What are the common causes of thrombocytopenia?

Common Causes of Thrombocytopenia

Thrombocytopenia (platelet count <150,000/μL) results from four primary mechanisms: decreased bone marrow production, increased peripheral destruction, splenic sequestration, or dilution, with the most common causes being immune thrombocytopenia, drug-induced thrombocytopenia, bone marrow disorders, and infections. 1, 2

Major Mechanistic Categories

Decreased Platelet Production

• Bone marrow disorders including myelodysplastic syndromes, leukemias, and other malignancies impair megakaryocyte function 1, 2
• Aplastic anemia and megaloblastic anemia directly affect platelet production 2
• Bone marrow fibrosis disrupts normal platelet generation 2
• Viral infections can suppress bone marrow production of platelets 1
• Inherited thrombocytopenias such as thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, and MYH9-related disease affect platelet production 1, 2

Increased Platelet Destruction

Primary Immune Thrombocytopenia (ITP)

• Primary ITP is an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets, representing the most common cause in patients with isolated thrombocytopenia and no systemic illness 1, 2, 3

Secondary Immune Thrombocytopenia

• Autoimmune disorders including systemic lupus erythematosus, antiphospholipid syndrome, and immune thyroid disease 1, 2
• Infections including HIV, hepatitis C virus (HCV), and Helicobacter pylori 1, 2
• Lymphoproliferative disorders such as chronic lymphocytic leukemia 1, 2
• Common variable immune deficiency (CVID) can present with ITP as an initial feature 1
• Recent vaccinations particularly measles, mumps, and rubella in children 1, 2

Drug-Induced Thrombocytopenia

• Medication-related thrombocytopenia should always be considered and may be difficult to exclude 3
• Drug-dependent antibody testing requires specialized immunoassays and should be collected during the acute thrombocytopenic episode or within 3 weeks, as antibodies disappear rapidly 1

Heparin-Induced Thrombocytopenia (HIT)

• HIT is a serious antibody-mediated reaction that typically presents with moderate thrombocytopenia (30-70 × 10⁹/L) occurring 5-10 days after heparin initiation 1, 4
• HIT can progress to heparin-induced thrombocytopenia with thrombosis (HITT), causing venous and arterial thromboses including deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction 4
• The 4T score evaluates degree of thrombocytopenia, timing, presence of thrombosis, and absence of other causes 1

Thrombotic Microangiopathies

• Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) cause increased platelet destruction 3
• Disseminated intravascular coagulation (DIC) results in platelet consumption 1
• Antiphospholipid syndrome can cause both thrombocytopenia and thrombosis 1

Pregnancy-Related Causes

• Gestational thrombocytopenia is the most common cause in pregnancy, typically presenting with mild thrombocytopenia (platelet count >70,000/μL) 1
• Preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) can cause thrombocytopenia in pregnant patients 1

Splenic Sequestration

• Liver disease with portal hypertension leads to splenomegaly and splenic sequestration of platelets 1
• Hepatic disease with impaired hemostasis contributes to thrombocytopenia 2

Special Populations

• Cyanotic congenital heart disease causes thrombocytopenia due to polycythemia and hyperviscosity triggering platelet consumption, with platelet counts inversely correlating with hematocrit levels 1
• 22q11.2 deletion syndrome is associated with characteristically lower platelet counts and large platelets 1

Critical Diagnostic Distinctions

Red Flags Requiring Immediate Evaluation

When thrombocytopenia presents with any of the following, emergency hospitalization may be required 3, 5:

• Splenomegaly, hepatomegaly, or lymphadenopathy suggests secondary causes rather than primary ITP 1, 3
• Constitutional symptoms (fever, weight loss, bone pain) suggest underlying infection or malignancy 1, 3
• Abnormal hemoglobin, white blood cell count, or white cell morphology indicates pancytopenia rather than isolated thrombocytopenia 1
• Non-petechial rash is not typical of ITP 1
• Schistocytes on peripheral smear suggest thrombotic microangiopathy 1

Pseudothrombocytopenia

• EDTA-dependent platelet agglutination can falsely lower platelet counts and must be excluded by repeating the count in heparin or sodium citrate tubes 1, 3, 5

Clinical Severity and Bleeding Risk

• Platelet count >50,000/μL: Generally asymptomatic 5
• Platelet count 20,000-50,000/μL: Mild skin manifestations (petechiae, purpura, ecchymosis) 5
• Platelet count <10,000/μL: High risk of serious bleeding 5

This algorithmic approach prioritizes life-threatening causes (HIT, TTP-HUS, HELLP syndrome) that require emergency intervention, followed by common causes (primary ITP, drug-induced) in stable patients, while systematically excluding pseudothrombocytopenia and secondary causes through targeted history, examination, and laboratory testing.