Für Sie Recherchiert 2/2023
Zanon E.
Value Health 2022 25:12 (S29)
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Abstract
Objectives: Damoctocog alfa pegol (Jivi® Bayer) is an extended half-life recombinant factor VIII (rFVIII) approved for the treatment and prophylaxis of bleeding in previously treated hemophilia A patients aged ≥12 years. The clinical efficacy and safety of damoctocog alfa pegol were demonstrated in the PROTECT VIII Phase II/III international multicenter trial. An experience monitoring survey was performed to evaluate physicians’ experience with damoctocog alfa pegol. Methods: A CAWI (Computer Assisted Web Interviewing) survey was performed to assess Italian hematologists’ satisfaction and concern about the drug in clinical practice. It involved 15 centers with patients on prophylaxis with damoctocog alfa pegol for at least 3 months. Results: Ninety-one of 1947 patients with hemophilia A without reported inhibitors were treated with damoctocog alfa pegol. The main reasons for switching were reduced injections and the perception of better bleeding control. Reduced weekly infusions were reported in 89% of patients. Respectively, 80% and 86% of patients reported zero total bleeds and zero joint bleeds, a significant increase compared to previous treatment, where patients with zero total bleeds and joints bleeds were respectively 46% and 55% (p=0.05). According to 71% of respondents, joint function of patients who switched to damoctocog alfa pegol improved. All the clinicians were satisfied with the drug. The reported perception of patient satisfaction was good. Conclusions: This experience monitoring survey confirms the clinical study outcomes: prophylactic use of damoctocog alfa pegol was able to reduce bleeding rate and joint bleeding rate in most patients, improving joint health and patients’ quality of life, and reducing the number of weekly infusions. As a result, the annual drug consumption and overall prophylaxis costs for damoctocog alfa pegol could be reduced in compliance with the dosages indicated in the product characteristics summary.
Zhang W., Ferri Grazzi E., O'Hara J., Burke T.
Value Health 2022 25:12 (S125)
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Abstract
Objectives: The rare bleeding disorder haemophilia A (HA) has substantial treatment burden. Recombinant FVIII (rFVII) therapies with extended half-lives (EHL) are available, offering reduced infusion frequency and resultant treatment burden versus standard half-life (SHL) products. While the EHL, damoctocog alfa pegol, has flexible dosing options, real-world data on utilization is scarce. This analysis examines treatment and utilization patterns of damoctocog alfa pegol in the real-world setting. Methods: Data were collected from patients who switched to damoctocog alfa pegol in Germany in 2020, following the CHESS II (Cost of Haemophilia in Europe: a Socioeconomic Survey II) methodology, a European, retrospective, burden-of-illness study. Patients comprised of male non-inhibitor HA adults, treated prophylactically with damoctocog alfa pegol for at least 3 months in the real-world setting. Results: Thirty-three HA patients met the inclusion criteria (3 [9%] moderate and 30 [91%] severe]. Thirty patients had consumption data available. Mean (SD) time since damoctocog alfa pegol switch was 32.1 (18.6) weeks and 24 (80%) patients were treated with SHL prior to switching. Post switch, weekly infusion frequency and IU consumption reduced in 93% and 83% of the sample, respectively. Mean (SD) utilization observed with damoctocog alfa pegol was 3,485 (684.2) IU/kg/year vs 5,040 (1,890.8) on previous treatment. Supplemental bleeding data were available in 22 patients; lower IU consumption and infusion frequency were reported in 91% and 100% of patients, respectively. Mean (SD) utilization in this sub-cohort was 3,530 (774.9) versus 5,591 (1,920.9) on previous treatment; 82% experienced lower annualised bleeding rate (ABR), 9% reported an increase, and 9% no change. Mean (SD; median) ABR reduced from 4.6 (4.4; 2.2) to 2.1 (1.8; 1.5). Conclusions: While limited in sample size, the results suggests damoctocog alfa pegol may reduce patient treatment burden and overall annual treatment utilization in the German real-world setting, while providing improved or equivalent bleeding outcomes.
Chandler M., Charafi L., Moulton T., Recht M.
Am. J. Hematol. 2023 98: (E18-E19)
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Abstract
Background: The ATHNdataset is a Health Insurance Portability and Accountability Act (HIPAA)-compliant, de-identified database, sponsored by the American Thrombosis and Hemostasis Network. Over 40,000 people with a bleeding or clotting disorder followed at United States hemophilia treatment centers have submitted health information, including 15,747 hemophilia A patients. Objective: To evaluate the effectiveness of damoctocog alfa pegol (BAY 94- 9027/Jivi®) to treat mild and moderate hemophilia A patients aged 12 years and older in a real-world setting. Methods: The ATHNdataset was queried for people with hemophilia A aged ≥12 years of age treated with damoctocog alfa pegol, and patients with mild and moderate disease severity, treated either prophylactically or episodically, were identified. Collected data included baseline demographic data, treatment history, comorbidities, inhibitor history and bleeding rates. The data were captured via patient chart review between January 1, 2010 and October 31, 2020. Results: At the data cutoff, 35 patients with mild and moderate hemophilia A were being treated with damoctocog alfa pegol and thus included in this analysis. Of these, 12 patients (34.3%) had mild hemophilia A and 23 patients (65.7%) had moderate disease. The majority of patients were male (33/35 [94.2%]) and mean age was 34.9 years (median = 31.5). Of the total, 1 patient (2.9%) had a history of inhibitors. Patients had an average of 1.3 years of therapy with damoctocog alfa pegol and 48.6% of patients had over 12 months of treatment. The vast majority of patients (31/35, 88.6%) included in this analysis had documented bleeding rates in the ATHN system (Table 1). Of the 31 patients with a recorded annualized bleed rate (ABR), 19 (61.3%) were on prophylaxis. For the entire group, the mean total ABR was 0.07. Mean joint ABRs and spontaneous ABRs were zero. In the subgroup of patients who were on prophylaxis with damoctocog alfa pegol (n = 19), the mean total ABRs, joint ABRs and spontaneous ABRs were zero (Table 1). The majority of prophylaxis patients 14/19 (73.7%) had moderate hemophilia. However, 5/12 (41.7%) of the mild patients were also on prophylaxis. All patients on prophylaxis (19/19, 100.0%) had zero total bleeds during the entire observational period. The majority of patients who were on prophylaxis 13/19 (68.4%) were treated twice-weekly with a mean weekly dose of 83.5 IU/kg/wk. Thirty-seven percent of patients (n = 13) included in this analysis were treated on-demand with a mean dose of 39.9 IU/kg/dose. Conclusions: These data show that damoctocog alfa pegol provides protection from bleeding events in mild and moderate hemophilia A patients 12 years and older in the real-world setting. Mean ABR was low in this patient population with 100% of patients on prophylaxis who had ABR data experiencing zero bleeds. These data should be interpreted with caution owing to limitations of realworld studies. (Table Presented).
Marquardt N., Goldmann G., Herbst K., Nadal J., Oldenburg J.
Haemophilia 2023 29: (97)
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Abstract
Introduction: Damoctocog alfa pegol (BAY 94-9027, Jivi®) is an extended half-life factor (F) VIII treatment indicated for use in previously treated patients aged ≥12 years with haemophilia A. We report an intra-patient comparison of the effectiveness and utilisation of damoctocog alfa pegol vs the recombinant FVIII, octocog alfa (BAY 81-8973, Kovaltry®), in a real-world setting. Methods: This single-centre, observational, intra-patient, comparison study was performed using data from the Haemophilia Treatment Centre Bonn, Germany. Patients with haemophilia A aged ≥12 years were included. Baseline demographics and clinical characteristics at the time of switch were obtained. Pre-and post-switch data on annualised bleeding rates (ABRs), infusion frequency and utilisation were collected. Results: Overall, 46 patients switched to damoctocog alfa pegol, of whom 40 (87%) had severe disease and 6 (13%) had moderate disease. Median (Q1;Q3) age at the time of switch was 37.0 (29.0;54.0) years. Individuals received damoctocog alfa pegol for 12 months. Median (Q1;Q3) total and traumatic ABRs decreased from 0.33 (0;1) and 0.28 (0;0.66), respectively, with octocog alfa, to 0 (0;1) and 0 (0;1), respectively, with damoctocog alfa pegol. Median (Q1;Q3) spontaneous and joint ABRs both remained at 0 (0;0). Pre-switch, treatment with octocog alfa was received twice weekly (2×W; n=6), three times weekly (3×W; n=10), four times weekly (n=3), every 2 days (E2D; n=14) and on demand (n=5). Post-switch, treatment with damoctocog alfa pegol was received 2×W (n=12), 3×W (n=7), E2D (n=16), every 3 days (n=1), every 4 days (n=1) and on demand (n=4). For octocog alfa vs damoctocog alfa pegol, mean (SD) annualised consumption was 4605 (±2206) IU/kg/year vs 3831 (±2003) IU/kg/year, and the mean (SD) number of infusions per year was 177 (±70) vs 139 (±73). No safety signals were reported. One individual experienced prolonged bleeding from puncture sites post-switch and was excluded from analysis. Discussion/Conclusion: Treatment with damoctocog alfa pegol resulted in numerical decreases in median total ABRs and reduced utilisation compared with prior octocog alfa treatment. This singlecentre experience provides real-world evidence supporting the use of damoctocog alfa pegol as an effective alternative therapy for individuals currently receiving octocog alfa.
Oldenburg J., Wenning S., Holstein K., Von Depka Prondzinski M., Filip J., Miesbach W., Severin K., Eichler H., Halimeh S.
