A recent article published in the journal Haemophilia describes the health complications facing aging hemophilia patients. The lead author of the article was Barbara A. Konkle, MD, Director, Penn Comprehensive Hemophilia and Thrombosis Program, Hematology/Oncology, University of Pennsylvania.
While historically, the life expectancy of a person with hemophilia has been significantly lower than unaffected individuals from the general population, that trend has been reversed over the last few decades. A person with hemophilia can now reasonably expect to live into middle age and beyond. The availability of effective antiviral drugs to treat HIV and hepatitis C virus (HCV), the advent and proliferation of safer factor concentrates and the comprehensive care provided through the hemophilia treatment center network are the main factors contributing to improved health for older patients with hemophilia.
“Today, increasing numbers of persons with haemophilia (PWH) are middle-aged and older, and they face the same age-related health issues as the general population. The impact of these risks on PWH is unclear, however, and there is a paucity of information about how to manage co-morbidities in this patient population,” explained the authors.
Konkle and coauthors reviewed prior research studies, identifying five co-morbidities (co-existing medical conditions in addition to the hemophilia diagnosis) commonly seen in aging hemophilia patients: cardiovascular disease (CVD), liver disease, cancer, renal disease and joint disease.
Previously, patients with hemophilia A (factor VIII deficiency) were thought to be protected against CVD, the leading cause of death in U.S. males since the 1950s. The study data present enough conflicting reports to not only call that theory into question but support the opposite conclusion. “Several coagulation proteins have been implicated as possible CVD risk factors, FVIII among them. Results from the prospective atherosclerosis risk in communities (ARIC) study, which included 12,681 participants from four U.S. communities, showed that the FVIII level progressively increases with age and is one of the established risk factors for CVD. Whether FVIII deficiency offers protection from CVD is unclear, however, and the literature contains conflicting reports,” stated the authors.
Chronic liver disease associated with HCV is another major co-morbidity cited by the authors. It is the leading cause of death in people with hemophilia. Up to 98% of hemophilia patients treated with plasma-derived clotting factor concentrates prior to 1985 contracted HCV. Most of them developed chronic liver disease, which resulted in fibrosis (liver scarring), end-stage liver disease (ESLD) and cirrhosis. Investigators also found that HCV patients 65 and older may have cirrhosis rates as high as 60%; about 10% of them experienced ESLD within 5–10 years. Researchers added that “the risk of liver failure markedly increases with older age.”
Hemophilia patients co-infected with HCV and HIV, noted the authors, experience even higher rates of complications, such as reduced HCV clearance, increased hepatic inflammation and accelerated progression to cirrhosis, liver disease and liver failure.
Cancer, often linked to HCV and HIV, another co-morbidity, is a primary cause of death in aging hemophilia patients. The authors cited the findings of a Netherlands study, conducted from 2000-2007, which found that malignancies other than liver cancer were the primary cause of death for a person with hemophilia over 40 years old. A U.S. survey from 1993 to 1995 of the causes of death in 2,950 adults with hemophilia revealed a twofold increase for non-HIV-related or HCV-related cancers, compared with what would be expected in the general population.
The authors expressed “surprise” at the mortality rates associated with the fourth co-morbidity, renal (kidney) disease. Findings from a prior study suggest that adults with hemophilia showed a 50-fold increased risk of death from renal disease when compared to the general population. Hypertension, as the second most common cause of end-stage renal disease (ESRD) in the elderly, was mentioned specifically. The authors suggest that hypertension may be even more prevalent in the older hemophilia population, leading to bleeding in the kidney. They also cited HIV, HIV/HCV co-infection and the presence of inhibitors in hemophilia patients as other factors that can be linked to renal disease. Further possible complications linked to renal disease are anemia, kidney failure and uremia, a toxic condition resulting when waste products normally excreted in the urine build up in the bloodstream.
The fifth co-morbidity, joint disease or arthropathy, is a common condition in the aging hemophilia population. “Decreased use of a target joint results in ongoing muscle atrophy, ankylosis, contractures, osteoporosis, bone cysts and, eventually, crippling arthritis. Studies have suggested that these outcomes may be prevented in haemophilia patients by beginning factor prophylaxis at an early age. However, as this treatment option would not have been available to older PWH when they were children, joint disease and arthropathy are common in these individuals,” explained the authors.
The authors suggested multiple management strategies for each of these co-morbidities to help clinicians care for their aging patients. “The growing number of ageing persons with hemophilia is a testament to advances in haemophilia care that have occurred over the last two decades. Yet this newfound longevity carries with it the increased risk for age-related health issues not previously recognized in PWH, such as cardiovascular disease and cancer. Research efforts are increasingly being focused on the identification of optimal strategies to treat co-morbidities in older haemophilia patients,” concluded the authors.
The study was funded by Baxter Healthcare.
Source: Konkle B, Kessler C, Aledort L, Andersen J, Fogarty P, Kouides P, Quon D, Ragni M, Zakarija A, Ewenstein B. Emerging Clinical Concerns in the Ageing Haemophilia Patient. Haemophilia (2009); 15 (4): 926-931.