Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal A systematic review and meta-analysis

Abstract

Urgent reversal of warfarin is required for patients who experience major bleeding or require urgent surgery. Treatment options include the combination of vitamin K and coagulation factor replacement with either prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). However, the optimal reversal strategy is unclear based on clinically relevant outcomes. We searched in MEDLINE, EMBASE and Cochrane library to December 2015. Thirteen studies (5 randomised studies and 8 observational studies) were included. PCC use was associated with a significant reduction in all-cause mortality compared to FFP (OR= 0.56, 95 % CI; 0.37-0.84, p=0.006). A higher proportion of patients receiving PCC achieved haemostasis compared to those receiving FFP, but this was not statistically significant (OR 2.00, 95 % CI; 0.85-4.68). PCC use was more likely to achieve normalisation of international normalised ratio (INR) (OR 10.80, 95 % CI; 6.12-19.07) and resulted in a shorter time to INR correction (mean difference -6.50 hours, 95 %CI; -9.75 to -3.24). Red blood cell transfusion was not statistically different between the two groups (OR 0.88, 95 % CI: 0.53-1.43). Patients receiving PCC had a lower risk of post-transfusion volume overload compared to FFP (OR 0.27, 95 % CI; 0.13-0.58). There was no statistically significant difference in the risk of thromboembolism following administration of PCC or FFP (OR 0.91, 95 % CI; 0.44-1.89). In conclusion, as compared to FFP, the use of PCC for warfarin reversal was associated with a significant reduction in all-cause mortality, more rapid INR reduction, and less volume overload without an increased risk of thromboembolic events.

Acute subdural hematoma in patients on oral anticoagulant therapy: management and outcome

“…Regarding vitamin K antagonists, several experimental and clinical studies reported PCC as the optimal reversal treatment in a bleeding situation, more effective than any other factor substitution. 6,13 This was well reflected in our study patients, with no significant difference observed between the vitamin K antagonist subgroup and the no-OAT group in terms of rebleeding or functional outcome. However, vitamin K antagonist treatment was associated with a higher number of comorbidities, resulting in a high mortality rate at follow-up.…”

“…The effectiveness of desmopressin and thrombocyte concentrate in patients treated with antiplatelet agents or prothrombin complex concentrates (PCC) in patients treated with a vitamin K antagonist has been reported in several studies and has recently been addressed in 2 systematic reviews. 6,9 Additionally, through the increasing use of direct oral anticoagulants (DOACs), intracranial hemorrhage and its management are receiving more attention. Nevertheless, there has been less study of the clinical management and outcome in patients who suffer isolated aSDH while on OAT, and to our knowledge no study exists concerning patients on DOACs.…”

Prothrombin Complex Concentrate for Vitamin K Antagonist-Associated Intracranial Hemorrhage ― Global Evidence and the Japanese Perspective ―

“…In the large metaanalysis comparing PCC and FFP for VKA reversal in a range of settings, the risk of TEEs was similar between groups (TEEs occurred in 15/358 [4.2%] and 17/349 [4.8%] of patients who received PCC and FFP, respectively). 46 In addition, an integrated analysis of the 2 largest RCTs comparing a 4F-PCC and plasma 44, 45 showed no increased risk of TEEs with 4F-PCC in patients requiring VKA reversal owing to major hemorrhage or prior to urgent surgical procedures. 55 …”

“…46 This meta-analysis included 13 studies, 6 of which were conducted exclusively in patients with ICH. Subgroup analyses by bleeding site were also conducted; administration of PCC significantly reduced all-cause mortality compared with FFP in patients with intracranial bleeding (P=0.04), but not in those with extracranial bleeding (P=0.18).…”

Prothrombin complex concentrates or recombinant factor VIIa are more effective than fresh-frozen plasma at lowering INR in patients with liver disease

“…Their results show that the use of PCCs led to more rapid INR correction, a greater reduction in all-cause mortality, and less post-transfusion complications such as volume overload. 2 Though this article describes the role of PCCs in the reversal of supratherapeutic INR-a topic that is deficient in literature-it unfortunately includes patients with warfarininduced coagulopathy rather than liver disease. Their review also does not focus on INR reversal specifically for the purpose of urgent surgical intervention.…”