Subscribe to RSS
DOI: 10.5482/HAMO-12-08-0015
Anticoagulation therapy in haemophilia
Managing the unknownAntikoagulatorische Therapie bei HämophilieUmgang mit dem UnbekanntenPublication History
received:
28 August 2012
accepted in revised version:
06 February 2013
Publication Date:
28 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00034925/201304/lookinside/thumbnails/10-5482-hamo-12-08-0015_de-1.jpg)
Summary
Patients with haemophilia (PWH) are relatively protected from cardiovascular death. Recent insights have shown that this is not due to less formation of atherosclerosis than in non-haemophilic men, therefore protection from the final occlusive thrombus will be the major determinant. Prevalence and incidence rates of cardiovascular disease (especially non-fatal events) are scarce, although ongoing studies are addressing this issue.
Meanwhile, because the haemophilia population is aging, we are increasingly confronted with cardiovascular events. The main cardio vascular risk factors that should be part of regular screening programs are hypertension, overweight, lipometabolic disorders and smoking. Anticoagulation therapy in haemophilia is feasible, provided that individual tailored coagulation therapy and close monitoring is provided.
Here, we present our view on anticoagulation management in PWH. There is an absolute need for risk assessment tools and prospective validation of suggested anticoagulation management strategies in PWH. Until then, we are managing the unknown.
Zusammenfassung
Patienten mit Hämophilie sind relativ geschützt vor kardiovaskulär bedingtem Tod. Nach neuen Erkenntnissen ist dies nicht darauf zurückzuführen, dass die Arteriosklerose geringer ausgeprägt ist als bei Männern ohne Hämophilie, daher wird der Schutz vor dem letztlich okklusiven Thrombus der ausschlaggebende Faktor sein. Daten zur Prävalenz und Inzidenz kardiovaskulärer Erkrankungen (besonders für nicht tödliche Ereignisse) liegen kaum vor, jedoch werden zurzeit Studien dazu durchgeführt.
Inzwischen sehen wir uns angesichts der alternden, von Hämophilie betroffenen Population zunehmend mit kardiovaskulären Ereignissen konfrontiert. Die wichtigsten kardiovaskulären Risikofaktoren eines regelmäßigen Screening Programms sollten Hypertonie, Übergewicht, metabolisches Syndrom und Rauchen sein. Eine antikoagulatorische Therapie der Hämophilie ist möglich, wenn sie individuell angepasst wird und unter engmaschiger Kontrolle erfolgt.
Hier legen wir unsere Sicht der antikoagulatorischen Behandlung von Hämophilie-Patienten dar. Es besteht ein Bedarf an Methoden zur Risikobeurteilung und zur prospektiven Validierung der für Hämophilie-Patienten vorgeschlagenen Behandlungsstrategien zur Antikoagulation. Bis dahin bewegen wir uns auf unbekanntem Terrain.
-
References
- 1 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801-809.
- 2 Libby P, Ridker PM, Hansson GK. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 2009; 54: 2129-2138.
- 3 Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-1695.
- 4 Croce K, Libby P. Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol 2007; 14: 55-61.
- 5 Coughlin SR. Thrombin signalling and proteaseactivated receptors. Nature 2000; 407: 258-264.
- 6 Totani L, Evangelista V. Platelet-leukocyte interactions in cardiovascular disease and beyond. Arterioscler Thromb Vasc Biol 2010; 30: 2357-2361.
- 7 Breitenstein A, Tanner FC, Luscher TF. Tissue factor and cardiovascular disease: quo vadis?. Circ J 2010; 74: 3-12.
- 8 Tushuizen ME, Diamant M, Sturk A, Nieuwland R. Cell-derived microparticles in the pathogenesis of cardiovascular disease: friend or foe?. Arterioscler Thromb Vasc Biol 2011; 31: 4-9.
- 9 Di Cera E. Thrombin as procoagulant and anticoagulant. J Thromb Haemost 2007; 05 (Suppl. 01) 196-202.
- 10 Levi M, Schultz M, Van Der PT. Disseminated intravascular coagulation in infectious disease. Semin Thromb Hemost 2010; 36: 367-377.
- 11 Darby SC, Kan SW, Spooner RJ. et al. Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. Blood 2007; 110: 815-825.
- 12 Koumbarelis E, Rosendaal FR, Gialeraki A. et al. Epidemiology of haemophilia in Greece: an overview. Thromb Haemost 1994; 72: 808-813.
- 13 Plug I, Van Der Bom JG, Peters M. et al. Mortality and causes of death in patients with hemophilia, 1992-2001: a prospective cohort study. J Thromb Haemost 2006; 04: 510-516.
- 14 Rosendaal FR, Varekamp I, Smit C. et al. Mortality and causes of death in Dutch haemophiliacs, 1973-86. Br J Haematol 1989; 71: 71-76.
- 15 Tagliaferri A, Rivolta GF, Iorio A. et al. Mortality and causes of death in Italian persons with haemophilia, 1990-2007. Haemophilia 2010; 16: 437-446.
- 16 Triemstra M, Rosendaal FR, Smit C. et al. Mortality in patients with hemophilia. Changes in a Dutch population from 1986 to 1992 and 1973 to 1986. Ann Intern Med 1995; 123: 823-827.
- 17 Tuinenburg A, Rutten A, Kavousi M. et al. Coronary artery calcification in hemophilia A: no evidence for a protective effect of factor VIII deficiency on atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32: 799-804.
- 18 Biere-Rafi S, Tuinenburg A, Haak BW. et al. Factor VIII deficiency does not protect against atherosclerosis. J Thromb Haemost 2012; 10: 30-37.
