Effects of extended-release dipyridamole in vitro on thrombin indices measured by calibrated automated thrombography in poststroke survivors

Victor Serebruany, Yanti Sani, Ilya Pokov, Alex Schevchuck, Alan Fong, Lionel Thevathasan, Daniel F Hanley

Research output: Contribution to journalArticle

Abstract

Randomized trials suggested superior stroke prevention with extended-release dipyridamole (ERD) in combination with low-dose aspirin than either with aspirin or dipyridamole alone. Thrombin generation (TG) is a critical step in clot formation and represents a cornerstone biomarker of atherothrombosis. We, therefore, sought to define the effect of ERD in escalating concentrations on the time course of TG using the Calibrated Automated Thrombogram (CAT) technology in patients after ischemic stroke. Serial plasma samples were obtained from 20 patients with ischemic stroke documented by neuroimaging and who were treated with aspirin for at least 30 days. The impact of 75-, 150-, 250-, and 300-nM ERD on TG was assessed using fluorogenic substrate CAT technology. The following integrated CAT indices were calculated for each ERD dose and compared with the vehicle: TGmax, start time (tstart) peak time (tpeak), and mean time (tmean). Preincubation of platelet-poor plasma with ERD resulted in a dose-dependent significant inhibition of TG. The TGmax was gradually reduced from 447 ± 21 nM at baseline to 354 ± 31 nM (P = 0.008) for 75-nM ERD, 298 ± 24 nM for 150-nM ERD, 248 ± 26 nM for 250-nM ERD, and finally to 240 ± 23 nM for 300-nM ERD (P <0.0001 for all). The tmean was reduced only for the highest (250-300 nM) ERD concentrations. The tstart was only slightly delayed, but not different (1.5 vs. 1.8 vs.1.9 minutes; P = 0.09), for all ERD concentrations. The tpeak was not affected by ERD. ERD in vitro affects thrombin activity indices predominantly by a dose-dependent inhibition of endogenous thrombin potential and demonstrated a trend to delayed initiation of thrombin production. These preliminary data, while intriguing, require confirmation in poststroke patients receiving orally dosed ERD to determine whether these findings are clinically relevant.

Original languageEnglish (US)
Pages (from-to)407-412
Number of pages6
JournalAmerican Journal of Therapeutics
Volume19
Issue number6
DOIs
StatePublished - Nov 2012

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Dipyridamole
Thrombin
Survivors
Aspirin
Stroke
In Vitro Techniques
Technology
Thrombin Time
Fluorescent Dyes
Neuroimaging

Keywords

  • Dipyridamole
  • in vitro
  • stroke
  • thrombin generation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Effects of extended-release dipyridamole in vitro on thrombin indices measured by calibrated automated thrombography in poststroke survivors. / Serebruany, Victor; Sani, Yanti; Pokov, Ilya; Schevchuck, Alex; Fong, Alan; Thevathasan, Lionel; Hanley, Daniel F.

In: American Journal of Therapeutics, Vol. 19, No. 6, 11.2012, p. 407-412.

Research output: Contribution to journalArticle

Serebruany, Victor ; Sani, Yanti ; Pokov, Ilya ; Schevchuck, Alex ; Fong, Alan ; Thevathasan, Lionel ; Hanley, Daniel F. / Effects of extended-release dipyridamole in vitro on thrombin indices measured by calibrated automated thrombography in poststroke survivors. In: American Journal of Therapeutics. 2012 ; Vol. 19, No. 6. pp. 407-412.
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