populations