Efficacy of Prothrombin Complex Concentrate Reducing Perioperative Blood Loss in Cardiac Surgery

Efficacy of Prothrombin Complex Concentrate Reducing Perioperative Blood Loss in Cardiac Surgery, Compared With Fresh Frozen Plasma: Study Protocol for a Non-inferiority, Randomized Controlled Trial

This non-inferiority, randomized controlled trial aims to evaluate whether coagulation-guided low-dose four-factor prothrombin complex concentrate (PCC) is non-inferior to fresh frozen plasma (FFP) in reducing cumulative chest tube drainage from 1 hour after trial drug administration to 24 hours after surgery in patients undergoing valvular heart surgery.

Patients undergoing elective valvular heart surgery who develop post-cardiopulmonary bypass coagulation factor deficiency will be enrolled in this study. Participants will be randomly assigned to one of two groups: the PCC group or the FFP group.

Intervention: Patients in the PCC group will receive 8-15 IU/kg four-factor prothrombin complex concentrate, while those in the FFP group will receive 6-10 mL/kg fresh frozen plasma, guided by coagulation monitoring results.

The primary hypothesis is that coagulation-guided low-dose PCC is non-inferior to FFP in reducing cumulative chest tube drainage between 1 hour after trial drug administration and 24 hours after surgery.

The secondary hypotheses are that PCC provides better haemostasis and reduces the number of red blood cell units transfused between 1 hour after trial drug administration and 24 hours after surgery, as well as within 7 days postoperatively.

This study is designed to provide evidence on whether coagulation-guided low-dose PCC can serve as an effective and safe alternative to FFP in managing post-cardiopulmonary bypass coagulopathy during valvular heart surgery.

Inclusion Criteria:

1. Age between 18 and 80 years.
2. Undergoing elective valve repair, valve replacement or complex valvular surgery through CPB.
3. Signing of the informed consent form.
4. A combined assessment of plasma activated partial thromboplastin time (plasma-aPTT) and activated clotting time (ACT) is performed 20 minutes after heparin neutralization following CPB. We considered patients who meet the following criteria to have post-CPB coagulation factor deficiencies: (1) at least moderate bleeding, as determined using a validated bleeding severity scale; (2) a targeted ACT within ±10% of baseline; and (3) a plasma-aPTT exceeding 45 seconds or more than 1.5 times baseline. The requirement could be waived when bleeding was severe and required immediate intervention.

Exclusion Criteria:

1. History of cardiac surgery.
2. Severe hepatic and renal dysfunction before surgery.
3. Coagulopathy before surgery, including inherited or acquired coagulation factor deficiencies, thrombocytopenia, platelet dysfunction and other bleeding disorders.
4. Patients undergoing emergency surgery in whom discontinuation of anticoagulant therapy was not feasible [INR > 1.2（or above upper normal limit）after discontinued use of warfarin; withdrawal of clopidogrel less than 5 days and low molecular weight heparin less than 12 hours before surgery, etc].
5. Allergy to allogeneic blood products.
6. Pregnancy.
7. Other serious diseases that may affect patient survival time, such as cancers.