Drug-Induced Blood Dyscrasias

Overview & Mechanisms - Blood Cell Busters

Adverse drug reactions (ADRs) damaging blood cells (RBCs, WBCs, platelets) or bone marrow. Leads to anemia, leukopenia, agranulocytosis, thrombocytopenia, pancytopenia, or aplastic anemia. Mechanisms:

• Immune-mediated Destruction:
  • Hapten-induced (e.g., Penicillin causing hemolytic anemia)
  • Innocent bystander (e.g., Quinidine causing thrombocytopenia)
  • True Autoimmune (e.g., Methyldopa causing hemolytic anemia)
• Direct Dose-Dependent Toxicity:
  • Myelosuppression (e.g., Chemotherapeutic agents, Linezolid)
• Idiosyncratic Reactions: Unpredictable, often severe, not dose-related.
  • Aplastic anemia (e.g., Chloramphenicol, NSAIDs)
  • Agranulocytosis (e.g., Clozapine, Carbimazole, Propylthiouracil)
• Oxidative Hemolysis:
  • In G6PD deficient individuals with oxidant drugs (e.g., Primaquine, Sulfonamides, Dapsone).

⭐ Chloramphenicol exhibits two forms of bone marrow toxicity: a common, dose-related, reversible erythroid suppression, and a rare, fatal, idiosyncratic aplastic anemia unrelated to dose or duration of therapy.

Aplastic Anemia & Agranulocytosis - Marrow Mayhem

• Aplastic Anemia (Pancytopenia + Hypocellular Marrow)

  • Key Drugs:
    • Dose-dependent: Chemotherapy, chloramphenicol (early, reversible suppression).
    • Idiosyncratic: Chloramphenicol (late, irreversible aplasia, fatal), NSAIDs (phenylbutazone), sulfonamides, gold, anticonvulsants (carbamazepine, phenytoin), PTU.
  • Clinical: Anemia (fatigue), thrombocytopenia (bleeding), neutropenia (infections).
  • Dx: BM biopsy (<25% cellularity, ↑fat).
  • Rx: Stop drug, support (transfusions, antibiotics), IST (ATG, cyclosporine), BMT.

• Agranulocytosis (Severe Neutropenia: ANC < 500/µL)

  • Key Drugs: Clozapine, antithyroids (PTU, methimazole), sulfonamides, carbamazepine, ticlopidine, metamizole.
  • Clinical: Sudden fever, sore throat, mouth ulcers; sepsis risk.
  • Dx: CBC (isolated neutropenia). BM: myeloid arrest/hypocellular.
  • Rx: Stop drug, IV antibiotics, G-CSF.

  ⭐ Clozapine mandates regular ANC monitoring (e.g., weekly for 18 wks) for agranulocytosis risk.

Thrombocytopenia & Hemolytic Anemia - Platelet Plunge & RBC Rupture

Drug-Induced Thrombocytopenia (DITP):

• Mechanism: Immune (drug-dependent Abs).
• Onset: 5-14 days; rapid on re-exposure.
• Key Drugs: Heparin (HIT: ⚠️ paradoxical thrombosis risk!), Quinine, Sulfonamides, Vancomycin, GP IIb/IIIa inhibitors (Abciximab: rapid).
• Features: Bleeding, petechiae.
• Rx: Stop drug. Platelets if severe. HIT: non-heparin anticoagulants.

Drug-Induced Hemolytic Anemia (DIHA):

• Mechanisms:
  • Immune: Hapten (Penicillin G), Immune Complex (Quinidine), Autoimmune (Methyldopa).
  • Oxidative: Dapsone, Primaquine (G6PD def.).
• Features: Anemia, jaundice, ↑LDH, +ve DAT.
• Rx: Stop drug. Steroids for immune.

⭐ HIT: prothrombotic despite ↓platelets. Suspect if platelet drop >50% or thrombosis 5-14 days post-heparin.

Diagnosis, Management & Prevention - Spotting & Stopping Trouble

• Diagnosis: Key: drug exposure timeline. Bone marrow biopsy if severe/unclear.
• Management: STOP drug immediately! Supportive (transfusions, G-CSF). Immunosuppression for immune cases.
• Prevention: Genetic tests (e.g., G6PD, HLA-B*5701). Monitor high-risk drugs (clozapine, MTX). Patient education.

⭐ Clozapine mandates regular WBC monitoring due to high risk of agranulocytosis.

High‑Yield Points - ⚡ Biggest Takeaways

• Aplastic anemia: Key offending drugs include chloramphenicol, gold salts, carbamazepine, and NSAIDs.
• Agranulocytosis: Strongly associated with clozapine, thiouracils (e.g., propylthiouracil), and sulfonamides.
• Megaloblastic anemia: Caused by methotrexate, phenytoin, trimethoprim due to folate antagonism or impaired absorption.
• Hemolytic anemia: Especially in G6PD deficiency, triggered by sulfonamides, dapsone, primaquine, nitrofurantoin.
• Thrombocytopenia: Heparin (HIT) is critical; also quinidine, sulfonamides, valproic acid.
• Drug-induced lupus (procainamide, hydralazine, isoniazid) can present with pancytopenia.