Blood 106(8): 2723-2729

Aggregometry detects platelet hyperreactivity in healthy individuals

From the Department of Pediatrics, Hematology-Oncology Section, and the Department of Medicine, Thrombosis Research Section, Baylor College of Medicine, Houston, TX.

Reprints: Paul F. Bray, Thrombosis Research Section, Baylor College of Medicine, One Baylor Plaza, BCM 286, N1319, Houston, TX 77030; e-mail: ude.cmt.mcb@yarbp.

Received 2005 Mar 29; Accepted 2005 Jun 6.

Abstract

Aggregometry is widely used to assess platelet function, but its use in identifying platelet hyperreactivity is poorly defined. We studied platelet aggregation in 359 healthy individuals using the agonists adenosine diphosphate (ADP), epinephrine, collagen, collagen-related peptide, and ristocetin. We also assessed the reproducibility of these assays in 27 subjects by studying them repeatedly on at least 4 separate occasions. Healthy subjects exhibited considerable interindividual variability in aggregation response to agonists, especially at concentrations lower than those typically used in clinical laboratories. For each agonist tested at these submaximal concentrations, a small proportion of individuals demonstrated an unusually robust aggregation response. Subjects who exhibited such in vitro hyperreactivity to one agonist tended to demonstrate a similar response to others, suggesting that hyperreactivity is a global characteristic of platelets. Epinephrine and collagen-related peptide were especially reliable and efficient in detecting hyperreactivity. For epinephrine, excellent reproducibility persisted for up to 3 years, and hyperreactivity was associated with female sex and higher fibrinogen levels (P < .02). We recommend these assays as appropriate candidates for future studies requiring accurate assessment of increased platelet reactivity. These include clinical studies to improve risk assessment for arterial thrombosis, as well as genetic studies to establish determinants of the hyperreactive platelet phenotype.

Abstract

No subjects had diabetes.

For subjects with less than 60% aggregation, n = 310; for those with at least 60% aggregation, n = 49. No subjects had diabetes.

Acknowledgments

The authors thank Dr O'Brian Smith for his provision of statistical support, Jennifer Wood and David Lopez for assistance with data acquisition, and Susana Larrucea for synthesizing CRP.

Acknowledgments

Notes

Prepublished online as Blood First Edition Paper, June 21, 2005; DOI 10.1182/blood-2005-03-1290.

Supported by National Institutes of Health grants RR17665 (D.L.Y.) and HL65229 (P.F.B.), and Baylor College of Medicine.

D.L.Y. designed parts of this study, analyzed the data, and wrote most of the paper. C.W.S. and A.L.B. performed the research under the direction of J.-f.D. P.F.B. designed much of this study and wrote parts of the paper.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.

Notes

Prepublished online as Blood First Edition Paper, June 21, 2005; DOI 10.1182/blood-2005-03-1290.

Supported by National Institutes of Health grants RR17665 (D.L.Y.) and HL65229 (P.F.B.), and Baylor College of Medicine.

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