Patients With Haemophilia Research Articles

Mental, emotional and social dimensions of quality of life and their relationship with physical and functional status in adults with haemophilia

IntroductionA comprehensive treatment for patients with haemophilia (PwH) should focus on how the disease interferes with their mental, emotional and social environment to analyse if all the therapeutic efforts invested in their physical status have positive impact on a life worth living. AimTo analyse the correlation between the physical status of a cohort of adults with haemophilia and their mental, emotional and social states regarding their treatment modality; Also, to investigate which variables are most related to quality of life (QoL), joint health and emotional, mental and social states. MethodsIn this cross-sectional, 102 adults with haemophilia divided into a prophylactic group (G1, n = 77) and on-demand group (G2, n = 25) were included. Demographic and clinical characteristics, health joint (HJHS), presence of synovitis with ultrasound, self-perceived functionality (HAL) and QoL (A36-HaemoQoL), were analysed. ResultsIn G1 all the variables that defined the physical status correlated (rho: 0.33 to 0.72) to the mental and social spheres. The emotional state correlated with the self-perceived ones. In G2 physical status did not correlate with the three states. According to the regression models, HAL was the variable that most influenced the QoL (together with the bleedings in the last year, R2 = 0.61), emotional (R2 = 0.16), mental (together with HJHS, R2 = 0.41) and social states (R2 = 0.39). In addition, the HJHS was influenced by synovitis, HAL, mental health, age and the bleeding history (R2 = 0.83). ConclusionEmotional, mental and social states of PwH in prophylaxis are correlated to their physical status, being the self-perceived functionality the variable that most influenced in their QoL.

Functional clinical motor performance tests to assess potential fall risks in patients with haemophilia: A case-control study.

Patients with haemophilia (PwH) are at increased risk of falls due to haemophilic arthropathy. Yet, studies on clinical tests associated with the risk of falling are scarce in PwH. (1) To evaluate the feasibility of different clinical motor performance tests associated with the risk of falling in PwH; (2) to evaluate PwH's performance of these tests compared to a control group; (3) to identify possible influencing factors that affect performance. Twenty-nine severe and moderate PwH (57.0 years, IQR: 48.0-61.5) and 29 healthy age- and BMI-matched control participants (CG) performed 13 different clinical tests (SPPB, timed up and go, push and release, functional reach, single-leg stance, knee and grip strength). Haemophilia joint health score (HJHS), kinesiophobia (TSK-11), subjective physical performance (HEP-Test-Q), falls efficiency (FES-I) and falls were assessed. No adverse events occurred. PwH showed impaired performance in all clinical tests, a lower falls efficiency and a higher HJHS than CG. PwH with higher HJHS, lower HEP-Test-Q and higher TSK-11 scores showed higher deficits. Largest discrepancies were observed in the single-leg stance with eyes open and knee extensor strength, where orthopaedically majorly affected PwH showed worse performance compared to minorly affected PwH and the CG, respectively. The prevalence of ≥1 fall in the last year was 27.6% (PwH) and 10.3% (CG). These clinical tests are feasible in PwH. Impaired joint status, a high kinesiophobia and low physical performance impair performance. These tests can be used by clinicians for gaining specific information on functional motor abilities of patients.

Clinical Efficacy of Intra-articular Tranexamic Acid Injection in the Management of Hemophilia with Total Hip Arthroplasty: A 24-month Retrospective Cohort Study.