Hamostaseologie 2023 43: (S38-S39)
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Abstract
Introduction Damoctocog alfa pegol (BAY 94-9027) is an extended half-life recombinant factor VIII product approved for treatment of previously treated patients (PTPs) aged ≥ 12 years with haemophilia A [1, 2]. Previous analyses of the ongoing, real-world HEM-POWR study reported data from several clinical sites [3], with most patients recruited from Germany. Here we present effectiveness and safety data from the updated interim analysis of the HEM-POWR study for a subgroup of PTPs from German study sites. Method HEM-POWR is a prospective, open-label, Phase IV cohort study (NCT03932201), and includes PTPs with mild, moderate or severe haemophilia A receiving damoctocog alfa pegol prophylactically or on demand. Primary and secondary outcomes included annualised bleeding rate (ABR) and safety. The safety analysis set (SAF) comprised PTPs with informed consent and ≥ 1 study dose in the observation period; inclusion in the full analysis set (FAS) required patients to fulfil all inclusion criteria, have a first documented dose of damoctocog alfa pegol in the study and ≥ 1 documented infusion during the observation period. Data were collected in patient diaries and physician records. Ethical approval was obtained for all sites (Tab. 1). Results At data cut-off (17 August 2022), 61 PTPs were included in the SAF of this sub-population. Most patients presented with severe disease (50/61, 82.0 %; moderate 10/61, 16.4 %; mild 1/61, 1.6 %) and were aged ≥ 18 to < 65 years (50/61, 82.0 %; aged ≥ 12 to < 18 years, 6/61, 9.8 %, Table 1). The median (Q1, Q3) observation period in the SAF was 262.0 (6.0, 406.0) days. Most patients were pretreated with damoctocog alfa pegol (58/61, 95.1 %), with 52/57 (91.2 %; 1 patient missing) having received prophylactic treatment. The median (Q1, Q3) prescribed dose per infusion per kg of damoctocog alfa pegol at baseline during the observation period was 34.9 (26.3, 44.0) IU/kg. A total of 14/61 patients (23.0 %) reported treatment-emergent adverse events, none of which were study drug-related. No inhibitor development or deaths were reported. A total of 30 patients were included in the FAS and 27/30 (90.0 %) had severe haemophilia A. Total median (Q1, Q3), mean (SD) ABR during the observation period was 0.0 (0.0, 1.1), 1.2 (2.8). Total ABR decreased by 0.0 (-2.0, 0.0), 1.3 (3.0) compared with prior to damoctocog alfa pegol initiation. Data for bleed subtypes are summarised in Table 2. Overall, 22/30 patients (73.3 %) had no bleeds during the observation period, 26/30 (86.7 %) had no spontaneous bleeds and 24/30 (80.0 %) had no joint bleeds. PTPs had a mean (SD) 1.9 (0.9) infusions to control for a bleed, with 48.4 % of bleeds controlled with a single infusion (Fig. 1). Conclusion These results from the updated interim analysis of the HEM-POWR study provide valuable insights into real-world clinical practice in Germany, inform German stakeholders, and further reinforce the favourable real-world effectiveness and safety of damoctocog alfa pegol in PTPs with mild, moderate or severe haemophilia A. (Table Presented).
Herbst K., Oldenburg J., Alvarez Román M.T., Sanabria M., Castaman G., Janbain M., Matsushita T., Meijer K., Schmidt K., Reding M.
Hamostaseologie 2023 43: (S39-S40)
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Abstract
Introduction Damoctocog alfa pegol (BAY 94-9027) is a PEGylated, extended half-life recombinant factor VIII product, approved for treatment of previously treated patients (PTPs) aged ≥ 12 years with haemophilia A [1, 2]. Real-world effectiveness and safety of damoctocog alfa pegol has been previously reported in earlier analyses of the HEM-POWR study [3]. Here we present the first safety results from the updated interim analysis. Method HEM-POWR is a prospective, open-label, Phase IV cohort study (NCT03932201) in PTPs with mild, moderate or severe haemophilia A. Eligible patients included PTPs receiving damoctocog alfa pegol as prophylaxis or on-demand. The primary outcome was annualised bleeding rate (ABR) and secondary outcomes included safety. Data were collected in patient e-diaries and physician records. The safety analysis set (SAF) comprised PTPs with informed consent and ≥ 1 study dose in the observation period. Ethical approval was obtained for all sites (Tab. 1). Results At data cut-off (17 August 2022), 270 PTPs were enrolled, of which 268 (99.3 %) were included in the SAF. Two enrolled patients (0.7 %) were subsequently excluded from SAF analysis as they did not receive ≥ 1 dose of damoctocog alfa pegol during the observation period (mean [SD] 264.7 [237.9] days). Almost half of patients were from Germany (61/268, 22.8 %) and Japan (52/268, 19.4 %). Most patients presented with severe disease (221/268, 82.5 %) (Table 1). While most patients were aged ≥ 18 to < 65 years (224, 83.6 %), 28 (10.5 %) adolescent ( < 18 years) and 15 (5.6 %) older ( ≥ 65 years) patients were included. Most patients (225/268, 84.0 %) were pretreated with damoctocog alfa pegol within 12 months of enrolment. The most common prophylaxis dosing regimen was every 3-4 days, both prior to enrolment (115/210, 54.8 %) and during the observation period (130/268, 50.4 %). A total of 110/268 patients (41.0 %) had a comorbidity, most commonly hypertension (41/268, 15.3 %), chronic pain (41/268, 15.3 %) and chronic arthropathy (35/268, 13.1 %) (Tab. 2). Overall, 59/268 patients (22.0 %) reported any treatment-emergent adverse event (TEAEs), with 19/268 (7.1 %) reporting serious TEAEs (Table 2). Four adverse events of special interest (AESI) were reported in 2/268 patients (0.8 %); all were hypersensitivity reactions. No drug-related TEAEs, inhibitor development or deaths were reported. The most common TEAEs included various injuries or procedural complications (19/268, 7.1 %), infections or infestations (12/268, 4.5 %) and musculoskeletal or connective tissue disorders (10/268, 3.7 %). Conclusion These updated interim data continue to support the favourable safety and tolerability profile of damoctocog alfa pegol in PTPs with mild, moderate or severe haemophilia A in a real-world setting. (Figure Presented).
Pathogenesis and treatment of osteoporosis in patients with hemophilia
Lin X., Gao P., Zhang Q., Jiang Y., Wang O., Xia W., Li M.
Arch. Osteoporosis 2023 18:1
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Abstract
Introduction: Hemophilia is a rare X-linked recessive inherited bleeding disorder caused by mutations of the genes encoding coagulation factor VIII (FVIII) or IX (FIX). Patients with hemophilia (PWH) often have a high risk of osteoporosis and fractures that is usually ignored. Herein, we review the underlying mechanisms of osteoporosis and the increased risk of fractures and their treatment in patients with FVIII or FIX deficiency. Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to identify original research articles, meta-analyses, and scientific reviews on the mechanisms or treatment of osteoporosis in PWH. Results: The pathogenic mechanisms of osteoporosis in PWH are multifactorial and remain unclear. The available evidence shows that FVIII and FIX deficiency may directly affect bone metabolism by interfering with the RANK/RANKL/OPG pathway. Other potential mechanisms of osteoporosis in PWH include thrombin deficiency and the unloading and immobilization of bone, which will affect osteoblast and osteoclast activity by changing the cytokine profiles. The treatment of osteoporosis in PWH includes antiresorptive, anabolic, and dual-action drugs; weight-bearing exercise; fall prevention; and prophylactic coagulation factor replacement therapy. However, clinical studies of the efficacy of anti-osteoporotic agents in osteoporosis of PWH are urgently needed. Conclusion: This review summarizes recent progress in research on the pathogenesis of osteoporosis in PWH and provides insights into potential treatment for osteoporosis in PWH.
Chantrain V.-A., Lambert C., De Smet P., Lobet S., Foubert A., Meeus M., Hermans C., Roussel N.A.
[Article in Press] Haemophilia 2023 :
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Abstract
INTRODUCTION: Pain is a major issue in people with haemophilia (PwH). Few studies comprehensively assessed pain in PwH using a biopsychosocial framework and studies in mild PwH are lacking. AIM: To assess pain prevalence, pain interference and their relationship with health-related quality of life (HR-QoL) in male adults with haemophilia. METHODS: A survey was initiated by the Belgian national member organisation. Pain in the last 24 h, pain severity (BPI-PS) and pain interference (BPI-PI) scores were obtained with the Brief Pain Inventory short-form (BPI). HR-QoL was evaluated with the EQ-5D-3L, giving the health utility index (EQ-HUI). Associations between EQ-HUI, BPI-PS and BPI-PI were analysed using Pearson's correlation test. A multiple regression analysed the relationship between HR-QoL and BPI-PS, with age and haemophilia severity as confounding factors. RESULTS: Within 185 respondents (97, 31 and 57 respectively severe, moderate and mild PwH), 67% (118/177) reported pain. In severe, moderate and mild PwH, respectively 86% (79/92), 71% (22/31) and 32% (17/54) reported pain. Median [IQR] BPI-PS, BPI-PI and EQ-HUI scores were respectively 1.5 [.0; 4.0], 1.6 [.0; 3.6] and .81 [.69; 1.00]. PwH reported pain interference with general activity (56% (99/176)), psychosocial factors such as mood (53% (93/175)), and sleep (51% (90/177)). Moderate correlations were found between EQ-HUI, BPI-PS and BPI-PI. After adjusting for age and haemophilia severity, BPI-PS explained 14% of HR-QoL variance. CONCLUSIONS: Pain is a major issue amongst PwH, including people with mild haemophilia. Pain interferes with activities, emotions, sleep and HR-QoL, arguing for a comprehensive biopsychosocial approach of pain.
