Bone fragility in patients affected by congenital diseases non skeletal in origin
Bleeding, Damage Common In Pediatric Hemophilia Despite Prophylaxis
Although prophylaxis is the gold standard of treatment for children with hemophilia, a new report highlights the need to vigilantly monitor patients for signs of "hidden" joint damage.
The ankles are an area of particular concern, according to the authors of a new study published in Thrombosis Research.
Hemophilic arthropathy is the most common complication of hemophilia, wrote the study authors. In many cases, arthropathy leads to disability and diminished quality of life.
Primary prophylactic infusion of coagulation factor is used to prevent joint bleeding and bone damage. However, despite prophylaxis, some patients still develop joint damage, suggesting that subclinical bleeding is relatively common.
"It usually manifests as joint discomfort, which disappears with the new dose of replacement factor," they wrote.
Previous research shows that MRI can detect joint damage in children without a known history of joint bleeding. The problem, the authors said, is that MRI is not routinely used in daily clinical practice.
They wanted to better understand the problem of hidden joint damage in children and to analyze whether certain age groups or certain joints were more prone to damage. They recruited 106 patients with severe hemophilia who were taking prophylaxis and who were between the ages of 2 and 18 years. Eighty-eight percent of the participants had hemophilia A; the rest had hemophilia B. The investigators evaluated the participants' joints and conducted follow-up examinations at their clinic.
Primary prophylaxis is defined as regularly scheduled prophylaxis designed to prevent bleeding. Secondary prophylaxis is administered after a patient has experienced joint bleeding. In the study, 59 participants were on secondary prophylaxis, while 47 participants were taking primary prophylaxis.
Of 636 joints evaluated, about a quarter (163 joints) had at least 1 joint bleed. The most frequent site of joint bleeding was the ankle (48.5%), followed by the elbow (27.6%) and the knee (23.9%).
In terms of joint damage, the investigators found it occurred more frequently in patients on secondary prophylaxis. While just 21.3% of participants on primary prophylaxis had joint damage, 72.9% of participants on secondary prophylaxis had joint damage. Joint damage was defined in the study as having a Hemophilia Early Arthropathy Detection with Ultrasound score of at least 1. On the other hand, the investigators said people on primary prophylaxis had a greater number of damaged joints at older ages. Participants 11 years and older had a greater frequency and degree of arthropathy. They said cartilage was most frequently involved in joint damage, followed by synovitis and bone damage.
The investigators said their study shows that although prophylaxis is the best treatment for children with hemophilia, it does not prevent joint bleeding, symptomatic or otherwise.
"The routine evaluation of joint health is relevant, particularly of the ankle," they concluded.
They added, however, that their research aligns with previous studies suggesting ultrasound is a reliable method by which to detect early signs of arthropathy.
Reference
Daffunchio C, Galatro G, Faurlin V, Neme D, Caviglia H. The hidden joint in children with haemophilia on prophylaxis. Thromb Res. 2023;226:86-92. Doi:10.1016/j.Thromres.2023.04.012
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Unmet Needs In Hemophilia: Prophylaxis, Bleeding, Quality Of Life
A pair of studies presented at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition highlight the continuing gaps in hemophilia care, even with the availability of prophylactic therapies.1,2 There is a persistent unmet need for more effective therapies for hemophilia. Despite advancements in treatment, more than one-third of patients still experience bleeding episodes, and joint damage remains a significant issue.
The ability to manage hemophilia A (HA) through factor VIII (FVIII) replacement therapies and non-factor therapies (NFT) has sustained the progress of this treatment approach, but bleeding episodes continue to affect the physical health and quality of life (QoL) of patients.1 One of the studies sought to evaluate the unmet needs of individuals with moderate to severe HA who are on prophylactic treatment, shedding light on patient- and physician-reported outcomes.
The research utilized data from the Adelphi Hemophilia Disease Specific Programme, a real-world cross-sectional survey conducted in the US between July 2023 and March 2024. The study analyzed responses from 47 hemophilia-treating physicians regarding 244 patients and incorporated voluntary patient-reported outcomes to capture the broader impact of the disease.
Patients included in the analysis had no inhibitors, known baseline FVIII activity levels, and were receiving prophylactic treatment with standard half-life (SHL), extended half-life (EHL) therapies, or emicizumab (NFT). Data on annual bleeding rate (ABR), joint health, therapy utilization, and employment status were descriptively analyzed.
Demographics and FVIII Activity LevelsThe patient cohort had a mean age of 27.4 years, with 81.6% aged 18 years or older. At the time of the survey, 92 patients had FVIII activity levels of 2.0–5.0%, 90 had levels of 1.0–2.0%, and 62 had levels below 1.0%.
Treatment OutcomesAmong the patients, 113 received SHL therapy, 40 received EHL therapy, and 67 were treated with NFT. ABR data were available for patients treated for over a year:
Despite prophylactic treatment, 39 patients (16%) experienced 1 or more bleeds in the previous year, with rates varying by treatment group: SHL (41.0%), EHL (52.2%), and NFT (37.9%).
Joint Health and Therapy UtilizationJoint problems were reported in 25% of patients within the last year. Among these, 44.3% used therapies such as physical therapy (26.2%), yoga or Pilates (13.9%), or massage (9.4%) to manage symptoms. Furthermore, 23% required aids like braces or crutches due to joint damage.
