For investigators

Fresh frozen plasma (FFP) is the standard treatment for severe bleeding following cardiac surgery, even though the evidence for its efficacy is scarce. Use of prothrombin complex concentrate (PCC), in preference to FFP, is rising in the UK but there has been no large randomised controlled trial to compare the clinical effectiveness and safety of PCC versus FFP in this patient group.

We hypothesise that PCC is superior to FFP in reducing a composite of mortality, organ failure or infection up to 90 days in adult patients who develop severe bleeding following cardiac surgery, and is more cost effective.

Inclusion criteria

• Age > 18 years, undergoing cardiac surgery (elective and urgent procedures) not described in the exclusion criteria
• The patient is able to give consent

Exclusion criteria

• Emergency and salvage procedures*
• First time isolated coronary artery bypass graft surgery given the low risk of significant bleeding
• First time isolated aortic valve replacement (excluding active endocarditis)
• First time isolated mitral valve replacement
• Surgeries that do not involve cardiopulmonary bypass
• Heart transplant
• Use of warfarin within 3 days prior to surgery
• Use of direct oral anticoagulants (i.e. dabigatran, rivaroxban, apixaban or edoxaban etc.) within 48 hours prior to surgery (or 72 hours if patient has renal impairment – i.e. estimated glomerular filtration rate of <30 ml/min)
• Any contraindication to PCC or FFP or LG-Octaplas, for example: known or suspected allergy to heparin, sodium citrate dihydrate, sodium dihydrogenphosphate dihydrate and glycine, history of heparin-induced thrombocytopenia, history of blood transfusion reaction due to IgA deficiency with known antibodies against IgA
• Patients refusing blood transfusion for any reason
• Inherited bleeding disorder (i.e. any inherited clotting factor deficiencies, or platelet disorders)
• Pregnancy as PCC is contraindicated
• Documented thrombophilia defects (antiphospholipid syndrome, severe protein S deficiency, antithrombin deficiency)
• Documented venous thromboembolism in the last 3 months prior to surgery
• Patients who are expected to require extracorporeal membrane oxygenation after cardiac surgery
• Patient previously randomised into this trial and has not reached 90 days post randomisation

 * The National Institute for Cardiovascular Outcomes Research definition categorises cardiac surgeries as elective and non-elective; the latter is further subdivided into:

• Urgent procedures include patients who have not been scheduled for routine admission from the waiting list but who require intervention or surgery on the current admission for medical reasons. On average they present to hospital 1-3 days before surgery, and they cannot be sent home without a procedure.
• Emergency procedures include unscheduled patients with ongoing refractory cardiac compromise, where there should be no delay in surgery/intervention irrespective of the time of day. On average they present to hospital one day prior to surgery.
• Salvage procedures include patients requiring cardiopulmonary resuscitation (external cardiac massage) enroute to the operation theatre or prior to the induction of anaesthesia.

Primary endpoint

A composite of any of the following new events up to 90 days from randomisation:

• All-cause mortality
• Acute respiratory failure
• Acute myocardial injury
• Acute renal failure requiring renal replacement therapy (excluding dialysis during cardiopulmonary bypass)
• Acute liver injury
• Acute intestinal injury
• Focal neurological deficit
• Infection

Secondary endpoints

• Components of the primary outcome
• Clinical evidence of haemostasis
• Length of stay in hospital
• Duration of mechanical ventilation
• Hospital readmission
• Safety
• Quality of life
• Cost-effectiveness