Prostacyclin in lieu of anticoagulation with heparin for extracorporeal circulation.
Prolonged extracorporeal circulation (ECC) using heparin as anticoagulant may be associated with pronounced thrombocytopenia and excessive bleeding. We, therefore, tested the hypothesis that reversible inhibition of platelet function, in lieu of heparinization, might preserve platelets and prevent coagulation in a perfusion circuit. When 500 ml of fresh heparinized (one U/ml) human blood was recirculated in a perfusion circuit constructed of standard silicone rubber components and a membrane oxygenator (0.95 M2), platelet counts declined to 9 +/- 2 (SEM) % of initial levels within 15 mins; plasma levels of the platelet specific protein LA-PF4 rose to 15 +/- 2 micrograms/ml within one hour indicating extensive release of platelet granule contents, and leukocyte counts declined to 91 +/- 4% within 15 mins. Prostacyclin (PGI2, greater than or equal to 25 eta M) or prostaglandin E1 (20 microM) and theophylline (12 mM) prevented platelet loss and release of granule contents. When heparin was reversed with protamine, however, immediate coagulation ensured. This occurred despite the absence of detectable activation of Hageman factor as evidenced by stability of plasma concentrations of prekallikrein in systems anticoagulated with heparin or citrate and despite our inability to detect thromboplastin-like properties in isolated leukocytes. Thus, coagulation in the presence of platelet inhibition suggests that alternative pathways, independent of platelet activation may exist. Platelet inhibition does preserve platelets preventing contact initiated release, but cannot serve by itself for anticoagulation.
D001777:Blood Coagulation / Q000187:drug effects*; D011464:Epoprostenol / Q000008:administration & dosage*; D005112:Extracorporeal Circulation / Q000379:methods*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D010976:Platelet Count; D011288:Prekallikrein / Q000032:analysis; D011453:Prostaglandins / Q000008:administration & dosage*
D005338:Fibrin Fibrinogen Degradation Products; D011453:Prostaglandins; D006493:Heparin; D011288:Prekallikrein; D011464:Epoprostenol