Clinical Applications of 4-Factor Prothrombin Complex Concentrate: A Practical Pathologist's Perspective

Abstract

A 4-factor prothrombin complex concentrate (4F-PCC), containing therapeutic doses of vitamin K-dependent coagulation factors, was recently licensed in the United States for reversal of vitamin K antagonist therapy. However, given the emergence of several oral anticoagulants for which there are no specific reversal agents, and the existence of many other complex bleeding disorders, it is likely that clinicians will seek to use 4F-PCCs for any number of off-label indications. Thus, the goal of this review is to explore practical issues regarding 4F-PCC, with an emphasis on issues relevant to blood bankers and pathologists. Specifically, our aims are to (1) examine the role of 4F-PCC in vitamin K antagonist reversal, (2) review its potential use in the treatment of hemorrhage due to novel oral anticoagulants, and (3) explore potential uses in liver disease, trauma-associated bleeding, and rare coagulopathies. Safety and other practical considerations of 4F-PCCs will also be discussed.

Successful Use of Four Factor-Prothrombin Complex Concentrate for Congenital Factor X Deficiency in the Setting of Neurosurgery

“…Because our blood bank does not carry 3-factor prothrombin complex concentrate (3F-PCC; containing therapeutic levels of factors II, IX, and X), we did not further consider administering it to our patient, although theoretically, it could have been used. 2 We had performed the ACDF procedure before a purified FX concentrate was commercially available in the United States, 3 so using such a concentrate also was never considered. Instead, our focus was on 4F-PCC.…”

“…As noted earlier herein, FX deficiency is not a specific on-label indication for 4F-PCC administration, and its safety and efficacy in this setting are not well established. 2 Despite the presence of vitamin K-dependent anticoagulants in the formulation (ie, protein C and protein S), 4F-PCC has been associated with thromboembolic complications. 6,7 This fact was our most significant concern in the use of 4F-PCC for our patient; we weighed carefully the many benefits of this treatment against this risk.…”

“…Although FFP was initially discussed, the blood bank staff and the medical team ultimately decided that administration of 4F-PCC (Kcentra, CSL Behring) would be the optimal approach in this case. Because of the limited literature regarding 4F-PCC for surgical interventions in FX deficiency, 2 we planned a presurgical 4F-PCC, to ensure its safety and efficacy. Based on the patient's weight (100 kg) and the typical content of FX in 4F-PCC (25-51 U/mL), 2 a 10 U/kg dose (1000 U) was administered 30 days before the operation, with the expectation of achieving approximately 50% FX activity with such dosing.…”

“…1 Historically, fresh frozen plasma (FFP) had been a mainstay of therapy in the United States for treatment or prevention of bleeding associated with FX deficiency. 1 With the United States Food and Drug Administration (FDA) approval of a 4factor prothrombin complex concentrate (4F-PCC; containing therapeutic levels of factors II, VII, IX, and X) 2 in 2013, as well as a purified FX concentrate approved in late 2015, 3 there are now several more specific therapeutic options available. However, there have been few published reports of use of factor concentrates in managing the health of adults with congenital FX deficiency, particularly in the surgical setting.…”

“…However, there have been few published reports of use of factor concentrates in managing the health of adults with congenital FX deficiency, particularly in the surgical setting. 2,4,5 Moreover, there is virtually no guidance available in the literature on how best to proceed in bleeding prophylaxis in the neurosurgical setting for such patients. Herein, we report our experiences with the use of 4F-PCC to correct coagulation abnormalities before a neurosurgical procedure in the setting of congenital FX deficiency.…”