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A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
Published on: June 5, 2019
Infusible platelet membranes retain partial functionality of the platelet GPIb/IX/V receptor complex.
S S Graham1, N J Gonchoroff, J L Miller
1Department of Pathology, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY 13210, USA.
American Journal of Clinical Pathology
|February 24, 2001
Summary
Infusible platelet membranes (IPMs) show potential for treating bleeding disorders. These membranes retain partial function of the glycoprotein Ib/IX/V complex, enabling von Willebrand factor binding and improving hemostasis.
Area of Science:
- Biomaterials Science
- Hematology
- Nanotechnology
Background:
- Infusible platelet membranes (IPMs) derived from human platelets have demonstrated efficacy in correcting bleeding times in thrombocytopenic models.
- Previous studies indicated IPMs are non-immunogenic and well-tolerated, lacking dose-limiting toxicity.
Purpose of the Study:
- To investigate the retention and functionality of the platelet glycoprotein (GP) Ib/IX/V complex within IPM preparations.
- To assess the interaction of IPMs with von Willebrand factor (vWF) and its modulation by specific agents.
Main Methods:
- IPMs were prepared from human platelets.
- vWF binding assays were performed on IPMs, with and without ristocetin or botrocetin.
- The effect of anti-GPIb-alpha monoclonal antibodies on vWF binding was evaluated.
Main Results:
- IPMs did not exhibit spontaneous vWF binding.
- Saturable vWF binding to IPMs was induced by ristocetin (Kd = 0.31 ± 0.03 μg/mL).
- The monoclonal antibody AN-51 inhibited vWF binding by 67.8% ± 5.8%, while other antibodies were ineffective. Botrocetin-induced binding was minimal.
Conclusions:
- The platelet GPIb/IX/V complex retains partial functionality in IPMs, enabling modulated vWF binding.
- This retained functionality is a likely mechanism contributing to the hemostatic efficacy of IPMs.
- IPMs represent a promising therapeutic strategy for bleeding disorders.
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