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KEY CONCEPTS
The most common drug-induced hematologic disorders include aplastic anemia, agranulocytosis, megaloblastic anemia, hemolytic anemia, and thrombocytopenia.
Drug-induced hematologic disorders are generally rare adverse effects associated with drug therapy.
The incidence of rare adverse drug reactions (ADRs) is usually established by postmarketing surveillance and reporting.
Rechallenging a patient with an agent suspected of inducing a blood disorder is not generally recommended.
Drug-induced hematologic disorders can occur by two mechanisms: direct drug or metabolite toxicity or an immune reaction.
The primary treatment of drug-induced hematologic disorders is removal of the drug in question and symptomatic support of the patient.
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Hematologic disorders have long been a potential risk of modern pharmacotherapy. Granulocytopenia (agranulocytosis) was reported in association with one of medicine’s early therapeutic agents, sulfanilamide, in 1938.1 Some agents cause predictable hematologic disease (eg, antineoplastics), but others induce idiosyncratic reactions not directly related to the drugs’ pharmacology. The most common drug-induced hematologic disorders include aplastic anemia, agranulocytosis, megaloblastic anemia, hemolytic anemia, and thrombocytopenia.
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The incidence of idiosyncratic drug-induced hematologic disorders varies depending on the condition and the associated drug. Few epidemiologic studies have evaluated the actual incidence of these adverse reactions, but these reactions appear to be rare. Women are generally more susceptible than men to the hematologic effects of drugs. The incidence varies based on geography, which suggests that genetic differences may be important determinants of susceptibility. Drug-induced thrombocytopenia is the most common drug-induced hematologic disorder, with reports suggesting that between 0.1% and 5% of patients who receive heparin develop heparin-induced thrombocytopenia (HIT).2,3 The Berlin Case-Control Surveillance Study was conducted from 2000 to 2009 to assess the incidence and risks of drug-induced hematologic disorders and found that almost 30% of all cases of blood dyscrasias were “possibly” attributable to drug therapy.4
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Although drug-induced hematologic disorders are less common than other types of adverse reactions, they are associated with significant morbidity and mortality. Aplastic anemia is the leading cause of death followed by thrombocytopenia, agranulocytosis, and hemolytic anemia.5 Similar to most other adverse drug reactions (ADRs), drug-induced hematologic disorders are more common in elderly adults than in the young; the risk of death also appears to be greater with increasing age.
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The MedWatch program supported by the Food and Drug Administration6 is the most common avenue for postmarketing surveillance to establish the incidence of ADRs. Many facilities have similar drug-reporting programs to follow ADR trends and to determine whether an association between a drug and an ADR is causal or coincidental. These programs enable practitioners to confirm that an adverse event is the result of drug therapy rather than one of many other potential causes; general guidelines are readily available.7,8
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Because drug-induced blood disorders are potentially dangerous, rechallenging a patient with a suspected agent in an attempt to confirm a diagnosis is not recommended. In vitro ...