LAUSR

We read with much interest the article “Initiation of a fixeddose fourfactor prothrombin complex concentrate protocol” published by Fuh. L et al. in your esteemed journal. In this study, authors have included 63 patients with supra-therapeutic INR on warfarin retrospectively, and have assessed the role of a fixed dose of 1500 units of fourfactor prothrombin complex concentrate (4F-PCC) in achieving adequate hemostasis [1]. While authors have tried to focus on achieving a target INR of < 1.4 for CNS bleed and < 2 for other bleeds, the reader needs to be aware that in the landmark RCT by Sarode et al. two independent co-primary study endpoints that were included are hemostatic efficacy assessed over a 24h period from start of infusion and reduction of INR to < 1.3 within 30 min [2]. The above two criteria are of utmost significance as the goal of administration of 4F-PCC is not only a reversal of INR but also having an improvement in morbidity and mortality. While authors have reported a high mortality of 30%, the prior RCT had reported a mortality of 5.6% in the 4F-PCC arm and 4.6% in the fresh frozen plasma (FFP) arm [2]. In the prior studies including 4F-PCC, the commonest type of bleeding reported has been gastrointestinal [2, 3]. Authors have reported 76% of CNS bleed as compared to 12% by Sarode et al. Could the authors provide the reason regarding the same? Would the mortality be lesser if the distribution of etiologies were different? More so would there be a difference in mortality among patients receiving recommended dose versus a fixeddose as in this study? With the use of INR based dosing, and a minimum dosing regimen of 25 U of 4F-PCC, effective hemostasis was achieved in 70–80% of patients in prior studies [2, 4]. We strongly feel that the administration of 4F-PCC should be based on the patient’s initial clinical presentation along with the baseline INR. We also commend the authors on the pharmacist–driven administration of 4F-PCC. Patients with supra-therapeutic INR require administration of vitamin K before administration of 4 F–PCC. However, to date, all studies have been able to achieve an adherence rate in 90% of subjects. Interdisciplinary decision making before administration would further improve the adherence to administration of vitamin K, rapid administration of the drug and ultimately the outcome [5, 6]. Finally in the prior studies administration of 4 F–PCC also reported the requirement of additional blood products and fresh frozen plasma [2, 3, 6, 7]. What was the additional product requirement in these patients?