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Optimizing long-term joint health in the treatment of hemophilia
Gualtierotti R., Giachi A., Suffritti C., Bedogni L., Franco F., Poggi F., Mascetti S., Colussi M., Ahmetovic D., Begnozzi V., Boccalandro E.A., Solimeno L.P., Peyvandi F.
[Article in Press] [In Process] Expert Rev. Hematol. 2024 :
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Abstract
Introduction: The improved quality of care and increased drug availability have shifted the goal of treating people with hemophilia from life-threatening bleeding prevention to joint health preservation and quality of life amelioration. Many tools are now available to the clinician in order to optimize the management of hemophilic arthropathy. Areas covered: This paper reviews the pivotal role of ultrasound evaluation in early detection of joint bleeding and differential diagnosis of joint pain, with a focus on the feasibility of a long-term monitoring of joint health through the use of artificial intelligence and telemedicine. The literature search methodology included using keywords to search in PubMed and Google Scholar, and articles used were screened by the coauthors of this review. Expert opinion: Joint ultrasound is a practical point-of-care tool with many advantages, including immediate correlation between imaging and clinical presentation, and dynamic evaluation of multiple joints. The potential of telemedicine care, coupled with a point-of-care detection device assisted by artificial intelligence, holds promises for even earlier diagnosis and treatment of joint bleeding. A multidisciplinary approach including early intervention by physical medicine and rehabilitation (PMR) physicians and physiotherapists is crucial to ensure the best possible quality of life for the patient.
Non-drug Index Terms
access to medication, arthralgia, arthropathy, artificial intelligence, bleeding prophylaxis, cartilage, clinician, diagnosis, differential diagnosis, early intervention, echography, hemarthrosis, hemophilia, hemophilic arthropathy, human, physiotherapist, quality of life, review, synovitis, systematic review, telemedicine, therapy
Moghadam A.A., Manafzadeh A.R., Nikoonia M.R., Moazezi S.S., Nekoei K.D., Ramezan F., Bashash D., Hamidpour M., Tabibian S.
Transfus. Apheresis Sci. 2024 63:6
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Abstract
Background: One of the major problems for patients with severe hemophilia A (HA) is the development of neutralizing antibodies against factor VIII. This study aimed to analyze the molecular and clinical profiles of patients with severe HA and to determine if certain genetic variants predispose to inhibitor development in these patients. Methods: A single-center study was conducted among patients with severe HA between March 20, 2000, and June 31, 2023. Demographic data and laboratory results of patients were collected. The inverse-shifting PCR (IS-PCR) technique was initially used to screen patients for intron 22 and 1 inversions (Inv-22 and Inv-1). Results: A total of 480 patients with severe HA (408 without inhibitors and 72 with inhibitors) were enrolled in this study. The median age of the patients at the time of diagnosis was 6 months (IQR: 3 months to 18 months). Inv-22 was observed in 199 (41.5 %) of the cases. Among those patients who developed inhibitors, 53 (73.6 %) were classified as high-titer and 19 (26.4 %) as low-titer. Inv-22, positive family history of inhibitor formation, and history of intense injections revealed a statistically significant association with the risk of inhibitor development. Conclusion: The results of this study confirm the important role of different genetic variants, family history of inhibitor formation, and history of intense injections for the formation of inhibitors in patients with severe HA. This would allow us to stratify the patients which can have important clinical implications, especially in terms of their management and outcome.
Drug Index Terms
(Based on full text)
blood clotting factor 8 inhibitor, DNA fragment (endogenous compound), genomic DNA (endogenous compound)
Non-drug Index Terms
(Based on full text)
activated partial thromboplastin time, age, anatomical region, antibody titer, article, circumcision, clinical feature, clinical outcome, cohort analysis, consanguinity, contusion, demographics, diagnosis time, disease severity, ecchymosis, electronic medical record, epistaxis, frameshift mutation, gene mutation, genetic variability, hematuria, hemophilia A (diagnosis), high risk patient, human, intermediate risk patient, intron, inverse shifting polymerase chain reaction, low risk patient, major clinical study, missense mutation, nonsense mutation, polymerase chain reaction, prothrombin time, Sanger sequencing, sensitivity and specificity
Ferri Grazzi E., Hawes C., Camp C., Hinds D., O’Hara J., Burke T.
Health Qual. Life Outcomes 2024 22:1
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Abstract
Background: Haemophilia A (HA; Factor VIII deficiency) is a congenital X-linked bleeding disorder characterized by trauma-related or spontaneous bleeding events, most notably arising within the intraarticular space and resulting in chronic inflammation and degeneration of affected joints. Endogenous clotting factor activity relative to normal levels determines the severity of HA symptoms, as mild (> 5–40%), moderate (1–5%), or severe (< 1%). Within the current environment of rapid evolution in HA management, we seek to understand the interplay of condition severity and health-related quality of life (HRQoL) to characterise and differentiate unmet needs among people with HA (PwHA). Methods: A generalised linear regression model (GLM) was developed to explore the relationship between HA severity and EQ-5D-5 L index score from adult HA patients sampled in the “Cost of Haemophilia across Europe – a Socioeconomic Survey II” (CHESS II) cross-sectional, retrospective burden of illness study among adults with hereditary haemophilia A or B from eight European countries. HA patients of any severity with no active inhibitors during the 12 months prior to data capture and a completeEQ-5D-5 L response were included. A base GLM model was specified with covariates for demographic and clinical characteristics (age, body mass index, country, employment, HA severity, annual bleeding rate, problem joints, and chronic pain). Results: Of 381 evaluable patients, 221 (58.0%) had severe HA, 96 (25.2%) had moderate HA, and 64 (16.8%) had mild HA. Among the covariates included in the GLM model and after controlling for haemophilia-related outcomes, a significant association was observed between mild HA and higher EQ-5D-5 L index score (average marginal effects, 0.084; p = 0.016) relative to severe HA. Patient country of residence and magnitude of HA-related chronic pain were also associated with significant differences in index scores, with the latter showing a negative relationship with HRQoL outcomes. Conclusions: Condition severity and chronic pain are significant predictors of HRQoL in PwHA. Durable bleeding protection and effective management of chronic pain have the potential to address unmet treatment needs in this population.
