Aplastic Anemia

Aplastic anemia (AA) is a rare, life-threatening bone marrow failure syndrome defined by pancytopenia (deficiency of all three blood cell lines) and a hypocellular bone marrow with no evidence of infiltration or fibrosis ^[2]B2b.

Also Called / Synonyms

• Aplastic anemia (AA)
• Acquired aplastic anemia (to distinguish from inherited forms)
• Idiopathic aplastic anemia (when no cause identified)
• Bone marrow aplasia
• Hypoplastic anemia (historical term)

Classification of Severity

Severity classification guides treatment decisions and prognosis. The Camitta criteria are the most widely used:

Classification by Etiology

AA is broadly divided into acquired and inherited forms. Acquired AA is most common and is thought to be immune-mediated in the majority of cases. Inherited bone marrow failure syndromes (IBMFS) such as Fanconi anemia , dyskeratosis congenita , and SAMD9/SAMD9L-related disorders must be excluded, especially in children and young adults ^[4]D5[5]D5.

Clinical Significance

Aplastic anemia is a medical emergency with a high mortality if untreated; severe AA carries a 1-year mortality of >70% with supportive care alone, but outcomes improve dramatically with immunosuppressive therapy or hematopoietic stem cell transplantation.

Pearl: Aplastic anemia is a diagnosis of exclusion; the workup must rule out hypocellular myelodysplastic syndrome (MDS), inherited bone marrow failure syndromes, and other causes of pancytopenia before initiating therapy ^[2]B2b[3]D5.

The bone marrow in aplastic anemia is defined by its profound emptiness. On gross examination, aspirates and biopsy cores appear strikingly hypocellular, with fatty replacement occupying the vast majority of the medullary space. The normal hematopoietic marrow, expected to be 40-70% cellular for a given age, is reduced to <25% cellularity in severe disease, and often to <5% in very severe cases. This fatty transformation is not merely passive; the microenvironment itself is altered, as evidenced by studies showing that bone marrow mesenchymal stem cells (MSCs) from children with severe aplastic anemia have a slower expansion rate and smaller cumulative population doubling (1.83 ± 1.21 vs 3.36 ± 0.87 in controls; p = 0.046), despite retaining normal morphology and immunophenotype ^[7]B3b.

Bone Marrow Biopsy: The Diagnostic Gold Standard

A trephine biopsy is essential for diagnosis and must be at least 1.5-2 cm in length to avoid sampling error (patchy involvement can occur early). The core shows:

• Marked hypocellularity with fat predominance (often >90% fat spaces).
• Residual lymphocytes and plasma cells scattered in the stroma, these are a hallmark, not a contaminant.
• Absent or markedly reduced megakaryocytes, erythroid islands, and myeloid precursors.
• No fibrosis, no blasts, no dysplastic features (the latter would point toward hypoplastic MDS).

The differential from hypoplastic myelodysplastic syndrome (hMDS) is critical and hinges on morphology: in aplastic anemia, the rare residual cells show no dysplasia on aspirate smears or biopsy sections. The 2008 WHO classification distinguished refractory cytopenia of childhood (RCC) from aplastic anemia, but a retrospective review of 186 children treated with horse antithymocyte globulin and cyclosporine found that 33% had aplastic anemia, 49% had RCC, and 18% had refractory cytopenia with multilineage dysplasia, yet the morphological boundary did not predict clinical outcomes ^[2]B2b. This suggests that morphology alone, while diagnostic, has limited prognostic power.

Flow Cytometry and Immunohistochemistry

Flow cytometry on aspirates typically reveals a paucity of CD34+ progenitor cells (<0.1% of events). In cases with borderline histology, immunohistochemistry for CD34 on the biopsy can quantify residual hematopoietic stem cells. A CD34+ count of <0.03% of nucleated cells supports aplastic anemia ^[10]D5. Additionally, the presence of a paroxysmal nocturnal hemoglobinuria (PNH) clone (by high-sensitivity flow cytometry for GPI-anchored proteins) is found in 40-70% of aplastic anemia patients and helps distinguish immune-mediated from inherited forms ^[10]D5.

