Pharmacology: Drug-Induced Thrombocytopenia

Drug-Induced Thrombocytopenia

• Incidence: 10 cases per 1,000,000 population
• Symptoms:
  • Early phase: increased bruising, petechiae, ecchymoses, and epistaxis
  • Later phase: bleeding of mucous membrane and purpura
• Examples of drugs and their mechanisms:
  • Immunologic reactions:
    • Quinidine, sulfonamides, rifampin, heparin
    • Vancomycin, penicillin, cephalosporin - Hapten-type immune reaction
    • Gold compounds, procainamide– platelet specific antibody
  • Antineoplastics – direct toxicity reaction
  • Heparin – Type I & Type II

Heparin-Induced Thrombocytopenia

• Type I:
  • Non-immunologic response, mild, reversible
  • Occurs in 10-20% of patients on heparin
  • Platelet count slowly returns to baseline
  • Usually asymptomatic
• Type II:
  • Immunologic response, more severe
  • Less common (1 to 5% for heparin, 0.8% for LMWH)
  • Platelet count generally begins to decline 5 to 10 days after the start
  • Risk factors: patients who had recent major surgery

Drug-Induced Hematological Disorders (DIHD)

• Goal:
  • To discuss the various types of DIHD
  • To recommend the appropriate laboratory analysis, diagnostic assessment, and management in DIHD
  • To propose appropriate pharmacotherapy plans based on the different types of DIHD

Case Study

• A 45-year-old lady presented to the clinic complaining of weakness, fatigue, and shortness of breath
• She reports easy bruising and petechiae on her skin
• She is a known case of T2DM and HPT, and is currently on Amlodipine 10 mg OD and Metformin 500 mg BD

General Information

• Some agents cause predictable hematologic disease (e.g., antineoplastics), but others induce idiosyncratic reactions not directly related to the drugs’ pharmacology
• Associated with significant drug-related morbidity and mortality
• Aplastic anemia was the leading cause of death, followed by thrombocytopenia, agranulocytosis, and hemolytic anemia
• The risk of getting DIHD and the risk of death from DIHD is higher with increasing age

Types of DIHD

• Drug-induced agranulocytosis
• Drug-induced thrombocytopaenia
• Drug-induced haemolytic anaemia
  • DI immune haemolytic anaemia
  • DI oxidative haemolytic anaemia
• Drug-induced megaloblastic anaemia
• Drug-induced aplastic anaemia

Drug-Induced Agranulocytosis

• Definition:
  • Leucopenia: TWBC less than 3000/μl
  • Neutropenia: neutrophil count less than 1500/μl
  • Granulocytopenia: Granulocyte count less than 1500/μl (includes eosinophil & basophil)
  • Agranulocytosis: (severe neutropenia) a reduction in the number of mature myeloid cells in the blood (granulocytes and immature granulocytes [bands]) to a total count of 500 cells/mm3 or less
• Examples of drugs and their mechanisms:
  • Penicillin – hapten-type reaction
  • Quinidine, phenothiazine – innocent bystander phenomenon
  • High dose B-lactam antibiotics, carbamazepine, valproic acid – autoimmune reaction
  • Clozapine, ticlopidine – direct toxicity to progenitor stem cells
• Symptoms:
  • Sore throat, fever, malaise, weakness, chills
• Duration: Can appear within days to weeks after initiation of therapy
• Treatment:
  • Removal of offending drug
  • Symptomatic treatment (e.g., Abx for infection)
  • Colony-stimulating factors (e.g., GM-CSF, G-CSF)