Solulin increases clot stability in whole blood from humans and dogs with hemophilia
作者： Jonathan H. Foley , Karl-Uwe Petersen , Catherine J. Rea , Lori Harpell , Sandra Powell
DOI: 10.1182/BLOOD-2011-11-392308
关键词:
摘要: Solulin is a soluble form of thrombomodulin that resistant to proteolysis and oxidation. It has been shown increase the clot lysis time in factor VIII (fVIII)–deficient plasma by an activated thrombin-activatable fibrinolysis inhibitor (TAFIa)–dependent mechanism. In present study, blood was drawn from humans dogs with hemophilia, thromboelastography used measure tissue factor–initiated fibrin formation tissue-plasminogen activator–induced fibrinolysis. The kinetics TAFI protein C activation thrombin-Solulin complex were determined describe relative extent anticoagulation antifibrinolysis. severe hemophilia A, stability increased > 4-fold presence while minimally affecting time. Patients receiving fVIII/fIX prophylaxis showed similar trend Solulin. catalytic efficiencies be 1.53 0.02/μM/s, respectively, explaining its preference for antifibrinolysis over at low concentrations. Finally, hemophilic given had improved strength assays. conclusion, antifibrinolytic properties are exhibited human (in vitro) dog vivo/ex vivo) Our findings suggest therapeutic utility range very doses.
ashpublications.org
bloodjournal.org参考文章(31)
C. T. Esmon, N. L. Esmon, A. R. Rezaie, Le-Wen Liu, C. W. Carson, Occupancy of anion binding exosite 2 on thrombin determines Ca2+ dependence of protein C activation. Journal of Biological Chemistry. ,vol. 269, pp. 11807- 11812 ,(1994) , 10.1016/S0021-9258(17)32644-3
C T Esmon, N L Esmon, K W Harris, Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation. Journal of Biological Chemistry. ,vol. 257, pp. 7944- 7947 ,(1982) , 10.1016/S0021-9258(18)34276-5
C. J. REA, J. H. FOLEY, J. INGERSLEV, B. SØRENSEN, Factor XIII combined with recombinant factor VIIa: a new means of treating severe hemophilia A Journal of Thrombosis and Haemostasis. ,vol. 9, pp. 510- 516 ,(2011) , 10.1111/J.1538-7836.2010.04171.X
GJ Jr Broze, DA Higuchi, Coagulation-Dependent Inhibition of Fibrinolysis: Role of Carboxypeptidase-U and the Premature Lysis of Clots From Hemophilic Plasma Blood. ,vol. 88, pp. 3815- 3823 ,(1996) , 10.1182/BLOOD.V88.10.3815.BLOODJOURNAL88103815
Christine Hough, Seiki Kamisue, Cherie Cameron, Colleen Notley, Shawn Tinlin, Alan Giles, David Lillicrap, None, Aberrant splicing and premature termination of transcription of the FVIII gene as a cause of severe canine hemophilia A: similarities with the intron 22 inversion mutation in human hemophilia. Thrombosis and Haemostasis. ,vol. 87, pp. 659- 665 ,(2002) , 10.1055/S-0037-1613063
C. T. ESMON, N. L. ESMON, S. KUROSAWA, A. E. JOHNSON, Interaction of thrombin with thrombomodulin. Annals of the New York Academy of Sciences. ,vol. 485, pp. 215- 220 ,(1986) , 10.1111/J.1749-6632.1986.TB34583.X
K. E. BRUMMEL-ZIEDINS, R. F. BRANDA, S. BUTENAS, K. G. MANN, Discordant fibrin formation in hemophilia Journal of Thrombosis and Haemostasis. ,vol. 7, pp. 825- 832 ,(2009) , 10.1111/J.1538-7836.2009.03306.X
Alan R. Giles, Kenneth G. Mann, Michael E. Nesheim, A combination of factor Xa and phosphatidylcholine-phosphatidylserine vesicles bypasses factor VIII in vivo. British Journal of Haematology. ,vol. 69, pp. 491- 497 ,(1988) , 10.1111/J.1365-2141.1988.00483.X-I1
Benny Sørensen, Jørgen Ingerslev, None, Platelet infusion supports recombinant factor VIIa in a patient with severe haemophilia A and inhibitor--clinical outcome and laboratory observations. Thrombosis and Haemostasis. ,vol. 103, pp. 1275- 1276 ,(2010) , 10.1160/TH10-01-0019
Leon W. Hoyer, Molecular pathology and immunology of factor VIII (hemophilia A and factor VIII inhibitors) Human Pathology. ,vol. 18, pp. 153- 161 ,(1987) , 10.1016/S0046-8177(87)80333-7