Abstract 149: Phosphatidylserine Promotes Thrombosis in Pediatric CPB Model

Autor: Andrew D Meyer, Anjana Raghunath, Patricia Heard, Robin Kamucheka, Crystal Lafleur, Michael Scherer, Andrew P Cap
Rok vydání: 2017
Předmět:
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology. 37
ISSN: 1524-4636
1079-5642
Popis: Over 18,000 children per year receive cardiopulmonary bypass (CPB) surgery. Unfortunately, common CPB-related thrombotic complications continue to result in significant mortality and morbidity. Previous ex-vivo CPB studies using animal blood document an increase in platelet-derived microparticles (PMPs), which are small (0.1-1 micron) membrane vesicles that may be 50 to 100-fold more pro-coagulant than activated platelets. Our hypothesis is that increased duration and magnitude of shear stress in an ex-vivo pediatric CPB circuit increases the generation of PMP expressing pro-thrombotic phosphatidylserine. We constructed an ex-vivo CPB circuit that circulates heparinized human blood from healthy adult volunteers for six hours at pediatric flow rates ( e.g., 0.3, 0.5, and 0.7 L/min). Our protocol normalizes each run through the circuit to a normal hematocrit, pH, ionized calcium, and an activated clotting time of 180 to 220 sec. An aliquot of static blood controls is maintained in a similar test environment without CPB circuitry. PMP-PS (CD41a+/phosphatidylserine[PS]) concentration and pro-coagulant function are measured in platelet-depleted plasma using high-resolution flow cytometry (BS FACS Canto II with PMT) and STA®-Procoag-PPL. Thrombin generation ( e.g. , calibrated automated thrombogram) and clot formation ( e.g. , thromboelastography) further define the coagulation function of pump-produced PMP-PS. At 0.5 L/min the circuit generates an exponential increase in PMP-PS and decreasing PPL clot time compared to static blood control ( p
Databáze: OpenAIRE