Co-Morbidities Associated with Depression and Anxiety in Older Patients with Hemophilia
Authors: Poston Jacqueline N , Le Binh , Dupervil Brandi , Soucie J Michael 
Published: December 2024

Introduction
When compared with the general population ages 45+ years (y), depression and anxiety are more common among older adults with hemophilia (JM Soucie, et al. Haemophilia 2022). Anxiety and depression are associated with increased pain and decreased treatment adherence (ML Witkop et al, Patient Prefer Adherence 2019). The risk factors for developing depression and anxiety in this patient population have not been studied.
Methods
Data on the presence of comorbidities were collected on patients with hemophilia A (HA) or hemophilia B (HB) who were at least 45 y old and enrolled in Community Counts (CC), a US based registry for bleeding disorders surveillance, between 05/2013 and 12/2023. We used data reported at enrollment and during subsequent annual surveillance visits to 146 hemophilia treatment centers (HTCs) throughout the US to compare differences in potential risk factors between patients with hemophilia who developed new onset depression and/or anxiety compared to those who did not during the follow-up period. Differences in these associations were assessed for statistical significance using odds ratios (OR) and 95% confidence intervals (CI). CIs that did not include 1 were indicative of significance at the level p &lt; 0.05.
Results
During the surveillance period, 2,308 patients with HA and 865 with HB aged 45+ y had data collected during 10,681 HTC visits. The median age was 55 y, and most were non-Hispanic (92.3%) and white (85.5%). There were 265 females and 2,908 males. Most (3,060 (96.4%)) patients had health insurance.1,710 (54%) patients were employed, 546 (17.2%) were retired, and 630 (19.9%) were disabled. A history of depression and/or anxiety was reported by 23.9% of patients at enrollment, with similar rates reported between patients with severe (29.7%), moderate (22.6%) and mild (20.3%) hemophilia. A history of anxiety was a risk factor for developing depression (OR 6.11, 95% CI 4.12-9.06) and a history of depression was a risk factor for developing anxiety (OR 8.50, 95% CI 5.52-13.08).
Of 1,883 patients with ongoing follow up without a history of depression or anxiety, 7.3% (138) developed either depression and/or anxiety during follow up. Those who were 45-64y had higher risk than those 65+y (OR 1.77, 95% 1.17-2.68). Demographic and socioeconomic characteristics such as race and employment status were not associated with increased risk. Among comorbid conditions, diabetes (OR 2.11, 95% CI 1.48-3.01) and bone disease (e.g., fracture, osteoporosis) (OR 1.71, 95%CI 1.19-2.46) were associated with increased risk. Adverse outcomes that occurred in the year prior to onset of depression and/or anxiety were associated with an increased risk, including: &gt;3 joint bleeds (OR 2.50, 95% CI 1.35-4.64), hospitalization (OR 1.83, 95% CI 1.08-3.10), chronic pain (OR 2.0, 95% CI 1.32-3.02), opioid use (OR 1.66, 95% CI 1.11-2.50) and restricted activity (OR 2.65, 95% CI 1.80-3.90).
Depression and/or anxiety developed in patients without a history of depression or anxiety regardless of hemophilia severity (8.5% of severe, 6.8% of moderate, 6.7% of mild), however, the impact of some risk factors varied by severity. Joint bleeding and opioid use were stronger risk factors among patients with severe hemophilia, whereas, chronic pain, bone disease, obesity and diabetes were stronger for those with moderate or mild hemophilia.
Regarding treatment, emicizumab use was associated with decreased risk of depression and anxiety in patients with severe HA (OR 0.36, 95% CI 0.17-0.76). For patients with moderate HA, prophylactic hemostatic treatment had a decreased risk of depression and/or anxiety (OR 0.23, 95% CI 0.06-0.80). Prophylaxis use did not impact risk of depression or anxiety in patients with HB regardless of severity.
Conclusions
Depression and anxiety are common in the older CC hemophilia population and can develop in patients without a history of mental health conditions. Anxiety and/or depression developed irrespective of hemophilia severity, but there were differences in the distribution of risk factors across severities. In addition, effective hemostatic prophylaxis appears essential to reduce complications associated with increased risk of anxiety and/or depression for patients with severe and moderate HA.