Total hip arthroplasty (THA) effectively treats end-stage hemophilic hip arthropathy. Given hemophilia's unique characteristics, perioperative bleeding remains a significant risk for patients undergoing THA. Tranexamic acid (TXA), an efficient antifibrinolytic agent, may benefit the outcomes of THA for patients with hemophilia (PWH). This study aims to explore the clinical efficacy of intra-articular injection of TXA in treating perioperative bleeding in PWH and assess its additional clinical benefits. The retrospective study comprised data of PWH who received THA from January 2015 to December 2021 in the research center. A total of 59 individuals were included in the study, divided into a TXA group (n = 31) and a non-TXA group (n = 28). We compared various parameters, including total blood loss (TBL), visible blood loss (VBL), occult blood loss (OBL), intraoperative coagulation factor VIII (FVIII) consumption, perioperative total FVIII consumption, hemoglobin (HB), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), length of hospital stay, hospitalization costs, length of surgery, total protein, activated partial thromboplastin time (APTT), D-dimer, rate of joint swelling, hip joint range of motion (ROM), visual analogue scale (VAS), and Harris hip joint function scale (HHS) between the two groups. Follow-up assessments were conducted for up to 24 months. A Student's t test was utilized for the statistical analysis. This study demonstrated that intra-articular TXA effectively reduced TBL (1248.19 ± 439.88 mL, p < 0.001), VBL (490.32 ± 344.34 mL, p = 0.003), and OBL (757.87 ± 381.48 mL, p = 0.004) in PWH who underwent THA. TXA demonstrated effectiveness in reducing VAS scores on POD1, POD7, and POD14 and joint swelling rates on POD1, POD7, POD14, and at discharge (p < 0.05). Additionally, the TXA group achieved higher HHS ratings at all follow-up time points (p < 0.05), showing superior hip joint mobility, lower postoperative inflammation levels, reduced factor VIII consumption during surgery, and less postoperative nutritional loss. No statistically significant differences were observed between the two groups in terms of hospital stay, hospitalization costs, surgery duration, and coagulation indicators. Intra-articular injection of TXA reduces perioperative bleeding in PWH undergoing THA while also improving joint mobility, post-operative rehabilitation, and quality of life. This may provide value for the future application of TXA in PWH.

Self-conducted sonographic monitoring of the knee in patients with haemophilia-A feasibility study.

To evaluate whether patients with haemophilia (PwH) can be enabled to perform ultrasonography (US) of their knees without supervision according to the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol and whether they would be able to recognize pathologies. Five PwH (mean age 29.6 years, range 20-48 years) were taught the use of a portable US device and the HEAD-US protocol. Subsequently, the patients performed US unsupervised at home three times a week for a total of 6 weeks with a reteaching after 2 weeks. All images were checked for mapping of the landmarks defined in the HEAD-US protocol by a radiologist. In a final test after the completion of the self-sonography period, participants were asked to identify scanning plane and potential pathology from US images of other PwH. On the images of the self-performed scans, 82.7% of the possible anatomic landmarks could be identified and 67.5% of the requested images were unobjectionable, depicting 100% of the required landmarks. There was a highly significant improvement in image quality following reteaching after 2 weeks (74.80±36.88% vs. 88.31±19.87%, p<.001). In the final test, the participants identified the right scanning plane in 85.0% and they correctly identified pathology in 90.0% of images. Appropriately trained PwH can perform the HEAD-US protocol of their knee with high quality and are capable to identify pathologic findings on these standardized images. Asynchronous tele-sonography could enable early therapy adjustment and thereby possibly reduce costs.

Major Orthopaedic Surgery in Persons with Haemophilia A with and without Inhibitors Treated by Emicizumab: A Mid-Term, Large, and Successful Series at a Single Center.

Introduction: Patients with Haemophilia (PWH) need orthopaedic treatments and often they undergo surgery. Classically, PWH with inhibitors have to face such procedures earlier than other patients. Major orthopaedic surgery is not easy and complications are frequent. Emicizumab is the first monoclonal antibody introduced for haematological prophylaxis for PWH with inhibitors, achieving an efficacious haemostasis also in patients with severe haemophilia A with inhibitors, later demonstrated for PWH without inhibitors. A few years ago, emicizumab was also proposed for PWH undergoing surgery, as it supports excellent bleeding control. The literature on orthopaedic surgery using an emicizumab protocol is scarce: only isolated case reports with short-term follow-ups are available. Aim: The purpose of this study is the assessment of the mid-term outcomes of major orthopaedic surgery performed in a population of patients with and without inhibitors and an emicizumab regimen. Methods: We reviewed the records of 13 PWH (eight with high-titre inhibitors, five without) with a mean age of 54.6 years, undergoing 15 orthopaedic surgical procedures between 2017 and 2022: primary knee and hip arthroplasty, revision, pseudotumor excision, or amputation. Their prophylaxis consisted of the combination of emicizumab and boluses of rFVIIa (PWH with inhibitors) or rFVIII (PWH without inhibitors). The clinical parameters of evaluation were: VAS, Haemophilic Joint Health Score (HJHS), and standard radiologic studies. Follow-up was conducted at 1, 3, 6 months, and then yearly. The survival rate of all implants was also assessed. Results: The mean follow-up was 38.8 months (range: 12-65). All patients were successfully treated without complications during surgery. During the postoperative period, a patient affected by a septic complication two months after his pseudotumor excision underwent an above-the-knee amputation. All patients were regularly discharged to the rehabilitative ward, reporting satisfaction for pain reduction and improved joint and global function at the VAS and HJHS scores. No revisions or implant failures were recorded. Conclusions: A prophylaxis regimen with emicizumab and factor replacement in PWH with or without inhibitors undergoing major orthopaedic surgery ensures effective bleeding control and good postoperative clinical outcomes at mid-term follow-up, and may be routinely adopted in dedicated high-volume hospitals. This series is the most consistent to date reported at a single Haemophilia centre.

