What causes thrombocytopenia (low platelet count)?

Causes of Thrombocytopenia (Low Platelet Count)

Thrombocytopenia is caused by decreased platelet production, increased destruction, splenic sequestration, or dilution, with immune-mediated destruction and drug-induced mechanisms being the most common etiologies in clinical practice. 1, 2

Major Categories of Thrombocytopenia

Decreased Platelet Production

• Bone marrow disorders including myelodysplastic syndromes, leukemias, and other malignancies can cause decreased platelet production 1
• Inherited thrombocytopenias such as thrombocytopenia-absent radius syndrome and Wiskott-Aldrich syndrome 1
• Chemotherapy and radiation therapy affecting bone marrow function 1

Increased Platelet Destruction

• Primary immune thrombocytopenia (ITP) - an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets in response to an unknown stimulus 3, 1
• Secondary immune thrombocytopenia associated with:
  • Autoimmune diseases, particularly antiphospholipid syndrome 3, 1
  • Viral infections including hepatitis C (HCV) and human immunodeficiency virus (HIV) 3, 1
  • Lymphoproliferative disorders 1
• Drug-induced thrombocytopenia from numerous medications 1, 2
• Heparin-induced thrombocytopenia (HIT) - an antibody-mediated reaction that can lead to thrombosis 3, 4
• Thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) 3, 2
• Disseminated intravascular coagulation (DIC) 3

Splenic Sequestration

• Hypersplenism due to liver disease or portal hypertension 2
• Infiltrative diseases of the spleen 1

Other Causes

• Pregnancy-related conditions such as HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) 2, 5
• Post-transfusion purpura linked to alloimmunization 3
• Dilutional thrombocytopenia following massive transfusion 3
• Pseudothrombocytopenia (laboratory artifact) - not a true thrombocytopenia 1, 2

Clinical Presentation and Diagnosis

Clinical Features

• Patients with platelet counts >50 × 10³/μL are generally asymptomatic 2
• Platelet counts between 20-50 × 10³/μL may present with mild skin manifestations (petechiae, purpura, ecchymosis) 2
• Platelet counts <10 × 10³/μL carry high risk of serious bleeding 2
• Some conditions (HIT, antiphospholipid syndrome, TTP) can paradoxically present with both thrombocytopenia and thrombosis 3, 2

Diagnostic Approach

• Initial evaluation should include peripheral blood smear to exclude pseudothrombocytopenia 1, 2
• Complete blood count and peripheral smear examination are essential 1
• The 4T score helps assess clinical probability of HIT based on:
  • Thrombocytopenia severity (typically 30-70 × 10⁹/L in HIT)
  • Timing of onset (typically 5-10 days after starting heparin)
  • Thrombosis or other clinical sequelae
  • Other potential causes of thrombocytopenia 3
• Testing for HIV and HCV is recommended in adults with suspected ITP 1
• Bone marrow examination may be necessary in selected cases, particularly in patients >60 years or those with systemic symptoms 1

Special Considerations

Heparin-Induced Thrombocytopenia

• HIT is a serious antibody-mediated reaction due to antibodies against platelet Factor 4-heparin complex 4
• Can progress to heparin-induced thrombocytopenia with thrombosis (HITT) 4
• Thrombotic events may include deep vein thrombosis, pulmonary embolism, stroke, and limb ischemia 4
• If platelet count falls below 100,000/mm³ or recurrent thrombosis develops, heparin should be promptly discontinued 4

Primary Immune Thrombocytopenia

• Defined as platelet count <100 × 10⁹/L in absence of other causes 3
• Physical examination should be normal aside from bleeding manifestations 1
• Presence of splenomegaly, hepatomegaly, or lymphadenopathy suggests secondary causes 1

Drug-Induced Thrombocytopenia

• Many medications can cause thrombocytopenia through immune or non-immune mechanisms 1, 2
• Common culprits include heparin, glycoprotein IIb/IIIa inhibitors, antibiotics, and chemotherapeutic agents 3
• Typically resolves after discontinuation of the offending drug 2

By understanding these various causes of thrombocytopenia, clinicians can develop a systematic approach to diagnosis and management, ultimately improving patient outcomes by addressing the underlying etiology.