Oleshko O., Werwitzke S., Klingberg A., Witte T., Eichler H., Klamroth R., Holstein K., Hart C., Pfrepper C., Knöbl P., Greil R., Neumeister P., Reipert B.M., Tiede A.
Blood Adv. 2023 7:1 (122-130)
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Abstract
The root cause of autoantibody formation against factor VIII (FVIII) in acquired hemophilia A (AHA) remains unclear. We aimed to assess whether AHA is exclusively associated with autoantibodies toward FVIII or whether patients also produce increased levels of autoantibodies against other targets. A case-control study was performed enrolling patients with AHA and age-matched controls. Human epithelial cell (HEp-2) immunofluorescence was applied to screen for antinuclear (ANA) and anticytoplasmic autoantibodies. Screening for autoantibodies against extractable nuclear antigens was performed by enzyme immunoassay detecting SS-A/Ro, SS-B/La, U1RNP, Scl-70, Jo-1, centromere B, Sm, double-stranded DNA, and α-fodrin (AF). Patients with AHA were more often positive for ANA than control patients (64% vs 30%; odds ratio [OR] 4.02, 1.98-8.18) and had higher ANA titers detected than controls. Cytoplasmic autoantibodies and anti-AF immunoglobulin A autoantibodies were also more frequent in patients with AHA compared with controls. Autoantibodies against any target other than FVIII were found in 78% of patients with AHA compared with 46% of controls (OR 4.16, 1.98-8.39). Results were similar preforming sensitivity analyses (excluding either subjects with autoimmune disorders, cancer, pregnancy, or immunosuppressive medication at baseline) and in multivariable binary logistic regression. To exclude that autoantibody staining was merely a result of crossreactivity of anti-FVIII autoantibodies, we tested a mix of 7 well-characterized monoclonal anti-FVIII antibodies. These antibodies did not stain HEp-2 cells used for ANA detection. In conclusion, a diverse pattern of autoantibodies is associated with AHA, suggesting that a more general breakdown of immune tolerance might be involved in its pathology.
Al Aseri Z.A., Alkhamis W.S., Alshanqiti W.A.
Signa Vitae 2023 19:1 (1-8)
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Abstract
Patients with hemophilia or von Willebrand disease may present to the emergency department (ED) with life-threatening bleeding, as severe hemorrhage can lead to hemodynamic instability and bleeding in the central nervous system, throat, and neck. Thus, inappropriate, or delayed management could lead to serious treatment-related complications or even death, and therefore, emergency medical staffs should be well-equipped with the latest knowledge to properly and timely treat these patients. The goal of treatment in emergency settings is to achieve hemostasis by replacing clotting factor levels, prevent hemodynamic instability, and prompt initiation of further specialized treatments. In this study, we searched Medline, PubMed, Embase and Google Scholar for papers addressing hemophilia-and Von Willebrand disease (VWD)-related bleeding and factors in emergency settings to determine evidence-based approaches for managing severe hemorrhage in these patients in the ED.
van Leeuwen F.H.P., Timmer M.A., de Jong P.A., Fischer K., Foppen W.
[Article in Press] [In Process] Haemophilia 2023 :
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Abstract
Introduction: Ultrasound is increasingly used as addition to physical examination for detection of subclinical joint changes in haemophilia. However, the added value of ultrasound to physical examination for detecting synovial proliferation is not fully established. Aim: To determine the diagnostic accuracy of swelling at physical examination for ultrasound-detected synovial proliferation in haemophilia. Methods: PubMed and EMBASE were searched up to 2 August 2022. Studies reporting original data on occurrence of swelling at physical examination and synovial proliferation on ultrasound of index joints in persons with haemophilia were included. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Diagnostic accuracy parameters of swelling at physical examination for ultrasound-detected synovial proliferation were determined. Summary sensitivity and specificity were calculated using a bivariate random-effects model. Results: Fifteen studies reporting on swelling at physical examination and synovial proliferation on ultrasound in 2890 joints of 627 patients were included. Prevalence of subclinical synovial proliferation ranged between 0% and 55%. Sensitivity of swelling was low [summary estimate.34; 95% confidence interval (CI).24-.46], while specificity was high (summary estimate.97; CI.92-.99). Predictive values varied widely due to inter-study differences in prevalence of synovial proliferation. Conclusion: Joint swelling has low sensitivity for presence of ultrasound-detected synovial proliferation in haemophilia, suggesting underestimation of synovial proliferation by physical examination alone. Consequently, ultrasound screening may generate important information on synovial changes which would otherwise remain undetected.
Badulescu O.V., Bararu Bojan I., Badescu M.C., Filip N., Chelsău A., Ciocoiu M., Vladeanu M., Filip A., Forna N., Sirbu M.T., Ungureanu C., Sîrbu P.-D.
[In Process] Diagn. 2023 13:1
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Abstract
Haemophilia is a rare genetic disorder, that results from various degrees of deficiency of coagulation factor VIII (haemophilia A), or factor IX (haemophilia B), with an X-linked transmission. The patients affected are in the majority of cases males (who inherit the affected X-chromosome from the maternal side), with rare cases of females with haemophilia (FVIII or FIX < 40 IU/dL), situations in which both X-chromosomes are affected, or one is affected, and the other one is inactive (known as carrier). The hypocoagulable state due to the deficiency of clotting factors, manifests as an excessive, recurrent tendency to bleeding, which positively correlates with plasmatic levels. Severe haemophilia results in hemarthrosis, although recent data have shown that moderate or even mild disease can lead to joint bleeding. Recurrent episodes of haemorrhages, usually affecting large joints such as knees, elbows, or ankles, lead to joint remodelling and subsequent haemophilic arthropathy, which may require arthroplasty as a last therapeutic option. Orthopaedic patients have the highest risk among all for deep vein thrombosis (DVT) and venous thromboembolism (VTE) with morbid and potentially fatal consequences. While for the rest of the population thromboprophylaxis in orthopaedic surgery is efficient, relatively safe, and widely used, for patients with haemophilia who are considered to have a low thromboembolic risk, there is great controversy. The great heterogeneity of this particular population, and the lack of clinical trials, with only case reports or observational studies, makes thromboprophylaxis in major orthopaedic surgery a tool to be used by every clinician based on experience and case particularities. This review aims to briefly summarise the latest clinical data and to offer an insight into the current recommendations that readers would find useful in daily practice.
Mancuso M.E., Holstein K., O‘Donnell J.S., Lobet S., Klamroth R.
[Article in Press] Haemophilia 2023 :
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Introduction: Synovitis, a common feature in haemophilia, is triggered by the presence of blood in joints, and represents the first step towards the development of chronic arthropathy. Synovitis may be detected early by means of ultrasound or magnetic resonance imaging scan; clinical joint scores are less sensitive in this setting. Regular long-term prophylaxis with clotting factor concentrates, as primary prophylaxis and tailored to individual needs, has high efficacy in preventing synovitis. In general, higher factor levels lower bleeding risk, but no direct correlation between factor levels and synovitis incidence has been demonstrated. Aim: This study aimed to develop an expert consensus relating to the definition, pathophysiology, diagnosis, prevention, follow-up and treatment of synovitis, recognising its relevance for joint health and taking into account existing knowledge gaps. Methods: A Delphi consensus study was designed and performed. An expert group prepared 22 statements based on existing literature; a wider expert panel subsequently voted on these. Results: Retention of panellists was high. Four statements required amending and consensus on all statements was achieved after three rounds of voting. Conclusion: This e-Delphi consensus study addressed the importance of synovitis in joint health of people with haemophilia and highlighted knowledge gaps in this field. Studies on the natural course of synovitis are lacking and the biological mechanisms underlying this process are not yet fully elucidated. While basic and clinical research proceeds in this field, expert consensus can help guide clinicians in their routine clinical practice, and Delphi methodology is often used to produce best-practice guidelines.
How to translate and implement the current science of gene therapy into haemophilia care?
Hermans C., Gruel Y., Frenzel L., Krumb E.
Ther. Adv. Hematol. 2023 14:
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Abstract
Gene-based therapy opens an entirely new paradigm in managing people with haemophilia (PWH), offering them the possibility of a functional cure by enabling continuous expression of factor VIII (FVIII) or factor IX (FIX) after transfer of a functional gene designed to replace the PWH’s own defective gene. In recent years, significant advances in gene therapy have been made, resulting in clotting factor activity attaining near-normal levels, as reflected by ‘zero bleeding rates’ in previously severely inflicted patients following a single administration of adeno-associated viral (AAV) vectors. While this new approach represents a major advancement, there are still several issues that must be resolved before applying this technology in clinical practice. First, awareness, communication, and education about the therapeutic potential and modalities of gene therapy must be further strengthened. To this end, objective, unbiased, transparent, and regularly updated information must be shared, in an appropriate way and understandable language with the support of patients’ organizations. Second, healthcare providers should adopt a patient-centred approach, as the ‘one size fits all’ approach is inappropriate when considering gene therapy. Instead, a holistic patient view taking into account their physical and mental dimensions, along with unexpressed expectations and preferences, is mandatory. Third, the consent procedure must be improved, ensuring that patients’ interests are maximally protected. Finally, gene therapy is likely to be first delivered in a few centres, with the highest expertise and experience in this domain. Thus, patients should be managed based on a hub-and-spoke model, taking into account that the key to gene therapy’s success lies in an optimal communication and collaboration both within and between haemophilia centres sharing their experiences in the frame of international registries. This review describes recent progress and explains outstanding hurdles that must be tackled to ease the implementation of this paradigm-changing new therapy.