Non-drug Index Terms
(Based on full text)
adult, age distribution, article, bleeding, body mass, chronic pain, cohort analysis, cross-sectional study, demographics, disease burden, disease severity, employment status, Europe, European Quality of Life 5 Dimensions 5 Level questionnaire, hemophilia A, hemophilia B, human, major clinical study, male, quality of life, residence characteristics, retrospective study, unmet medical need
Ferri Grazzi E., Becker T., Brandt S., Duport G., Garcia Diego D.-A., Lupi A., McKeown W., Morgan D., Camp C., Hawes C., Blenkiron T., O’Hara J., Burke T.
Adv. Ther. 2024 41:10 (3888-3904)
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Abstract
Introduction: Haemophilia A (HA) is a congenital bleeding disorder caused by a deficiency/absence of factor VIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5–40%), moderate (1–5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the ‘Cost of Haemophilia in Europe: A Socioeconomic Survey II’ (CHESS II) study. Methods: CHESS II was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18 years) individuals with haemophilia A or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. Results: Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. Conclusion: This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA.
Drug Index Terms
(Based on full text)
recombinant blood clotting factor 8 (drug therapy)
Non-drug Index Terms
(Based on full text)
adult, aged, arthropathy, article, bleeding, chronic pain, clinical outcome, cohort analysis, controlled study, cross-sectional study, disease burden, disease severity, European Quality of Life 5 Dimensions 5 Level questionnaire, European Quality of Life 5 Dimensions Visual Analogue Scale, female, France, Germany, health care utilization, hemophilia A (disease management, drug therapy), human, Italy, long term care, major clinical study, male, middle aged, patient-reported outcome, physician, prophylaxis, quality of life, retrospective study, Spain, substitution therapy, United Kingdom, work participation, work productivity and activity impairment questionnaire, young adult
Ultrasound assessment and scoring of tendinopathy in hemophilia: Development of the Tendon Haemophilic Damage - Ultrasound (THD-US) method
Donati D., Origlio F., Galletti S., Miceli M., Spinnato P., Valdrè L., Piscitelli L., Ricci V., Farella G.M., Vita F., Tedeschi R., Benedetti M.G.
[Article in Press] J Clin Ultrasound 2024 :
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Abstract
This study aimed to develop and validate the tendinopathy hemophilia detection with ultrasonography (THD-US) protocol for assessing hemophilia-related tendinopathy. Twenty male patients with hemophilic arthropathy underwent ultrasound evaluations of 200 tendons. The THD-US scoring method assessed structural changes, hyperemia, and calcifications, revealing various tendon abnormalities. This protocol provides a standardized, efficient method for assessing tendinopathy in hemophilia patients, potentially improving patient management and outcomes.
Non-drug Index Terms
adolescent, adult, article, clinical article, controlled study, diagnosis, diagnostic test accuracy study, echography, hemophilia, hemophilic arthropathy, human, hyperemia, male, patient care, protocol, scoring system, tendinitis, tendon, therapy, ultrasound
Assessment of joint health in patients receiving prophylaxis for haemophilia A: a cross-sectional survey in five European countries
De la Corte-Rodríguez H., Bystrická L., Ball N., Olsen S., Golden K., Hakimi Z., Kragh N.
BMJ Open 2024 14:9 (e082204)
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Abstract
OBJECTIVES: To evaluate joint health, pain and health-related quality of life (HRQoL) in patients with moderate/severe haemophilia A in Europe. DESIGN: Multinational, cross-sectional survey, with retrospective data collection. Data were taken from the Adelphi Real World Haemophilia Disease Specific Programme Wave II, using surveys completed by physicians and patients between February 2020 and May 2021. SETTING: Haematologists/haemato-oncologists and their patients in France, Germany, Italy, Spain and the UK. PARTICIPANTS: Males aged ≥18 years with moderate or severe haemophilia A (baseline clotting factor level ≤5%), without existing inhibitors and currently receiving prophylaxis. Patients were grouped into those with or without haemophilia-affected joints (HAJs) based on bleeding, radiographic, surgical, mobility and joint pain data. PRIMARY OUTCOME MEASURE: Characterisation of humanistic and clinical outcomes in patients with or without HAJs. RESULTS: A total of 120 physicians provided data for 351 eligible patients; 209 (59.5%) patients had HAJs and 142 (40.5%) had no HAJs. Pain/discomfort was significantly different (p=0.01) and reported more frequently in the HAJ (85.7%) vs non-HAJ group (53.3%). Pain medication use was significantly higher in the HAJ versus non-HAJ group (73.2% vs 60.6%; p=0.01). Up to half of the patients with HAJs had synovitis (49.8%) or arthropathy (48.4%), and one-third had undergone joint surgery (35.4%). Overall health status was significantly worse in the HAJ versus non-HAJ group (mean (SD) EuroQol Visual Analogue Scale score: 65.5 (19.3) vs 81.1 (14.6); p=0.01). CONCLUSIONS: In this multinational real-world study, nearly two-thirds of adults with moderate/severe haemophilia A without inhibitors experienced HAJs despite prophylaxis. Individuals with HAJs had higher rates of pain and pain medication use, and lower HRQoL compared with those without HAJs. These data indicate that HAJs represent a clinically relevant burden and early identification/monitoring and management of affected joints should be an important consideration to help prevent long-term joint morbidity.
Non-drug Index Terms
(Based on full text)
adult, arthralgia, arthropathy, clinical trial, complication, cross-sectional study, drug therapy, etiology, Europe, hemarthrosis, hemophilia A, human, male, middle aged, multicenter study, prevention and control, quality of life, retrospective study, young adult
Treatment of Chronic Haemophilic Synovitis with PRP: Clinical and In Vitro Studies
Caviglia H., Landro M.E., Oneto P., Cambiaggi G., Galatro G., Berni M., Caliogna L., Carrera Silva E.A., Pasta G.
