Cone and plate(let) analyzer: Monitoring glycoprotein IIb/IIIa antagonists and von Willebrand disease replacement therapy by testing platelet deposition under flow conditions

D. Varon*, I. Lashevski, B. Brenner, R. Beyar, N. Lanir, I. Tamarin, N. Savion

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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 van 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 μm2. Severe van 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 van 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.

Original languageEnglish
Pages (from-to)S187-S193
JournalAmerican Heart Journal
Volume135
Issue number5 II
DOIs
StatePublished - 1998
Externally publishedYes

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