Structural Alterations at the Cellular Level

Beyond overall cellularity, the hematopoietic microenvironment is structurally compromised:

• MSC dysfunction: SAA-derived MSCs show lower alkaline phosphatase activity after osteogenic induction (optical density 1.46 ± 0.04 vs 2.27 ± 0.32; p = 0.013) and reduced von Kossa staining, indicating impaired osteogenic differentiation ^[7]B3b. This is not merely a secondary phenomenon, it may contribute to the failure of hematopoietic recovery.
• Clonal hematopoiesis: Somatic mutations in genes such as BCOR (encoding BCL6 corepressor) are recurrently found in aplastic anemia, mostly frameshifts, nonsense, or missense mutations scattered across the gene length that disrupt full-length protein expression ^[9]D5. These mutations are thought to provide a survival advantage to a clone under immune attack and are associated with better response to immunosuppressive therapy.
• Iron overload sequela: Chronic transfusion therapy leads to bone marrow hemosiderosis, but interestingly, the TPO-RA hetrombopag has intrinsic iron-chelating properties. In a post-hoc analysis of a phase II study, 51.4% of IST-refractory SAA patients showed decreased serum ferritin by a median of 49.0% at 18 weeks, suggesting that structural drug-mediated iron clearance may improve the bone marrow milieu ^[6]B2b.

Table: Comparative Bone Marrow Morphology in Aplastic Anemia vs. Hypoplastic MDS

Pearl: The empty marrow of aplastic anemia is never truly empty, the presence of a PNH clone by flow cytometry in ~50% of patients provides a vital diagnostic clue that the disease is immune-mediated, while BCOR mutations identify a subset with favorable response to immunosuppression ^[9]D5[10]D5.

Distribution of Hematopoietic Marrow in Aplastic Anemia

The hematopoietic bone marrow occupies the medullary cavities of the axial skeleton (vertebrae, sternum, pelvis, ribs) and proximal appendicular skeleton (femora, humeri) in adults. In aplastic anemia, this compartment undergoes a characteristic centrifugal involution: active marrow is progressively replaced by fatty marrow, beginning in the axial skeleton and extending to the appendicular bones. FLT PET imaging demonstrates a striking reduction in tracer uptake throughout the pelvis and axial skeleton in untreated patients, with the posterior iliac crest, the standard biopsy site, showing particularly diminished activity ^[15]C4. This spatial heterogeneity means that a single biopsy may underestimate residual hematopoietic activity; the entire marrow space must be considered when assessing disease severity or response.

Imaging Correlates

F-18 FLT PET provides a noninvasive map of the total hematopoietic marrow distribution. In a pilot study of 17 patients, all 11 untreated individuals exhibited an abnormal scan with reduced pelvic uptake, while 6 post-treatment patients showed variable improvement ^[15]C4. The technique reveals that the marrow space is not uniformly affected: some areas may retain patchy hematopoietic islands, whereas others are completely fatty. This topographic variation has clinical implications, biopsy from a single site may miss residual disease or overestimate aplasia. MRI, though not directly studied in these references, would show T1-hyperintense fatty replacement in affected areas.

Biopsy Site Considerations

The posterior iliac crest remains the standard biopsy site due to its accessibility and rich marrow content in health. However, in aplastic anemia, this site may be among the first to become fatty, leading to a false impression of global aplasia. Flow cytometry of bone marrow aspirate can help differentiate aplastic anemia from refractory cytopenia of childhood, but the spatial heterogeneity of marrow involvement complicates interpretation ^[12]B2b. When the iliac crest biopsy is nondiagnostic, alternative sites such as the sternum or vertebral bodies may be considered, though these are less commonly used due to procedural risk.

Pearl: In aplastic anemia, the hematopoietic marrow space undergoes a centrifugal fatty replacement that is often most pronounced at the standard biopsy site (posterior iliac crest), making FLT PET a valuable tool to assess the true extent of residual hematopoiesis across the entire axial skeleton ^[15]C4.

In aplastic anemia, the bone marrow's vascular and neural microenvironment is profoundly altered, leading to critical clinical consequences for blood product support, thrombotic risk, and immune-mediated destruction.

Blood Supply: Transfusion Support and Vascular Complications

The hypocellular marrow in aplastic anemia requires meticulous transfusion management . Platelet transfusion is a cornerstone of supportive care. The 2025 AABB and ICTMG guidelines recommend a restrictive platelet transfusion strategy (transfuse at ≤10 × 10⁹/L in stable patients) over a liberal strategy, as restrictive approaches probably do not increase mortality or bleeding risk ^[16]A1c. For patients undergoing invasive procedures, a threshold of 50 × 10⁹/L is recommended ^[16]A1c. Thrombopoietin receptor agonists (TPO-RA) such as eltrombopag and romiplostim are used to stimulate platelet production, achieving platelet response rates of 50-90% in immune thrombocytopenia and also showing efficacy in aplastic anemia ^[21]D5. However, cyclosporine -A (CsA), a common immunosuppressive agent in AA, is associated with intracranial thrombotic complications, including cerebral venous thrombosis and arterial thrombosis, with a significant risk that warrants vigilance ^[20]C4. These vascular events can compromise cerebral blood supply and require prompt recognition.

Innervation: Neural Regulation and Complications

The bone marrow is richly innervated by sympathetic nerve fibers that regulate hematopoietic stem cell (HSC) mobilization and the bone marrow microenvironment. In aplastic anemia, disruption of this neural regulation may contribute to HSC dysfunction. Clinically, CsA therapy can cause neurotoxicity, including posterior reversible encephalopathy syndrome (PRES) and seizures, though these are not directly addressed in the provided references. The thrombotic complications from CsA ^[20]C4 also have neurological manifestations.

Lymphatic Drainage: Immune-Mediated Bone Marrow Destruction

The immune system plays a central role in aplastic anemia pathogenesis. T cell-mediated destruction of hematopoietic stem cells is a hallmark, as evidenced by transcriptomic studies in paroxysmal nocturnal hemoglobinuria (PNH), a closely related disorder ^[17]B3b. The bone marrow contains lymphatic vessels that facilitate immune cell trafficking; in AA, activated cytotoxic T cells infiltrate the marrow and attack HSCs, leading to pancytopenia. This immune attack is the target of immunosuppressive therapy.

Pearl: In aplastic anemia, the bone marrow's blood supply is critically dependent on transfusion support, with restrictive platelet strategies recommended ^[16]A1c; vascular complications from immunosuppressive therapy like cyclosporine-A can cause life-threatening thrombosis ^[20]C4; and the immune-mediated destruction of hematopoietic stem cells, involving T cell dysregulation, is a key pathogenic mechanism ^[17]B3b.

Bone marrow biopsy in aplastic anemia reveals a markedly hypocellular marrow with fatty replacement, typically <25% cellularity in severe disease and <50% in moderate cases ^[23]D5. The residual cellular elements consist predominantly of lymphocytes, plasma cells, and stromal cells; hematopoietic precursors are severely reduced across all three lineages. Megakaryocytes are virtually absent, and when present, they are small and non-dysplastic ^[23]D5[25]D5.

Distinguishing Aplastic Anemia from Hypocellular Myelodysplastic Syndrome

The critical histologic challenge is separating aplastic anemia from hypocellular myelodysplastic syndrome (MDS) and hypocellular acute myeloid leukemia (AML). In aplastic anemia, there is no dysplasia in any lineage, blasts are <5% of marrow cellularity, and there is no abnormal localization of immature precursors (ALIP) ^[23]D5. By contrast, hypocellular MDS shows dysplastic changes in at least 10% of cells in one or more lineages, and may harbor micromegakaryocytes on immunohistochemistry (IHC) ^[25]D5. Hypocellular AML requires ≥20% blasts in the marrow or peripheral blood ^[23]D5.

Immunohistochemistry and Ancillary Studies

IHC is essential for accurate classification. CD34 staining highlights residual progenitor cells; in aplastic anemia, CD34+ cells are markedly reduced (<1% of marrow cells), whereas in hypocellular MDS/AML, CD34+ clusters or increased numbers may be seen ^[23]D5. CD117 (c-kit) identifies mast cells and rare blasts; its absence supports aplastic anemia. CD3 and CD20 highlight the reactive lymphocytic infiltrate, which is polyclonal. Flow cytometry shows no aberrant myeloid or lymphoid populations ^[23]D5. In pediatric cases, IHC for CD61 (megakaryocytes) and CD42b helps detect micromegakaryocytes, which are absent in aplastic anemia but present in refractory cytopenia of childhood (RCC) ^[25]D5.