Structural alterations and pain perception at the ankle joint in patients with haemophilia.

Patients with haemophilia (PwH) suffer from chronic pain due to joint alterations induced by recurring haemorrhage. This study aimed to investigate the relationship between structural alterations and pain perception at the ankle joint in PwH. Ankle joints of 79 PwH and 57 healthy controls (Con) underwent ultrasound examination (US) and assessment of pain sensitivity via pressure pain thresholds (PPT). US discriminated between joint activity (synovitis) and joint damage (cartilage and/or bone degeneration) applying the HEAD-US protocol. Based on US-findings, five subgroups were built: PwH with activity/damage, PwH with activity/no damage, PwH with no activity/no damage, controls with activity/no damage and controls with no activity/no damage. Joint activity and joint damage were significantly increased in ankles of PwH compared to Con (p ≤.001). Subgroup analysis revealed that structural alterations negatively impact pain perception. This is particularly evident when comparing PwH with both activity/damage to PwH with no activity/no damage at the tibiotalar joint (p=.001). At the fibulotalar joint, no significant differences were observed between PwH subgroups. Further analysis showed that both joint activity and joint damage result in an increase in pain sensitivity (p ≤.001). The data suggest a relation between joint activity, joint damage and pain perception in PwH. Even minor changes due to synovitis appear to affect pain perception, with the effect not intensifying at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitised pain state most robustly, whereas initial changes do not seem to significantly affect pain perception.

Paradox pain sensitivity using cuff pressure or algometer testing in patients with hemophilia.

Pain is a common comorbidity in patients with hemophilia (PwH) due to hemophilic arthropathy. This study aims to explore pain sensitivity in PwH methodologically investigating in cuff pressure testing compared to algometer testing. 37 PwH and 35 healthy control subjects (Con) enrolled in this study. Joint health status was assessed. Subjective pain was evaluated using numeric rating scales. Pain sensitivity was measured with pressure algometry and cuff pressure algometry. Pressure pain thresholds of the algometer (PPTa) were measured at knee, ankle joints, and forehead. Subsequently, thresholds of cuff pressure were measured at the left and right lower legs (PPTcuff). In both, lower values represent higher pain sensitivity. PwH exerted a worse joint health status than Con. Pain sensitivity was higher in PwH compared to Con as PPTa of the knee and ankle joints were lower in PwH. No difference was observed in PPTa at the forehead. Contrastingly, lower pain sensitivity was detected in PwH by higher PPTcuff values compared to Con in both legs. While PPTa of the knee and ankle joints are lower in PwH, PPTcuff are higher in PwH compared to Con. This reveals a paradox situation, highlighting that PwH experience local, joint- and hemophilic arthropathy-related pain, whereas pain sensitivity of non-affected soft tissue structures is lower. The reasons explaining the PPTcuff results remain elusive but might be explained by coping strategies counteracting chronic joint pain, resulting in lower sensitivity at non-affected structures.

Force-sensing treadmill gait analysis system can detect gait abnormalities in haemophilia patients without arthropathy.

