Management of Antibiotic Induced Thrombocytopenia

General

• platelet counts between 100 and 150 × 10⁹/L do not necessarily indicate disease if they have been stable for more than 6 months,² and the adoption of a cutoff value of 100 × 10⁹/L may be more appropriate to identify a pathologic condition
• Antibiotic-induced thrombocytopenia presents a particularly thorny dilemma in which the dual problems of infection and antibiotic-induced bleeding risk must be effectively balanced
• published reports regarding antimicrobial-induced thrombocytopenia describes decreasing platelet count and development of thrombocytopenia within 4 days after exposure to ciprofloxacin and piperacillin/tazobactam consistent
• most episodes of thrombocytopenia among critically ill patients appears to be driven by other factors than antimicrobials, especially underlying severe infection.

Evidence from Study:

• single center observational cohort study at an urban community teaching hospital seeking to compare the risk of hemorrhage associated mortality with that of non-hemorrhage associated mortality in antibiotic-induced thrombocytopenia.
• Mortality is considered hemorrhage associated if an active bleed is noted within one week prior to death.
• Thrombocytopenia is classified as mild, moderate, or severe depending on platelet nadir: “mild” is a decline to <150,000/µL, “moderate” is a decline to <50,000/µL, and “severe” is a decline to <20,000/µL.
• To qualify as antibiotic-induced, the platelet reduction must have begun between two and ten days after antibiotic induction (Visentin et al Hematology/Oncology Clinics of North America 2008)

Evidence of Risk

• A cut-off of 20% was chosen in order to include as many patients as possible for these analyses and at
• the same time avoid that a decrease in platelet count was due to measurement variability.
• found that that a 20% decrease in platelet count was associated with 28-day mortality; Threequarters
• of patients with relative thrombocytopenia never reached a platelet count ≤ 100 x 109/L but still retained a 71% increased risk of death if the episode occurred within day 1-4 after study entry.
• Therefore, this finding suggest that platelet count decrease influence prognosis in critically ill patients even when the threshold for absolute thrombocytopenia is never reached

Conclusion:

• Antibiotic-managed patients who develop thrombocytopenia would appear to be at greater risk of death from non-hemorrhagic causes, particularly sepsis complications, than from hemorrhagic causes.
• Absent a severely low platelet count, history of bleed, and/or active bleed, a patient may benefit more from continuing with effective antibiotics--even putatively thrombocytopenic antibiotics--than from discontinuing them or substituting them for suboptimal antibiotics

Reference:

1. Hemorrhage Risk in Antibiotic-Induced Thrombocytopenia: Rethinking Priorities. Blood Dec 2014, 124 (21) 2786
2. The Potential of Antimicrobials to Induce Thrombocytopenia in Critically Ill Patients: Data from a Randomized Controlled Trial. November 28, 2013