Drug-Induced Haematological Disorders
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Direct answer
Drug-induced haematological disorders are blood abnormalities caused by medicines, including haemolysis, marrow aplasia, methaemoglobinaemia and cytopenias affecting a single cell line, such as neutropenia or thrombocytopenia. Most arise from oxidative injury, immune mechanisms or direct marrow toxicity, and the drug group often predicts which pattern will appear.
What you must remember
- Haemolysis in G6PD deficiency: Oxidant drugs such as primaquine, dapsone and sulfonamides trigger haemolysis, with Heinz bodies on the smear.
- Immune haemolysis: Methyldopa is the classic cause of autoimmune haemolytic anaemia with a positive direct antiglobulin test.
- Aplasia: Chloramphenicol causes idiosyncratic aplastic anaemia, which is not dose-related, and carbamazepine is another recognised cause.
- Methaemoglobinaemia: Dapsone, primaquine, nitrates and local anaesthetics such as benzocaine and prilocaine cause it, and methylene blue is the antidote.
- Thrombocytopenia: Heparin, quinine and linezolid are classic drug causes, with quinine acting through immune mechanisms.
- Neutropenia: Clozapine, carbimazole and propylthiouracil cause agranulocytosis, so white cell counts are monitored.
- Megaloblastic change: Methotrexate and trimethoprim act as folate antagonists and can produce macrocytosis.
- Dose-dependent versus idiosyncratic: Marrow suppression is often dose-related, whereas aplasia and agranulocytosis are usually idiosyncratic.
Working through a drug-linked cytopenia
A 26-year-old man develops dark urine, jaundice and anaemia four days after starting a sulfonamide for a urinary infection. The pattern points to a drug-triggered haemolytic process until proven otherwise.
- Identify the lineage: Decide whether red cells, white cells, platelets or all three are affected, since each pattern points to a different drug group.
- Review the timeline: Note when the drug started, because idiosyncratic reactions often appear within days to weeks, while dose-dependent toxicity follows cumulative exposure.
- Examine the smear: Look for Heinz bodies, bite cells and spherocytes, which suggest oxidative or immune haemolysis.
- Test for G6PD: Assess G6PD status when an oxidant drug is suspected, ideally once haemolysis has settled, because a recent haemolytic episode can give a falsely normal result.
- Test for antibodies: Perform a direct antiglobulin test where immune haemolysis is suspected, as with methyldopa or high-dose penicillin.
- Stop and monitor: Withdraw the suspected drug and follow the counts, since many drug-induced cytopenias improve after the drug is stopped.
- Report the reaction: Report the suspected adverse reaction to the national pharmacovigilance system, which in India is the Pharmacovigilance Programme of India.
Where the exam tries to catch you
Most traps involve antidote safety, the link between dose and toxicity and monitoring of agranulocytosis.
- Trap: Giving methylene blue for methaemoglobinaemia in a G6PD-deficient patient. Correct: Methylene blue can trigger haemolysis in G6PD deficiency, so alternatives such as ascorbic acid are considered.
- Trap: Assuming chloramphenicol aplasia is dose-related. Correct: Its aplastic anaemia is idiosyncratic and unpredictable, unlike the dose-dependent marrow suppression it can also cause.
- Trap: Attributing methyldopa-related anaemia to bone marrow failure. Correct: Methyldopa causes autoimmune haemolytic anaemia, which is confirmed by a positive Coombs test.
- Trap: Continuing clozapine despite a falling neutrophil count. Correct: Clozapine can cause agranulocytosis, so counts are monitored and the drug is stopped when neutropenia becomes severe.
Frequently asked questions
Which drugs cause haemolysis in G6PD deficiency?
Primaquine, dapsone, sulfonamides and nitrofurantoin are classic oxidant drugs that cause haemolysis in G6PD deficiency. Rasburicase and quinine are also recognised triggers in this setting.
Which drug is classically linked to idiosyncratic aplastic anaemia?
Chloramphenicol is classically linked to idiosyncratic aplastic anaemia, which is not dose-related and can occur after small exposures. Its dose-dependent marrow suppression is a separate effect.
Which drugs cause methaemoglobinaemia and how is it treated?
Dapsone, primaquine and nitrates, along with local anaesthetics such as benzocaine and prilocaine, cause methaemoglobinaemia. Intravenous methylene blue is the standard antidote, but it is avoided in G6PD deficiency.
Which antipsychotic needs regular white cell monitoring because of agranulocytosis?
Clozapine needs regular white cell and neutrophil monitoring because it can cause agranulocytosis, a serious fall in neutrophils. Monitoring schedules follow the prescribing protocol, and the drug is stopped if neutropenia becomes severe.
Why do quinine and heparin cause thrombocytopenia?
Quinine and heparin can cause immune-mediated thrombocytopenia through drug-dependent antibodies that activate platelets. In heparin-induced thrombocytopenia the antibody targets platelet factor 4 bound to heparin, which can lead to thrombosis rather than bleeding.