Administration of Prothrombin Complex Concentrate vs. Standard Transfusion During/After Heart Transplantation

This study will be a randomized (1:1; PCC vs. plasma), open-label trial of hemostatic therapies during heart transplantation. The goal is to enroll 60 patients. Informed consent will be obtained from patients meeting the inclusion and exclusion criteria before the initiation of any study specific procedures. Eligible patients will be randomized to receive either PCC or plasma transfusion. The efficacy of interventions will be evaluated after 30 minutes of protamine administration. After the heart transplantation, thrombocytopenia and/or hypofibrinogenemia may worsen bleeding associated with vitamin K dependent factor deficiencies. Transfusion of platelets and/or cryoprecipitate is permitted if abnormal laboratory values are observed during the rewarming phase of CPB; platelet count \<100 x 103/µl, and fibrinogen \<200 mg/dl, respectively. Laboratory tests (hematocrit, platelet count, PT, PTT, POC-PT, coagulation factor and inhibitor levels (e.g., factor II, antithrombin), thromboelastometry or thromboelastography, endogenous thrombin generation) will also be obtained at baseline, twice during surgery and at 12-24 hours after surgery.

Half of subjects enrolled will be randomized to the Kcentra (PCC) group.

Drug: Kcentra

Half of subjects enrolled will be randomized to the standard transfusion group and receive fresh frozen plasma intra-operatively.

Drug: Frozen Plasma Product, Human

Kcentra will be administered in 2 divided doses; Pre-bypass (5-10 units/kg based on body weight and preoperative INR and post-protamine based of the pre-bypass dose and the preoperative INR; daily maximum dose not to exceed 5000 IU (50 IU/kg)

If the patient is randomized to receive standard transfusion they will receive 2 U of fresh frozen plasma intravenously before cardiopulmonary bypass and then up to 4-8 U of plasma added to the cardiopulmonary bypass reservoir during rewarming.

Time frame: From patient out of room time until 24 hours after

Primary outcome: Amount of chest tube output in the first 24 hours

Time frame: 30 Minutes post-treatment (after the last dose is completed)

INR value

Time frame: 30min Post-Protamine

30 min after the administration of study drug (Kcentra or FFP)

Time frame: In OR (from OR entry to OR out of room time); postoperatively (patient out of room time) to 24 hours after; from 24 hours after until 30 days post surgery or until discharge (whichever comes first)

Total hemostatic blood product use, including plasma, platelets, and cryoprecipitate.

Time frame: Intraoperatively(from start of first intervention until start of second intervention;after 2nd intervention(post-bypass)until patient out of room time) & Postoperatively(from patient out of room time until 24 hours after;24 hours after until 30 days)

Red Blood Cell Use Intraoperatively and Postoperatively

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who needed circulatory support (ECMO or VAD)

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who needed mechanical ventilation for more than 72 hours

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who needed a tracheostomy

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who experience renal failure requiring dialysis

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who experienced sepsis infection morbidity consisted of sepsis syndrome, septic shock, or mediastinitis. In addition, the diagnosis of sepsis included organisms isolated from the cultures along with elevated temperature and white blood cell counts.

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who died

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who experienced a stroke or postoperative neurological dysfunction (seizures, delirium, unconsciousness, encephalopathy)

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who experienced gastrointestinal complications requiring bowel resection

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who experience peripheral vascular complications requiring surgery (thrombectomy, bypass, and amputations)

Time frame: 30 days post-operative or until discharge (whichever comes first)

Percentage of patients who develop a deep vein thrombosis and/ or pulmonary thromboembolism

Time frame: At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment

Plasma coagulator factor levels will be analyzed via blood laboratory tests

Time frame: At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment

Thrombin Generation assay will be analyzed via blood laboratory tests

Time frame: 30 days post-operative or until discharge (whichever comes first)

Surgical Re-Exploration that is related to heart transplant surgery

Optimized Administration of Prothrombin Complex Concentrate (PCC) vs. Standard Transfusion During/After Heart Transplantation - OPSTAHT