Cefoperazone-induced Coagulopathy in Critically Ill Patients Admitted to Intensive Care Unit

Background: N-methylthiotetrazole side chain (NMTT) of cefoperazone was attributed to inhibit the vitamin K epoxide enzyme.This mechanism is similar to warfarin; thus, vitamin K was suggested to antagonize the hematological effects of cefoperazone.The literature on critically ill patients receiving cefoperazone and its clinical significance on bleeding diathesis is sparse.Objectives: To assess the incidence of cefoperazone-induced coagulopathy (CIC), its clinical impact on bleeding episodes, and transfusion requirements.Predisposing factors and the role of prophylactic and therapeutic vitamin K were evaluated.Materials and methods: Prospective observational study of adult intensive care unit (ICU) patients (>18 years) receiving cefoperazone between December 2017 and December 2018.We excluded those on warfarin, those with preexisting elevated prothrombin time/international normalized ratio (PT/INR), and with bleeding manifestations.Relevant laboratory investigations and specific outcomes were noted for 6 days following therapy.Panel data regression was used to determine predictors of coagulopathy.Results: Among 65 patients, 17 (26%) had probable CIC.Hypoalbuminemia and vancomycin co-administration were risk factors for CIC.Hemoglobin drops and blood transfusions were not different between INR non-elevated and elevated groups (11 vs 8 gm/dL; p = 0.06 and 11 vs 8 units; p = 0.23, respectively).Prophylactic vitamin K did not offer any benefit toward preventing INR elevation.Therapeutic vitamin K significantly reduced INR when elevated [absolute risk reduction (ARR):57.5% and number needed to treat (NNT):1.7]. Conclusion:Results of this study revealed that CIC is not uncommon in ICUs.Based on the findings of the study, we suggest INR monitoring in patients receiving nephrotoxic agents and patients with hypoalbuminemia.We also recommend vitamin K administration in patients with elevated INR.