Subscribe to RSS
Download PDF
DOI: 10.1160/TH11-11-0811
Two global haemostatic assays as additional tools to monitor treatment in cases of haemophilia A
Financial support: Financial support for this investigation was obtained from the Swedish Society for Medical Research, the Swedish Doctors’ Society, the Karolinska Institutet Research Foundation, the Tore Nilson Foundation, the Johan & Jakob Söderberg Foundation and unrestricted grant from Baxter, Sweden.
Publication History
Received:
29 November 2011
Accepted after major revision:
23 March 2012
Publication Date:
22 November 2017 (online)
Summary
Haemophilia A patients with similar levels of factor VIII (FVIII) may have different bleeding phenotypes and responses to treatment with FVIII concentrate. Therefore, a test which determines overall haemostasis may be appropriate for treatment monitoring in some patients. We studied two global haemostatic methods: endogenous thrombin potential (ETP) and overall haemostatic potential (OHP) before and after injection of FVIII concentrate in patients with haemophilia A treated prophylactically and on-demand. A significant correlation between FVIII and both ETP and OHP was observed, while ETP and OHP differed between patients with severe and mild clinical phenotypes. Both ETP and OHP differed significantly between severe, moderate and mild haemophilia A and controls. ETP and OHP increased after intravenous injection of FVIII concentrate in both groups of patients, but in spite of higher pre-treatment values of both ETP and OHP in patients treated prophylactically, and much higher post-treatment FVIII levels in comparison with the values in patients treated on-demand, no difference after treatment was observed for either ETP or OHP. ETP and OHP may be additional alternatives for monitoring (and even for individual tailoring) treatment in patients with haemophilia A.
-
References
- 1 Nilsson IM, Berntorp E, Löfqvist T. et al. Twenty-five years experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 1992; 232: 25-32.
- 2 Blanchette VS, Manco-Johnson M, Santagostino E. et al. Optimizing factor prophylaxis for the haemophilia population: where do we stand?. Haemophilia 2004; 10 (Suppl. 04) 97-104.
- 3 Manco-Johnson MJ, Abshire TC, Shapiro AD. et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe haemophilia. N Engl J Med 2007; 357: 535-544.
- 4 Rainsford SG, Hall A. A three-year study of adolescent boys suffering from haemophilia and allied disorders. Br J Haematol 1973; 24: 539-551.
- 5 Aledort LM, Haschmeyer RH, Pettersson H. A longitudinal study of orthopaedic outcomes for severe factor-VIII-deficient haemophiliacs. The Orthopaedic Outcome Study Group. J Intern Med 1994; 236: 391-399.
- 6 van den Berg HM, Fischer K, Mauser-Bunschoten EP. et al. Long-term outcome of individualized prophylactic treatment of children with severe haemophilia. Br J Haematol 2001; 112: 561-565.
- 7 Feldman BM, Pai M, Rivard GE. et al. Association of Haemophilia Clinic Directors of Canada Prophylaxis Study Group. Tailored prophylaxis in severe haemophilia A: interim results from the first 5 years of the Canadian Haemophilia Primary Prophylaxis Study. J Thromb Haemost 2006; 04: 1228-1236.
- 8 Wielders S, Mukherjee M, Michiels J. et al. The routine determination of the endogenous thrombin potential, first results in different forms of hyper- and hypo-coagulability. Thromb Haemost 1997; 77: 629-636.
- 9 Keularts IM, Hamulyak K, Hemker HC. et al. The effect of DDAVP infusion on thrombin generation in platelet rich plasma of von Willebrand type 1 and mild haemophilia A patients. Thromb Haemost 2000; 84: 638-642.
- 10 Kawaguchi C, Takahashi Y, Hanesaka Y. et al. The in vitro analysis of the coagulation mechanism of activated factor VII using thromboelastogram. Thromb Haemost 2002; 88: 768-772.
- 11 Beltrán-Miranda CP, Khan A, Jaloma-Cruz AR. et al. Thrombin generation and phenotypic correlation in haemophilia A. Haemophilia 2005; 11: 326-334.
- 12 Dargaud Y, Béguin S, Lienhart A. et al. Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B. Thromb Haemost 2005; 93: 475-480.
- 13 Sorensen B, Ingerslev J. Tailoring haemostatic treatment to patient requirements – an update on monitoring haemostatic response using thrombelastography. Haemophilia 2005; 11 (Suppl. 01) 1-6.
- 14 Hvas AM, Sorensen HT, Norengaard L. et al. Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe haemophilia. A J Thromb Haemost 2007; 05: 2408-2414.
- 15 Goldenberg NA, Hathaway WE, Jacobson L. et al. Influence of factor VIII on overall coagulability and fibrinolytic potential of haemophilic plasma as measured by global assay: monitoring in haemophilia A. Haemophilia 2006; 12: 605-614.
- 16 Livnat T, Martinowitz U, Zivelin A. et al. A highly sensitive thrombin generation assay for assessment of recombinant activated factor VII therapy in haemophilia patients with an inhibitor. Thromb Haemost 2011; 105: 688-695.
- 17 He S, Antovic A, Blombäck M. A simple and rapid laboratory method for determination of haemostasis potential in plasma II. Modifications for use in routine laboratories and research work. Thromb Res 2001; 103: 355-361.
- 18 Antovic A, Blombäck M, Sten-Linder M. et al. Identifying hypocoagulable states with a modified global assay of overall haemostasis potential in plasma. Blood Coagul Fibrinolysis 2005; 16: 585-596.
- 19 Berntrop E, Björkman S. The pharmacokinetics of clotting factor therapy. Haemophilia 2003; 09: 353-359.
- 20 Salvagno GL, Astermark J, Lippi G. et al. Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia?. Haemophilia 2009; 15: 290-296.
- 21 Ghosh K, Shetty S, Mohanty D. Milder clinical presentation of haemophilia A with severe deficiency of factor VIII as measured by one-stage assay. Haemophilia 2001; 07: 9-12.
- 22 Antovic A, Blombäck M, Bremme K. et al. Increased haemostasis potential persists in women with previous thromboembolism with or without APC resistance. J Thromb Haemost 2003; 01: 2531-2535.
- 23 Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood 2007; 110: 1723-1729.
- 24 Biere-Rafi S, Tuinenburg A, Haak BW. et al. Factor VIII deficiency does not protect against atherosclerosis. J Thromb Haemost 2012; 10: 30-37.
- 25 Tuinenburg A, Rutten A, Kavousi M. et al. Coronary artery calcification in haemophilia A: No evidence for a protective effect of factor VIII deficiency on atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32: 799-804.
- 26 Biere-Rafi S, Baarslag MA, Peters M. et al. Cardiovascular risk assessment in haemophilia patients. Thromb Haemost 2011; 105: 274-278.