Prothrombin complex concentrate mitigates diffuse bleeding after cardiopulmonary bypass in a porcine model

Abstract

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.

Fig 1

Study design. CPB, cardiopulmonary bypass; PCC, prothrombin complex concentrate; SBT, skin bleeding time.

Fig 2

Individual animal levels of (a) FII, (b) FVII, (c) FIX, and (d) FX at baseline and after CPB and subsequent administration of PCC. Concentration values expressed as percentages of the baseline means, shown as dashed lines. CPB, cardiopulmonary bypass; FII, factor II; FVII, factor VII; FIX, factor IX; FX, factor X; PCC, prothrombin complex concentrate.

Fig 3

Individual animal suture hole blood losses after CPB and administration of saline or PCC in comparison with those of a control group which did not undergo CPB. Horizontal lines indicate median values. CI, 95% confidence interval; CPB, cardiopulmonary bypass; PCC, prothrombin complex concentrate.

Fig 4

Peak thrombin generation in individual animals at baseline and after CPB and subsequent administration of saline or PCC. Medians depicted as horizontal lines. In the table inset, grouped comparison indicated between saline and PCC; all other comparisons paired. CI, 95% confidence interval; CPB, cardiopulmonary bypass; PCC, prothrombin complex concentrate.