Investigation of a novel, heritable bleeding diathesis of thoroughbred horses and development of a screening assay

Jeffrey W. Norris, Suzanne M. Pratt, Joong Hyuck Auh, Sandra J. Wilson, Dana Clutter, K G Magdesian, Gregory L. Ferraro, Fern Tablin

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background: Bleeding in racing horses associated with exercise appears to be multifactorial, and clinical investigation into severe cases rarely occurs. Previously, we reported a severe bleeding diathesis in a Thoroughbred mare. Herein, we describe the cellular physiology of this defect, provide a diagnostic tool for identifying it, and demonstrate that the dysfunction is heritable. Hypothesis: The subject has a heritable defect in platelet secretion that reduces thrombin generation in the absence of additional plasma factors and delays the onset of thrombin production even in the presence of these factors. Animals: The study included 3 clinically normal Thoroughbred horses: the subject and her offspring. Methods: Washed platelets were examined for their ability to (1) translocate phosphatidylserine to the outer leaflet of the platelet membrane as determined by annexin-V binding, (2) generate thrombin as assessed by the activity of the prothrombinase enzyme complex, and (3) bind fibrinogen and form aggregates as determined by flow cytometry. Results: Subject and offspring platelets created procoagulant surfaces by translocating phosphatidylserine. The subject's platelets demonstrated reduced prothrombinase activity, resulting in decreased production of thrombin relative to control platelets. Subject and offspring platelets bound less fibrinogen than control platelets when stimulated with thrombin. Conclusions and Clinical Importance: The subject mare has a transmissible defect that involves reduced generation of thrombin by activated platelets, resulting in decreased aggregation and ineffective clotting. A flow cytometric assay of fibrinogen binding to washed platelets discriminates individuals with this platelet dysfunction and may be useful for discerning subclinical congenital or acquired platelet dysfunctions.

Original languageEnglish (US)
Pages (from-to)1450-1456
Number of pages7
JournalJournal of Veterinary Internal Medicine
Volume20
Issue number6
DOIs
StatePublished - Nov 2006

Keywords

  • Annexin-V binding
  • Fibrinogen binding
  • Horse
  • Inherited coagulopathy
  • Platelet aggregation
  • Prothrombinase

ASJC Scopus subject areas

  • veterinary(all)

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