Joint damage in patients with haemophilia (PwH) is commonly assessed by imaging, but few reports have described how structural changes in joints, for example, haemophilic arthropathy (HA)-affect gait ability. We evaluated gait function among PwH with HA, PwH without HA, and people without haemophilia (non-PwH) using a Zebris FDM-T treadmill (FDM-T), an easy-to-use gait assessment instrument with a force sensor matrix. The following gait parameters were collected: centre of pressure trajectory intersection (COPi) anterior/posterior variability, COPi lateral variability, COPi anterior/posterior symmetry, COPi lateral symmetry, single-limb support line (SLSL) length, and SLSL variability. Participants walked at their typical gait speed. The physical function of the PwH was assessed by the Hemophilia Joint Health Score (HJHS). Parameters were compared among the three groups. Twelve PwH with HA, 28 PwH without HA, and 12 non-PwH were enrolled. Gait speed significantly differed between groups (non-PwH, 3.1±0.7; PwH without HA, 2.0±0.7; PwH with HA; 1.5±0.4). The COPi anterior/posterior variability, COPi lateral variability, SLSL length, and SLSL variability were greater in the PwH groups than in the non-PwH group. The COPi lateral symmetry differed between PwH with HA and the other groups. The HJHS was not correlated with gait parameters among PwH with HA. Gait parameters and speed were abnormal in both PwH with HA and PwH without HA. The FDM-T can be used to identify early stages of physical dysfunction that cannot be detected by conventional functional assessments such as the HJHS.

Haemophilia and Cancer: A Literature Review.

Opinions in the literature on the impact of cancer on patients with haemophilia are contradictory. There is a lack of data on the clinical presentation and management of cancer in patients with haemophilia (PWH). Papers were found following a comprehensive search in PubMed, Google Scholar, and Scopus using the terms "cancer" and "haemophilia" without time limits and using the English language as a filter. The references from all the retrieved original articles and reviews were assessed for additional relevant articles. The emergence of malignancies is one of the important causes of morbidity and mortality in PWH. In the past decade, the literature mainly focused on the epidemiology and outcome of blood-borne cancers in the haemophilia patient group, as the incidence of hepatitis B virus (HBV), hepatitis C (HCV), and HIV infection were high among them. However, with the introduction of recombinant clotting factor concentrates (CFCs), physicians now pay attention to non-virus-related malignancies. Bleeding and thrombotic complications are important causes of morbidity and mortality in critically ill patients with cancer; replacement therapy with factor VIII or IX or others should be maintained during antitumour treatment. Overall, managing cancer in patients with haemophilia requires careful evaluation and individualised planning involving a multidisciplinary team of physicians experienced in haematology, oncology, and surgery.

Bleeder's Femur: The Proximal Femoral Morphology in Hemophilic Patients Who Underwent Total Hip Arthroplasty.

Patients with hemophilia (PWH) constantly suffer hemarthrosis, which leads to deformity of the hip joint. Therefore, PWH who are going to receive total hip arthroplasty (THA) should be exclusively treated before the surgery with careful measurement of their proximal femur. Hence, we conducted a retrospective study to explore the anatomical parameters of and differences in the proximal femur in hemophilic patients who underwent THA. The retrospective study comprised data of adult patients who received total hip arthroplasty from 2020 to 2022 in the research center. Patients having a diagnosis of hemophilic arthritis and received THA were included in experimental group, and patients with hip arthritis or femoral head necrosis were taken as control group. Parameters including femoral offset, neck-shaft angle (NSA), medullary cavity of 20 mm above mid-lesser trochanter level (T+20), mid-lesser trochanter level (T), and 20 mm blow it (T-20), and canal flare index (CFI), femoral cortical index (FCI) were measured on X-ray and CT images with PACS by two independent doctors. Data was analyzed by SPSS 20. Kolmogorov-Smirnov test was used to test data normality. Student's t-test was performed between PWH and control group. p < 0.05 was considered statistically significant. Among the 94 hips, 39 (41.5%) were included in group hemophilia and 55(58.5%) in control group. The mean age of the patients was 49.36 ± 12.92 years. All cases were male patients. Data demonstrated significantly smaller femoral cortical index (FCI), femoral offset, medullary cavity of 20 mm above mid-lesser trochanter level, mid-lesser trochanter level, and 20 mm below it, and neck-shaft angle (NSA) was obviously larger in PWH than control group (p < 0.05). No significant difference was found in canal flare index (CFI). Hemophilic patients undergoing THA were prone to longer and thinner proximal femur. Preoperative morphological analysis of femur is recommended.

