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

Causes of Thrombocytopenia

Major Mechanistic Categories

Thrombocytopenia results from four primary mechanisms: decreased platelet production, increased platelet destruction, splenic sequestration, and dilution. 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 suppress bone marrow production of platelets through cytokine-induced myelosuppression, including HIV, hepatitis C, parvovirus, and cytomegalovirus. 1, 3

• Nutritional deficiencies such as megaloblastic anemia from B12 or folate deficiency affect platelet production. 2

• Bone marrow suppression occurs with chronic alcohol use, certain medications, and iron overload. 1

• Inherited thrombocytopenias such as thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, MYH9-related disease, and 22q11.2 deletion syndrome affect platelet production from birth. 1, 2, 3

Increased Platelet Destruction

Immune-Mediated Destruction

• Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated destruction of otherwise normal platelets and remains a diagnosis of exclusion. 1, 2, 3

• Secondary immune thrombocytopenia occurs with multiple associated conditions including:

  • HIV and hepatitis C infections (may precede other symptoms by years) 1, 3
  • Autoimmune disorders including systemic lupus erythematosus 1, 2, 3
  • Antiphospholipid syndrome (found in approximately 40% of otherwise typical adult ITP patients) 3
  • Common variable immune deficiency 1
  • Lymphoproliferative disorders 1, 2
  • H. pylori infection (eradication therapy can normalize platelet counts) 1, 3
  • Recent vaccinations including live attenuated virus vaccines 2, 3

• Drug-induced thrombocytopenia occurs with heparin, quinidine, sulfonamides, GPIIb-IIIa inhibitors, vancomycin, cefazolin, oxacillin, clindamycin, doxycycline, SMX-TMP, and certain antimitotic chemotherapies. 1, 3

• Heparin-induced thrombocytopenia (HIT) typically presents with moderate thrombocytopenia (30-70 G/L) occurring 5-10 days after heparin initiation and is paradoxically associated with thrombosis rather than bleeding. 1

Non-Immune Destruction

• Thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome cause platelet consumption through microvascular thrombosis. 1

• Disseminated intravascular coagulation (DIC) causes consumption of platelets and coagulation factors through widespread fibrin and platelet deposition. 4, 1

• HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) in pregnancy causes platelet destruction. 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. 4, 3

Splenic Sequestration

• Hepatic disease with portal hypertension and splenomegaly causes increased splenic sequestration of platelets. 1

Dilution

• Massive transfusion or fluid resuscitation can dilute circulating platelets. 5

Pregnancy-Related Causes

• Gestational thrombocytopenia is the most common cause in pregnancy, typically presenting with mild thrombocytopenia (platelet count >70,000/μL) and must be distinguished from ITP, pregnancy-induced hypertension/preeclampsia, and HELLP syndrome. 1, 3

Critical Diagnostic Considerations

The first step in evaluating thrombocytopenia is to exclude pseudothrombocytopenia by examining a peripheral blood smear and repeating the platelet count in a heparin or sodium citrate tube. 1, 3

• A complete blood count with differential distinguishes isolated thrombocytopenia from pancytopenia, which suggests bone marrow failure or infiltrative processes. 1, 2

• HIV and hepatitis C testing should be performed routinely in all adults with suspected ITP, regardless of risk factors or local prevalence, as these infections may be clinically indistinguishable from primary ITP and can occur years before other symptoms develop. 1, 3

• Comprehensive medication history including over-the-counter drugs and recent changes is essential to identify drug-induced causes. 1, 3

• Bone marrow examination is mandatory for patients over 60 years to exclude myelodysplastic syndromes, leukemias, or other malignancies, regardless of other typical ITP features. 1, 3

• Physical examination findings of splenomegaly, hepatomegaly, or lymphadenopathy indicate secondary causes and exclude primary ITP. 1, 3

Common Pitfalls to Avoid

• Missing pseudothrombocytopenia (EDTA-dependent platelet agglutination) by failing to review the peripheral blood smear leads to unnecessary workup. 1, 3

• Overlooking drug-induced thrombocytopenia by not obtaining comprehensive medication history including recent changes. 3

• Failing to test for HIV, HCV, and H. pylori in adults with apparent ITP misses treatable secondary causes. 1, 3

• Not recognizing conditions where thrombocytopenia paradoxically presents with thrombosis rather than bleeding, including antiphospholipid syndrome, heparin-induced thrombocytopenia, and thrombotic microangiopathies. 1, 5

• Delaying bone marrow examination in patients >60 years regardless of other typical ITP features can miss malignancies. 3