Learning Objective
By the end of this section, students should be able to identify common hematologic adverse effects of drugs, recognize the responsible agents, and understand the underlying mechanisms, which are high-yield for USMLE Step 1 pharmacology.
Drug-Induced Hematologic Reactions
| Reaction | Causal Agents | Notes / Clinical Features |
|---|---|---|
| Agranulocytosis | Dapsone, Clozapine, Carbamazepine, Propylthiouracil, Methimazole, Ganciclovir, Colchicine | Severe reduction in neutrophils → risk of infection; monitor WBC count |
| Aplastic anemia | Carbamazepine, Methimazole, NSAIDs, Benzene, Chloramphenicol, Propylthiouracil | Pancytopenia due to bone marrow failure; presents with fatigue, infections, bleeding |
| Direct Coombs–positive hemolytic anemia | Penicillin, Cephalosporins, Methyldopa | Autoimmune hemolysis; check Coombs test; hemolysis resolves with drug discontinuation |
| DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) | Phenytoin, Carbamazepine, Minocycline, Sulfa drugs, Allopurinol, Vancomycin | T-cell mediated hypersensitivity: fever, rash, eosinophilia, systemic organ involvement |
| Hemolysis in G6PD deficiency | Sulfonamides, Dapsone, Primaquine, Aspirin, Nitrofurantoin | Oxidative stress → hemolytic anemia; presents with jaundice, hemoglobinuria |
| Megaloblastic anemia | Hydroxyurea, Phenytoin, Methotrexate, Sulfadiazine | Impaired DNA synthesis → macrocytosis, hypersegmented neutrophils |
| Thrombocytopenia | Heparin, Quinidine, Ganciclovir, Vancomycin, Linezolid | Reduced platelet count; heparin can also cause thrombosis (HIT) |
| Thrombotic complications | Combined oral contraceptives, Hormone replacement therapy, SERMs, Testosterone supplements, Epoetin alfa | Increased blood viscosity and platelet aggregation → risk of DVT, PE, MI, stroke |
Activity
Step 1 Pearls
- Clozapine → agranulocytosis; monitor absolute neutrophil count (ANC).
- Methimazole / Propylthiouracil → agranulocytosis + aplastic anemia.
- Penicillin → Coombs-positive hemolytic anemia.
- DRESS syndrome → phenytoin, carbamazepine, sulfa drugs; systemic involvement is key.
- G6PD deficiency → hemolysis with oxidative drugs (primaquine, sulfonamides).
- Heparin → thrombocytopenia, possible thrombosis (HIT).
- Hormonal agents → thrombotic risk; estrogen increases coagulation.