Guasch S., Scott L.C., Figueroa J., Buckner T.W., Mattis S., Tran D.Q., Kempton C.L.
[Article in Press] Haemophilia 2023 :
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Abstract
Introduction: In chronic diseases, disease-related distress can impact disease outcomes. Distress and haemophilia-related distress has been demonstrated in people with haemophilia (PwH). The association of haemophilia-related distress on disease outcomes among PwH is unknown. Aim: To study the association of haemophilia-related distress with haemophilia specific outcomes, including adherence to prophylactic therapy, the presence of a target joint, healthcare utilization and work-impairment. Methods: In a cross-sectional study, adults with haemophilia A or B were enrolled in a study to validate the haemophilia-related distress questionnaire (HRDq). In this planned analysis, univariate and multivariate associations between the HRDq total score and disease outcomes were explored. Results: The 114 participants in this analysis were male, mostly with haemophilia A (92%) and severe disease (52%) with a median age of 31.9 years. On univariate analysis, HRDq total score (5-point change) was associated with the presence of a target joint (P =.002), high healthcare utilization (P =.011), poor adherence (P =.033) and work-impairment (P ≤.001). After adjustment for age, race, severity and other potential confounders, adherence (aβ 0.33, 95% CI.17,.49) and work-impairment (aβ 4.69, 95% CI 3.27-6.1) remained statistically significantly associated with HRDq total score. Conclusion: Haemophilia-related distress is associated with poor adherence to factor prophylaxis and work-impairment. The direction of the association (causation) is yet to be determined and requires future study.
Sharma R., Jamwal M., Senee H., Kaur J., Kumar N., Arora A., Gainder S., Ahluwalia J., Das R.
Blood Coagul. Fibrinolysis 2023 34:1 (82-83)
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Abstract
Hemophilia A is an X-linked recessive disorder caused by genetic abnormalities in the F8. Klinefelter syndrome is sex chromosome aneuploidy caused by nondisjunction during meiosis in the germ cells or mitotic cell divisions in the early embryonic cells. We here report an intriguing case of a prenatal diagnosis where a rare association of hemophilia A and Klinefelter syndrome was found in a fetus. This case highlights the diagnostic difficulty where the inverse-PCR for intron 22 inversion defect leading to hemophilia A did not amplify. Indirect molecular testing was done using multiallelic extragenic variable number tandem repeat (VNTR) DXS52 (St14) and polymorphic markers. The interpretation was further complicated by the presence of Klinefelter syndrome. This case highlights the challenges faced when such rare combinations are found during prenatal diagnosis.
Liu Y., Zhou Y., Wang B., Liu J.
Quant. Imaging Med. Surg. 2023 13:1 (512-517)
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Pezeshkpoor B., Oldenburg J., Pavlova A.
Hamostaseologie 2022 42:6 (390-399)
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Abstract
Hemophilia A and hemophilia B are rare congenital, recessive X-linked disorders caused by lack or deficiency of clotting factor VIII (FVIII) or IX (FIX), respectively. The severity of the disease depends on the reduction of coagulation FVIII or FIX activity levels, which is determined by the type of the pathogenic variants in the genes encoding the two factors (F8 and F9, respectively). Molecular genetic analysis is widely applied in inherited bleeding disorders. The outcome of genetic analysis allows genetic counseling of affected families and helps find a link between the genotype and the phenotype. Genetic analysis in hemophilia has tremendously improved in the last decades. Many new techniques and modifications as well as analysis softwares became available, which made the genetic analysis and interpretation of the data faster and more accurate. Advances in genetic variant detection strategies facilitate identification of the causal variants in up to 97% of patients. In this review, we discuss the milestones in genetic analysis of hemophilia and highlight the importance of identification of the causative genetic variants for genetic counseling and particularly for the interpretation of the clinical presentation of hemophilia patients.
McLaughlin P., Hurley M., Chowdary P., Stephensen D., Khair K.
Disabil Rehabil 2022 44:26 (8412-8419)
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Abstract
PURPOSE: To explore the life experiences of pain in people with severe haemophilia and understand how such experiences influence beliefs and sensation of pain in adulthood. METHODS: A qualitative inquiry approach using focus groups and semi-structured individual interviews was used. Participants included people with severe haemophilia living with chronic pain. Data were analysed using reflexive thematic analysis. RESULTS: Fourteen men with a median age of 47 (range 23-73) agreed to take part. Eleven participated in two focus groups and three were interviewed over telephone. Two themes were conceptualised from the data: (i) haemophilia and pain - an evolving life biography (the personal narrative, historical, social, and medical context, continuous adaptation of activity choices, surveillance of pain and its meaning); (ii) "My normal isn't normal" - identity and self-agency (pain as a feature of life and identify with severe haemophilia, loss of enjoyable activities balanced against staying active, barriers to participation). CONCLUSIONS: Pain is a constantly evolving, lifetime feature for many adults with haemophilia and it is viewed as part of their identity with their condition. Healthcare professionals working in haemophilia should try to better understand the influence of an individuals lived experience with their haemophilia on beliefs and behaviours of pain.Implications for rehabilitationSevere haemophilia is a rare bleeding disorder that results in musculoskeletal joint disease.Adults with severe haemophilia have experienced multiple episodes of bleeding related musculoskeletal pain since childhood.Pain beliefs and behaviours in adulthood appear to be influenced by a lifetime of painful experiences associated with haemophilia.In order to better support people with haemophilia and chronic pain, healthcare professionals in haemophilia need to better understand how an individuals lived experience of pain helps inform their beliefs about it.
Ghosh M., Bhattacharyya M.
Indian J. Hematol. Blood Transfus. 2022 38: (S70)
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Abstract
Introduction: Patients with hemophilia, receiving prophylaxis should be on regular monitoring of joint bleeding. Clinical evaluation only may not be sufficient for evaluation of joint bleed which may be done by imaging. Magnetic resonance imaging is the most important modality for early detection of joint bleeding. Nowadays ultrasound has emerged as one of the most useful imaging for early evaluation of bleeding in Hemophiliacs. Aims & Objectives: The purpose of the study is detection of subclinical bleeds in patients with hemophilia receiving prophylaxis with the help of imaging and to look for the effectiveness of prophylaxis. Materials & Methods: The study was conducted at Institute of Haematology and Transfusion Medicine, Kolkata from April 2021 to August 2022. The most frequently involved joints of the patients were evaluated for acute bleeding and annual bleeding rates were calculated. Ultrasound imaging of the most frequent involved joints was done and was correlated with the clinical features. Result: A total 109 patients aged 1 to 38 years receiving Hemophilia prophylaxis were included in the study. Out of the study population, 46.78% presented clinically without any breakthrough bleeding and 44.03% with annual bleeding rates less than two. Imaging results has shown no abnormality in 33% of patients, 20.18% with features of joint bleeding, and 64.21% patients were detected to have other abnormality. Seven percentage had imaging reports involving multiple joints. Among the patients without breakthrough bleeding, 26.41% had ultrasound features suggestive of either bleeding or other abnormality. Among patients with annual bleeding rates less than two, 10.4% showed imaging features suggestive of joint bleed, 64.56% without any abnormality and 54.16 were detected with some other abnormality. Conclusions: Early initiation of prophylaxis, even at low dose serves as an effective measure to decrease bleeding in hemophilia patients. Ultrasound Imaging may be considered as a routine examination for early detection of changes in hemophiliacs even in clinically asymptomatic patients and patients with low annual bleeding rates.
Konigs C., Bidlingmaier C.
Hamostaseologie 2022 42:1 (S24-S31)
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Abstract
Objectives Initial treatment in patients with haemophilia remains challenging. The choice of therapy, timing, dose and frequency have been and are still under intense debate. New treatment options like novel factor concentrates and non-factor therapies broaden the discussion. Design The German Paediatric Haemophilia Research Database (GEPHARD) is a multicentre prospective observational study including children and adolescents with haemophilia A or B (FVIII or FIX levels <25 IU/dL) in a German treatment centre after January 1st, 2017. A cross-sectional analysis was performed in June 2021. Results 249 children and adolescents from 22 participating centres in Germany were analysed in this cross-sectional analysis. 203 patients suffered from haemophilia A (PwHA) and 46 from haemophilia B (PwHB). The median age at diagnosis for Pw severe HA or HB was 6 or 2 months, the median age at analysis was 33 or 35 months for Pw severe HA or B, respectively. 117 Pw severe HA received treatment, including plasma derived concentrates (n = 43), standard recombinant concentrates (n = 23), extended half live concentrates (n = 33) and non-replacement therapies (n = 18). For Pw severe HB, plasma derived concentrates (n = 3), standard recombinant concentrates (n = 8) and extended half live concentrates (n = 14) were used. Current inhibitors were reported in 16 PwHA and 1 PwHB. Conclusions GEPHARD was successfully established as a national cohort for newly diagnosed PwH in Germany. Epidemiological and treatment data were presented. Longitudinal analyses of this growing cohort will allow to value treatment strategies and their outcome in the evolving treatment landscape.
Miesbach W., Oldenburg J., Klamroth R., Eichler H., Koscielny J., Holzhauer S., Holstein K., Hovinga J.A.K., Alberio L., Olivieri M., Knöfler R., Male C., Tiede A.