Int. J. Mol. Sci. 2024 25:17
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Abstract
Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair. A total of 116 joints, including knees (63%), elbows (19.8%), and ankles (17.2%), were treated with intra-articular injections of PRP. Moreover, we also show here the number of extracellular DNA traps (ETs) and the PRP effect in the synovial fluid of patients at the time of treatment and six months after. Clinically, it is demonstrated that PRP is effective in reducing bleeding episodes (p < 0.001) and pain (p < 0.0001) and improving the hemophilia joint health score (HJHS) (p < 0.001) at one year of follow-up. Furthermore, our results demonstrate that PRP inhibits ET formation in vitro and reconstitutes the immune system’s cellular components in the synovial fluid of patients after treatment. We conclude that PRP can be considered an effective, safe, and easy treatment for hemophilic synovitis.
Drug Index Terms
(Based on full text)
biological marker, cytokine, hemosiderin, hydroxyl radical
Non-drug Index Terms
(Based on full text)
adult, analgesia, angiogenesis, ankle, article, articular cartilage, bleeding, child, chronic hemophilic synovitis, clinical effectiveness, clinical evaluation, controlled study, elbow, extracellular trap, female, follow up, hemarthrosis, hemophilia (therapy), human, in vitro study, iron blood level, knee, major clinical study, male, nociception, plasma, platelet-rich plasma cell, synovial fluid, synovitis (therapy), tenosynovitis, thrombocyte rich plasma, visual analog scale, young adult
Cross-reacting antiporcine factor VIII inhibitors in patients with acquired hemophilia A
Stephen M., Elbaz C., Hanif H., Pavenski K., Teitel J., Sholzberg M.
Res. Pract. Thromb. Haemost. 2024 8:6
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Drug Index Terms
(Based on full text)
blood clotting factor 8 inhibitor, Cross-reacting antiporcine factor VIII inhibitor, hematologic agent, unclassified drug
Non-drug Index Terms
(Based on full text)
anticoagulation, article, bleeding, clinical article, enzyme linked immunosorbent assay, female, follow up, hematoma, hemophilia A, human, male, platelet count, retrospective study
Clinical Outcomes of Total Knee Arthroplasty in Patients Who Have Hemophilic Arthropathy: A Prospective Study
Beckers G., Massé V., Barry J., St-Louis J., Isler M., Vendittoli P.-A., Morcos M.W.
[Article in Press] J. Arthroplasty 2024 :
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Abstract
Background: Total knee arthroplasty (TKA) is considered the gold standard treatment for patients who have advanced hemophilic knee arthropathy. However, special considerations are required for these patients. This prospective study reports on the need for soft-tissue procedures, implant types, complication rates, mean 53.3 months implant survivorship, and patient-reported outcome measures of TKA in hemophilic patients. Methods: There were twenty primary TKAs that were performed on 15 hemophilic patients from 2012 to 2023. The mean follow-up was 53.3 months (range, 6 to 128). The necessity for additional soft tissue procedures, implant type, complications, and revision rates were recorded. Knee Injury and Osteoarthritis Outcome Score, Knee Society Score, Hemophilia-specific Quality of Life Questionnaire for Adults, Hemophilia Activities List, and range of motion, were compared preoperatively and at the last follow-up. Results: At the last follow-up, implant survivorship was 90%. There were 2 revisions: one for aseptic loosening and one for periprosthetic joint infection. Additional soft tissue procedures included 2 quadriceps snips (10%). Tibial augments, tibial stubby stems, and both tibial and femoral traditional stems were used in one (5%), 4 (20%), and one (5%) TKAs, respectively. A constrained posterior-stabilized bearing was necessary in one case. Clinically and statistically significant improvements were found between the preoperative and final follow-up values of all patient-reported outcome measures, knee flexion (73 versus 108 °, P < 0.001), and flexion contracture (11 versus 4 °, P = 0.002). Conclusions: This study showed that TKA, in patients who have hemophilic knee arthropathy, is a reliable treatment option that improves knee function and patients’ quality of life with acceptable implant survival rates at midterm follow-up (mean 53.3 months). Standard implants and approaches can be used in most cases. Despite good outcomes, hemophilic patients carry additional risks for complications that require specific considerations. It is paramount for these patients to be treated in specialized centers by experienced surgeons to achieve good results.
Non-drug Index Terms
adult, adverse device effect, aged, article, clinical outcome, complication, controlled study, flexion contracture, follow up, graft survival, hemophilia, hemophilic arthropathy, human, knee function, Knee Injury and Osteoarthritis Outcome Score, Knee Society Score, major clinical study, male, patient-reported outcome, periprosthetic joint infection, postoperative complication, prospective study, prosthesis loosening, quadriceps femoris muscle, quality of life, questionnaire, range of motion, survival rate, therapy, total knee arthroplasty
Factor VIII Level in the Potential Female Carrier Mothers of Patients with Hemophilia A and Its Impact on Joint Health
El Gawad Tantawy A.A., Ragab I.A., El-Sayed Saqr H.M., Ezz El Din El D.M., El Kader M.S.M.A., Elkyal A.E.E.
