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1.
Haemophilia ; 30(3): 827-835, 2024 May.
Article En | MEDLINE | ID: mdl-38600680

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


Ankle Joint , Hemophilia A , Pain Perception , Humans , Hemophilia A/complications , Hemophilia A/physiopathology , Ankle Joint/physiopathology , Ankle Joint/pathology , Male , Adult , Pain Perception/physiology , Female , Middle Aged , Young Adult , Ultrasonography , Pain Threshold
2.
Haemophilia ; 30(3): 780-790, 2024 May.
Article En | MEDLINE | ID: mdl-38507270

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


Gait Analysis , Gait , Hemophilia A , Humans , Hemophilia A/complications , Hemophilia A/physiopathology , Gait Analysis/methods , Male , Adult , Gait/physiology , Young Adult , Joint Diseases/physiopathology , Joint Diseases/diagnosis , Female , Middle Aged , Adolescent
3.
J Back Musculoskelet Rehabil ; 37(3): 599-609, 2024.
Article En | MEDLINE | ID: mdl-38160338

BACKGROUND: Haemophilic arthropathy is likely to influence posture and muscle stiffness in adolescent male haemophilia patients (HP). OBJECTIVE: This study aimed to investigate the possible change in upright standing posture and stiffness of the superficial postural muscles in HP. METHODS: Twenty-two HP aged between 12 and 19 years and twenty-two healthy peers were included in the study. The photogrammetry was used to assess the upright standing posture from sagittal and frontal planes. Also, stiffness of the superficial postural muscles was evaluated using the myotonometry. RESULTS: A significant difference was found in the craniovertebral, lumbar lordosis, knee flexion-valgus, and ankle plantar flexion angles between the groups (p< 0.05). Craniovertebral, knee flexion, and knee valgus angles were lower; whereas lumbar lordosis and ankle plantar flexion angles were higher in HP compared to the healthy peers. Stiffness of the rectus femoris muscle was lower in HP (p< 0.001). CONCLUSION: This study revealed that the ankle, knee, lumbar, and craniovertebral segments' posture angles were changed and the stiffness of the rectus femoris muscle decreased in HP. Postural alterations and reduced rectus femoris stiffness should be considered in management of the musculoskeletal complications of haemophilia.


Hemophilia A , Posture , Humans , Male , Hemophilia A/physiopathology , Hemophilia A/complications , Adolescent , Posture/physiology , Child , Young Adult , Case-Control Studies , Quadriceps Muscle/physiopathology , Quadriceps Muscle/physiology , Range of Motion, Articular/physiology
4.
Platelets ; 33(1): 168-170, 2022 Jan 02.
Article En | MEDLINE | ID: mdl-33426985

B-cell lymphoproliferative diseases may be associated with acquired hemostasis disorders, such as acquired hemophilia A (AHA) caused by autoantibodies that neutralize factor VIII activity, and δ-storage pool deficiency, an abnormality of platelet function due to defective dense granules and impaired secretion. We describe the case of a 67-year-old man in whom these two acquired bleeding disorders were concomitantly present as the first clinical manifestation of an indolent non-Hodgkin lymphoma. Immunosuppressive therapy with prednisone was initially started to eradicate anti-FVIII antibodies, subsequently boosted with cyclophosphamide and rituximab, these medications being also chosen to treat the associated indolent lymphoma. Bleeding symptoms were first tackled with limited benefit by using rFVIIa and then rescued using recombinant porcine FVIII. After a 6 month's follow-up lymphoma and AHA were in remission and platelet function was improved. This case underlines the need of multiple and complex diagnostic and therapeutic approaches to rare acquired bleeding disorders associated with lymphoproliferative diseases.


Albinism/complications , Hemophilia A/etiology , Hemorrhagic Disorders/complications , Hermanski-Pudlak Syndrome/complications , Lymphoma, Non-Hodgkin/complications , Aged , Hemophilia A/physiopathology , Humans , Male
5.
J Chin Med Assoc ; 85(2): 228-232, 2022 02 01.
Article En | MEDLINE | ID: mdl-34698692