[Article in Press] Hamostaseologie 2022 :
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Abstract
Gene therapy has recently become a realistic treatment perspective for patients with haemophilia. Reviewing the literature and our personal experience from clinical trials, we discuss key aspects of haemophilia A and B gene therapy with vectors derived from adeno-associated virus (AAV), including predictable results, risks, adverse events, and patient-reported outcomes. Patient selection, informed consent, administration, and monitoring of gene therapy as well as data collection are explained. We also discuss the need for interdisciplinary cooperation with hepatology and other specialties. We emphasize structural and organizational requirements for treatment centres according to the hub-and-spoke model and recommend the use of electronic diaries to ensure safe and timely collection and exchange of data. Electronic diaries will play a key role as primary source of data for pharmacovigilance, post-marketing clinical studies, national and international registries, as well as health technology and benefit assessment. Reimbursement aspects and the future of gene therapy in adolescents and children are also considered. In a rapidly evolving scientific environment, these recommendations aim to support treatment providers and payers to prepare for the implementation of gene therapy following marketing authorization.
Acquired Haemophilia A: A Review of What We Know
Mingot-Castellano M.E., Marco P., Rodríguez-Martorell F.J., Nuñez-Vázquez R.J.
[In Process] J. Blood Med. 2022 13: (691-710)
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Abstract
Autoantibodies against plasma coagulation factors could be developed by some individuals inducing severe and sometimes fatal bleedings. This clinical entity is called acquired haemophilia. It should be suspected in subjects with acute abnormal bleedings, without personal or familiar history of congenital bleeding disorders with an unexplained prolonged aPTT. It is rare disease, although its incidence may be underestimated due to the low knowledge about it by many specialists, the frequent use of anticoagulant or antiplatelet therapies in the affected population that can mask the diagnosis and, sometimes, a so withering effect that avoid its confirmation. Mortality ranges between 9% and 33% depending on the series in the first 2 months after diagnosis. This mortality is attributed in up to 40% of the cases to infections in the context of immunosuppressive treatments used to eliminate the inhibitor. Factor VIII levels below 1% and high inhibitor titers are conditions of worse response rates. Advanced age, patient’s ECOG, and underlying conditions are key prognostic factors for response to treatment and patient survival. To reduce morbidity and mortality in these patients, it is important to have clinical knowledge and access to guidelines to achieve an early diagnosis and to optimize the haemostatic and immunosuppressive treatment. This review aims to contribute to the dissemination of basic concepts on the epidemiology etiopathogenesis, diagnosis, treatment and management of these patients, as well as risk factors to get remission and the longest overall survival to allow individualized care. Especial awareness will be proposed in patients with some underlying conditions like cancer, autoimmune diseases, children, pregnancy or drugs.
Klamroth R., Ay C., De Moerloose P., Fontana P., Windyga J., Astermark J., Berntorp E., Carvalho M., Dolan G., Hermans C., Holme P.A., Kenet G., Mancuso M.E., Marquardt N., Nunez R., Pabinger I., Rodgers R., Valk P.V.D., Yuste V.J., Zupan I.P.
Haemophilia 2023 29:1 (21-32)
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Abstract
Introduction: As people with haemophilia (PWH) receive better treatment and live longer they are more likely to encounter cardiovascular disease (CVD) and other comorbidities. ESC guidelines for the acute management of patients presenting with acute coronary syndrome (ACS) are based on the non-haemophilia population. Aim: To review the guidelines and propose relevant adaptations for PWHA without inhibitors who are treated with prophylaxis and present with ACS. Methods: As part of the ADVANCE Group, 20 European haemophilia experts used a modified Delphi approach to develop and gain consensus on proposed adaptations of the ESC guidelines for PWHA without inhibitors. Results: Of the 32 Class I recommendations across both guidelines, adaptions were considered necessary and proposed for 15. The adaptions highlight the need to provide sufficient FVIII trough levels at the time of antithrombotic treatment in people with haemophilia A (HA) without inhibitors. Patients receiving emicizumab prophylaxis and requiring oral anticoagulation therapy or combined single antiplatelet plus oral anticoagulation therapy will require additional FVIII replacement therapy. Conclusion: In the absence of high-quality clinical evidence, the combined expert opinion used to develop these adaptions to the current ESC guidelines may help to guide clinicians in their treatment decisions when a PWHA presents with ACS.
Accessibility and visibility of genetic testing for haemophilia across Europe: Where do we stand?
Lannoy N., Hermans C.
Haemophilia 2023 29:1 (256-273)
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Abstract
Introduction: Haemophilia is characterized by bleeding complications resulting from clotting factor VIII (FVIII) or IX (FIX) deficiency. Identifying the causal pathogenic genetic variant denotes a vital aspect of haemophilia management. Aim: This study evaluated the accessibility and performances of genetic testing for haemophilia across Europe. The types of genetic analyses, techniques used, turn-around time (TAT) and costs were collected and analysed, as were data updating and quality control. Methods: Reported data were retrieved from open access resources, including international databases, Google, laboratory websites, PubMed and government organizations. Results: Overall, 51 genetic laboratories across 15 European countries providing recently updated molecular haemophilia testing were identified. Gene sequencing for small variants of both F8 and F9 genes was provided in most surveyed laboratories. Almost two-thirds of them offer analysis for inversions using a polymerase chain reaction (PCR) method and detection of copy number variation (CNV) using multiplex ligation-dependent probe amplification (MLPA). Cost and TAT were found to vary considerably. In total, 74% of laboratories exhibited a last modified date or change history. The same percentage of laboratories was in possession of an ISO 15189 standard accreditation, whereas only few of them recently performed external quality assessment schemes (EQA) for haemophilia. Conclusion: Despite several initiatives to improve access to genetic testing for haemophilia, such access must still be improved. Our study similarly revealed the large heterogeneity of the variants tested, techniques employed, TAT, cost and quality among the surveyed laboratories.
Endothelial dysfunction and atherosclerosis related miRNA-expression in patients with haemophilia
Noone S., Schubert R., Fichtlscherer S., Hilberg T., Alesci S., Miesbach W., Klophaus N., Wehmeier U.F.
Haemophilia 2023 29:1 (61-71)
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Introduction: Elevated markers of endothelial dysfunction and inflammation indicate worse endothelial function in the aging haemophilia population. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. Several miRNAs have been shown to be involved in the process of endothelial dysfunction and atherosclerosis. Aim: The aim of this study was to determine the underlying molecular pathways of endothelial dysfunction and inflammation in haemophilia patients. Methods: A total of 25 patients with severe or moderate haemophilia A (20 patients) or B (5 patients), 14 controls and 18 patients with coronary artery disease (CAD) after myocardial infarction were included in this study. Expression of miRNA-126, -155, -222, -1, -let7a, -21 and -197 were analysed using a real time polymerase chain reaction. Network-based visualisation and analysis of the miRNA-target interactions were performed using the MicroRNA ENrichment TURned NETwork (MIENTURNET). Results: Expression of miRNA-126 (p <.05) and miRNA-let7a (p <.05) were significantly higher in CAD patients compared to haemophilia patients and controls. MiRNA-21 (p <.05) was significantly elevated in CAD patients compared to controls. MiRNA-155 (p <.05), miRNA-1 (p <.05) and miRNA-197 (p <.05) were significantly higher expressed in CAD and haemophilia patients compared to controls and showed a strong correlation with increased levels of interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1). The network analysis revealed interactions in the cytokine signalling, focal adhesion and VEGFA-VEGFR2 pathway (Vascular endothelial growth factor, -receptor). Conclusion: This study characterises miRNA expression in haemophilia patients in comparison to CAD patients and healthy controls. The results imply comparable biological processes in CAD and haemophilia patients.
Elsheikh E., Lavin M., Heck L.A., Larkin N., Mullaney B., Doherty D., Kennedy M., Keenan C., Guest T., O'Mahony B., Fazavana J., Fallon P.G., Preston R.J.S., Gormley J., Ryan K., O'Connell N.M., Singleton E., Byrne M., McGowan M., Roche S., Doyle M., Crowley M.P., O'Shea S.I., Reipert B.M., Johnsen J.M., Pipe S.W., Di Paola J., Turecek P.L., O'Donnell J.S.
[Article in Press] J Thromb Haemost 2023 :
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Abstract
BACKGROUND: Previous 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. OBJECTIVES: To 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. METHODS: The 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. RESULTS: We 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. CONCLUSION: Our 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.
van Leeuwen F.H.P., van Bergen E.P.D., Timmer M.A., van Vulpen L.F.D., Schutgens R.E.G., de Jong P.A., Fischer K., Foppen W.
[Article in Press] J Thromb Haemost 2023 :
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Abstract
BACKGROUND: Previous studies suggest that subclinical bleeding occurs in persons with hemophilia. OBJECTIVES: To investigate whether patients with lifelong access to prophylaxis showed signs of previous subclinical bleeding on magnetic resonance imaging (MRI) in joints without a history of joint bleeding. METHODS: This single center cross-sectional study included persons with severe hemophilia A on prophylaxis, aged 16-33 years, with lifetime bleeding records available. Per participant, one index joint without a history of joint bleeding was evaluated with 3-Tesla MRI, including hemosiderin sensitive sequences. MRI scans were reviewed according to the International Prophylaxis Study Group (IPSG) additive MRI scale (range 0-17/joint). Hemosiderin deposits with/without synovial hypertrophy were considered signs of previous subclinical bleeding. Additionally, physical examination was performed, followed by ultrasound examination according to the Hemophilia Early Arthropathy Detection with Ultrasound protocol. RESULTS: In 43 patients with a median age of 23.5 years, 43 joints (16 elbows, 13 knees, 14 ankles) without reported bleeds were evaluated with MRI. The median IPSG MRI score was 1 (range 0-9). Signs of previous subclinical bleeding were observed in 7/43 joints (16%, 95% CI 7-30): 7/7 joints showed hemosiderin deposits, with concomitant synovial hypertrophy in 2/7 joints. MRI changes were accompanied by swelling and ultrasound-detected synovial hypertrophy in one ankle only. None of the other joints showed abnormalities at physical examination and ultrasound. CONCLUSIONS: In this study, 16% of the joints without reported bleeds showed signs of previous subclinical bleeding, providing evidence for subclinical bleeding in severe haemophilia patients with lifelong access to prophylaxis.