QJM 2023 116: (i272)
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Abstract
Background: Hemophilia A is an X-linked bleeding disorder. The characteristic bleeding phenotype in patients with severe hemophilia is recurrent spontaneous hemarthrosis with development of hemophilic arthropathy. Heterozygous female carriers with factor VIII (FVIII) activity level lower than 40% may be at risk for bleeding that is usually comparable to that seen in males with mild hemophilia. Aim of the Work: To assess factor VIII level in mothers of known patients of hemophilia A correlating it with the frequency of clinically and radiologically documented arthropathy. Patients and Methods: A cross sectional study included 40 mothers of patient with hemophilia A during the period from September 2020 to September 2021. Studied participants were subjected to detailed analysis of bleeding history, six major joints range of motion (ROM) examination, functional independence score in hemophilia (FISH), FVIII level one stage assessment and magnetic resonant imaging (MRI) of the reported affected joints. Results: Mean age of mothers is 42.25 ± 7.74 years. Eleven mothers (27.5%) had no bleeding symptoms, 16 (40%) had one bleeding symptoms and 13 (32.5%) had two or more bleeding symptoms. As regard joint pain, 13 (32.5%) had severe pain, 3 (7.5%) had ankle pain and 2 (5%) had elbow pain with a mean pain score of 2.5563.32, and 7 (17.5%) had bilateral pain. Mean FVIII activity was 43.33 IU (6 22.79), ranging from FVIII (0 < 30 IU) in 13 (32.5%), FVIII (30 <60) in 18 (45.0%) and FVIII - 60 IU in 9 (22.5%) among the studied participants. Knees were the most affected joints with decreased mean ROM (6SD) in right and left knees of (123.25 (612.06) and 120.00 (615.81)) respectively. The median MRI scores were studied was 5 (2.6%) with median osteochondral changes of 4 (2.5%) and median soft tissue changes of 1 (0-1), their median FISH score of 8 (8-9). By comparing groups at the level of factor VIII, there was no significant difference according to anthropometric bleeding parameters, pain, and MRI score. None of participants needed hospital admission, factor VIII replacement or packed red cells replacement. Conclusion: Potential female hemophilia A carriers are at risk of spontaneous bleeding which may entail bleeding in the joints, causing early joint damage. They showed reduced overall joint ROM and structural osteochondral changes in MRI joint examination which mandates further studies about early detection of potential female hemophilia carriers for the possible need of early medical intervention.
Drug Index Terms
(Based on full text)
blood clotting factor 8
Non-drug Index Terms
(Based on full text)
adult, ankle pain, arthralgia, arthropathy, bleeding, clinical article, conference abstract, cross-sectional study, diagnosis, drug therapy, early intervention, erythrocyte concentrate, female, fluorescence in situ hybridization, hemarthrosis, hemophilia, hemophilia A, hemophilic arthropathy, hospital admission, human, joint examination, male, mother, MRI scanner, nuclear magnetic resonance imaging, phenotype, range of motion, therapy
A post hoc analysis of PROTECT VIII Kids assessing long-term efficacy and safety of damoctocog alfa pegol in adolescents with severe haemophilia A
Eur J Haematol 2024 113:3 (386)
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Drug Index Terms
(Based on full text)
blood clotting factor 8 (drug therapy, adverse drug reaction), macrogol (drug therapy, drug administration)
Non-drug Index Terms
(Based on full text)
adolescent, child, drug therapy, female, hemophilia A, human, male, severity of illness index, treatment outcome
Plain language summary on "Interim analyses of the multinational real-world prospective cohort HEM-POWR study evaluating the effectiveness and safety of damoctocog alfa pegol in patients with hemophilia A"
Eur J Haematol 2024 113:3 (387)
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Drug Index Terms
(Based on full text)
blood clotting factor 8 (drug therapy, adverse drug reaction, drug administration)
Non-drug Index Terms
(Based on full text)
drug therapy, hemophilia A, human, prospective study, treatment outcome
Proactive Systematic Hemophilia Carrier Screening: A Step Towards Gender Equity in Hemophilia Care
Krumb E., Lambert C., Van Damme A., Hermans C.
[Article in Press] Blood Adv 2024 :
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Abstract
Despite numerous efforts to raise awareness, many hemophilia carriers and female persons with hemophilia (PWHs) remain undiagnosed. Between May 2021 and April 2023, we identified potential and obligate carriers of hemophilia A (HA) and B (HB) by updating pedigrees of all PWHs followed at the Cliniques universitaires Saint-Luc, Brussels. Retrospective data on previously screened females were collected, including bleeding history, coagulation factor levels, and testing for the proband's pathogenic variant. Additionally, a proactive approach involved sending 125 invitation letters to unscreened or incompletely screened individuals, through related PWHs. In pedigrees of 287 male PWHs (226 HA, 61 HB) and 7 female index patients from 236 families (184 HA, 52 HB), a total of 900 female individuals were identified. Of those, 454 were obligate and/or genetically proven carriers, and 118 were noncarriers. Genetic testing was conducted in 133 obligate, 237 potential, and 4 sporadic carriers, with 190 obligate and 328 potential carriers remaining untested. Among carriers with known factor levels (261/454), 42 (23.0%) HA and 23 (29.5%) HB carriers, had a factor level below 40 IU/dL. Carriers with a factor deficiency were screened on average 6 years earlier than other females (p=0.034). This study represents the first systematic effort to identify potential carriers among families of all PWHs within a single center, emphasizing the challenges in comprehensive screening for female individuals genetically linked to one or more PWHs. Such initiatives are vital for achieving equitable access to hemophilia care for all potentially affected individuals, irrespective of gender. Clinical.Trials.gov identifier: NCT05217992.
Drug Index Terms
blood clotting factor
Non-drug Index Terms
adolescent, adult, article, bleeding, Brussels Capital Region, diagnosis, etiology, female, gender, gender equity, genetic screening, hemophilia, hemophilia A, human, major clinical study, male, pedigree, retrospective study, screening
Spontaneous resolution and bone regeneration in hemophilic pseudotumor: A rare case report and literature review
Singh K., Gupta S., Aggarwal S.
[Article in Press] Spec Care Dentist 2024 :
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Abstract
AIM: Hemophilic pseudotumor (HP) is a very rare complication of hemophilia seen in only 1-2% of the cases. Although it is much more common in long bones, pelvis and small bones of hands and feet and very rarely involving jaw bones. METHOD AND RESULT: In the present case, the presence of a rare hemophilic pseudotumor of the mandible with the positive history of Hemophilia B justifies that the history, clinical and radiological examinations were sufficient to arrive at conclusive diagnosis precluding invasive diagnostic procedures such as biopsy hence avoiding the risk of hemorrhage, infection, or fistula. This case also highlights that patient was conservatively managed with Factor IX replacement alone with a very good clinical outcome. CONCLUSION: HP should be considered as a differential diagnosis of any progressive swelling of hard and soft tissues occurring in a patient with severe haemophilia.