- 19 Coppola A, Tagliaferri A, Franchini M. The management of cardiovascular diseases in patients with hemophilia. Semin Thromb Hemost 2010; 36: 91-102.
- 20 Dolan G. The challenge of an ageing haemophilic population. Haemophilia 2010; 16 (Suppl. 05) 11-16.
- 21 Konkle BA. Clinical challenges within the aging hemophilia population. Thromb Res 2011; 127 (Suppl. 01) S10-S13.
- 22 Mannucci PM, Schutgens RE, Santagostino E, Mauser-Bunschoten EP. How I treat age-related morbidities in elderly persons with hemophilia. Blood 2009; 114: 5256-5263.
- 23 Schutgens RE, Tuinenburg A, Roosendaal G. et al. Treatment of ischaemic heart disease in haemophilia patients: an institutional guideline. Haemophilia 2009; 15: 952-958.
- 24 Dalldorf FG, Taylor RE, Blatt PM. Arteriosclerosis in severe hemophilia. A postmortem study. Arch Pathol Lab Med 1981; 105: 652-654.
- 25 Foley CJ, Nichols L, Jeong K. et al. Coronary atherosclerosis and cardiovascular mortality in hemophilia. J Thromb Haemost 2010; 08: 208-211.
- 26 Bilora F, Dei RC, Girolami B. et al. Do hemophilia A and von Willebrand disease protect against carotid atherosclerosis? A comparative study between coagulopathics and normal subjects by means of carotid echo-color Doppler scan. Clin Appl Thromb Hemost 1999; 05: 232-235.
- 27 Bilora F, Boccioletti V, Zanon E. et al. Hemophilia A, von Willebrand disease, and atherosclerosis of abdominal aorta and leg arteries: factor VIII and von Willebrand factor defects appear to protect abdominal aorta and leg arteries from atherosclerosis. Clin Appl Thromb Hemost 2001; 07: 311-313.
- 28 Bilora F, Zanon E, Petrobelli F. et al. Does hemophilia protect against atherosclerosis? A case-control study. Clin Appl Thromb Hemost 2006; 12: 193-198.
- 29 Sartori MT, Bilora F, Zanon E. et al. Endothelial dysfunction in haemophilia patients. Haemophilia 2008; 14: 1055-1062.
- 30 Sramek A, Reiber JH, Gerrits WB, Rosendaal FR. Decreased coagulability has no clinically relevant effect on atherogenesis: observations in individuals with a hereditary bleeding tendency. Circulation 2001; 104: 762-767.
- 31 Tuinenburg A, Mauser-Bunschoten EP, Verhaar MC. et al. Cardiovascular disease in patients with hemophilia. J Thromb Haemost 2009; 07: 247-254.
- 32 Kulkarni R, Soucie JM, Evatt BL. Prevalence and risk factors for heart disease among males with hemophilia. Am J Hematol 2005; 79: 36-42.
- 33 Siboni SM, Mannucci PM, Gringeri A. et al. Health status and quality of life of elderly persons with severe hemophilia born before the advent of modern replacement therapy. J Thromb Haemost 2009; 07: 780-786.
- 34 Miesbach W, Alesci S, Krekeler S, Seifried E. Comorbidities and bleeding pattern in elderly haemophilia A patients. Haemophilia 2009; 15: 894-899.
- 35 Ragni MV, Moore CG. Atherosclerotic heart disease: prevalence and risk factors in hospitalized men with haemophilia A. Haemophilia 2011; 17: 867-871.
- 36 Fransen van de Putte DE, Fischer K. et al. Non-fatal cardiovascular disease, malignancies, and other co-morbidity in adult haemophilia patients. Thromb Res 2012; 130: 157-162.
- 37 Biere-Rafi S, Baarslag MA, Peters M. et al. Cardiovascular risk assessment in haemophilia patients. Thromb Haemost 2011; 105: 274-278.
- 38 Fransen van de Putte DE, Fischer K. et al. Increased prevalence of hypertension in haemophilia patients. Thromb Haemost 2012; 108: 750-755.
- 39 Hofstede FG, Fijnvandraat K, Plug I. et al. Obesity: a new disaster for haemophilic patients? A nationwide survey. Haemophilia 2008; 14: 1035-1038.
- 40 Majumdar S, Morris A, Gordon C. et al. Alarmingly high prevalence of obesity in haemophilia in the state of Mississippi. Haemophilia 2010; 16: 455-459.
- 41 Walsh M, Macgregor D, Stuckless S. et al. Healthrelated quality of life in a cohort of adult patients with mild hemophilia A. J Thromb Haemost 2008; 06: 755-761.
- 42 Girolami A, Randi ML, Ruzzon E. et al. Myocardial infarction, other arterial thrombosis and invasive coronary procedures, in hemaophilia B: a critical evaluation of reported cases. J Thromb Thrombolysis 2005; 20: 43-46.
- 43 Girolami A, Ruzzon E, Fabris F. et al. Myocardial infarction and other arterial occlusions in hemophilia a patients. A cardiological evaluation of all 42 cases reported in the literature. Acta Haematol 2006; 116: 120-125.
- 44 Connolly S, Pogue J, Hart R. et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367: 1903-1912.
- 45 Fransen van de Putte DE, Schutgens RE, Pulles AE. et al. Cardiovascular disease in haemophilia patients. 4-2-0011. EAHAD. Ref Type: Generic..
- 46 Vidi VD, Matheny ME, Agarwal V. et al. Validation of long-term benefits of bivalirudin versus unfractionated heparin in routine clinical practice after percutaneous coronary intervention. Am J Cardiol 2010; 106: 1234-1240.