Three‐factor prothrombin complex concentrates for refractory bleeding after cardiovascular surgery within an algorithmic approach to haemostasis

Abstract

Background/Objectives Prothrombin complex concentrates (PCC) are increasingly administered off-label in the United States to treat bleeding in cardiovascular surgical patients and carry the potential risk for acquired thromboembolic sideeffects after surgery. Therefore, we hypothesized that the use of low-dose 3-factor (3F) PCC (20-30 IU/kg), as part of a transfusion algorithm, reduces bleeding without increasing postoperative thrombotic/thromboembolic complications. Materials/MethodsAfter IRB approval, we retrospectively analysed 114 consecutive, complex cardiovascular surgical patients (age > 18 years), between February 2014 and June 2015, that received low-dose 3F-PCC (Profilnine â ), of which seven patients met established exclusion criteria. PCC was dosed according to an institutional perioperative algorithm. Allogeneic transfusions were recorded before and after PCC administration (n = 107). The incidence of postoperative thromboembolic events was determined within 30 days of surgery, and Factor II levels were measured in a subset of patients (n = 20) as a quality control measure to avoid excessive PCC dosing. ResultsTotal allogeneic blood product transfusion reached a mean of 12Á4 -9Á9 units before PCC and 5Á0 -6Á3 units after PCC administration (P < 0Á001). The mean PCC dose was 15Á8 -7Á1 IU/kg. Four patients (3Á8%) each experienced an ischaemic stroke on postoperative day 1, 2, 4 and 27. Seven patients (6Á5%) had acquired venous thromboembolic disease within 10 days of surgery. Median factor II level after transfusion algorithm adherence and PCC administration was 87%.Conclusions 3F-PCC use for refractory bleeding after cardiovascular surgery resulted in reduced transfusion of allogeneic blood and blood products. Adherence to this algorithmic approach was associated with an acceptable incidence of postoperative thrombotic/thromboembolic complications.

4-Factor Prothrombin Complex Concentrate Dosing Strategies: A Retrospective Evaluation

“…However, it should be noted that in general, doses of 10-20 IU/kg of 3FPCC have been found to be safe and effective. [17][18][19][20][21][22][23][24] This study was strengthened by the fact that it was multicenter, acquiring data from multiple hospitals varying in size, trauma level, and stroke center status. Data collection was completed by a single data collector and data extraction was standardized therefore diminishing inter-rater variability.…”

Thromboembolic disease in COVID-19 patients: A brief narrative review

“…Patients with refractory respiratory failure who fail traditional rescue therapies may require veno-venous (VV) ECMO, with a smaller proportion needing veno-arterial (VA) support [95,96]. Acquired von Willebrand disease, thrombocytopenia, and bleeding are known complications in patients on ECMO [97][98][99][100]. Studies have described the use of VV ECMO without anticoagulation to reduce bleeding risks, however, the artificial contact surface of ECMO circuit itself causes continuous activation of coagulation, creating a prothrombotic environment [101,102].…”

Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease

“…Prothrombin is available in the form of a concentrate of multiple factors, referred to as prothrombin complex concentrate, and it exists in 2 forms: 3-factor PCC (3F-PCC) consisting of Factors II (prothrombin), IX, and X, as well as Protein C and S, and 4-factor PCC (4F-PCC) that also contains Factor VII [115] . Its indication is currently only for urgent reversal of the VKA warfarin in adults with acute major bleeding; however, multiple off-label uses exist including reversal of direct oral anticoagulants in major bleeding or surgery [116 , 117] , treatment of bleeding in congenital deficiencies of any of the coagulation factors found in PCC (the vitamin K-dependent factors), prophylactic usage to reduce perioperative bleeding and reduce transfusion requirements [118] , [119] , [120] , and in traumatic bleeding alongside FFP to correct coagulopathy [121] , [122] , [123] . Clinicaltrials.gov lists multiple ongoing studies investigating PCC for usage in reducing perioperative bleeding [NCT02740335, NCT04244981, NCT03341156] as well as treatment of coagulopathy and bleeding including the prehospital setting [NCT03981484, NCT04019015].…”