Drug Index Terms
blood clotting factor, blood clotting factor 9
Non-drug Index Terms
adult, article, bone regeneration, case report, clinical article, clinical outcome, complication, diagnosis, differential diagnosis, drug therapy, edema, hemophilia, hemophilia B, human, human tissue, long bone, mandible, pseudotumor, swelling, therapy
Clot-Wave-Analyse könnte individualisierte Therapie bei Hämophilie A verbessern
Hamostaseologie 2024 44:4 (240)
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Original (Non-English) Title
Clot-Wave-Analyse könnte individualisierte Therapie bei Hämophilie A verbessern
Drug Index Terms
(Based on full text)
blood clotting factor 8 (drug therapy)
Non-drug Index Terms
(Based on full text)
blood clotting test, hemophilia A, human, personalized medicine, procedures, therapy
Quality of life of siblings of adolescents with severe haemophilia (FRATHEMO): An ancillary study to the TRANSHEMO project
Nguyen N.A.T., Auquier P., Beltran Anzola A., Harroche A., Huguenin Y., Hochart A., Meunier S., Frotscher B., Nguyen P., Schneider P., Berger C., Lebreton A., Vanderbecken S., De Raucourt E., D'Oiron R., Oudot-Challard C., Baumstarck K., Boucekine M., Tabélé C., Rosso-Delsemme N., Sannié T., Giraud N., Chambost H., Resseguier N.
Haemophilia 2024 30:4 (1071-1076)
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Non-drug Index Terms
(Based on full text)
adolescent, aged, anxiety, bleeding, bleeding disorder, child, chronic disease, hemophilia, human, letter, male, quality of life, questionnaire, school child, sibling
The association between unemployment and treatment among adults with hemophilia
Qvigstad C., Sørensen L.Q., Tjønnfjord G.E., Holme P.A., Pabinger I., Hermans C., Roseline d'Oiron , Klamroth R., Oldenburg J., Marquardt N., Staritz P., Katsarou O., Martinowitz U., Lubetsky A., Kenet G., Tagliaferri A., Mancuso M.E., Schutgens R., Windyga J., Zupan I., Yuste V.J., Nunez R., de Moerloose P., Berntorp E., Astermark J., Tait C., Dolan G.
Res. Pract. Thromb. Haemost. 2024 8:5
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Abstract
Background: People with hemophilia often experience pain and suffer from comorbidities related to their bleeding disorder. Consequently, unemployment due to disability is prevalent among people with hemophilia. Objectives: To explore associations between unemployment due to disability and treatment while adjusting for known risk factors for unemployment. Methods: Collecting data from 20 hemophilia centers from 15 European countries, the Age-related DeVelopments ANd ComorbiditiEs in hemophilia study recruited 785 participants aged 40 years and over with hemophilia A or B. A comprehensive electronic case report form included items related to patient characteristics, demographic information, past and current treatment regimens, and medical history, including a lifelong history of comorbidities. Baseline data from the Age-related DeVelopments ANd ComorbiditiEs in hemophilia study was analyzed using descriptive statistics and logistic regression models. Results: Employment status was available for 756 of 785 participants aged 40 to 88 years (median, 53 years). We used regression analysis to compare people with hemophilia who were fully employed with those who were unemployed due to disability. This analysis included 424 participants. Using multivariable logistic regression, we found that age (odds ratio [OR], 1.07; P <.01), severe hemophilia (OR, 10.81; P <.01), current smoker (OR, 2.53; P <.01), and psychiatric disorder (OR, 4.18; P =.02) were associated with increased odds of unemployment due to disability. In contrast, prophylactic treatment (OR, 0.44; P =.01) was associated with decreased odds. Conclusion: Our analysis suggests that by maintaining factor levels above a critical threshold (3%-5%), prophylactic treatment for people with hemophilia could help avoid unemployment due to disability. While prophylaxis is more costly and can be burdensome, the benefits to material well-being and quality of life could be substantial.
Non-drug Index Terms
(Based on full text)
adult, age, article, cross-sectional study, current smoker, data analysis software, disability, disease association, disease severity, employment status, female, full time employment, hemophilia, hemophilia A, hemophilia B, human, logistic regression analysis, male, mental disease, middle aged, multicenter study, obesity, observational study, parttime employment, prophylaxis, prospective study, R (version 4.3.2) software, R package (version 2.0.0) software, retirement, risk factor, unemployment
Acquired hemophilia A after SARS-CoV-2 infection: a causal or casual association?
Zugasti I., Guardia A., Jordà-Sánchez R., Cuartas-González A., Nomdedeu M., Arellano-Rodrigo E.
Emerg. 2024 36:3 (228-231)
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Original (Non-English) Title
Hemofilia A adquirida tras la infección por SARS-CoV-2: ¿una asociación causal o casual?
Non-drug Index Terms
(Based on full text)
acquired hemophilia A (complication), coronavirus disease 2019, hemophilia A (complication), human, letter
Sexual functioning in men with haemophilia: Data from the haemophilia in the Netherlands-6 study
van Gastel T.C.M., Teela L., Mauser-Bunschoten E.P., Coppens M., Peters M., Fijnvandraat K.C.J., Haverman L., Gouw S.C.
[Article in Press] [In Process] Haemophilia 2024 :
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Non-drug Index Terms
adult, hemophilia, human, letter, major clinical study, male, Netherlands, sexuality
Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review
Reding M.T., Lalezari S., Kenet G., Di Minno G., Ducore J., Solms A., Shah A., Holme P.A., Poulsen L.H., Meijer K., Simpson M., Mancuso M.E.
[Article in Press] Drugs R D 2024 :
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Abstract
Damoctocog alfa pegol (BAY 94-9027, Jivi®), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies. The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate®), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta®; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate®/Adynovi®; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate®; NCT02483208). Damoctocog alfa pegol was generally well tolerated and none of the patients in any of the clinical trials, including the PROTECT VIII clinical program, HEM-POWR, or ongoing single-center studies, developed FVIII inhibitors. Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences.