Predicting the development of hemophilic arthropathy in patients with hemophilia based on patient age: a retrospective single-center database study

ABSTRACT Background Patients with hemophilia (PWH) develop hemophilic arthropathy of the major joints due to recurrent hemarthrosis. This study retrospectively estimated the age at which PWH may expect to develop hemophilic arthropathy and undergo joint replacement surgery. Research design and methods Using retrospective data from PWH at a Czech orthopedic center, Kaplan Meier analyses were used to estimate the cumulative proportions of patients with hemophilic arthropathy and undergoing joint replacement surgery as a function of age. Results Based on 1028 joint examinations in 167 PWH, hemophilic arthropathy of the knees, elbows, ankles and hips was estimated to develop by a median age of 48, 51, 52 and 61 years, respectively, with ≈80% of patients having such damage by ≈70 years of age. Hemophilic arthropathy of the shoulder occurred much later (median >80 years). In patients undergoing knee or hip replacement surgery, hemophilic arthropathy of the knee and hip occurred at a median age of ≈50 and ≈60 years, respectively, with replacement surgery occurring at a median of ≈70 and >75 years. Conclusions In PWH, the risk of developing hemophilic arthropathy accumulates continuously over the patient’s lifetime, allowing predictions about the ages at which such damage and joint replacement surgery may occur.

“Hermes” - Hemophilia Related Mental Illness: A Cross-Sectional, Multicenter Study in Switzerland

Background: The availability of clotting factor concentrates and prophylactic home treatment for patients with hemophilia (PWH) A and B in developed countries greatly improved clinical outcomes. As the life expectancy of affected patients has increased, the management of comorbidities has become a greater focus within the comprehensive care setting. However, most studies focus on somatic complications. The past two decades revealed a growing body of work reporting increased prevalence of mental health problems in PWH. Given the severity and chronicity of the disease, internalizing disorders (i.e. anxiety, depression) as well as externalizing disorders (i.e. substance dependency, irritability and aggression) seem to go hand in hand with hemophilia. We aimed to assess the prevalence of comorbid mental health problems among PWH in Switzerland. We investigated age effects on this relationship as well as potentially influencing factors (illness factors and environmental factors) that may account for these. We also aimed to assess health-related quality of life (HRQoL) and age dependency in this setting. We are heading to identify targets of prevention/early intervention of mental health problems and foster improvement of evidence-based interdisciplinary treatment in PWH. Methods:This multicenter, cross-sectional study was conducted within six hemophilia treatment centers in Switzerland. Study participants were aged 6-99 years with congenital hemophilia of any severity. All participants or their legal guardians provided written informed consent, and the study was approved by the cantonal medical ethics committee of the responsible states. Participants aged 12 or older underwent a detailed personal psychological assessment followed by completing an online survey utilizing validated psychological measures (HRQoL, psychosocial functioning, somatic comorbidities/parental factors). Participants younger than 12 years underwent a detailed personal psychological assessment with one parent/legal guardian followed by an online survey to be completed by their parent/guardian. In all participants younger than 18 years, we assessed one parent/legal guardian additionally. Results:A total of n=164 PWH participated in the study (133 adult and 31 pediatric participants). Data analyses showed a median age of 39.26 years (SD 20.41). The majority of participants had hemophilia A (n=134, 82%), while hemophilia B was diagnosed in n=30 (18%) of participants. A severe hemophilia was reported in n=85 (52%), a moderate in n=31 (19%) and a mild hemophilia in n=48 (29%). Prophylactic treatment regimen was used in n=97 (59%). Out of n=156 participants with completed neuropsychiatric diagnostic interview, n=38 (24%) participants showed a psychiatric disorder over lifetime. This was significantly associated with disease severity, being more prevalent in moderate and severe hemophilia. We could not detect an association with age, so age does not moderate this association. In n=153 participants with available data on HRQoL, we found a lower HRQoL also to be associated with disease severity (moderate and severe). Moderation analyses could not confirm an association with age. Conclusion:Our data show an association of (lifetime) psychiatric diagnoses and a lower health-related quality of life in hemophilia depending on disease severity. This association is evident in moderate and severe hemophilia and is independent of age despite recent progress in development and use of new therapies going along with suggested lower hemophilia disease burden. Further analyses including somatic and treatment factors as well as parenting are ongoing and will be presented.

