Prothrombin complex concentrate mitigates diffuse bleeding after cardiopulmonary bypass in a porcine model.
BACKGROUND
Extracorporeal circuit priming and intravascular volume expansion during cardiopulmonary bypass (CPB) may lead to dilutional coagulopathy and excessive diffuse postoperative bleeding. Prothrombin complex concentrate (PCC) containing clotting factors II (FII), VII (FVII), IX (FIX), and X (FX) could be of potential value in correcting dilutional coagulopathy and reducing blood loss.


METHODS
Anaesthetized pigs underwent CPB with hypothermia for 2 h at 25°C followed by 1 h of normothermia. Approximately 1 h after CPB, animals randomly received either isotonic saline 1 ml kg⁻¹ or PCC 30 IU kg⁻¹ in a volume of 1 ml kg⁻¹. Diffuse coagulopathic bleeding was assessed as suture hole blood loss from a Gore-Tex patch placed over a full-thickness incision in the left carotid artery.


RESULTS
After CPB, levels of FII, FVII, FIX, and FX declined from baseline by 32% to 48%, and PCC fully or partially reversed those deficits. Median suture hole blood loss after administration of saline placebo was 74 ml. PCC reduced suture hole bleeding by a median of 54 ml with a 95% confidence interval of 6-112 ml (P=0.026) compared with saline. PCC, but not saline, normalized skin bleeding time. Peak thrombin generation markedly decreased after CPB, but then returned in PCC-treated animals to a level higher than baseline by 28.7 nM (14.5-41.1 nM; P=0.031).


CONCLUSIONS
PCC was effective in correcting dilutional coagulopathy and reducing diffuse bleeding in an in vivo large-animal CPB model. Further research is warranted on PCC as a haemostatic agent in CPB.
Kaspereit
F
F
Department of Preclinical Research and Development, CSL Behring GmbH, Marburg, Germany.
Hoffmann
S
S
Pragst
I
I
Dickneite
G
G
D000818:Animals; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D001779:Blood Coagulation Factors / Q000378:metabolism / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003029:Coagulants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006488:Hemostasis, Surgical / Q000379:methods; D008297:Male; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D011517:Prothrombin Time; D034421:Sus scrofa; D013917:Thrombin / Q000096:biosynthesis
D001779:Blood Coagulation Factors; D003029:Coagulants; C025667:prothrombin complex concentrates; D013917:Thrombin