{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T05:23:13Z","timestamp":1741411393744,"version":"3.38.0"},"reference-count":40,"publisher":"American Veterinary Medical Association (AVMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To develop an antibody-based flow cytometric assay to detect coated platelets in dogs and to characterize the interaction of recombinant human coagulation factor VIIa with activated platelets from dogs with hemophilia A.<\/jats:p>\n<jats:p><jats:bold>Sample<\/jats:bold>\u2014Platelets from 4 dogs with hemophilia A, 4 dogs with hemophilia B, 4 dogs with von Willebrand disease, and 6 hemostatically normal dogs.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014Freshly isolated platelets were activated with thrombin, convulxin, or a thrombin-convulxin combination. Resulting platelet phenotypes were resolved on the basis of P-selectin and fibrinogen expression, and binding of recombinant human coagulation factor VIIa to these distinct platelet subpopulations was measured by use of a flow cytometric assay.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014Coated platelets were identified on the basis of expression of \u03b1-granule fibrinogen and were generated in response to stimulation with the thrombin-convulxin combination but not to stimulation with either agonist alone. Approximately 70% of the platelets from dogs with hemophilia A, hemophilia B, and von Willebrand disease and from the control dogs had the coated platelet phenotype. Recombinant human coagulation factor VIIa bound preferentially to coated platelets with a mean \u00b1 SD binding equilibrium constant of 2.6 \u00b1 0.5\u03bcM.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Formation of coated platelets in dogs was similar to that in humans. Recombinant human coagulation factor VIIa bound preferentially to coated platelets from dogs.<\/jats:p>\n<jats:p><jats:bold>Impact for Human Medicine<\/jats:bold>\u2014A similar mechanism of action for recombinant human coagulation factor VIIa may exist in dogs and humans. The potential for use of dogs in the study of bleeding disorders in humans was strengthened.<\/jats:p>","DOI":"10.2460\/ajvr.72.8.1007","type":"journal-article","created":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T07:09:30Z","timestamp":1312182570000},"page":"1007-1014","source":"Crossref","is-referenced-by-count":3,"title":["Development of a flow cytometric assay for detection of coated platelets in dogs and evaluation of binding of coated platelets to recombinant human coagulation factor VIIa"],"prefix":"10.2460","volume":"72","author":[{"given":"Tom","family":"Knudsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Kjalke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Tranholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy C.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asger L.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemarie T.","family":"Kristensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"J Thromb Haemost","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1111\/j.1538-7836.2005.01274.x","article-title":"Coated-platelets: an emerging component of the pro-coagulant response","volume":"3","author":"Dale","year":"2005"},{"key":"ref2","series-title":"Blood","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1182\/blood.V95.5.1694.005k24_1694_1702","article-title":"Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin","volume":"95","author":"Alberio","year":"2000"},{"key":"ref3","series-title":"Arterioscler Thromb Vasc Biol","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1161\/01.ATV.0000155987.26583.9b","article-title":"Platelet heterogeneity: variation in coagulation complexes on platelet subpopulations","volume":"25","author":"Kempton","year":"2005"},{"key":"ref4","series-title":"Nature","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/415175a","article-title":"Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface","volume":"415","author":"Dale","year":"2002"},{"key":"ref5","series-title":"Blood","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1182\/blood-2002-02-0354","article-title":"Thrombospondin and fibrinogen bind serotonin-derivatized proteins on COAT-platelets","volume":"100","author":"Szasz","year":"2002"},{"key":"ref6","series-title":"J Thromb Haemost","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1111\/j.1538-7836.2007.02389.x","article-title":"Preferential localization of recombinant factor VIIa to platelets activated with a combination of thrombin and a glycoprotein VI receptor agonist","volume":"5","author":"Kjalke","year":"2007"},{"key":"ref7","series-title":"J Exp Med","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1084\/jem.90.2.97","article-title":"Canine hemophilia: observations on the course, the clotting anomaly, and the effect of blood transfusions","volume":"90","author":"Graham","year":"1949"},{"key":"ref8","series-title":"Blood","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1182\/blood.V41.4.577.577","article-title":"Expression