The use of infrared thermography for non-invasive detection of bleeding and musculoskeletal abnormalities in patients with hemophilia: an observational study

BackgroundIn patients with hemophilia (PwH), bleeding often occurs in joints and muscles, and early detection of hemorrhage is important to prevent the onset and progression of mobility impairment. Complex-Image analysis such as ultrasonography, computed tomography, and magnetic resonance imaging are used to detect bleeding. On the other hand, no simple and rapid method to detect the active bleeding has been reported. Local inflammatory responses occur when blood leaks from damaged vessels, and the temperature at the site of active bleeding could be expected to increase in these circumstances, leading to an increase in surrounding skin temperature. Therefore, the purpose of this study was to investigate whether the measurement of skin temperature using infrared thermography (IRT) can be used as a diagnostic aid to detect active bleeding.MethodsFifteen PwH (from 6 to 82 years old) complaining of discomfort such as pain were examined. Thermal images were obtained simultaneously at the affected sides and comparable unaffected sides. The average skin temperature of the affected side and of the unaffected side were measured. The temperature differences were calculated by subtracting the average skin temperature at the unaffected side from the affected side.ResultsIn eleven cases with active bleeding, the skin temperature at the affected side was more than 0.3 °C higher (0.3 °C to 1.4 °C) compared to the unaffected side. In two cases without active bleeding, there were no significant differences in skin temperature between the affected and unaffected sides. In two cases with previous rib or thumb bone fracture, the skin temperature at the affected side was 0.3 °C or 0.4 °C lower than that of the unaffected side, respectively. In two cases with active bleeding in which longitudinal evaluation was conducted, the difference in skin temperature decreased after hemostatic treatment.ConclusionThe analysis of skin temperature deference using IRT was a useful supportive tool to readily assess musculoskeletal abnormalities and bleeding in PwH as well as to determine the success of the hemostatic treatment.

Antithrombotic Treatment in Patients With Hemophilia: an EHA-ISTH-EAHAD-ESO Clinical Practice Guidance.

Cardiovascular disease is an emerging medical issue in patients with hemophilia (PWH) and its prevalence is increasing up to 15% in PWH in the United States. Atrial fibrillation, acute and chronic coronary syndromes, venous thromboembolism, and cerebral thrombosis are frequent thrombotic or prothrombotic situations, which require a careful approach to fine-tune the delicate balance between thrombosis and hemostasis in PWH when using both procoagulant and anticoagulant treatments. Generally, PWH could be considered as being naturally anticoagulated when clotting factors are <20 IU/dL, but specific recommendations in patients with very low levels according to the different clinical situations are lacking and mainly based on the anecdotal series. For PWH with baseline clotting factor levels >20 IU/dL in need for any form of antithrombotic therapy, usually treatment without additional clotting factor prophylaxis could be used, but careful monitoring for bleeding is recommended. For antiplatelet treatment, this threshold could be lower with single-antiplatelet agent, but again factor level should be at least 20 IU/dL for dual antiplatelet treatment. In this complex growing scenario, the European Hematology Association in collaboration with the International Society on Thrombosis and Haemostasis, the European Association for Hemophilia and Allied Disorders, the European Stroke Organization, and a representative of the European Society of Cardiology Working Group on Thrombosis has produced this current guidance document to provide clinical practice recommendations for health care providers who care for PWH.

A first Tunisian pilot study investigating sexual dysfunctions in patients with hemophilia.

