In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. suppl_1 ( 2017-05)
Abstract:
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 〈 0.001, Figure 1, n=4). Platelet count, prothrombin time, and activated partial thromboplastin time do not change over time. Results also document an increase in peak thrombin potential and clot formation that correlate strongly with the increase in PMP-PS. PMP-PS may be a clinically relevant biomarker and therapeutic target to decrease life-threatening CPB surgery coagulation complications.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.37.suppl_1.149
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
1494427-3
Permalink