TAILORED TREATMENT FOR SUPPORTING SPORTS IN HAEMOPHILIA
Hilberg T.
Haemophilia 2023 29: (5)
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Abstract
Physical activity helps to reduce risk factors for all-cause mortality in the general population. Therefore, the WHO recommends at least 150-300 minutes of moderate-intensity-aerobic physical activity, or at least 75-150 minutes of vigorous-intensity-aerobic physical activity; or an equivalent combination of moderate- and vigorous-intensity activity throughout theweek, for adults between 18-64 years. For the last few years, this has also been recommended for people with disabilities. Hence, it is important to encourage people with haemophilia (PwH) to practice physical activity and sports. However, practising sports can sometimes come hand-in-hand with sports-injuries and, therefore, additional bleeding into musculoskeletal tissue and joints. At the same time, many younger PwH do not have haemophilic arthropathy and want to practise more risky sports. The HTCt's have to deal with this double-edged sword, e.g., to encourage doing sports, but making sure to practise them safely. For this, the first step is finding the right type of sports by checking individual conditions and preferences. There are many interesting types of sports, which are commonly unknown. The choice is better defensive than offensive, and needs to include experts in the field of sports and musculoskeletal system. The next step should be to improve treatment and knowledge about, e.g. compliance to the therapy, peaks and troughs of factor levels, the right gap between factor treatment and activity, and the backgrounds and use of pharmacokinetics. In addition, knowledge about the best treatment after injury will also be meaningful and provide safety. All these points will help to support sports and safe practise in PwH
THE BURDEN OF HAEMOPHILIA DEPENDS FROM WHERE YOU WERE BORN
Siebert M., Bicker M., Gündüz B., Zappek J.
Haemophilia 2023 29: (189-190)
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Abstract
Introduction: Haemophilia is a rare disorder with a prevalence as 1:5000 male births for haemophilia A and 1:20000 male birth for haemophilia B. Although prophylaxis with factor concentrates or non factor medication like monclonal antibodies is considered as the gold standard for the treatment of haemophilia for many patients this treatment is often unattainable. Either because it is too expensive and can lead to a heavy economic burden if accessed privately, or because treatments might not be on the market in countries where patients need it (1). Methods: In Ukraine (with Crimea and Sevastopol statistics absent) around 1900 adult and 600 child hemophilia patients were registered at the hospitals. 80-90% of children under 14 years old with severe hemophilia become disabled. The same applies to 100% of the patients above 18 years of age with severe hemophilia (2). Results: Since March 2022 many patients with severe haemophilia A and B and other bleeding disorders from the Ukraine had to leave their home country.With the support of the Deutsche Bluthilfe e.V. some of them found a new home inDuisburg. For the first time of their lifes they receive adequate haemophilia treatment, physiotherapy and if needed a joint replacement. Even some of the younger patients can try sporting activities for the first time. Discussion/Conclusion: As inWestern Europe and North America prophylaxis is available for nearly each patient with severe haemphilia in the rest of the world many patients still become diabled or die due to their disease. As volunteers of the humantarian aid program of the World Haemohilia Federation we still believe that one day we can close the gap and all patients with haemophilia have acess to adequate treatment no matter where they live
THE UNDERDIAGNOSED DISEASE IN HAEMOPHILIA: SARCOPENIA AND ULTRASOUND
Nally A.P., Sliba G., Martínez M., Nally F., Dolabella G., Morales F., Barahona E.
Haemophilia 2023 29: (30)
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Abstract
Introduction: Sarcopenia is the progressive loss of muscle mass, strength and/or functional. A consequence of articular hemorrhage on the skeletal muscle is the accelerated loss of muscle mass. Inactivity secondary to symptoms of haemophilic arthropathy results in muscle atrophy and deconditioning, which perpetuates and exacerbates pain and functional deficits. The loss of muscle mass is also responsible for joint suffering. The weakness plus muscle stiffness produced by muscle atrophy and fat replacement will affect joints given the traction they exert on their bone insertion, facilitating the osteoarthritis process. Musculoskeletal ultrasound (MskUs) is a simple, economical and easyto-implement method that allows quick assessment of the muscles and can be used to investigate skeletal muscle structure and determine muscle loss. Methods: MskUs joint screening of 23 patients (2-64years) with Haemophilia A (22) and B (1) was performed and underlying muscle status taken into account.Muscle parameters of thickness in cross section area and echo-intensity were considered to distinguish between normal and pathologic muscles. Contralateral comparison was also determined in this evaluation. Results: 70% of patients presented joint commitment (cartilage damage in 61% and bone damage in 39.%), with ankle affection in 13 patients (7 bilateral ), knee in 8 ( 6 bilateral ) and elbows in 5. Muscles involved around the knee were specially compromise, since lower limbs were the most commonly affected in our patients. A decrease in the thickness and volume of the quadriceps muscle was reported in these patients with chronic joint pathology. Discussion/Conclusion: Haemophiliac arthropathy is frequently associated with muscle atrophy, reduced rate of muscle contraction, and muscle wasting. Changes in joint range of motions, strength and reaction time have been tied to declines in mobility. These are critical factors in balance impairments and fall risk associated. Sarcopenia leads tomuscle weakness, impaired gait and balance. We want to highlight the importance of MskUs as a tool for detecting and monitoring muscle volume loss in order to help maintain muscle functionality and joint preservation. Diagnose muscle loss and report measurements may show promise in providing determination of severity. Further research on the cause-effect impact of sarcopenia in haemophilic arthropathy is required.
Chowdary P., Waqif E., Watissée M., Chadwick N., Hay C., Mathias M., Collins P.
Haemophilia 2023 29: (60-61)
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Introduction: The extended half-life (EHL) registry was established in 2016 to ascertain the long-term outcomes in patients with HaemophiliaA(HA) and B(HB) receiving replacement therapy. The aim was to quantify disease burden and quality of life at baseline and after switching to EHLs. Methods: The study is a prospective, observational cohort study that enrolled patients switching EHLs or on standard replacement therapy after informed consent following local ethics approval and was registered at www.clinicaltrials.gov (NCT02938156). The study was paused during the COVID pandemic. Here the baseline results are presented for pain, activity and quality of life and their correlations. Pain evaluation was assessed through the brief pain inventory (BPI) 7-day recall, quality of life by EuroQol-5 Dimension (EQ5D5L) and physical activity through the international physical activity questionnaire (IPAQ). The BPI assess severity of pain and the interference with activities. IPAQ assess physical activity undertaken across a comprehensive set of domains. Three levels of physical activity are used to classify the populations: 'low', 'moderate', and ' high'. Results: A total of 231 HA and 97 HB were included in the analysis, of whom 231 had switched to EHL products and 96 were on standard replacement therapy. The levels of Physical Activity were similar between Haemophilia types, with approximately 46%, 32% and 22% of patients reporting high, moderate, and low physical activity, respectively. BPI mean (±SD) severity score in HA was 2.86 (±2.1), HB 3.24 (±2.0); interference score HA 3.22 (±2.8), HB 3.09 (±2.5), mean EQ5D5L visual analogue scale (VAS) for HA 72.92 (±15.5) and HB 71.10 (±18.2). Within instruments, IPAQ sub-scores and BPI average scores were highly correlated. Between instruments, the strongest linear correlations were seen between theVAS and the BPI scores (R=-0.59, p< 0.0001, n=206 for the average interference score, R=-0.57, p< 0.0001, n=208 for the average pain severity, v.s. the VAS). Correlations between the IPAQ total score and either VAS or BPI scores were weaker, even when limiting to patients with moderate or high activity and using a log scale given the skewed distribution of the IPAQ summary measure. Discussion/Conclusion: The study demonstrates for the first time a strong correlation between pain and quality of life, and weaker correlation between physical activity and quality of life.
Christoforou P., Kourampa A., Varaklioti A., Pirpiri T., Balomenou A., Katsarou O.
