Chronic complications and age-related comorbidities in people with hemophilia
- W Keith Hoots, MD
W Keith Hoots, MD
- Director, Division of Blood Diseases and Resources
- National Heart, Lung and Blood Institute
- National Institutes of Health, Bethesda, Maryland
- Amy D Shapiro, MD
Amy D Shapiro, MD
- Medical Director
- Indiana Hemophilia and Thrombosis Center
Hemophilia A (factor VIII [factor 8] deficiency) and hemophilia B (factor IX [factor 9] deficiency) are X-linked inherited coagulation factor deficiencies. The availability of factor replacement products has dramatically improved care for individuals with these conditions, resulting in dramatic improvements in life expectancy. However, as people with hemophilia live longer, they are more likely to develop chronic complications of hemophilic bleeding as well as age-related comorbidities such as heart disease and cancer, and many of the treatments for heart disease, cancer, and other conditions also increase the risk of bleeding.
This topic review discusses the management of these chronic complications and age-related comorbidities in people with hemophilia.
Separate topic reviews discuss diagnosis, routine care including factor prophylaxis, treatment of bleeding, surgery, inhibitor eradication, and genetics of hemophilia.
●Diagnosis – (See "Clinical manifestations and diagnosis of hemophilia".)
●Comprehensive care including factor prophylaxis – (See "Hemophilia A and B: Routine management including prophylaxis".)
- Raffini L, Manno C. Modern management of haemophilic arthropathy. Br J Haematol 2007; 136:777.
- Jansen NW, Roosendaal G, Lafeber FP. Understanding haemophilic arthropathy: an exploration of current open issues. Br J Haematol 2008; 143:632.
- 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.
- Soucie JM, Cianfrini C, Janco RL, et al. Joint range-of-motion limitations among young males with hemophilia: prevalence and risk factors. Blood 2004; 103:2467.
- Siegel ME, Siegel HJ, Luck JV Jr. Radiosynovectomy's clinical applications and cost effectiveness: a review. Semin Nucl Med 1997; 27:364.
- Triantafyllou SJ, Hanks GA, Handal JA, Greer RB 3rd. Open and arthroscopic synovectomy in hemophilic arthropathy of the knee. Clin Orthop Relat Res 1992; :196.
- Dunn AL, Busch MT, Wyly JB, Abshire TC. Radionuclide synovectomy for hemophilic arthropathy: a comprehensive review of safety and efficacy and recommendation for a standardized treatment protocol. Thromb Haemost 2002; 87:383.
- Rampersad AG, Shapiro AD, Rodriguez-Merchan EC, et al. Radiosynovectomy: review of the literature and report from two haemophilia treatment centers. Blood Coagul Fibrinolysis 2013; 24:465.
- Rodriguez-Merchan EC. Therapeutic options in the management of articular contractures in haemophiliacs. Haemophilia 1999; 5 Suppl 1:5.
- Schick M, Stucki G, Rodriguez M, et al. Haemophilic; arthropathy: assessment of quality of life after total knee arthroplasty. Clin Rheumatol 1999; 18:468.
- Nelson IW, Sivamurugan S, Latham PD, et al. Total hip arthroplasty for hemophilic arthropathy. Clin Orthop Relat Res 1992; :210.
- Luck JV Jr, Kasper CK. Surgical management of advanced hemophilic arthropathy. An overview of 20 years' experience. Clin Orthop Relat Res 1989; :60.
- Solimeno LP, Mancuso ME, Pasta G, et al. Factors influencing the long-term outcome of primary total knee replacement in haemophiliacs: a review of 116 procedures at a single institution. Br J Haematol 2009; 145:227.
- Rodriguez-Merchan EC. Orthopaedic surgery in persons with haemophilia. Thromb Haemost 2003; 89:34.
- Rodríguez-Merchán EC. Total Knee Arthroplasty in Hemophilic Arthropathy. Am J Orthop (Belle Mead NJ) 2015; 44:E503.
- Anagnostis P, Vakalopoulou S, Slavakis A, et al. Reduced bone mineral density in patients with haemophilia A and B in Northern Greece. Thromb Haemost 2012; 107:545.
- Anagnostis P, Vakalopoulou S, Charizopoulou M, et al. Vitamin D deficiency in patients with haemophilia: an underestimated commorbidity. Haemophilia 2013; 19:e308.
- Linari S, Montorzi G, Bartolozzi D, et al. Hypovitaminosis D and osteopenia/osteoporosis in a haemophilia population: a study in HCV/HIV or HCV infected patients. Haemophilia 2013; 19:126.
- Miles BS, Anderson P, Agostino A, et al. Effect of intracranial bleeds on the neurocognitive, academic, behavioural and adaptive functioning of boys with haemophilia. Haemophilia 2012; 18:229.
- Zhai J, Weng X, Zhang B, et al. Surgical Treatment for Hemophilic Pseudotumor: Twenty-three Cases with an Average Follow-up of 5 Years. J Bone Joint Surg Am 2017; 99:947.
- Goedert JJ, Eyster ME, Lederman MM, et al. End-stage liver disease in persons with hemophilia and transfusion-associated infections. Blood 2002; 100:1584.
- Mazepa MA, Monahan PE, Baker JR, et al. Men with severe hemophilia in the United States: birth cohort analysis of a large national database. Blood 2016; 127:3073.
- Eyster ME, Diamondstone LS, Lien JM, et al. Natural history of hepatitis C virus infection in multitransfused hemophiliacs: effect of coinfection with human immunodeficiency virus. The Multicenter Hemophilia Cohort Study. J Acquir Immune Defic Syndr 1993; 6:602.