Table: Histologic Features Distinguishing Aplastic Anemia from Hypocellular MDS and AML

Pearl: The histologic sine qua non of aplastic anemia is a profoundly hypocellular marrow with absent dysplasia and blasts; immunohistochemistry for CD34 and CD117 is mandatory to exclude residual blasts that would shift the diagnosis toward hypocellular MDS or AML ^[23]D5[25]D5.

Therapeutic Development of Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for severe aplastic anemia (SAA) ^{[28]A1c[29]A1c}. The development of this approach has focused on optimizing graft sources and conditioning regimens to reduce graft failure and graft-versus-host disease (GVHD). Current guidelines recommend bone marrow as the preferred graft source and rabbit antithymocyte globulin (ATG) over horse ATG for conditioning ^[29]A1c. Fludarabine-containing regimens are preferred, particularly for patients at high risk of graft failure ^[29]A1c. A novel conditioning regimen, FABT (Fludarabine-ATG-Busulfan-Thiotepa), combined with post-transplant cyclophosphamide (PTCy), has shown efficacy in haploidentical HSCT for SAA patients lacking HLA-identical sibling donors. In a prospective phase II trial of 36 patients, the FABT regimen with low-dose ATG (2 mg/kg/day) and PTCy resulted in successful engraftment with a median follow-up of 21 months (range 2 to 30 months) ^[30]C4. These therapeutic developments have expanded access to curative therapy for SAA patients, effectively reconstituting hematopoiesis through donor stem cell engraftment.

Platelet Transfusion Support During Development of HSCT

Platelet transfusion support is critical during the peri-transplant period to prevent bleeding. The 2025 AABB and ICTMG guidelines recommend a restrictive transfusion strategy (prophylactic platelet transfusion at a threshold of 10 × 10⁹/L) over a liberal strategy, as it does not increase mortality or bleeding risk across most clinical populations ^[16]A1c. This approach is particularly relevant during the development of HSCT protocols to minimize transfusion-related complications.

Infection Management in the Development of HSCT

Infections remain a major challenge during HSCT development. Colistimethate sodium (CMS) has been used for sepsis in hematological disease patients, including those undergoing HSCT. A retrospective study of 81 patients showed that CMS was efficacious and safe for managing sepsis, with careful monitoring for renal insufficiency ^[31]B3b. This supports the development of comprehensive supportive care protocols alongside HSCT.

Genetic and molecular variations underlie a substantial proportion of aplastic anemia cases, distinguishing inherited bone marrow failure syndromes from acquired immune-mediated disease. These anomalies influence presentation, treatment response, and long-term outcomes, making their recognition essential for precision management .

Inherited Bone Marrow Failure Syndromes

Germline pathogenic variants in DNA repair and telomere maintenance genes cause syndromes that frequently present with aplastic anemia. Fanconi anemia (FA) is the most common, with biallelic mutations in FANC genes leading to defective interstrand crosslink repair. In a phase II trial of eltrombopag for FA-related bone marrow failure, 37.5% of pediatric patients achieved a partial response at 6 months, with enhanced benefit in those with somatic mosaicism or prior gene therapy ^[32]C4. Dyskeratosis congenita (mutations in TERT, TERC, DKC1) and AMeD syndrome (aplastic anemia, mental retardation, dwarfism; ADH5 variants) are rarer but carry distinct risks. A 6-year-old with AMeD syndrome and myelodysplastic syndrome with increased blasts was successfully treated with cord blood transplantation after myeloablative conditioning, suggesting feasibility despite the syndrome's fragility ^[35]C4. STAT1 gain-of-function (GOF) mutations cause chronic mucocutaneous candidiasis and can trigger severe aplastic anemia via dysregulated JAK-STAT signaling; a heterozygous p.Cys174Arg variant was identified in a 32-year-old with pancytopenia and absent erythroid precursors ^[36]C4[38]C4.

Somatic Mutations and Clonal Evolution

Acquired aplastic anemia often harbors somatic mutations that drive clonal hematopoiesis. Paroxysmal nocturnal hemoglobinuria (PNH) clones, glycosylphosphatidylinositol-anchored protein-deficient (GPI[-]) cells due to PIGA mutations, expand under immune pressure. In one case, 71.9% of granulocytes and 15.3% of erythrocytes were GPI-deficient, with the clone size fluctuating over time ^[37]C4. These clones may wax and wane with immunosuppressive therapy and can precede or accompany aplastic anemia. Post-transplant, distinguishing donor- vs. recipient-derived myelodysplastic neoplasia (MDS) is critical; single-cell mutational profiling resolved a U2AF1S34Y variant as recipient-derived in a mixed chimerism setting ^[34]C4.

Hypoplastic MDS vs. Aplastic Anemia

Hypoplastic myelodysplastic neoplasia (MDS-h) shares clinical and morphological features with aplastic anemia but is distinguished by clonal cytogenetic or molecular abnormalities. In three low-risk MDS-h cases treated with immunosuppressive therapy, all achieved transfusion independence, but one developed late clonal evolution to secondary acute myeloid leukemia over 9-17 years ^[33]C4. Serial monitoring of mutational dynamics, including stable, fluctuating, and newly emerging clones, is essential to differentiate MDS-h from aplastic anemia and guide therapy.

Controversies and Guideline Disagreement

Pearl: Genetic variations, both inherited (FA, STAT1 GOF, AMeD syndrome) and somatic (PNH clones, MDS-associated mutations), are common in aplastic anemia and directly impact treatment decisions, including the choice of immunosuppressive therapy, conditioning regimen, and long-term surveillance for clonal evolution ^{[32]C4[33]C4[36]C4}.

Magnetic Resonance Imaging (MRI)

MRI is the primary modality for assessing bone marrow cellularity in aplastic anemia, with T1-weighted sequences providing direct visualization of the marrow fat-to-water ratio ^[26]D5. In healthy adults, vertebral marrow signal is isointense to intervertebral discs on T1-weighted images; in aplastic anemia, the marked reduction in hematopoietic cells leads to diffuse fatty replacement, producing a hyperintense T1 signal that approaches subcutaneous fat intensity. This pattern is most reliably assessed in the lumbar spine and proximal femora. Short tau inversion recovery (STIR) sequences show correspondingly suppressed signal due to the absence of cellular water. MRI can also detect focal areas of residual hematopoiesis (islands of intermediate T1 signal) and extramedullary hematopoiesis, which appears as paravertebral or splenic masses with intermediate T1 and STIR signal ^[26]D5. The degree of fatty replacement on MRI correlates with bone marrow biopsy cellularity, making it a useful noninvasive tool for serial monitoring, particularly when biopsy is contraindicated or when there is discrepancy between histology and clinical status.

Positron Emission Tomography (PET)

PET with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) or 3'-18F-fluoro-3'-deoxy-L-thymidine (FLT) can evaluate metabolic activity of the bone marrow. In untreated aplastic anemia, FDG uptake is typically diffusely low (SUVmax < 2.0 in the axial skeleton) due to hypocellularity ^[26]D5. FLT-PET, which reflects cellular proliferation, shows markedly reduced uptake in the marrow space, distinguishing aplastic anemia from hypercellular marrow disorders ^[26]D5. However, a critical pitfall is the effect of granulocyte colony-stimulating factor (G-CSF) therapy: G-CSF can induce diffuse, intense FDG uptake (SUVmax up to 8-10) in the bones, mimicking disseminated metastatic disease ^[43]C4. This effect is transient and resolves after G-CSF cessation. PET is also valuable for detecting extramedullary hematopoiesis, which shows moderate FDG uptake in the spleen, liver, or paravertebral regions, and for identifying the optimal site for bone marrow biopsy when conventional sites are fibrotic or heterogeneous ^[26]D5.

Computed Tomography (CT) and Ultrasound

CT is not sensitive for marrow cellularity but may reveal osteoporosis secondary to prolonged corticosteroid use or splenomegaly from extramedullary hematopoiesis. Ultrasound is useful for evaluating splenic size and for guiding biopsy of extramedullary hematopoietic masses. Neither modality replaces MRI or PET for marrow assessment.

Imaging Modality Comparison

Pearl: MRI is the most specific imaging tool for assessing bone marrow cellularity in aplastic anemia, while PET should be interpreted with caution in patients receiving growth factors, as G-CSF can cause diffuse FDG uptake that mimics malignant infiltration ^[26]D5[43]C4.

