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DOI: 10.1160/TH04-10-0706
Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B
Publication History
Received
31 October 2004
Accepted after resubmission 29 February 2004
Publication Date:
14 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200503/lookinside/thumbnails/10-1160-th04-10-0706-1.jpg)
Summary
In haemophilia patients, a relationship is usually observed between the clinical expression of the disease and plasmatic factor VIII/factor IX (FVIII/FIX) activity. However, it is known from clinical experience, that some haemophilia patients, despite similar FVIII/FIX plasma levels, could exhibit different bleeding phenotype. After determining preanalytical test conditions, we evaluated the thrombin generation capacity from haemophilia plasma samples in various conditions and the potential usefulness of thrombin generation test (TGT) in haemophilia patients. In a series of 46 haemophilia patients (34 haemophilia A and 12 haemophilia B patients), we found a significant correlation between plasmatic FVIII/FIX levels and endogenous thrombin potential (ETP), peak and time to peak obtained by thrombin generation measurement. In addition, a correlation was found between severe clinical bleeding phenotype and ETP. Our results suggest that TGT could be a promising tool to evaluate haemostasis capacity in patients with haemophilia. Our ex vivo results, obtained 24 hours after FVIII concentrate administration, showed that in patients presenting similar plasmatic FVIIII levels, thrombin generation capacity may be significantly different. These results suggest that in patients with haemophilia, TGT could be useful for individually tailoring prophylactic regimens as well as for adapting clotting factors infusions in surgical situations, in addition to FVIII/FIX plasma clotting activities.
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References
- 1 Mannucci PM, Tuddenham EG. The hemophilias – from royal genes to gene therapy. N Engl J Med 2001; 344: 1773-9.
- 2 Al Dieri R, Peyvandi F, Santagostino E. et al. The thrombogram in rare inherited coagulation disorders: its relation to clinical bleeding. Thromb Haemost 2002; 88: 576-82.
- 3 Chantarangkul V, Clerici M, Bressi C. et al. Thrombin generation assessed as endogenous thrombin potential in patients with hyper-or hypo-coagulability. Haematologica 2003; 88: 547-54.
- 4 Siegemund T, Petros S, Siegemund A. et al. Thrombin generation in severe haemophilia A and B: the endogenous thrombin potential in platelet-rich plasma. Thromb Haemost 2003; 90: 781-6.
- 5 Varadi K, Negrier C, Berntorp E. et al. Monitoring the bioavailability of FEIBA with a thrombin generation assay. J Thromb Haemost 2003; 1: 2374-80.
- 6 Hemker HC, Beguin S. Phenotyping the clotting system. Thomb Haemost 2000; 84: 747-51.
- 7 Hemker HC, Giesen P, AlDieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33: 4-15.
- 8 Hope MJ, Bally MB, Webb G. et al. Production of large unilamellar vesicles by rapid extrusion procedure. Characterization of size distribution, trapped volume and ability to maintain a membrane potential. Biochim Biophys Acta 1985; 812: 55-65.
- 9 Hedegaard E, Jensen B. Nano-scale densitometric quantitation of phospholipids. J Chromatogr 1981; 225: 450-4.
- 10 Ghosh K, Shetty S, Mohanty D. Milder clinical presentation of hemophilia A with severe deficiency of factor VIII as measured by one-stage assay. Haemophilia 2001; 7: 9-12.
- 11 Nowak-Gottl U, Escuriola C, Kurnik K. et al. Haemophilia and thrombophilia. Hamostaseologie 2003; 23: 36-40.
- 12 Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterized by poor anticoagulant response to activated protein C : prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
- 13 Bertina RM, Koeleman BP, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
- 14 Nichols WC, Amano K, Cacheris PM et al. Moderation of hemophilia A phenotype by the factor V R506Q mutation. Blood 1996; 88: 1183-7.
- 15 Lee DH, Walker IR, Teitel J. et al. Effect of the factor V Leiden mutation on the clinical expression of severe hemophilia A. Thromb Haemost 2000; 83: 387-91.
- 16 Curvers J, Thomassen MC, Rimmer J. et al. Effects of hereditary and acquired risk factors of venous thrombosis on a thrombin generation-based APC resistance test. Thromb Haemost 2002; 88: 5-11.
- 17 Wielders S, Mukherjee M, Michiels J. et al. The routine determination of the endogenous thrombin potential, first results in different forms of hyper- and hypocoagulability. Thromb Haemost 1997; 77: 629-36.
- 18 Tans G, van Hylckama Vlieg A, Thomassen MC. et al. Activated protein C resistance determined with a thrombin generation-based test predicts for venous thrombosis in men and women. Br J Haematol 2003; 122: 465-70.
- 19 Dacosta A, Mismetti P, Tardy B. et al. Thrombosis and carbamazepine: hazard or causality?. Therapie 1994; 49: 355-6.
- 20 Simon JP, Hanesse B, Trechot P. et al. Repeated thromboses during treatment with carbamazepine. Therapie 1993; 48: 491
- 21 Nakaso K, Shimoda M, Yasui K. et al. A case of superior sagittal sinus thrombosis following long-term medication with carbamazepine. Rinsho Shinkeigaku 2000; 40: 617-20.
- 22 Ulrich ML, Rotzinger S, Asghar SJ. et al. Effects of dextroamphatamine, lithium chloride, sodium valproate and carbamazepine on intraplatelet Ca2+ levels. J Psychiatry Neurosci 2003; 28: 115-25.
- 23 Giansily-Blaizot M, Al Dieri R, Schved JF. Thrombin generation measurement in factor VII-depleted plasmas compared to inherited factor VII-deficient plasmas. Pathophysiol Haemost Thromb 2003; 33: 36-42.