Haemophilia 2023 29: (61)
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Abstract
Introduction: Population pharmacokinetics (PK) provides options for individualized replacement therapy prophylaxis in hemophilia. The aim of the study is to compare the effectiveness of standard (SHL) and extended half-life (EHL) products in our haemophilia population, with an emphasis on t1/2 and clinical response. Methods: The study included 145 PK profiles (WAPPS-Haemo) in 90 severe hemophiliacs, mean age 36 years (IQR 18-67) and a mean BMI (body mass index) of 24.65 (IQR 19.9-48.9): 67 (74.44%) haemophilia A and 23 (25.56%) haemophilia B. Mean follow-up was 26.5months (IQR 5-48). The study included 55 EHL and 31 SHL FVIII products but also 28 EHL and 3 SHL FIX products. FVIII/FIX levels were measured using one stage clotting STAGO and chromogenic method (BCS SIEMENS). Samples were collected before and 1,24,48 and 72 hours after intravenous FVIII administration with a median dose of 40.68 IU/Kg (IQR 32.3-46.1 IU/Kg) and 24.68 IU/Kg (IQR 19.2-27.4 IU/Kg) EHL and SHL respectively in patients with hemophilia A and a mean FIX dose of 41.67 IU/Kg (IQR 38.75-44.6 IU/Kg) and 42.2 IU/Kg (IQR 30.8-53.6 IU/Kg) EHL and SHL respectively in patients with hemophilia B. Median t1/2 and in vivo recovery were compared with blood type, BMI and clinical response. Results: FVIII EHL products had a median t1/2of 17.25 hours (IQR 8.25-30.75) compared to SHL's 12 hours (IQR 6.5-18.75) (p<0.001). The median t1/2 of FIX agents was 92.37 hours (IQR 59.25-179) and 23.5 hours (IQR 23-24) for EHL and SH respectively. Mean recovery, did not differ between SHL and EHL: 2.12% (IQR 1.76-2.55) and 2.06% (IQR 1.61-3.06) for hemophilia A, while for hemophilia B to be 0.89% (IQR 0.59-1.21) and 0.97% (0.69-0.81) respectively. The t1/2did not correlate with blood type or BMI. In the 75 patients switched from SHL to EHL agents, there was a statistically significant decrease in weekly infusions, decrease in annual bleeds and an improvement in HJHS (Haemophilia Joint Health Score) in target joints. Discussion/Conclusion: The use of PK studies contributes to personalized prophylactic treatment and allows for fewer infusions by maintaining greater levels of coagulation factors for longer periods of time. The longer t1/2of EHLs compared to SHLs seem to improve patient compliance and quality of life.
Strauss A.C., Muellejans P., Koob S., Goldmann G., Pennekamp P.H., Wallny T.A., Oldenburg J., Strauss A.C.
[Article in Press] Hamostaseologie 2023 :
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Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Von Willebrand Disease, Hemophilia, and Other Inherited Bleeding Disorders in Pregnancy
Pacheco L.D., Saade G.R., James A.H.
Obstet. Gynecol. 2023 141:3 (493-504)
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Abstract
Inherited bleeding disorders, which comprise von Willebrand disease (VWD), hemophilia, other congenital clotting factor deficiencies, inherited platelet disorders, defects of fibrinolysis, and connective tissue disorders, have both maternal and fetal implications. Although mild platelet defects may actually be more prevalent, the most common diagnosed bleeding disorder among women is VWD. Other bleeding disorders, including hemophilia carriership, are much less common, but hemophilia carriers are unique in that they are at risk of giving birth to a severely affected male neonate. General guidance for maternal management of inherited bleeding disorders includes obtaining clotting factor levels in the third trimester, planning for delivery at a center with hemostasis expertise if factor levels do not meet the minimum threshold (eg, less than 0.50 international units/1 mL [50%] for von Willebrand factor, factor VIII, or factor IX), and using hemostatic agents such as factor concentrates, desmopressin, or tranexamic acid. General guidance for fetal management includes prepregnancy counseling, the option of preimplantation genetic testing for hemophilia, and consideration of delivery of potentially affected male neonates with hemophilia by cesarean delivery to reduce the risk of neonatal intracranial hemorrhage. In addition, delivery of possibly affected neonates should occur in a facility where there is newborn intensive care and pediatric hemostasis expertise. For patients with other inherited bleeding disorders, unless a severely affected neonate is anticipated, mode of delivery should be dictated by obstetric indications. Nonetheless, invasive procedures such as fetal scalp clip or operative vaginal delivery should be avoided, if possible, in any fetus potentially affected with a bleeding disorder.
Franchini M., Focosi D.
Thromb. Res. 2023 222: (7-11)
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Liver-related aspects of gene therapy for hemophilia: need for collaborations with hepatologists
Miesbach W., Foster G.R., Peyvandi F.
[In Process] J. Thromb. Haemost. 2023 21:2 (200-203)
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Abstract
Adeno-associated virus-based gene therapies hemophilia allow long-term transgene expression with reduced annual bleeding rates. Various liver-related aspects are involved in the different phases of gene therapy, such as assessment of liver health in the pretherapy period, patient selection and follow-up, maintenance of liver health after gene therapy, and management of potential short- and long-term adverse events. Increase in alanine aminotransferease is a common adverse event that requires rapid evaluation and an immunosuppressive approach. It is therefore important that hemophilia treaters and hepatologists collaborate at all stages of gene therapy to assess potential safety issues and ensure the long-term success of gene therapy. Special attention should be given to patients with not well-defined conditions, e.g. patients with some degree of liver fibrosis or fatty liver disease, patients with a history of hepatitis C and hepatitis B infection, patients with HIV infection, and patients taking medications that may affect liver function.
Blood-induced inflammation in hemophilia
Knowles L.M., Wolter C., Menger M.D., Laschke M.W., Haegele F., Eichler H., Pilch J.
Hamostaseologie 2023 43: (S37)
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Abstract
Introduction The acute-phase response is elevated in hemophilia patients with acute and recent bleeds. Here, we provide evidence that the inflammatory response to injury is deregulated in hemophilia after bleeding. Method We analyzed blood-induced inflammation and arthrofibrosis in knee joints of transgenic mice with hemophilia A compared to coagulation-competent wildtype mice. Results To investigate inflammation in response to injury in hemophilia, we punctured the right knee of transgenic mice with hemophilia A with a hypodermic needle and analyzed the subsequent phases of wound healing. While this procedure caused only minor injuries in wildtype mice, we observed the development of large hematomas in the punctured knees of hemophilia mice between days 1 and 7 after puncture that turned irreversibly into arthrofibrosis by day 28. In contrast, blood injected into the knees of wildtype mice, was completely absorbed within 7 days and did not cause fibrosis. To assess inflammation during joint injury, we performed immunohistochemistry for detection of macrophages and neutrophils. In the knees of wildtype mice, we observed infiltrations of neutrophils and macrophages only on day 1 after blood injection while neutrophils in the punctured knees of hemophilia mice persisted beyond day 7. The pro-inflammatory effect in the punctured knees of hemophilia mice was also evident when we probed for macrophages, which in contrast to blood-injected control mice, became first visible after 7 days and persisted until day 56. No relevant blood cell infiltration occurred after saline injection of control mice. Conclusion We conclude that the presence of free blood in joints causes inflammation and that the pro-inflammatory effect of blood is amplified in hemophilia mice.
Digital joint discovery tool to support hemophilia patient education
Goldmann G., Marquardt N., Oldenburg J.
Hamostaseologie 2023 43: (S42)
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Abstract
Introduction Recurrent joint bleeding is the most frequent clinical manifestation of severe hemophilia. Unless appropriately managed, even subclinical hemarthrosis can lead to the development of hemophilic arthropathy and chronic pain. The new joint discovery tool shows the anatomical structure of the ancle in different stages of hemophilic arthropathy. The aim of this project is to support HCPs patient information and communication on site (Fig. 1). Method Imaging diagnostics of hemophilic patients have been selected such as MRI, ultrasound and X-ray findings and integrated into the development process. This step was followed by a visual transposition as 3D-animation (incl. rotating, tilting, zooming) of the changes in the ancle joint and occurring joint hemorrhages in the course of the disease over time. Results Defined tissue structures can be visualized such as skin, skeleton, capsule as well as most important muscles, ligaments, fascias, vessels and nerves. Corresponding different stages can be visualized strengthening patient/caregiver education: 1. healthy joint 2. acute joint bleed 3. chronic joint bleed 4. first joint destruction 5. joint destruction. The pathomechanisms underlying the individual clinical picture e.g. changes in the joints such as swelling can be demonstrated. The interactive applications of the 3D-visualization can be sent to the physician via link. App (IOS) and web application are available to support patient communication and education. The joint can also be virtually projected into the room by means of augmented reality.[1] Conclusion This first joint discovery can contribute to raising patients awareness thus e.g. offering the potential to support adherence to a beneficial prophylactic treatment regime. User surveys have been prepared to accompany the current implementation. The device could be enlarged for further joints e.g. knee and elbow. Potential applications and future developments of this digital tool are currently under evaluation. (Figure Presented).
Dayo J., Miesbach W.
