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

Causes of Thrombocytopenia

Thrombocytopenia is primarily caused by decreased platelet production, increased platelet destruction, splenic sequestration, or dilution/clumping, with immune-mediated mechanisms and drug reactions being the most common etiologies in otherwise healthy individuals. 1, 2

Major Categories of Thrombocytopenia

Decreased Platelet Production

• Bone marrow disorders including myelodysplastic syndromes, leukemias, and other malignancies that impair megakaryocyte function 1, 2
• Inherited thrombocytopenias such as thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, and MYH9-related disease 2
• Viral infections that suppress bone marrow production of platelets 2

Increased Platelet Destruction

• Primary immune thrombocytopenia (ITP) - an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets 1, 2
• Secondary immune thrombocytopenia associated with:
  • Autoimmune disorders 1, 2
  • Infections (particularly viral) 2
  • Lymphoproliferative disorders 1, 2
• Drug-induced immune thrombocytopenia from:
  • Cinchona alkaloid derivatives (quinine, quinidine) 3
  • Sulfonamides 3
  • NSAIDs 3
  • Anticonvulsants 3
  • Disease-modifying antirheumatic drugs 3
  • Diuretics 3
• Heparin-induced thrombocytopenia (HIT) - typically moderate thrombocytopenia (30-70 G/L) occurring 5-10 days after initiation of heparin therapy 4

Thrombotic Microangiopathies

• Thrombotic thrombocytopenic purpura (TTP) 1
• Hemolytic uremic syndrome (HUS) 1
• Antiphospholipid syndrome 4
• Disseminated intravascular coagulation (DIC) 4, 5

Other Causes

• Splenic sequestration in patients with splenomegaly 6
• Pregnancy-related:
  • Gestational thrombocytopenia (most common, typically mild with counts >70,000) 4
  • Pregnancy-induced hypertension/preeclampsia and HELLP syndrome 4, 7
• Pseudothrombocytopenia - laboratory artifact due to platelet clumping in EDTA tubes 7, 3

Clinical Presentation and Severity

• Platelet count >50,000/μL: Generally asymptomatic 7
• Platelet count 20,000-50,000/μL: May have mild skin manifestations (petechiae, purpura, ecchymosis) 7
• Platelet count <10,000/μL: High risk of serious bleeding 7

Diagnostic Approach

1. Initial evaluation:

   • Confirm true thrombocytopenia by collecting blood in a tube containing heparin or sodium citrate to exclude pseudothrombocytopenia 7
   • Complete blood count with differential to identify isolated thrombocytopenia versus pancytopenia 2
   • Peripheral blood smear examination to assess platelet morphology and exclude pseudothrombocytopenia 1, 2

2. Distinguish acute from chronic thrombocytopenia by reviewing previous platelet counts 7

3. Assess for emergency causes requiring immediate hospitalization:

   • Heparin-induced thrombocytopenia - evaluate using 4T score based on:
     • Degree of thrombocytopenia (typically 30-70 G/L) 4
     • Timing (typically 5-10 days after starting heparin) 4
     • Presence of thrombosis 4
     • Absence of other causes 4
   • Thrombotic microangiopathies 7
   • HELLP syndrome in pregnant patients 7

4. Additional testing as indicated:

   • Testing for HIV and hepatitis C in adults with suspected ITP 1, 2
   • Bone marrow examination in selected cases (patients >60 years or with systemic symptoms) 1, 2

Important Clinical Considerations

• Physical examination should be normal in primary ITP aside from bleeding manifestations 1
• Presence of splenomegaly, hepatomegaly, or lymphadenopathy suggests secondary causes 1
• Constitutional symptoms like fever and weight loss suggest underlying infection or malignancy 1
• Drug-induced thrombocytopenia should always be considered and may require detailed medication review 1, 3
• In pregnancy, gestational thrombocytopenia must be distinguished from ITP, though this can be challenging 4

Treatment Considerations

• Transfusion of platelets is recommended for active hemorrhage or when platelet counts are <10,000/μL 7
• Patients with platelet counts <50,000/μL should avoid activities with high risk of trauma 7
• For primary ITP in children with no or mild bleeding, observation alone may be appropriate regardless of platelet count 2
• Treatment should always address the underlying cause when possible 6