Background: Little data is actually available on sexual health problems with sexual activity, and intimacy (sexual difficulty) in patients with hemophilia (PWH). We conducted this study to determine the prevalence of sexual difficulty in PWH and to determine factors associated with erectile dysfunction (ED). Methods: Based on The International Index of Erectile Function 15 (IIEF-15) questionnaire, we evaluated ED and other sexual problems in PWH. Results: Forty-Three (43) PWH were included in our study. The mean age was 33 years. Fourteen (32.6%) respondents were identified as having severe disease. The majority (93%) suffered from erectile dysfunction. Lack of desire and orgasm was observed in 76.7% of cases each. Lack of sexual satisfaction and global satisfaction were noted in 83.7% of cases and 88.4% of cases, respectively. Among PWH, older age was associated with ED. Conclusion: Our study illustrates the need for programs to assess and improve the sexual health of PWH in comprehensive hemophilia care.

Osteoporosis Remains Constant in Patients with Hemophilia-Long-Term Course in Consideration of Comorbidities.

Patients with hemophilia (PWHs) suffer from an increased risk of osteoporosis. Multiple hemophilia and hemophilic arthropathy associated factors correlate with a low bone mineral density (BMD) in PWHs. The aim of this study was to assess the long-term development of BMD in PWH as well as to analyze potentially influencing factors. A total of 33 adult PWHs were evaluated in a retrospective study. General medical history, specific-hemophilia-associated comorbidities, joint status using the Gilbert score, calcium level, and vitamin D level as well as at least two results of bone density measurements with a minimum range of 10 years per patient were taken into account. The BMD did not change significantly from one point of measurement to the other. A total of 7 (21.2%) cases of osteoporosis and 16 (48.5%) cases of osteopenia were identified. The two following significant correlations could be revealed: the higher the patients' body mass index, the higher their BMD (r = 0.41; p = 0.022). Moreover, a high Gilbert score came along with a low BMD (r = -0.546; p = 0.003). Even if PWHs frequently suffer from a reduced BMD, our data suggest that their BMD remains constant on a low level in the course of time. A risk factor of osteoporosis often found in PWHs is a vitamin D deficiency and joint destruction. Therefore, a standardized screening of PWHs on BMD reduction by collecting vitamin D blood level and assessing joint status seems appropriate.

Pain: a neglected symptom in hemophilia.

Repetitive bleeding attacks may cause joint pain and arthropathy in patients with hemophilia (PWH). Despite being a common symptom, pain is not a well-studied topic in this disease. The aim of this cross-sectional, observational study was to assess the frequency and intensity of pain and analyze the success rates ofpain treatment methods. Adult hemophilia patients were included in the study. The Multidimensional Hemophilia Pain Questionnaire (MHPQ) was used to assess pain. In addition to the MHPQ, demographic data were collected. Fifty adult hemophilia patients were included in the study. Thirty-one (62%) of the patients reported pain due to hemophilia in the last year. Twenty-six of them (81.2%) reported pain during bleeding attacks. The most successful pain coping strategy was clotting factor replacement. None of the participants used opioids or adjuvant analgesics. None of them used a physical therapy modality or interventional pain therapy method. While 67.6% of the patients were very dissatisfied or dissatisfied with their global pain treatment, only 16.1% of the patients were satisfied or very satisfied. Patients with higher pain during bleeding episodes were more likely to continue their prophylaxis. There was no significant difference between plasma-derived or recombinant-derived factor prophylaxis in terms of pain complaints. Pain is a frequent and important symptom of hemophilia, but most of the patients are not treated sufficiently. A multidisciplinary approach is needed to improve the life quality of the patients. In addition to successful bleeding prophylaxis, administration of a proper and adequate analgesic regimen and combined physical therapy modalities may decrease pain intensity and prevent the development of arthropathy.

Heterogeneity in the half-life of factor VIII concentrate in patients with hemophilia A is due to variability in the clearance of endogenous von Willebrand factor