Impact on Daily Life, Employment, Psychological BurdenThe study highlighted significant challenges related to quality of life for patients with hemophilia A. Among those unable to work full-time, a substantial 28.1% attributed their inability to the condition. Additionally, a striking 84.0% of patients reported avoiding physical activities, with 12.0% doing so frequently. Furthermore, 73.7% expressed difficulty in participating in sports and hobbies, underscoring the impact of HA on their daily lives and recreational pursuits.
A considerable 55% of individuals with the condition reported experiencing nervousness or anxiety. Furthermore, 80% expressed concerns about breakthrough bleeds, indicating a persistent worry about their health and well-being. Additionally, 40% of patients shared feelings of fear or worry associated with their condition, emphasizing the psychological challenges faced by those living with hemophilia A.
The Spectrum of Unmet Needs in HemophiliaComplementing these findings, the second study evaluated unmet needs among patients with HA and hemophilia B (HB) through real-world data collected from physicians and patients across 8 countries, including the US, UK, and Japan.2
The study found that the majority of patients were treated prophylactically, with SHL factor therapy being the most common for HA and EHL therapy predominating in HB. Despite these therapies, many patients experienced breakthrough bleeding and moderate to severe joint problems. Physicians reported that 25% of patients had joint issues at the initiation of prophylaxis, with 15% continuing to experience these issues after more than a year of treatment. Alarmingly, 32% of adults and 30% of adolescents reported moderate to severe joint pain during consultations in the preceding week.
Patients and physicians both highlighted the emotional toll of hemophilia, with 86% of patients expressing frequent worry about breakthrough bleeds and reporting associated anxiety, lack of energy, and fear. Physical activity avoidance was common, with 43% avoiding it often and 48% sometimes, particularly in countries like France, China, and Germany. In addition to stopping or reducing bleeds, improving QoL emerged as the most prioritized goal for patients, followed by joint protection and increased physical activity.
Patients with hemophilia across the spectrum still face regular challenges like frequent bleeding episodes, joint damage, and chronic pain, which negatively impact their quality of life. These findings show a continued unmet need for more effective therapies that not only focus on preventing bleeding but also improve joint health and address the psychological aspects of living with the disease. The authors emphasized that it is essential for stakeholders to prioritize innovative therapeutic strategies and holistic care models to enhance the overall well-being of individuals with hemophilia.
References
1. Malec L, Matino D, Wynne-Cattanach K, et al. Unmet Needs, Factor Consumption, and Healthcare Resource Use Among People with Hemophilia a: Real-World Analysis of the Adelphi Hemophilia Disease Specific Programme. Blood. 2024;144(Supplement 1):3973.
2. Malec L, Salehi H, Ball N, Lai S, Afonso M. Unmet Needs in People with Hemophilia Receiving Prophylaxis Treatment: A Real-World Survey. Blood. 2024;144(Supplement 1):2314.
Patterns Of Bleeding Events In Women And Girls With Hemophilia
Researchers recently characterized several patterns and outcomes related to bleeding in women and girls with hemophilia in a report published in the journal Haemophilia.
"[Women and girls with hemophilia] present with symptoms related to reproductive health, as well as with bleeding events typically observed in [men] with [hemophilia]," the study investigators stated in their report.
The study was a retrospective, noninterventional review of records regarding women and girls with hemophilia from 3 hemophilia treatment centers in the United States, with data obtained from April 2012 through mid-November 2018. Outcomes were evaluated for patients who had 2 or more hemophilia treatment center visits for management of hemostasis, and who required medical or surgical treatment related to hemostasis.
A total of 47 women and girls with hemophilia were evaluated. Of these patients, 37 had factor VIII deficiency, and 10 had factor IX deficiency. The median age at diagnosis was 22.6 years, and most patients (79%) had a diagnosis of mild hemophilia. Diagnoses were typically confirmed by family history and/or laboratory evidence.
Patients' first-time visits to the hemophilia treatment centers were most commonly related to family history/genetic counseling. The second most common reason for initial hemophilia treatment center visits was to address spontaneous or traumatic bleeds. Of patients with these types of bleeds, easy bruising occurred in 59% of patients, epistaxis in 35% of patients, joint bleeds in 29% of patients, excessive dental bleeding in 24% of patients, and other bleeds in 24% of patients.
Nearly half (49%) of women and girls with hemophilia in this study experienced spontaneous, traumatic, or joint bleeds over the course of the study. These bleeding events were managed using factor concentrates, desmopressin, an antifibrinolytic, or other treatment. Initial treatment typically was successful, with bleeding stopped in 52.2% of cases or reduced in 39.1%.
Heavy menstrual bleeding, however, was not sufficiently controlled in the majority (57.1%) of the 14 patients who reported this complication. Additionally, of 25 patients who experienced pregnancies, excessive bleeding was reported in 44.0% during delivery or postpartum with at least 1 pregnancy.
The study investigators that indicated a lack of specific guidelines in treating women and girls with hemophilia has led to varied approaches to management for this patient population. "Furthering clinical care for [women and girls with hemophilia] is needed to reduce the psychosocial, emotional, and economic impacts of a bleeding disorder diagnosis," the researchers concluded in their report.
Disclosure: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
ReferenceChaudhury A, Sidonio Jr R, Jain N, et al. Women and girls with haemophilia and bleeding tendencies: outcomes related to menstruation, pregnancy, surgery and other bleeding episodes from a retrospective chart review. Haemophilia. Published online December 24, 2020. Doi:10.1111/hae.14232
This article originally appeared on Hematology Advisor
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