Drug Index Terms
benzthiazide, blood clotting factor 8, fusion protein, recombinant blood clotting factor 8, sucrose
Non-drug Index Terms
adverse drug reaction, aged, bleeding, child, clinical trial, controlled study, genetic recombination, half life time, hemophilia A, hemostasis, human, major clinical study, multicenter study, pharmacokinetics, phase 3 clinical trial, prophylaxis, review, side effect, therapy
Differences and similarities in patient-reported outcomes among men and women with haemophilia
Kempton C.L., Guasch S.A., Buckner T.W., Mattis S., Fedewa S.A.
[Article in Press] Haemophilia 2024 :
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Abstract
Introduction: Both men and women can be diagnosed with haemophilia and the experience with haemophilia may be different between men and women. Aim: This study aimed to compare patient-reported outcomes in men versus women with haemophilia. Methods: This cross-sectional study is a post-hoc analysis of data collected as part of the Haemophilia-related Distress Questionnaire validation study. Adults aged ≥18 years with haemophilia A or B were recruited from one of two haemophilia treatment centres between July 2017 and December 2019. Outcomes included quality of life, measures of mental and physical health, and overall health. Unadjusted and multivariable linear regression models were used to examine potential mediators of sex-based differences in outcomes. Results: Of the 139 study participants included (21 women, 118 men), the mean age was 36.9 years and most (89.2%) had haemophilia A. Approximately 85.7% and 26.3% of women and men had mild haemophilia, respectively. PHQ-9 depression and PROMIS-29 Profile anxiety and fatigue scores were significantly higher in women than men in unadjusted and adjusted analyses. There were no statistically significant differences in other outcomes. Conclusions: Women with haemophilia are more likely to experience depression, anxiety, and fatigue than men with haemophilia. This study highlights the need for mental health services to be integrated into the care of women with haemophilia. Future research is needed to understand whether women with haemophilia are more or less likely to experience depression, anxiety, and fatigue than women without haemophilia as well as determine the impact of reduced mental health on clinical outcomes.
Non-drug Index Terms
adult, aged, anxiety, article, clinical outcome, cohort analysis, controlled study, cross-sectional study, depression, distress syndrome, fatigue, female, hemophilia, hemophilia A, human, major clinical study, male, mental health, mental health service, pain, Patient Health Questionnaire 9, patient-reported outcome, post hoc analysis, quality of life, questionnaire, validation study
Efficacy of rehabilitation interventions on functioning in patients with hemophilic arthropathy: A systematic review with meta-Analysis
Lippi L., De Sire A., Turco A., Santi R.M., Polverelli M., Ammendolia A., Follenzi A., Invernizzi M.
J. Back Musculoskelet. Rehabil. 2024 37:4 (853-870)
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Abstract
BACKGROUND: Hemophilic arthropathy is a detrimental condition that crucially affects functional outcomes in hemophilic patients. In recent years, due to the advances in systemic therapies, growing attention has been raised in the rehabilitation field in order to improve functional outcomes of hemophilic patients. However, the optimal rehabilitation modalities in these patients are far from being fully characterized. OBJECTIVE: The present study aimed to assess the effects of different rehabilitation interventions on physical functioning and health-related quality of life of hemophilic arthropathic patients. METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Five databases were systematically searched for randomized controlled trials (RCTs) published until June 22nd, 2023. The selection criteria included adult patients with hemophilia A and B receiving rehabilitation interventions. The outcomes were muscle strength, physical function, pain intensity, physical performance, and health-related quality of life. RESULTS: Out of 1,743 identified records, 17 studies were included in the qualitative synthesis. Rehabilitation interventions were categorized into exercise intervention, fascial therapy, and multimodal intervention. The findings suggested positive outcomes in terms of muscle modifications, range of motion improvements, joint health enhancements, pain intensity reduction, and quality of life improvements. More in detail, meta-Analyses showed significant improvements in pain intensity [ES:-1.10 cm (-1.37,-0.82), p< 0.00001], joint health [ES:-1.10 (-1.38,-0.82), p< 0.00001], In accordance, exercise interventions showed significant benefits in terms of joint health [ES:-2.54 (-3.25,-1.83), p< 0.00001)] and quality of life [ES: 1.17 (0.48, 1.86), p< 0.0000)]. CONCLUSION: Rehabilitation interventions have a positive impact on functional outcomes and health-related quality of life of hemophilic arthropathic patients. Further studies are needed to better elucidate the role of a comprehensive intervention combining different rehabilitation approaches to treat hemophilic arthropathy.
Non-drug Index Terms
(Based on full text)
adult, Cochrane Library, endurance training, evidence based practice, exercise, hemophilia A, hemophilia B, hemophilic arthropathy (disease management, rehabilitation), human, Medline, meta analysis, muscle strength, pain intensity, physical performance, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, quality of life, randomized controlled trial (topic), range of motion, resistance training, review, Scopus, Short Form 36, systematic review, Web of Science
Estimated prophylactic dose required to achieve 3% trough as a function of age and concentrate class in multi-country severe WAPPS-Hemo haemophilia patients
Hajducek D.M., Chelle P., Iorio A., Iserman E., Edginton A.N.
Haemophilia 2024 30:4 (925-932)
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Abstract
Introduction: Web-Accessible Population–Pharmacokinetic Service–Haemophilia (WAPPS-Hemo) data are available to study factor-concentrate usage, defined as the required weekly dose to achieve a 3% trough (WD3T), across standard and extended half-life (SHL/EHL) products. Aim: To provide baseline usage data including (i) differences across plasma-derived (pdSHL) versus recombinant (rSHL) products, (ii) SHL versus EHL, and (iii) effect of age and positive inhibitor history. Methods: PK profiles (n = 14,416 patients, 0.3–85.2 years) and linear mixed effects models were used to estimate usage versus age, controlling for significant factors, using 95% confidence intervals to perform comparisons across all ages and posthoc tests to assess the differences. Results: Average usage was significantly higher for pdSHL versus rSHL in patients with a positive inhibitor history (PIH; 1.9–2.5 times higher), for SHL versus EHL (4–10 times), and was significantly associated with age. Conclusion: Baseline usage patterns from 2017 to early 2023 provide a benchmark for assessing the impact of emerging technologies in haemophilia.