and linkage of genes for X-linked hemophilias A and B in the dog","volume":"41","author":"Brinkhous","year":"1973"},{"key":"ref9","series-title":"Br J Haematol","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1365-2141.1962.tb06493.x","article-title":"Canine factor-VII deficiency","volume":"8","author":"Mustard","year":"1962"},{"key":"ref10","series-title":"J Small Anim Pract","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.1748-5827.1974.tb05687.x","article-title":"The clinical aspects of canine factor-VII deficiency including some case histories","volume":"15","author":"Spurling","year":"1974"},{"key":"ref11","series-title":"J Thromb Haemost","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.1111\/j.1538-7836.2006.02203.x","article-title":"A novel missense mutation responsible for factor VII deficiency in research Beagle colonies","volume":"4","author":"Callan","year":"2006"},{"key":"ref12","series-title":"Ann N Y Acad Sci","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1749-6632.1981.tb29732.x","article-title":"Pathophysiology of platelet-aggregating von Willebrand factor: applications of the venom coagglutinin vWF assay","volume":"370","author":"Brinkhous","year":"1981"},{"key":"ref13","series-title":"Vet Pathol","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1354\/vp.37-6-581","article-title":"Two genetic defects in alphaIIb are associated with type I Glanzmann's thrombasthenia in a Great Pyrenees dog: a 14-base insertion in exon 13 and a splicing defect of intron 13","volume":"37","author":"Lipscomb","year":"2000"},{"key":"ref14","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.2460\/ajvr.2001.62.1797","article-title":"Molecular and genetic basis for thrombasthenic thrombopathia in Otterhounds","volume":"62","author":"Boudreaux","year":"2001"},{"key":"ref15","series-title":"Thromb Haemost","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1055\/s-0038-1649853","article-title":"Inherited platelet delta-storage pool disease in dogs causing severe bleeding: an animal model for a specific ADP deficiency","volume":"74","author":"Callan","year":"1995"},{"key":"ref16","series-title":"J Thromb Haemost","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1111\/j.1538-7836.2007.02683.x","article-title":"Scott syndrome dogs have impaired coated-platelet formation and calcein-release but normal mitochondrial depolarization","volume":"5","author":"Brooks","year":"2007"},{"key":"ref17","series-title":"Vet Clin Pathol","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1939-165X.2009.00141.x","article-title":"Evaluation of platelet function screening tests to detect platelet procoagulant deficiency in dogs with Scott syndrome","volume":"38","author":"Brooks","year":"2009"},{"key":"ref18","series-title":"J Hered","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1093\/jhered\/90.1.112","article-title":"A review of canine inherited bleeding disorders: biochemical and molecular strategies for disease characterization and carrier detection","volume":"90","author":"Brooks","year":"1999"},{"key":"ref19","series-title":"Thromb Haemost","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1055\/s-0037-1613245","article-title":"Collagen response and glycoprotein VI function decline progressively as canine platelets age in vivo","volume":"88","author":"Alberio","year":"2002"},{"key":"ref20","series-title":"J Thromb Haemost","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1111\/j.1538-7836.2008.03052.x","article-title":"Formation of coated platelets is regulated by the dense granule secretion of adenosine 5\u2032diphosphate acting via the P2Y12 receptor","volume":"6","author":"Kotova","year":"2008"},{"key":"ref21","series-title":"J Lab Clin Med","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.lab.2004.02.001","article-title":"Glycoprotein IIb\/IIIa inhibitors increase COAT-platelet production in vitro","volume":"143","author":"Hamilton","year":"2004"},{"key":"ref22","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"8752","DOI":"10.1073\/pnas.82.24.8752","article-title":"Purified human factor VIII procoagulant protein: comparative hemostatic response after infusions into hemophilic and von Willebrand disease dogs","volume":"82","author":"Brinkhous","year":"1985"},{"key":"ref23","series-title":"Semin Thromb Hemost","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1055\/s-2002-32661","article-title":"Preclinical pharmacology of albumin-free B-domain deleted recombinant factor VIII","volume":"28","author":"Brinkhous","year":"2002"},{"key":"ref24","series-title":"Blood","doi-asserted-by":"publisher","first-page":"2644","DOI":"10.1182\/blood.V81.10.2644.2644","article-title":"The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A","volume":"81","author":"Nichols","year":"1993"},{"key":"ref25","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"10095","DOI":"10.1073\/pnas.86.24.10095","article-title":"Canine