Hamostaseologie 2023 43: (S47)
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Abstract
Introduction Patients with hereditary hemophilia often clinically present with signs of spontaneous bleeding in joints. If bleeding occurs more than three times in the same joint within six months, it is defined as a target joint. Affected joints can be swollen, painful and restricted in movement. Most seriously patients can develop chronic destructive hemophilic arthropathy.Manual lymphatic drainage (MLD) is a special skin displacement technique used in complex decongestion therapy to treat swollen parts of the body and to remove interstitial inflammatory mediators by stimulation of lymphatic vascular system (LVS) (Fig. 1). Method The single-center randomized-controlled, cross-over-pilot study included 14 male hemophilia A o B patients with a target joint to evaluate effects of MLD on their joint condition. Study design (Fig. 1): Intervention group A started with an 8-week MLD treatment period (30 min MLD twice a week). This was followed by a wash-out phase of 4 weeks and a non-treatment period of further 8 weeks. Intervention group B was treated in reverse order of periods. A total of four parameters were examined directly pre and post each period: 1. Pain situation (Visual analogue scale, VAS) 2. Joint mobility (Range of motion, ROM) 3. Joint status (Hemophilia Health Joint Score, HJHS) 4. Irritation state of target joint (infrared thermography) Results VAS revealed a significant effectiveness of MLD treatment on pain situation (p < 0.003). A moderate (n = 2) to significant (n = 6) pain reduction was reported by 66.7 % of the patients after treatment period (threshold = -2 points) whereas 33.3 % showed mild (n = 2) to no (n = 1) pain reduction. The overall median pain was reduced by 2.5 ± 1.33 points, with group A (minus 3 points) benefiting more than group B (0 points) as group B showed a slight increase in pain during non-treatment period (median VAS + 1). In the evaluation of ROM, a slight, but non-significant change in extension (p = 0.202) and flexion (p = 0.010) could be observed. A change in joint mobility of ≥ 5 ° (clinically relevant) could be measured in 5 of 14 patients during MLD treatment period (Fig. 2). In the Hemophilia Health Joint Score, no significant effect could be detected. Nonetheless a median HJHS score reduction of -3 ± 0.78 points was determined in both groups during MLD period. For item score “joint pain”, a post-interventional reduction of at least -1 point was recorded in 58.3 % of the patients (n = 7). Infrared thermographyshowed no significant effect for MLD on joint irritation state. Overall, an average temperature change of + 0.35 °C ± 0.10 occurred. An increase in temperature occurred at n = 8 and a decrease in temperature at n = 4. Conclusion The pilot study showed that Manual lymph drainage can have a significant pain-relieving effect in patients with hemophilic arthropathy. VAS documentation and HJHS score could prove the pain-relieving effectiveness of this therapy. Multicentric, randomized control studies are required for further evaluation. (Table Presented)
Structural alteration and impact on pain perception in patients with haemophilia
Schmidt A., Sigl-Kraetzig M., Richter H., Vogler T., Tomschi F., Hilberg T.
Hamostaseologie 2023 43: (S47-S48)
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Abstract
Introduction Joint haemorrhage in patients with haemophilia (PwH) leads to changes of the synovium, cartilage, and bone, that can result in chronic pain. To date, it is unclear, which of the affected structures are the determinants of the enhanced pain state in PwH. To identify the distinct sources of pain, the structural joint condition was assessed by ultrasound (US) and pressure pain thresholds (PPT) were determined to gauge the sensitivity of pain. Method 79 patients with moderate or severe haemophilia A or B (PwH) (severe A = 54, B = 13; moderate A = 11, B = 1) were included. Thus, a total of 459 (n = 459) haemophilia-specific joints (ankle, knee, and elbow joints) of PwH were investigated sonographically and by means of PPT. Structural alterations were detected by applying the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) system. This US scanning protocol discriminates between activity of the joint by measuring the degree of synovitis and damage of the joint by evaluating the extent of cartilage and/or bone degeneration. Pain status was assessed by measuring PPT at landmarks selected on the basis of US-findings. The lower the PPT values, the higher the pain sensitivity. To identify whether an altered pain perception is associated with increased joint activity, three subgroups were analysed (Syn0 = none/minimal, Syn1 = mild/ moderate, Syn2 = severe). To explore the potential link between joint damage and an altered pain perception, destruction of cartilage and/or bone was clustered in four subgroups (Dam0 = none, Dam1 = mild, Dam2 = moderate, Dam3 = severe). Results A total of 156 (n) ankle, 149 knee, and 155 elbow joints were analysed. One-way ANOVA revealed a group-specific difference for PPT based on the severity of synovitis (Syn0 (n = 110) = 52.5 ± 28.3, Syn1 (n = 243) = 41.8 ± 21.2, Syn2 (n = 106) = 44.8 ± 20.5; mean ± SD in Newton; p 7le; .001) and joint damage (Dam0 (n = 282) = 48.8 ± 24.9, Dam1 (n = 38) = 43.1 ± 22.5, Dam2 (n = 40) = 37.8 ± 19.9, Dam3 (n = 99) = 38.4 ± 17.6; mean ± SD in Newton; p 7le; .001). Bonferroni- corrected post-hoc analysis revealed significant differences for synovitis between Syn0 vs. Syn1 (p 7le; .001) and Syn0 vs. Syn2 (p = .042) as well as for joint damage between Dam0 vs. Dam2 (p = .027) and Dam0 vs. Dam3 (p = .001). Spearman's correlation analysis suggests an inverse correlation between PPT and the magnitude of joint damage (r = -.199, p 7le; .001), but not for the degree of synovitis (r = -.075, p = .109). Conclusion Structural alterations in both the synovium and cartilage and/or osseous tissue lead to mechanical hyperalgesia in PwH. In synovitis, even mild changes seem to affect pain perception, with the effect not increasing at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitized pain state most robustly, whereas initial changes do not appear to significantly affect pain perception.
Von Mackensen S., Hafer L., Siebert M., Halimeh S.
Hamostaseologie 2023 43: (S80)
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Abstract
Introduction Since the beginning of the Russian-Ukrainian war, around 14 million people have fled from the Ukraine; of them around 1 million have come to Germany (as of 19.10.2022). Among them are also peole with haemophilia (PWH) who urgently need medical care. These patients have often previously experienced a different therapeutic standard of treatment in their home countries. This initial situation creates a particular relevance to evaluate the current health status (HS), orthopaedic joint status (OJS) and disease-specific quality of life (HRQoL) as well as the subjective physical functioning (PF) of these PWH. In this context, it is important to record what additional influence haemophilia care has on the refugee PWH, as this can well be modified by therapy options that are part of the standard therapy in Germany. Method All Ukrainian PWH who have fled Ukraine and are currently treated at German haemophilia treatment centres (HTCs) should be enrolled in the CALIGULA Study. For this purpose, an appeal was launched via the German Society of Thrombosis and Haemostasis Research (GTH) for patient recruitment by the respective HTCs. If not available, patient-reported outcome measures (PROs) were linguistically validated into Ukrainian. Haemophilia-specific PROs included instruments for the assessment of subjective physical functioning (HEP-Test-Q) and for the assessment of HRQoL (Haem-A-QoL, Haemo-QoL). In addition, a short ad-hoc questionnaire on the clinical care of the patients in the home country and on specific escape factors was developed. A validated refugee- specific questionnaire (PMLD: Postmigration living difficulties Questionnaire) to assess the stress experience of the refugee patients was also included. After obtaining the respective informed consent, PWH are asked to complete all Ukrainian PROs. Health care professionals (HCP) assess the OJS by means of the Haemophilia Joint Health Score (HJHS) and document the HS (e.g., form and severity of haemophilia, bleeding frequency and therapy) in a clinical report form. The collected data are analysed, interpreted, and compared with available data from German haemophilia patients.[1-10] Results So far, 20 PWH (8 Kids, 19 adults) from the HTC in Duisburg were enrolled; 15 further PWH were identified by 7 other HTCs in Germany. Data from these centres are not yet available. Results from all centres will be presented at the GTH congress. Conclusion The collection of data from refugee haemophilia patients on PROs, joint status and the general refugee situation is intended on the one hand to represent the current state of health of this special population group and on the other hand to enable a comparison with a German comparison group. In view of the current social situation characterised by humanitarian willingness to help, these data are indispensable in order to adapt the therapy to the special and individual needs of the patients in the further course and to enable appropriate treatment planning.
Alesci R.S., Halimeh S., Miesbach W., Koenigs C., Holstein K., Olivieri M.
Hamostaseologie 2023 43: (S55)
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Abstract
Introduction Patients with mild hemophilia (residual factor activity > 5 to < 40 %) represent a very heterogeneous group. Therapeutic approaches are as individual as the bleeding tendency. Patients may feel less perceived by the medical profession than patients with moderate or severe hemophilia. It is likely that the extent of disease and bleeding risk of patients with mild hemophilia are underestimated, resulting in an undersupply of factor concentrate, both during surgical procedures and trauma. So far, not much data exists on both joint problems of patients, nor on the management of surgical procedures. The aim of this patient survey is to gather insights into the treatment situation of patients aged 12 years and older with mild hemophilia A or B and their quality of life Method Using an anonymous cross-sectional patient survey, we documented online patients 'experience with factor concentrates and other treatments. Patients ≥ 12 years with diagnosed mild hemophilia A or B participated in the survey. We evaluated patients 'satisfaction regarding the therapy situation and the support by physicians, and assessed the impact on Quality of Life (EQ- 5D-5L). Results We could include 44 patients (35 hemophilia A, 5 hemophilia B, 3 unknown) with a median age at survey of 33 years (mean 36.0 years, 12-75 years). The median age at diagnosis was 6.0 years (mean 10.6, 0-37 years). Median factor activity was 14.0 % (mean 18.1; 4-55 %). 84.2 % (n = 32) were treated with factor concentrates in the past. The most frequent reasons for treatment were surgery or joint bleedings (each 65.6 %, n = 21). Approximately half of the patients (n = 20) had complications caused by untreated bleeding due to accidents (4), surgical bleeding (11), dental treatment (10), joint bleeding (10) and spontaneous bleeding (2). Only 4 patients (10.3 %) were prophylactically treated with factor concentrates. Health state indicates slight problems with mobility, slight problems with washing or dressing, slight problems with doing usual activities, moderate pain or discomfort and slight anxiety or depression. Conclusion Bleeding complications, especially joint bleeding, seem to be highly underestimated in patients with mild hemophilia A and B. Obvious, there is still a lack of awareness. To start an early prophylaxis to avoid joint damage (hemophilia arthropathy) should be discussed even in patients with mild hemophilia. The QoL is surprisingly reduced, too. More data about joint bleeding is needed.