BackgroundPrevious studies have reported marked interindividual variation in factor VIII (FVIII) clearance in patients with hemophilia (PWH) and proposed a number of factors that influence this heterogeneity. ObjectivesTo investigate the importance of the clearance rates of endogenous von Willebrand factor (VWF) compared with those of other FVIII half-life modifiers in adult PWH. MethodsThe half-life of recombinant FVIII was determined in a cohort of 61 adult PWH. A range of reported modifiers of FVIII clearance was assessed (including plasma VWF:antigen and VWF propeptide levels; VWF-FVIII binding capacity; ABO blood group; and nonneutralizing anti-FVIII antibodies). The FVIII-binding region of the VWF gene was sequenced. Finally, the effects of variation in FVIII half-life on clinical phenotype were investigated. ResultsWe demonstrated that heterogeneity in the clearance of endogenous plasma VWF is a key determinant of variable FVIII half-life in PWH. Both ABO blood group and age significantly impact FVIII clearance. The effect of ABO blood group on FVIII half-life in PWH is modulated entirely through its effect on the clearance rates of endogenous VWF. In contrast, the age-related effect on FVIII clearance is, at least in part, VWF independent. In contrast to previous studies, no major effects of variation in VWF-FVIII binding affinity on FVIII clearance were observed. Although high-titer immunoglobulin G antibodies (≥1:80) were observed in 26% of PWH, these did not impact FVIII half-life. Importantly, the annual FVIII usage (IU/kg/y) was significantly (p = .0035) increased in patients with an FVIII half-life of <12 hours. ConclusionOur data demonstrate that heterogeneity in the half-life of FVIII concentrates in patients with hemophilia A is primarily attributable to variability in the clearance of endogenous VWF.

Adherence and Cost Effectivity of Home-Based Prophylaxis Over Institutionalized Prophylaxis in Patients with Hemophilia

Purpose: Home-based prophylaxis in hemophilia facilitates the treatment of patients with hemophilia (PwH) at home resulting in an improved quality of life, experiencing less pain and greater flexibility in daily activities. This literature studies the cost effectivity and adherence to prophylaxis treatment after the implementation of home-based prophylaxis therapy in PwH registered under the Hemophilia Treatment Centre (HTC) of Assam Medical College and Hospital. Materials and Methods: PwH and their parents were advised for self/home infusion after being trained by a medical professional for 6 months. Data were collected on the skip in prophylaxis treatment by PwH and their traveling cost to access the prophylaxis treatment before and after the implementation of home infusion, through questionnaire and telephonic interview. Results: The mean number of days of skip in prophylaxis was significantly reduced from 25 (±11) to 4 (±2) days after implementation of home infusion. The mean transportation cost was also found to be significantly decreased from Rs. 3297 (±2251) to 440 (±279). Before home/self-infusion, 77% of the registered PwH were found to skip prophylaxis doses more than 12 times a year but after home infusion, no PwH were found to skip more than 12 doses a year. Conclusion: Home therapy facilitates the PwH to strictly adhere to the prophylaxis regime significantly reducing the skipping of doses to be administered to the PwH. The risks of regular traveling and the burden of transportation expenditure to avail the prophylaxis treatment was also found to be reduced significantly.

Risk of Fractures, Repeated Fractures and Osteoporotic Fractures among Patients with Hemophilia in Taiwan: A 14-Year Population-Based Cohort Study

The world is aging, and hemophilia patients are as well. The association between patients with hemophilia (PWH) and low bone mineral density is clear. However, the incidence of fractures in patients with hemophilia is inconclusive, and no research has yet explored repeated fractures among PWH. In this study, we investigated the incidence of all-site fractures, repeated fractures and osteoporotic fractures amongst PWH. The study compared the incidence of all-site fractures, repeated fractures and osteoporotic fractures occurring in all PWH who were enrolled in Taiwan's National Health Insurance Research Database between 1997 and 2013 with an age- and gender-matched group from the general population. Eight-hundred thirty-two PWH, along with 8320 members of the general population, were included in the final analysis. After multivariate COX regression analysis with an adjustment for confounding factors, it was found that PWH experienced a higher risk of osteoporotic fracture (HR: 1.25 with 95% CI of 1.03-2.52) but only saw a neutral effect with regards to both all-sites of fracture (HR: 1.00 with 95% CI of 0.92-1.09) and repeated fractures (HR: 1.01 with 95% CI of 0.92-1.10), when compared with the general population. This 14-year population-based cohort study showed that PWH had a higher risk of osteoporotic fracture, but that hemophilia only had a neutral effect in all-sites of fracture and repeated fractures. Screening, prevention and treatment for osteoporosis and further osteoporotic fractures among PWH, in order to improve quality of life and achieve healthy aging in this particular population, remain essential.