What are the causes of rapidly progressive thrombocytopenia?

Causes of Rapidly Progressive Thrombocytopenia

Rapidly progressive thrombocytopenia can be caused by multiple conditions including immune-mediated destruction, decreased platelet production, increased splenic sequestration, or platelet aggregation disorders. 1

Primary Categories of Rapidly Progressive Thrombocytopenia

Immune-Mediated Destruction

• Primary immune thrombocytopenia (ITP) - an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets 2, 1
• Secondary immune thrombocytopenia associated with:
  • Autoimmune disorders (including systemic lupus erythematosus) 2, 1
  • Infections (particularly HIV, HCV) 2
  • Lymphoproliferative disorders 2, 1
• Drug-induced immune thrombocytopenia (DITP) caused by:
  • Cinchona alkaloid derivatives (quinine, quinidine) 3, 4
  • Sulfonamides 4
  • NSAIDs 4
  • Anticonvulsants 4
  • Heparin (causing heparin-induced thrombocytopenia) 5, 6
  • Diuretics 4

Decreased Platelet Production

• Bone marrow disorders:
  • Myelodysplastic syndromes 2, 1
  • Leukemias and other hematologic malignancies 2, 1
  • Aplastic anemia 2
  • Megaloblastic anemia 2
  • Bone marrow fibrosis 2
• Inherited thrombocytopenias:
  • Thrombocytopenia-absent radius (TAR) syndrome 2, 1
  • Wiskott-Aldrich syndrome 2, 1
  • MYH9-related disease 2
  • Bernard-Soulier syndrome 2
  • Type IIB von Willebrand disease 2

Thrombotic Microangiopathies

• Thrombotic thrombocytopenic purpura (TTP) 1, 6
• Hemolytic uremic syndrome (HUS) 2, 6
• HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) 6

Other Causes

• Liver disease (including alcoholic liver cirrhosis) 2, 6
• Post-transfusion purpura 2
• Recent vaccination 2
• Splenic sequestration 6
• Disseminated intravascular coagulation (DIC) 5
• Pseudothrombocytopenia (EDTA-dependent platelet agglutination) - an in vitro artifact 2, 6

Diagnostic Approach for Rapidly Progressive Thrombocytopenia

Initial Assessment

• Exclude pseudothrombocytopenia by collecting blood in a tube containing heparin or sodium citrate and repeating the platelet count 6
• Perform peripheral blood smear examination to identify:
  • Schistocytes (suggesting TTP-HUS) 2
  • Leukocyte inclusion bodies (suggesting MYH9-related disease) 2
  • Abnormal platelet size or morphology (suggesting inherited thrombocytopenias) 2

Physical Examination Findings

• Look for:
  • Bleeding manifestations (petechiae, purpura, ecchymosis) 2, 6
  • Splenomegaly (suggesting sequestration or underlying hematologic disorder) 2
  • Hepatomegaly (suggesting liver disease or lymphoproliferative disorders) 2
  • Lymphadenopathy (suggesting lymphoproliferative disorders or infection) 2
  • Constitutional symptoms like fever and weight loss (suggesting infection or malignancy) 2, 1

Laboratory Evaluation

• Complete blood count with differential 2, 1
• Reticulocyte count (if anemia is present) 2
• HIV and HCV testing 2, 1
• Bone marrow examination in selected cases:
  • Patients older than 60 years 2
  • Those with systemic symptoms 2
  • When splenectomy is considered 2
  • To rule out malignancy 1

Clinical Pearls and Pitfalls

• Patients with platelet counts less than 10 × 10³ per μL have a high risk of serious bleeding and may require immediate intervention 6
• Heparin-induced thrombocytopenia can paradoxically cause thrombosis rather than bleeding and requires immediate discontinuation of heparin 5, 6
• Drug-induced thrombocytopenia can be severe and life-threatening; a careful medication history is essential 3, 4
• The presence of schistocytes on peripheral blood smear in a patient with rapidly progressive thrombocytopenia should raise suspicion for TTP-HUS, which requires urgent intervention 2
• In patients with isolated thrombocytopenia without other cytopenias or systemic illness, ITP or drug-induced thrombocytopenia are most likely 6, 7