Protect the Platelets
The frequency of drug-induced thrombocytopenia (DIT) in acutely ill patients is thought to be up to 25%, making it a common problem.1,2
Hundreds of drugs have been identified as causing DIT, due to either accelerated immune-mediated platelet destruction, decreased platelet production (bone marrow suppression), or platelet aggregation. The latter is the case in heparin-induced thrombocytopenia and thrombosis (HITT). DIT should be suspected in any patient who presents with acute thrombocytopenia from an unknown cause.3
Normal adult platelet counts usually are in the range of 140,000 to 450,000/mm3. A patient who presents with severe thrombocytopenia (less than 20,000 platelets/mm3) should strongly be suspected as having a drug-induced cause.
A patient also can present with moderate to severe thrombocytopenia (less than 50,000 platelets/mm3) and spontaneous bleeding from a drug-induced cause. The spontaneous bleeding can take the form of simple petechiae or ecchymoses, as well as mucosal bleeding or life-threatening intracranial or gastrointestinal hemorrhage. It may also present itself as bleeding around catheter insertion sites.
When DIT occurs, platelet count usually falls within two to three days of taking a drug that’s been taken before, or seven or more days after starting a drug the patient has not been exposed to. Once the offending drug is discontinued, platelet counts usually recover within 10 days.
Exclusions of other causes of thrombocytopenia, such as inflammatory processes and congenital disorders, as well as nondrug causes including sepsis, malignancy, extensive burns, chronic alcoholism, human immunodeficiency virus, splenomegaly, and disseminated intravascular coagulation, become part of the differential diagnosis.
Generally, the frequency and severity of bleeding manifestations correlate with the actual platelet count. Patients with a platelet count of less than 50,000/mm3 have an increased risk of spontaneous hemorrhage, but the severity may vary. Other risk factors include advanced age, bleeding history, and general bleeding diatheses.
A thorough physical examination and drug history are essential. Agents commonly associated with thrombocytopenia should be identified first followed by a more extensive review for other causes. A careful drug history should include prescriptions, over-the-counter medications (specifically quinine and acetaminophen), dietary supplements, folk remedies, other complementary and alternative therapies, and vaccinations.
The Agents
The top two suspects for DIT are antineoplastic agents and heparin. After these two, the agents most frequently associated with DIT development include:
- Quinine/quinidine;
- Phenytoin;
- Sulfonamide antibiotics;
- Cimetidine;
- Ranitidine;
- Rifampin/rifampicin;
- Carbamazepine;
- Thiazide diuretics;
- Penicillin;
- Oral antidiabetic drugs;
- Nonsteroidal anti-inflammatory drugs;
- Gold salts; and
- Procainamide.
A complete list of all case reports describing DIT, organized by generic
drug names, is available online at http://w3.ouhsc.edu/platelets/ditp.html.4
Management
Removal of the potentially offending agent, if known, is prudent before clinically significant bleeding occurs. If the offending agent is not discontinued, the platelet count will continue to decrease and bleeding will become more severe. If necessary, an alternate agent with a similar pharmacologic effect can be started. Daily platelet count monitoring is also recommended for management. Rare cases may require platelet transfusions, intravenous immunoglobulin therapy or plasmapheresis.
A complete blood count and peripheral blood smear may provide important indications into the mechanism of the disorder, but they’re not necessary for patient management. TH
