Causes of Thrombocytopenia
Thrombocytopenia (platelet count <150,000/μL) results from four primary mechanisms: decreased bone marrow production, increased platelet destruction, splenic sequestration, or dilution/clumping. 1, 2, 3
Decreased Platelet Production
Bone marrow disorders are a major category causing impaired megakaryocyte function and reduced platelet production. 1, 2
- Malignant conditions: Myelodysplastic syndromes, acute leukemias, lymphomas, and bone marrow metastases from solid tumors directly suppress platelet production 1, 4
- Aplastic anemia and megaloblastic anemia (vitamin B12 or folate deficiency) impair platelet production 2
- Viral infections (HIV, hepatitis C, EBV, CMV) can suppress bone marrow platelet production 1
- Inherited thrombocytopenias include thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, and MYH9-related disease 1, 2, 4
Increased Platelet Destruction
Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated destruction of otherwise normal platelets. 1, 2, 4
Secondary Immune Thrombocytopenia
Secondary immune causes have distinct triggers requiring specific management: 1
- Autoimmune disorders: Systemic lupus erythematosus, antiphospholipid syndrome, common variable immune deficiency 1
- Infections: HIV (treat with antivirals first), HCV (consider antiviral therapy), H. pylori (eradication therapy recommended) 1
- Lymphoproliferative disorders: Chronic lymphocytic leukemia, lymphomas 1, 2
- Drug-induced thrombocytopenia: Common culprits include quinine/quinidine, sulfonamides, NSAIDs, anticonvulsants, disease-modifying antirheumatic drugs, and diuretics 5
- Post-vaccination or post-bone marrow transplantation 1
Heparin-Induced Thrombocytopenia (HIT)
HIT typically presents with moderate thrombocytopenia (30,000-70,000/μL) occurring 5-10 days after heparin initiation and paradoxically causes thrombosis rather than bleeding. 1 The 4T score evaluates: degree of thrombocytopenia, timing of onset, presence of thrombosis, and absence of other causes. 1
Thrombotic Microangiopathies
- Thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and disseminated intravascular coagulation (DIC) cause platelet consumption through microvascular thrombosis 1, 4
- Antiphospholipid syndrome causes both thrombocytopenia and thrombosis 1
Pregnancy-Related Thrombocytopenia
- Gestational thrombocytopenia is the most common cause in pregnancy, presenting with mild thrombocytopenia (platelet count >70,000) 1
- Preeclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) requires emergency management 1
Splenic Sequestration
- Liver disease with portal hypertension causes splenomegaly and platelet sequestration 6
- Up to one-third of total platelet mass can be sequestered in an enlarged spleen 3
Special Consideration: Cyanotic Congenital Heart Disease
In cyanotic congenital heart disease, thrombocytopenia occurs secondary to polycythemia and hyperviscosity triggering consumption. 7 Platelet counts inversely correlate with hematocrit levels, with mild thrombocytopenia (100,000-150,000/μL) more common than severe (<50,000/μL). 7 This mechanism involves vascular stasis, widespread fibrin and platelet deposition, and consumption of coagulation proteins. 7
Critical Diagnostic Pitfall
Always exclude pseudothrombocytopenia first by examining a peripheral blood smear or repeating the platelet count in heparin or sodium citrate tubes. 1, 4, 3 EDTA-dependent platelet clumping causes falsely low automated platelet counts but represents no true clinical problem. 1