What are the causes of thrombocytopenia (low platelet count)?

Causes of Thrombocytopenia

Major Mechanistic Categories

Thrombocytopenia results from four primary mechanisms: decreased platelet production, increased platelet destruction, splenic sequestration, or dilution/clumping. 1, 2

Decreased Platelet Production

• Bone marrow disorders including myelodysplastic syndromes, leukemias, aplastic anemia, and bone marrow fibrosis impair megakaryocyte function and platelet production. 1, 2
• Viral infections (HIV, hepatitis C, EBV, CMV) suppress bone marrow production of platelets through direct marrow suppression. 1
• Nutritional deficiencies such as megaloblastic anemia from B12 or folate deficiency affect platelet production. 2
• Chronic alcohol use causes bone marrow suppression and decreased platelet production. 1
• Medications including chemotherapy agents, valproic acid, and certain antibiotics directly suppress megakaryocyte function. 1

Increased Platelet Destruction

Immune-Mediated Destruction

• Primary immune thrombocytopenia (ITP) is an autoimmune disorder with antibody-mediated destruction of otherwise normal platelets, diagnosed only after excluding all secondary causes. 3, 1, 2
• Secondary immune thrombocytopenia occurs with HIV, hepatitis C, H. pylori infection, autoimmune disorders (SLE, antiphospholipid syndrome), lymphoproliferative disorders, common variable immune deficiency, and post-vaccination. 1, 2
• Drug-induced immune thrombocytopenia can occur with antibiotics (vancomycin, cefazolin, sulfonamides), GPIIb-IIIa inhibitors, quinine, and certain chemotherapies, typically presenting 5-14 days after drug exposure. 1
• Heparin-induced thrombocytopenia (HIT) typically presents with moderate thrombocytopenia (30-70 G/L) occurring 5-10 days after heparin initiation, paradoxically associated with thrombosis rather than bleeding. 1

Non-Immune Destruction

• Thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) cause platelet consumption through microvascular thrombosis. 1
• Disseminated intravascular coagulation (DIC) causes consumption of platelets and coagulation factors through widespread fibrin and platelet deposition. 1
• Mechanical destruction occurs with extracorporeal circuits, intra-aortic balloon pumps, cardiac surgery with cardiopulmonary bypass, and prosthetic heart valves. 1

Splenic Sequestration

• Hepatic disease with portal hypertension causes splenomegaly and sequestration of up to 90% of circulating platelets. 4, 5
• Infiltrative disorders affecting the spleen can cause sequestration. 5

Dilutional Thrombocytopenia

• Massive transfusion or fluid resuscitation dilutes circulating platelets. 4

Special Populations and Conditions

• Pregnancy-related causes include gestational thrombocytopenia (most common, platelet count >70,000), preeclampsia/HELLP syndrome, and acute fatty liver of pregnancy. 1
• Cyanotic congenital heart disease produces mild thrombocytopenia (100,000-150,000/μL) due to polycythemia and hyperviscosity triggering platelet consumption, with platelet counts inversely correlating with hematocrit levels. 1
• Inherited thrombocytopenias such as thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, MYH9-related disease, and 22q11.2 deletion syndrome affect platelet production or quality. 1, 2

Critical Diagnostic Pitfalls to Avoid

• Pseudothrombocytopenia from EDTA-dependent platelet clumping can falsely lower automated counts and must be excluded by reviewing a peripheral blood smear or repeating the count in heparin or sodium citrate tubes. 1, 4
• Missing drug-induced thrombocytopenia requires obtaining a detailed medication history including over-the-counter drugs, herbal supplements, and quinine-containing beverages. 1, 6
• Overlooking HIT in any patient who received heparin within the past 3 months requires immediate calculation of the 4T score when thrombocytopenia develops. 1
• Failing to test for HIV and hepatitis C in all adults with suspected ITP, regardless of risk factors, as these infections may be clinically indistinguishable from primary ITP and can precede other symptoms by years. 1, 6, 2
• Not recognizing thrombotic conditions such as antiphospholipid syndrome, HIT, and thrombotic microangiopathies that paradoxically present with both thrombocytopenia and thrombosis rather than bleeding. 1, 4

Age-Specific Considerations

• Patients older than 60 years require bone marrow examination to exclude myelodysplastic syndromes, leukemias, or other malignancies, regardless of how typical the ITP presentation appears. 1, 6
• Children with thrombocytopenia most commonly have acute ITP following viral infection, with two-thirds recovering spontaneously within 6 months. 3, 1