- Lesens O, Deschênes M, Steben M, et al. Hepatitis C virus is related to progressive liver disease in human immunodeficiency virus-positive hemophiliacs and should be treated as an opportunistic infection. J Infect Dis 1999; 179:1254.
- Tradati F, Colombo M, Mannucci PM, et al. A prospective multicenter study of hepatocellular carcinoma in italian hemophiliacs with chronic hepatitis C. The Study Group of the Association of Italian Hemophilia Centers. Blood 1998; 91:1173.
- Darby SC, Ewart DW, Giangrande PL, et al. Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C. UK Haemophilia Centre Directors' Organisation. Lancet 1997; 350:1425.
- Gordon FH, Mistry PK, Sabin CA, Lee CA. Outcome of orthotopic liver transplantation in patients with haemophilia. Gut 1998; 42:744.
- Wilde J, Teixeira P, Bramhall SR, et al. Liver transplantation in haemophilia. Br J Haematol 2002; 117:952.
- Angelini D, Sood SL. Managing older patients with hemophilia. Hematology Am Soc Hematol Educ Program 2015; 2015:41.
- Tagliaferri A, Di Perna C, Santoro C, et al. Cancers in patients with hemophilia: a retrospective study from the Italian Association of Hemophilia Centers. J Thromb Haemost 2012; 10:90.
- Biron-Andreani C, de Moerloose P, D'oiron R, et al. Cancer detection and management in patients with haemophilia: a retrospective European multicentre study. Haemophilia 2014; 20:78.
- Kulkarni R, Soucie JM, Evatt BL, Hemophilia Surveillance System Project Investigators. Prevalence and risk factors for heart disease among males with hemophilia. Am J Hematol 2005; 79:36.
- Lim MY, Pruthi RK. Cardiovascular disease risk factors: prevalence and management in adult hemophilia patients. Blood Coagul Fibrinolysis 2011; 22:402.
- Sharathkumar AA, Soucie JM, Trawinski B, et al. Prevalence and risk factors of cardiovascular disease (CVD) events among patients with haemophilia: experience of a single haemophilia treatment centre in the United States (US). Haemophilia 2011; 17:597.
- Mannucci PM, Schutgens RE, Santagostino E, Mauser-Bunschoten EP. How I treat age-related morbidities in elderly persons with hemophilia. Blood 2009; 114:5256.
- Franchini M, Mannucci PM. Co-morbidities and quality of life in elderly persons with haemophilia. Br J Haematol 2010; 148:522.
- Coppola A, Tagliaferri A, Franchini M. The management of cardiovascular diseases in patients with hemophilia. Semin Thromb Hemost 2010; 36:91.
- Schutgens RE, Tuinenburg A, Roosendaal G, et al. Treatment of ischaemic heart disease in haemophilia patients: an institutional guideline. Haemophilia 2009; 15:952.
- Ferraris VA, Boral LI, Cohen AJ, et al. Consensus review of the treatment of cardiovascular disease in people with hemophilia A and B. Cardiol Rev 2015; 23:53.
- Schutgens RE, van der Heijden JF, Mauser-Bunschoten EP, Mannucci PM. New concepts for anticoagulant therapy in persons with hemophilia. Blood 2016; 128:2471.
- Staritz P, de Moerloose P, Schutgens R, et al. Applicability of the European Society of Cardiology guidelines on management of acute coronary syndromes to people with haemophilia - an assessment by the ADVANCE Working Group. Haemophilia 2013; 19:833.
- Bhave P, McGiffin D, Shaw J, et al. Guide to performing cardiac surgery in patients with hereditary bleeding disorders. J Card Surg 2015; 30:61.
- Esposito P, Rampino T, Gregorini M, et al. Renal diseases in haemophilic patients: pathogenesis and clinical management. Eur J Haematol 2013; 91:287.
- 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.
- 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; 4:510.
- Soucie JM, Nuss R, Evatt B, et al. Mortality among males with hemophilia: relations with source of medical care. The Hemophilia Surveillance System Project Investigators. Blood 2000; 96:437.
- Plug I, Peters M, Mauser-Bunschoten EP, et al. Social participation of patients with hemophilia in the Netherlands. Blood 2008; 111:1811.
- Bradley CS, Bullinger M, McCusker PJ, et al. Comparing two measures of quality of life for children with haemophilia: the CHO-KLAT and the Haemo-QoL. Haemophilia 2006; 12:643.
- du Treil S, Rice J, Leissinger CA. Quantifying adherence to treatment and its relationship to quality of life in a well-characterized haemophilia population. Haemophilia 2007; 13:493.
- Pollak E, Mühlan H, VON Mackensen S, et al. The Haemo-QoL Index: developing a short measure for health-related quality of life assessment in children and adolescents with haemophilia. Haemophilia 2006; 12:384.
- van der Net J, Vos RC, Engelbert RH, et al. Physical fitness, functional ability and quality of life in children with severe haemophilia: a pilot study. Haemophilia 2006; 12:494.
- http://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-Scientific-Advisory-Council-MASAC/MASAC-Recommendations (Accessed on September 12, 2016).
- CHRONIC COMPLICATIONS
- Other bleeding sequelae
- HIV and HCV infection
- Inhibitor development
- AGE-RELATED COMORBIDITIES
- Cardiovascular disease
- Chronic kidney disease
- Life expectancy
- Quality of life
- Causes of death
- SOCIETY GUIDELINES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS