Efficacy and Safety of Prothrombin Complex Concentrate in Patients Undergoing Major Cardiac Surgery

Introduction

Administration of coagulation factors after major cardiac surgery, with or without cardiopulmonary bypass, may be a strategy for reducing risk of bleeding and requirement for allogeneic blood transfusions. However, transfusion of large volumes of fresh frozen plasma (FFP) is restricted by the competing problem of heart failure, a common complication following cardiac surgery in patients with existing cardiac decompensation. Prothrombin complex concentrate (PCC) has a smaller volume of administration than FFP for a similar amount of coagulation factors, making it an attractive option in this situation. However, patients undergoing complex cardiac surgery may also have prothrombotic conditions and have a high risk of both venous and arterial thrombosis including ischemic neurological complications. We performed a retrospective analysis to investigate whether the use of PCC is safe and effective compared with FFP to treat coagulopathy in patients undergoing isolated coronary artery bypass graft (CABG), valve surgery (with or without concomitant CABG) and major aortic procedures. If the patient was on warfarin, this was stopped at least 5 days before the surgery and appropriate bridging was followed. For patients on dual antiplatelet therapy, P2Y12 receptor inhibitors such as Clopidogrel and Prasugrel were stopped 5-7days before the surgery and Aspirin was allowed to continue. The decision to use PPC or FFP was based on individual patient characteristics such as complexity of the surgery and previous history of increased bleeding during surgery and also ability to tolerate volume.

Methods

One hundred and seventy consecutive adult patients who underwent major cardiac surgery between January 2015 and December 2015 were studied. Among them, 87 received PCC (male/female = 55/32, mean age= 56 years) and 83 received FFP (male/female = 56/27, mean age = 58 years) to control coagulopathy. The decision on need for coagulation factor treatment and the choice of treatment was made by the treating team of the patient. Those who received both PCC and FFP were excluded. Blood loss within first 12 hours and 24hours from the end of operation, total use of allogeneic blood and platelet transfusion and patient outcomes in terms of thrombotic complications both venous and arterial, incidence of acute kidney injury and 30 day mortality were compared in the two groups. Antiplatelet drug effect on bleeding was also assessed.

Results

There was no significant difference in the amount of bleeding at the first 12 hours from the end of the operation in the two groups (p=0.25) :median and 95% confidence interval [CI] were 825mL [926-1317] and 787mL [804-1067] patients received PPC or FFP respectively. However, total blood loss within 24hours was significantly higher in patients who received PPC (median [CI] (1575mL [1658-2263]) compared to FFP (median [CI] (1213mL [1244-1641]), P=0.0034. There was no difference in the mean blood loss between patients continued Aspirin at the time of surgery and those who were not on Aspirin in either groups. The use of allogeneic blood (P=.001) and platelets (P=0.03) was significantly higher in patients receiving FFP compared to PPC. A significantly higher number of patients treated with FFP (9.6% vs 3.5%, p=0.002) developed cardiac failure related to circulatory overload. There was no difference in thrombotic events in the two groups: one patient from each group (1.1%) developed venous and arterial thrombosis respectively following surgery. Thirty day mortality rate was similar in the patients receiving FFP or PPC (4%) and none were directly related to surgery. There was no difference in the acute kidney injury in the two groups.

Conclusions

This retrospective analysis suggests that PCC may be an alternative to FFP in patients undergoing major cardiac surgery. Although there was a higher amount of bleeding within 24hours of surgery in patients treated with PCC, this may reflect the complexity, duration and the individual patient risk of bleeding due to selection bias. The use of PPC may reduce the number of allogeneic blood and platelet transfusion in these patients and reduce risk of circulatory overload. There was no increased risk of thrombosis with use of PCC. However, randomized controlled studies powered to evaluate efficacy and safety in patients receiving PCC versus FFP for coagulopathic bleeding after major cardiac surgery are warranted.