hemophilia B resulting from a point mutation with unusual consequences","volume":"86","author":"Evans","year":"1989"},{"key":"ref26","series-title":"Thromb Haemost","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1055\/s-0037-1614021","article-title":"Absence of circulating factor IX antigen in hemophilia B dogs of the UNC-Chapel Hill colony","volume":"84","author":"Herzog","year":"2000"},{"key":"ref27","series-title":"Blood","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1182\/blood-2004-02-0464","article-title":"Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells","volume":"105","author":"Haberichter","year":"2005"},{"key":"ref28","series-title":"Blood","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1182\/blood-2003-01-0290","article-title":"Comparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP)","volume":"102","author":"Olsen","year":"2003"},{"key":"ref29","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"4514","DOI":"10.1073\/pnas.75.9.4514","article-title":"Venom coagglutinin: an activator of platelet aggregation dependent on von Willebrand factor","volume":"75","author":"Read","year":"1978"},{"key":"ref30","series-title":"FEBS Lett","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/0014-5793(72)80680-X","article-title":"Protein A from Staphylococcus aureus. Its isolation by affinity chromatography and its use as an immunosorbent for isolation of immunoglobulins","volume":"28","author":"Hjelm","year":"1972"},{"key":"ref31","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"11863","DOI":"10.1074\/jbc.272.18.11863","article-title":"Incorporation of an active site inhibitor in factor VIIa alters the affinity for tissue factor","volume":"272","author":"Sorensen","year":"1997"},{"key":"ref32","series-title":"Blood","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1182\/blood.V70.2.475.475","article-title":"Increased surface expression of the membrane glycoprotein IIb\/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation","volume":"70","author":"Niiya","year":"1987"},{"key":"ref33","series-title":"Blood","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1182\/blood-2007-09-113837","article-title":"Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released","volume":"111","author":"Italiano","year":"2008"},{"key":"ref34","series-title":"Arterioscler Thromb Vasc Biol","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1161\/01.ATV.0000152726.49229.bf","article-title":"Role of mitochondrial permeability transition pore in coated-platelet formation","volume":"25","author":"Remenyi","year":"2005"},{"key":"ref35","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1073\/pnas.86.4.1382","article-title":"Effect of recombinant factor VIIa on the hemostatic defect in dogs with hemophilia A, hemophilia B, and von Willebrand disease","volume":"86","author":"Brinkhous","year":"1989"},{"key":"ref36","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1111\/j.1939-1676.2006.tb02915.x","article-title":"Detection of activated platelets in dogs with primary immune-mediated hemolytic anemia","volume":"20","author":"Weiss","year":"2006"},{"key":"ref37","series-title":"J Am Vet Med Assoc","first-page":"246","article-title":"Pulmonary thromboembolism associated with immune-mediated hemolytic anemia in dogs: ten cases (1982\u20131987)","volume":"195","author":"Klein","year":"1989"},{"key":"ref38","series-title":"J Am Anim Hosp Assoc","doi-asserted-by":"publisher","first-page":"220","DOI":"10.5326\/15473317-37-3-220","article-title":"Hemostatic abnormalities in dogs with primary immune-mediated hemolytic anemia","volume":"37","author":"Scott-Moncrieff","year":"2001"},{"key":"ref39","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1111\/j.1939-1676.2002.tb02378.x","article-title":"Prognostic factors for mortality and thromboembolism in canine immune-mediated hemolytic anemia: a retrospective study of 72 dogs","volume":"16","author":"Carr","year":"2002"},{"key":"ref40","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1111\/j.1939-1676.2008.0060.x","article-title":"Idiopathic immune-mediated hemolytic anemia: treatment outcome and prognostic factors in 149 dogs","volume":"22","author":"Piek","year":"2008"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/72\/8\/ajvr.72.8.1007.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/72\/8\/ajvr.72.8.1007.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/72\/8\/ajvr.72.8.1007.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:27:19Z","timestamp":1741350439000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/72\/8\/ajvr.72.8.1007.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8]]},"references-count":40,"journal-issue":{"issue":"8"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.72.8.1007","relation":{},"ISSN":["0002-9645"],"issn-type":[{"type":"print","value":"0002-9645"}],"subject":[],"published":{"date-parts":[[2011,8]]}}}