Increased anticoagulation during cardiopulmonary bypass by prostaglandin E1.
Prostaglandin E1 (PGE1) inhibits tissue factor/factor VIIa-dependent thrombin formation and platelet procoagulant activity. These pathways may trigger thrombin generation during cardiopulmonary bypass (CPB). We hypothesized that the therapeutic combination of PGE1 and heparin increases the degree of anticoagulation as measured by reduced thrombin generation during CPB. Patients undergoing primary coronary artery bypass grafting using CPB were anticoagulated with unfractionated porcine heparin and 12.5 ng x kg(-1) x min(-1) PGE1 (n = 20) or placebo (n = 20). Plasma markers that reflect thrombin generation (prothrombin fragment F1+2, thrombin-antithrombin complex) were determined, and postoperative bleeding was documented. Thrombin generation gradually increased in both groups during and after CPB but was lower in the PGE1 group. After CPB, the difference between mean levels of prothrombin fragment F1+2 was 1.9 nmol/L (95% confidence interval for difference 1.1 to 2.8; P = 0.001). The difference between mean levels of thrombin-antithrombin complex was 43.6 ng/mL (21.2 to 66.1; P = 0.001). A trend in reduced postoperative bleeding was observed in the PGE1 group with a difference of sample means of 183 mL (-5 to 371; P = 0.056). Adding PGE1 to unfractionated heparin enhances anticoagulation during CPB. The results suggest that reduced thrombin generation during surgery may decrease postoperative bleeding.


CONCLUSIONS
Cardiopulmonary bypass is associated with extensive thrombin generation even in the presence of clinically sufficient heparin anticoagulation. The addition of prostaglandin E1 to heparin enhances the degree of anticoagulation as measured by reduced thrombin formation during cardiopulmonary bypass.
Kozek-Langenecker
S A
SA
Department of Anethesiology and General Intensive Care, University of Vienna, School of Medicine, Austria. Sibylle.Kozek-Langenecker@univie.ac.at
Wanzel
O
O
Berger
R
R
Kettner
S C
SC
Coraim
F
F
D000368:Aged; D000527:Alprostadil / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation; D016063:Blood Loss, Surgical; D001794:Blood Pressure; D002315:Cardiopulmonary Bypass; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis
D000925:Anticoagulants; D011516:Prothrombin; D006493:Heparin; D013917:Thrombin; D000527:Alprostadil