Drug Index Terms
(Based on full text)
blood clotting factor 8, blood clotting factor 9
Non-drug Index Terms
(Based on full text)
adolescent, adult, aged, algorithm, article, child, data analysis software, drug half life, female, half life time, hemophilia, human, infant, major clinical study, male, maximum likelihood method, pediatric patient, pharmacokinetics, prophylaxis, R package v1.5.4., R programming language v.4.4, very elderly
Humanistic burden of haemophilia A without inhibitors: A cross-sectional analysis of the HemoLIFE study
Álvarez-Román M.T., Nuñez Vazquez R.J., Benitez Hidalgo O., Quintana Paris L., Entrena Ureña L., Lopez Jaime F.J., la De Corte-Rodríguez H., García Dasí M., Bosch P., Mingot Castellano M.E., Guerra Garaeta I., Soto-Ortega I.
Haemophilia 2024 30:4 (950-958)
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Abstract
Aim: To evaluate the impact of haemophilia A without inhibitors on humanistic outcomes in patients and caregivers. Herein, we report a cross-sectional analysis of the baseline data of persons with haemophilia (PWH) participating in the prospective study HEMOLIFE. Methods: These data are part of a prospective, observational, and multicentre study currently being conducted in 20 hospitals in Spain by haematologists. We included subjects 12 years or older diagnosed with haemophilia. The evaluations included the Maladjustment Scale, Haemophilia–Specific Quality of Life Questionnaire for Adults (HaemoQol)/HaemoQol Short Form (Children), haemophilia-specific version of the Work Productivity and Impairment Questionnaire plus the Classroom Impairment Questionnaire (WPAI+CIQ:HS), Haemophilia Activity List (HAL)/Paediatric Haemophilia Activities List (pedHAL), visual analogue scale (VAS) for evaluating pain, Coping Pain Questionnaire–Reduced (CAD-R), and Hospital Anxiety and Depression Scale (HADS). Results: A total of 81 PWH were recruited at 18 centres; 66 PWH were ≥18 years (i.e., adults), and PWH 15 were <18 years (i.e., paediatric patients). Out of the 79 evaluable subjects, 16 (20%) showed an impact of haemophilia on daily life, and the areas most affected were “leisure time” (58% showed maladjustment) and “work/studies” (47% showed maladjustment). Patients reported a higher impact of haemophilia on quality of life (mean [SD] of the transformed score) in the dimensions of “sport” (49.4 [28.6]), “physical health” (40.5 [25.8]) and “future” (37.7 [28.9]). In adults, according to HAL scores, greater impairment of function was observed in “lying/sitting/kneeling/standing,” “function of legs” and “leisure activities and sports,” with mean normalized scores of 64.7, 65.1 and 69.0, respectively. Productivity was mostly impacted by presenteeism. The pain was infrequent and moderate. According to the HADS scores, nine (11.5%) patients had clinical anxiety and depression. Conclusion: PWH without inhibitors exhibited impairments in adjustment, quality of life and functionality, especially related to leisure and sports activities, and exhibit relevant levels of anxiety and depression.
Non-drug Index Terms
(Based on full text)
absenteeism, adult, anxiety, article, Beck Depression Inventory, body mass, caregiver, cross-sectional study, depression, disease severity, distress syndrome, hematocrit, hemophilia, hemophilia A, Hepatitis C virus genotype 1, Hospital Anxiety and Depression Scale, human, human experiment, information seeking, job satisfaction, leisure, Likert scale, Mini Mental State Examination, multicenter study, observational study, pain, physical activity, physical examination, presenteeism, prevalence, prospective study, prothrombin time, quality of life, questionnaire, scoring system, Short Form 36, social support, visual analog scale
Functional clinical motor performance tests to assess potential fall risks in patients with haemophilia: A case-control study
Tomschi F., Brühl M., Schmidt A., Ransmann P., Strauss A.C., Hilberg T.
Haemophilia 2024 30:4 (1032-1042)
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Abstract
Introduction: 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. Aims: (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. Methods: 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. Results: 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). Conclusion: 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.
Non-drug Index Terms
(Based on full text)
adult, article, blood clotting, body mass, case control study, controlled study, dizziness, elbow flexion, fall risk, falling, grip strength, hemophilia, hemophilia A, hemophilic arthropathy, human, kinesiophobia, major clinical study, male, motor performance, muscle exercise, physical activity, physical performance, questionnaire, range of motion, timed up and go test, walking
Identifying hemophilia B carriers: Utility of aPTT, factor IX levels and ratios of factor IX to other Vitamin K dependent factors
Shu M., Malcolmson C., Bosch A., Markovic T., Wakefield C., Bouskill V., Carcao M.
Haemophilia 2024 30:4 (1003-1009)
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Abstract
Introduction: Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold-standard, however it is reserved for individuals with a high suspicion of carrier status. Aims: To describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIX:C) levels in HB carriers and assess the ratio of FIX:C to other Vitamin K dependent factors (FII:C, FVII:C, FX:C) as an indicator of HB carrier status. Methods: In this retrospective, single-centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIX:C were described and the relationship between FIX:C levels in carriers and severity of familial HB was analysed. Ratios of FIX:C to FII:C, FVII:C, FX:C were calculated. Results: Seventy-two female HB carriers (median age: 34 years; IQR 24–43) were included. Median aPTT and FIX:C levels were 33.0 s [IQR 30.0–37.0] and 57 IU/dL [IQR 43–74]. Fifteen carriers (21%) had mild HB (FIX:C levels of 10–40 IU/dL). FIX:C levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIX:C to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75. Conclusion: aPTT and FIX:C levels were unreliable in diagnosing HB carrier status. A low ratio of FIX:C to other Vitamin K dependent factors may be a useful marker of HB carrier status.
