Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.
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In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.
They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.
By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.
The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.
Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.
Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.
“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.
The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.
“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.
All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.
SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.