Fatigue, fever, and bruising, the triad of pancytopenia, bring most patients to medical attention. Anemia manifests as progressive pallor, exertional dyspnea, and tachycardia; neutropenia predisposes to recurrent bacterial and fungal infections, often with fever without localizing signs; thrombocytopenia produces petechiae, ecchymoses, and mucosal bleeding (gingival, epistaxis, menorrhagia). Gastrointestinal bleeding or intestinal ulceration may be the presenting feature in patients with concurrent inflammatory bowel disease or Behçet's disease, a scenario associated with high mortality ^[44]B2a. In thymoma-associated aplastic anemia, myasthenia gravis symptoms (ptosis, diplopia, dysphagia) may precede or accompany marrow failure ^[46]C4. Paroxysmal nocturnal hemoglobinuria (PNH) overlap, seen in up to 15% of AA patients, adds hemoglobinuria, abdominal pain, and thrombotic events to the clinical picture ^[49]C4.

Neurological Examination Findings

Neurological deficits are not primary to AA but arise from complications. Intracranial hemorrhage (spontaneous or traumatic) due to severe thrombocytopenia presents with acute headache, focal weakness, or altered consciousness. Cerebral sinus thrombosis, a hallmark of PNH, causes headache, papilledema, and seizures ^[49]C4. Spinal epidural hematoma is rare but can produce back pain and rapidly progressive paraplegia. Fundoscopic examination may reveal retinal hemorrhages. Meningeal signs should prompt evaluation for opportunistic infections (e.g., aspergillosis) in neutropenic patients. Any focal neurological deficit in a patient with AA warrants urgent neuroimaging and platelet transfusion if thrombocytopenic.

Phenotypic Variants

Red Flags

• Platelet count < 10 × 10⁹/L → risk of spontaneous intracranial hemorrhage; transfuse to maintain > 10 × 10⁹/L (or > 20 × 10⁹/L if febrile).
• Absolute neutrophil count < 200/μL → high risk of life-threatening bacterial/fungal infection; initiate empiric broad-spectrum antibiotics and consider G-CSF.
• Rapidly falling blood counts over days to weeks → may indicate very severe AA (VSAA) or evolution to MDS/AML.
• New focal neurological deficit → urgent CT/MRI to exclude hemorrhage or thrombosis.
• Hemoglobinuria or unexplained thrombosis → test for PNH clone ^[49]C4.

Atypical Presentations

AA may present with isolated thrombocytopenia or anemia, mimicking immune thrombocytopenia (ITP) or pure red cell aplasia. Bone marrow biopsy reveals the true hypocellularity. PNH-AA overlap can present with thrombosis (e.g., Budd-Chiari syndrome) before cytopenias are evident ^[49]C4. Thymoma-associated AA may be diagnosed only after thymectomy, with marrow failure appearing 2 weeks to several months postoperatively ^[46]C4. In children, growth failure or recurrent infections may be the only clue. A high index of suspicion and early bone marrow examination are essential to avoid diagnostic delay.

Pearl: The clinical spectrum of aplastic anemia extends beyond pancytopenia to include PNH-related thrombosis, thymoma-associated myasthenia, and intestinal ulceration; neurological deficits or rapid count decline demand urgent intervention ^{[44]B2a[46]C4[49]C4}.

Aplastic anemia is the standard term for acquired bone marrow failure with pancytopenia and hypocellularity. The synonym hypoplastic anemia appears in older literature but is less precise, as it may imply less severe marrow hypocellularity ^[51]B3b. No eponym is attached to the disease itself.

Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is a complement-driven hemolytic anemia that frequently coexists with aplastic anemia, forming the AA-PNH syndrome ^[52]D5. This overlap is clinically significant because PNH clones are present in a substantial proportion of aplastic anemia patients, and the presence of a PNH clone influences prognosis and therapy ^[52]D5.

Platelet Transfusion Refractoriness (PTR)

PTR is a common complication in aplastic anemia patients undergoing hematopoietic stem cell transplantation. Independent risk factors include splenomegaly (OR 26.98) and JAK2 mutation (OR 17.32) ^[51]B3b. No eponym is associated with this condition, but the term is essential in clinical documentation.

Table: Key Nomenclature in Aplastic Anemia

Pearl: Aplastic anemia itself lacks a classic eponym, but the AA-PNH overlap syndrome and platelet transfusion refractoriness are key nomenclature considerations in clinical practice ^{[51]B3b[52]D5}.