Drug Index Terms
(Based on full text)
antivitamin K, blood clotting factor 8 (endogenous compound), blood clotting factor 9 (endogenous compound), thromboplastin (endogenous compound)
Non-drug Index Terms
(Based on full text)
activated partial thromboplastin time, adult, article, bleeding, blood clotting, blood group ABO system, cohort analysis, data analysis software, disease carrier, female, genetic analysis, genetic screening, genetic variability, genotyping, gold standard, hemophilia B, heterozygosity, heterozygote, human, major clinical study, partial thromboplastin time, retrospective study, SPSS Statistics for Windows Version 28.0
Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS)
Fischer K., Lassila R., Peyvandi F., Gatt A., Gouw S.C., Hollingsworth R., Lambert T., Kaczmarek R., Carbonero D., Makris M., Ay C., Male C., Hermans C., Verhamme P., Lissitchkov T., Antoniades M., Penka M., Blatny J., Komrska V., Poulsen L.H., Kampmann P., Lehtinen A.-E., Susen S., Dargaud Y., Biron C., D'Oiron R., Harroche A., Klamroth R., Oldenburg J., Buehrlen M., Miesbach W., Langer F., Spannag P., Oliveri M., Platokouki H., Nomikou E., Katsarou O., Garypidou V., Economou M., Nemes L., Nolan B., O'Connell N., Paolo R., Castaman G., Rocino A., Zanon E., Tagliaferri A., Agnelli G., De Crisotofaro R., Schinco P., Tosetto A., Lejniece S., Gailiute N., Mäkelburg A., Laros-van Gorkom B., Brons P., Leebeek F.W.G., Schutgens R., Windyga J., Catarino C., Aires A., Fraga C., Morais S., Araújo F., Serban M., Davydkin I., Batorova A., Anzej Doma S., Martinez L.S., Palomo Bravo A., Ortega I.S., Bonanad S., Baghaei F., Astermark J., Holmström M., Fontana P., Schmugge M., Zulfikar B., Kavakli K., Khan M., Benson G., Lester W., Andrew P., Catherine B., Pinto F., Salta S., Farrelly C., Matthias M., Laffan M., Thynn Thynn Y., Mcdonald V., Austin S., Bella M., Hay C., Grainger J., Talks K., Shapiro S., Maclean R., Payne J.
Res. Pract. Thromb. Haemost. 2024 8:4
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Abstract
Background: Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited. Objectives: To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B. Methods: Inhibitor development in PTPs was collected since 2008 from 97 centers participating in European HAemophilia Safety Surveillance. Per concentrate, inhibitors were reported quarterly and the number of PTPs treated annually. Incidence rates (IRs)/1000 treatment years with 95% CIs were compared between concentrate types (plasma derived FVIII/FIX, standard half-life recombinant FVIII/FIX, and extended half-life recombinant (EHL-rFVIII/IX) concentrates using IR ratios with CI. Medians and IQRs were calculated for inhibitor characteristics. Results: For severe haemophilia A, inhibitor rate was 66/65,200 treatment years, IR 1.00/1000 years (CI 0.80-1.30), occurring at median 13.5 years (2.7-31.5) and 150 EDs (80-773). IR on plasma-derived pdFVIII (IR, 1.13) and standard half-life recombinant FVIII (IR, 1.12) were similar, whereas IR on EHL-rFVIII was lower at 0.13 (incidence rate ratio, 0.12; 95% CI, <0.01-0.70; P < .01). For severe hemophilia B, inhibitor rate was 5/11,160 treatment years and IR was 0.45/1000 years (95% CI, 0.15-1.04), at median 3.7 years (95% CI, 2.1-42.4) and 260 EDs (95% CI, 130 to >1000). Data were insufficient to compare by type of FIX concentrates. Conclusion: Low inhibitor rates were observed for PTPs with severe hemophilia A and B. Data suggested reduced inhibitor development on EHL-rFVIII, but no significant difference between plasma-derived FVIII and standard half-life recombinant FVIII. FIX inhibitor rates were too low for robust statistical analysis.
Drug Index Terms
(Based on full text)
blood clotting factor 8, blood clotting factor 8 concentrate, blood clotting factor 9, blood clotting factor concentrate, neutralizing antibody, recombinant blood clotting factor 8
Non-drug Index Terms
(Based on full text)
adolescent, adult, article, child, data analysis software, disease surveillance, drug safety, exposure, half life time, hemophilia, hemophilia A, hemophilia B, human, immunogenicity, incidence, monotherapy, phase 3 clinical trial (topic), risk factor, SPSS Version 29.0
Matched cohort study evaluating the hemostatic efficacy of fibrin sealant versus conventional approaches following dental surgery in patients with hemophilia
Pai N., Dhaimade P., Chaudhari V.L., Shanmukaiah C., Gujar H., Raj J.P.
[Article in Press] Int. J. Oral Maxillofac. Surg. 2024 :
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Abstract
Patients with hemophilia frequently require supplementary interventions, either invasive (suturing, gel foam, or cauterization) or non-invasive (fibrin sealant/glue), to attain hemostasis post dental procedures. This study aimed to compare the efficacy of fibrin sealant against traditional methods for achieving hemostasis post dental surgery. The medical records of patients with factor VIII or IX deficiency, or von Willebrand disease, who underwent dental procedures in the Department of Dentistry, Seth GSMC and KEM Hospital, were evaluated for inclusion in this retrospective matched cohort study. Cohort-1 included those treated with a fibrin sealant (Tisseel Lyo) with/without traditional hemostatic measures post-procedure, while cohort-2 (controls) included those in whom no fibrin sealant was used. A total of 128 patients, 64 in each group, were evaluated. There was no statistically significant difference in demographics, disease-related variables, dental complaints, or preoperative treatment given between the groups. However, there was a significant reduction (P < 0.001) in the requirement for secondary procedures for hemostasis (suturing, gel foam application, and/or cauterization) and postoperative requirement for factor replacement (P = 0.003) in the fibrin glue group as compared to the controls. In this study, fibrin sealant demonstrated superior efficacy in mitigating the necessity for active hemostasis control.
Drug Index Terms
blood clotting factor 8, gelfoam, glue
Non-drug Index Terms
adult, article, cauterization, cohort analysis, controlled study, dental procedure, dental surgery, drug therapy, female, hemophilia, hemophilia A, hemophilia B, hemostasis, human, male, preoperative treatment, retrospective study, special situation for pharmacovigilance, von Willebrand disease
