Retrospective study of rFVIIa, 4‐factor PCC, and a rFVIIa and 3‐factor PCC combination in improving bleeding outcomes in the warfarin and non‐warfarin patient

Abstract

In case of severe bleeding, the physician must rapidly and effectively halt bleeding without the risk of thromboembolic complications. Despite widespread use, no study has directly compared recombinant activated factor VII (rFVIIa), the rFVIIa and 3‐factor prothrombin complex concentrate (PCC) combination (“combination”), and 4‐factor PCC on their effectiveness in improving patient outcomes. This study examined the medical records of 299 patients, 65.2% on warfarin prior to admission, who received these hemostatic agents and were admitted to an ICU or through the emergency department at Oregon Health & Science University. Mortality, length of stay, change in international normalized ratio (INR), plasma use, and number of thromboembolic complications were used to assess effectiveness. In patients receiving warfarin, the combination group had the greatest decrease in INR as well as lowest overall INR, but experienced a higher number of clotting complications, while the rFVIIa group used the most plasma. Non‐warfarin patients in the combination group had the shortest length of stay among survivors, but the rFVIIa group had the lowest mortality. Based on this data, it may be prudent to further study the use of rFVIIa in treating extreme bleeding in the non‐warfarin patient, while this study supports other data that 4‐factor PCC may be the most prudent for the warfarin patient. Am. J. Hematol. 91:705–708, 2016. © 2016 Wiley Periodicals, Inc.

Effectiveness of prothrombin complex concentrate for the treatment of bleeding: A systematic review and meta‐analysis

“…Of these, full text was assessed, leading to the exclusion of another 109 studies, resulting in 17 studies that were included in the analysis. Studies included two prospective studies 23,24 and 15 retrospective studies, 25‐39 yielding a total of 3060 patients (Figure 1). Characteristics of the included studies are shown in Table 1.…”

“…Characteristics of the included studies are shown in Table 1. Studies were conducted in patients undergoing cardiothoracic surgery (10 studies with a total of 1678 patients) 23‐25,28‐30,35‐37,39 in trauma patients (four studies with a total of 932 patients), 31‐33,38 in patients undergoing orthotopic liver transplantation (two studies with a total of 383 patients) 26,34 and in patients who were bleeding from various causes (one study with a total of 78 patients) 27 …”

Prothrombin Complex Concentrates for Perioperative Vitamin K Antagonist and Non–vitamin K Anticoagulant Reversal

“…52 In another retrospective review, a significantly greater proportion of patients achieved a target international normalized ratio of <1.3 when receiving a combination of 3 factor- prothrombin complex concentrate and recombinantFVIIa (79.4%) compared with patients who received either recombinant FVIIa (45.7%) or 4 factor- prothrombin complex concentrate (50.0%) alone; however, this combination therapy was associated with a significantly higher proportion of deep vein thromboses (18.7%) compared with either recombinant FVIIa (4.2%) or 4 factor- prothrombin complex concentrate (6.1%). 53 The high number of patients achieving international normalized ratio <1.3 and experiencing deep vein thromboses with the combination therapy might be indicative of “double dosing” of coagulation factors and the fact that 3 factor- prothrombin complex concentrates lack small amounts of anticoagulant factors (protein C and S) present in 4 factor- prothrombin complex concentrates. 53…”

“…53 The high number of patients achieving international normalized ratio <1.3 and experiencing deep vein thromboses with the combination therapy might be indicative of “double dosing” of coagulation factors and the fact that 3 factor- prothrombin complex concentrates lack small amounts of anticoagulant factors (protein C and S) present in 4 factor- prothrombin complex concentrates. 53…”

Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies

“…[63][64][65] Deloughery et al performed a retrospective analysis of patients on warfarin who received rFVIIa (n ¼ 35), rFVIIa in combination with 3F-PCC (n ¼ 102), or 4F-PCC (n ¼ 58), with the majority of patients presenting with intracranial bleeds. 66 All three groups achieved a mean postadministration INR 1.5. The combination group was able to achieve a mean INR 1.3 but was associated with a significantly higher incidence of deep vein thrombosis.…”