PubMed · 5198188
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
V Earles. Fluids, electrolytes, and circulation.. https://pubmed.ncbi.nlm.nih.gov/5198188/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Platelet aggregation contributes to arresting bleeding at wound sites, but may cause occlusion of atherosclerotic vessels, thus curtailing blood flow to vital organs. According to current dogma, the integrin alphaIIbbeta3 plays an exclusive role in linking platelets to one another through interactions with fibrinogen or vWf. We demonstrate here that, depending on shearing flow conditions, this process may require vWf binding to glycoprotein Ibalpha, even when alphaIIbbeta3 is competent to bind adhesive ligands. Platelet activation induced solely by high shear stress is initiated by glycoprotein Ibalpha interaction with vWf, but results in aggregation only if the latter can bind concurrently to alphaIIbbeta3. In contrast, platelets exposed to high shear rate after activation by exogenous agonists such as ADP and epinephrine can aggregate when fibrinogen is the alphaIIbbeta3 adhesive ligand, yet only if vWf binding to glycoprotein Ibalpha can also occur. Thus, the latter interaction appears to provide a bond with biomechanical properties necessary to overcome the effects of high shear rate and initiate interplatelet cohesion. These findings highlight the distinct function of two adhesive receptors mediating platelet aggregation under varying fluid dynamic conditions, and modify the current interpretation of a crucial event in hemostasis and thrombosis.
Exposure of citrated whole blood samples to polystyrene plates under flow conditions with the cone and plate(let) analyzer (CPA) results in surface immobilization of plasma von Willebrand factor (vWF) followed by platelet deposition. Staining the plates allows measurement of the percentage of surface covered (SC) by the adhered particles and their average size (AS). Both SC and AS parameters depend on platelet count and hematocrit level and reach maximal values after 2 minutes; only AS is shear rate dependent. Under optimal assay conditions (2 minutes at 1800 sec(-1)) normal blood samples yielded an SC of 14.9% +/- 2.5% and an AS of 39.4 +/- 5.2 microm2. Severe von Willebrand disease (eight patients) yielded low SC (5.2% +/- 2.1%), which was restored to normal by testing with vWF precoated surfaces. Glanzmann's thrombasthenia (six patients) samples demonstrated no adhesion of platelet at all. Blocking of the glycoprotein (GP) IIb/IIIa receptor by the chimeric antibody abciximab, and of the GPIb by a recombinant vWF fragment, have yielded a dose-response inhibition demonstrating the crucial role of these receptors in platelet deposition on polystyrene plates in this system. Evaluation of a patient with severe von Willebrand disease receiving replacement vWF factor VIII therapy revealed a comparable response as tested by both the CPA and the Ricof methods. In vitro testing of the GPIIb/IIIa blocking by a nonpeptidic analogue tirofiban and abciximab revealed a good correlation between the CPA test and the routine aggregometry. Eleven patients treated by abciximab after coronary angioplasty were studied by the CPA during the first 24 hours, demonstrating a marked decrease in SC and AS, with some diversity in the responses. We conclude that the CPA test is suitable for evaluation of primary hemostasis and for monitoring of anti-platelet drugs.
Explore the source record for details and available documents.