Definition/General
Introduction:
Amegakaryocytic thrombocytopenia (AT) is a rare acquired disorder characterized by severe thrombocytopenia with absent or markedly reduced megakaryocytes in the bone marrow
Unlike congenital forms, it develops in previously healthy individuals
The condition may be idiopathic or secondary to various causes.
Origin:
Results from acquired suppression of megakaryopoiesis
Causes include autoimmune mechanisms (anti-thrombopoietin receptor antibodies)
Drug-induced megakaryocyte suppression
Viral infections
Toxic exposures
Malignancy-related suppression
Unlike congenital CAMT, no genetic mutations involved.
Classification:
Classified as primary (idiopathic) or secondary
Primary AT: no identifiable cause
Secondary AT: drug-induced (chemotherapy, antibiotics)
Viral-induced (EBV, CMV)
Autoimmune-associated
Malignancy-related
Radiation-induced.
Epidemiology:
Rare disorder with unknown exact incidence
Can occur at any age
No gender predominance
Associated with specific drugs or exposures
Better prognosis than congenital forms if reversible cause identified.
Clinical Features
Presentation:
Acute or subacute onset thrombocytopenia
Bleeding manifestations (petechiae, bruising)
Normal platelet size (unlike inherited forms)
No physical malformations
History of drug exposure or illness
Previously normal blood counts.
Symptoms:
Sudden onset bleeding tendency
Mucosal bleeding (epistaxis, gingival)
Skin petechiae and purpura
Menorrhagia (females)
No systemic symptoms initially
Fatigue if severe bleeding occurs.
Risk Factors:
Recent drug exposure (chemotherapy, antibiotics)
Viral infections
Autoimmune diseases
Malignancy treatment
Radiation exposure
Toxic exposures
Advanced age.
Screening:
Complete blood count (isolated thrombocytopenia)
Platelet size analysis (normal)
Bone marrow examination
Drug history review
Viral serology
Autoantibody testing
Thrombopoietin levels.
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Gross Description
Appearance:
Bone marrow aspirate shows normal cellularity for other lineages
Absent or markedly reduced megakaryocytes
Normal erythropoiesis and granulopoiesis
No abnormal infiltrates
May show reactive changes.
Characteristics:
Selective megakaryocytic depletion
Preserved bone marrow architecture
Normal other hematopoietic elements
No dysplastic changes
Reactive lymphoid elements possible.
Size Location:
Affects all bone marrow sites uniformly
No focal lesions
Normal spleen and lymph nodes typically
Systemic involvement unlikely
Reversible changes if cause identified.
Multifocality:
Diffuse megakaryocyte suppression
Uniform pattern across bone marrow sites
Potentially reversible with treatment
May progress to pancytopenia in some cases.
Microscopic Description
Histological Features:
Absent or severely reduced megakaryocytes (<1% expected)
Normal bone marrow cellularity other lineages
No dysplastic changes
Normal erythropoiesis
Normal granulopoiesis
Possible reactive lymphoid aggregates.
Cellular Characteristics:
Complete absence of megakaryocytes in severe cases
Rare, morphologically normal megakaryocytes may be present
Normal other cell morphology
No giant cells or atypical forms
Reactive changes in lymphoid elements.
Architectural Patterns:
Preserved bone marrow architecture
Selective cellular depletion
Normal sinusoidal pattern
No fibrosis
Appropriate fat-to-cell ratio for age.
Grading Criteria:
Severity by megakaryocyte count: Severe (<0.5% expected)
Moderate (0.5-2% expected)
Platelet count typically <50,000/μL
Thrombopoietin levels elevated
Response to treatment variable.
Immunohistochemistry
Positive Markers:
CD61 and CD41 highlight rare residual megakaryocytes
MPO shows normal granulopoiesis
Glycophorin A shows normal erythropoiesis
CD34 shows stem cells
CD68 marks macrophages.
Negative Markers:
Megakaryocyte markers essentially absent
Abnormal cell markers negative
Viral markers variable
Malignant markers negative
Dysplastic markers negative.
Diagnostic Utility:
Confirms megakaryocyte absence
Demonstrates normal other lineages
Excludes infiltrative processes
Quantifies residual megakaryocytes
Helps assess recovery
Guides treatment monitoring.
Molecular Subtypes:
Drug-induced AT
Autoimmune AT
Viral-induced AT
Idiopathic AT
Secondary AT (various causes)
Recovery patterns vary by cause.
Molecular/Genetic
Genetic Mutations:
No genetic mutations (acquired disorder)
Normal constitutional genetics
Acquired immune dysfunction
Drug-induced mechanisms
Viral-induced suppression
Toxic injury mechanisms.
Molecular Markers:
Elevated thrombopoietin levels
Anti-thrombopoietin receptor antibodies (some cases)
Drug metabolite effects
Viral antigen detection
Inflammatory markers
Normal genetic background.
Prognostic Significance:
Drug-induced forms often reversible
Viral-induced usually self-limiting
Autoimmune forms variable response
Idiopathic forms unpredictable course
Early recognition improves outcomes
Cause removal essential.
Therapeutic Targets:
Cause identification and removal
Corticosteroids (autoimmune cases)
Immunosuppressive agents
Thrombopoietin receptor agonists
Platelet transfusions (severe bleeding)
Supportive care.
Differential Diagnosis
Similar Entities:
Congenital amegakaryocytic thrombocytopenia
Immune thrombocytopenic purpura
Aplastic anemia (early)
Myelodysplastic syndrome
Acute leukemia
Viral suppression.
Distinguishing Features:
Acquired AT: Previous normal counts
Acquired AT: Drug/exposure history
Acquired AT: Normal platelet size
CAMT: Congenital onset
CAMT: Genetic mutations
ITP: Normal megakaryocytes
ITP: Peripheral destruction
MDS: Dysplastic changes.
Diagnostic Challenges:
Identifying underlying cause
Distinguishing from congenital forms
Excluding other cytopenias
Drug history correlation
Viral screening
Recovery monitoring.
Rare Variants:
Familial clustering (rare)
Atypical presentations
Partial recovery forms
Associated autoimmune diseases
Malignancy-associated.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Bone marrow aspirate and biopsy from [site], adequate for evaluation
Diagnosis
Amegakaryocytic Thrombocytopenia (Acquired)
Classification
Classification: Acquired thrombocytopenia with megakaryocyte suppression
Bone Marrow Cellularity
Cellularity: [X]% for age (normal), with selective megakaryocytic depletion
Lineage Assessment
Megakaryopoiesis: absent/markedly reduced. Erythropoiesis: normal. Granulopoiesis: normal
Morphological Features
Shows absent/markedly reduced megakaryocytes with normal other lineages
Special Studies
CD61/CD41: confirms megakaryocyte absence
Clinical correlation: drug history, viral serology
Recommend: cause investigation, TPO levels
Clinical Correlation
Findings consistent with acquired amegakaryocytic thrombocytopenia. Investigate underlying cause
Final Diagnosis
Bone marrow showing acquired amegakaryocytic thrombocytopenia