Piperacillin Induced Thrombocytopenia in Critical Care Patients as Compared to Non Critical Patients.

Introduction: Drug-induced thrombocytopenia in the critically ill is documented in the literature with limited frequency. Implicated agents are antiepileptics, anticoagulants, antiarrhythmics, histamine receptor antagonists, and antimicrobials .Piperacillin has only rarely been implicated as a cause of thrombocytopenia, and there is only limited evidence that this complication is caused by immune mechanisms.

Methods: We conducted a retrospective chart review of patients admitted during a 6-month period to determine the frequency of and potential risk factors associated with thrombocytopenia, and the association of acquired thrombocytopenia with the use of piperacillin ICU versus non ICU patients.

Results: Data were collected for 154 patients (M:71, F:83),), admitted to the ICU and Non-ICU setting. 55% of the patients were more than 65 years of age. Platelet drop occurred in 123 patients. Thrombocytopenic patients had a longer ICU stay (11.2 vs 5.6 days) and greater mortality (9% vs 3%) than nonthrombocytopenic patients .The patients developed thrombocytopenia as follows:Mild(100–150k): 22 pts-(15%) ; Moderate(50–100k): 7 pts-(5%) ;and Severe(<50k): 4 pts- (3%). The other drugs during hospitalization were heparin (30%), ceftazidime(11%), famotidine(9%), bactrim(0.3%),esomeprazole (11%), aspirin(18%). Patients received piperacillin for mean duration of 9 days. In patients with thrombocytopenia, the platelet levels dropped by a mean of 15.15% on Day 2 from pretreatment values (range, 2% to 61%) while they were receiving piperacillin. On average, the nadir platelet count was reached 7 days after treatment with piperacillin was initiated (range, 2 to14days). The median time required for platelet recovery was 8.4 days (range 5.6 in ICU to 11.2 in Non-ICU pts).Bleeding was unusual in patients with thrombocytopenia. Platelet transfusions failed to elevate platelet counts.

Discussion: Thrombocytopenia occurs in 23–63% of patients in the intensive care unit (ICU). Factors associated with the disorder in these patients include sepsis, disseminated intravascular coagulation (DIC), blood transfusions, central catheters, and drugs, some of which may have a significant effect on morbidity and mortality. The major mechanisms of drug-induced thrombocytopenia are immune-mediated platelet destruction and concentration-dependent bone marrow suppression. Bone marrow toxicity, mainly neutropenia, has been described as an uncommon secondary effect of most beta-lactams, and it is usually related to large cumulative doses.

Conclusion: Thrombocytopenia is associated with an increased ICU stay and increased mortality. Thrombocytopenic events associated with antimicrobial agents in the ICU may warrant further investigation because of the increased administration of these drugs to combat more virulent bacterial strains.