BACKGROUND: Total knee replacement (TKR) surgery is a treatment option for advanced hemophilic arthropathy. Due to its rarity and complexity, previous reports could only demonstrate the results of single-site studies including few cases. This population-based study aimed to investigate the major epidemiological characteristics, mean consumption of coagulation factors, length of hospital stays, complications, and failure rate of primary TKR for severe hemophilia patients in Taiwan. METHODS: A cohort of 996 hemophilia patients registered between 1995 and 2011 was included, and 103 primary TKRs were performed on 75 patients. Unilateral TKR was performed on 47 patients and bilateral TKRs on the remaining 28 patients, including 12 simultaneous and 16 staged surgeries. The mean age at surgery was 32.3 years (range, 17.3-55.7), and the mean follow-up duration was 77.9 months (range, 2.3-176.8). RESULTS: Failure was noted in 8 patients (8.5%) at mean 32.8 months (range, 2.3-95) after surgery. Four patients revealed aseptic loosening, whereas infection in 4. The 10-year prosthesis survivorship was 88.6%. For patients receiving unilateral TKR, the mean length of hospital stay was 15 days (range, 7-32). The mean cost of factor supplement was United States Dollar (USD) 43 543 with a mean 4-unit packed red blood cells transfusion (range, 0-38). The total admission cost was USD 48 326 (range, USD 4165-262 619). CONCLUSION: The prevalence of TKA for hemophilia patients was 7.5% in Taiwan. The mean hospital stay was 14 days, and the 10-year prosthesis survivorship was 88.6%. The mean daily factor usage was decreased from 235.7 units preoperatively to 202.1 units postoperatively. In comparison with the staged-bilateral TKRs, the simultaneous procedures significantly reduced the mean total cost from USD 101 923 to USD 61 587 (p = 0.023). Therefore, in terms of cost-effectiveness, bilateral simultaneous TKR is more preferable than staged procedures.


Arthroplasty, Replacement, Knee , Hemophilia A/physiopathology , Joint Diseases/physiopathology , Adolescent , Adult , Humans , Middle Aged , Patient Acuity , Retrospective Studies , Taiwan , Young Adult
6.
Andes Pediatr ; 92(2): 219-225, 2021 Apr.
Article Es | MEDLINE | ID: mdl-34106160

INTRODUCTION: In Chile, hemophilia was incorporated into the System of Explicit Health Guarantees (GES), which ensures access to treatment and financial protection for these patients. To support patients and their families, educational programs have been proposed that focus on managing possible complications of the pathology, first aid, and prophylaxis, however, there are no educational instances focused on the needs of the patients. OBJECTIVE: To know the educational needs of parents with hemophilic chil dren and adolescents regarding contents, people, place, methodology, and stage of the illness. Sub jects and Method: Descriptive qualitative study of 15 parents with hemophilic children in outpatient care. For the data collection, we used a semi-structured interview with five open questions, aimed at the search for educational needs such as what (contents), how (methodology), when (moment), who (person), and where (place) is education needed. For data analysis, were used the Berelson's content analysis technique. To guarantee the scientific validity of the qualitative results, the methodological rigor criteria of Guba and Lincoln were used. RESULTS: The most frequent educational needs reported by parents include content such as venipuncture training, injury prevention, pathophysiological as pects of the disease, among others; with methodology developed in group workshops and guided by a peer; in a comfortable and familiar place; in three stages of the disease's development (diagnosis, blee ding events, and development of autonomous activities), and provided by professionals and peers. CONCLUSION: Knowledge of educational needs is the basis for the creation of an educational program that guides the comprehensive care of hemophilic children and their parents.


Comprehensive Health Care , Hemophilia A/therapy , Hemophilia B/therapy , Needs Assessment , Parents/education , Adolescent , Ambulatory Care , Child , Chile , Female , Health Knowledge, Attitudes, Practice , Hemophilia A/physiopathology , Hemophilia B/physiopathology , Hemorrhage/prevention & control , Humans , Male , Phlebotomy , Qualitative Research , Self Care , Wounds and Injuries/prevention & control
7.
Int J Hematol ; 113(6): 884-892, 2021 Jun.
Article En | MEDLINE | ID: mdl-33677769

Since the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related diseases such as cardiovascular disease (CVD) have also become more prevalent in PwH. This cross-sectional study aimed to evaluate CVD risk factors and estimate 10-year risk for CVD events among PwH. Male patients ≥ 30 years were interviewed and examined. Blood tests were performed at the local laboratory. Eighty-two patients were included, of whom 83% had haemophilia A and half had severe disease. Median age at study entry was 43.0 years (interquartile range [IQR], 36.0-51.3). Prevalence of obesity, systemic arterial hypertension (SAH) and diabetes mellitus were 16%, 60% and 16%, respectively. Hypertriglyceridaemia, hypercholesterolaemia and low HDL blood levels were present in 18%, 41% and 30% of patients, respectively. Metabolic syndrome was found in 37%. The Framingham Risk Score showed that 39% of PwH had a high risk of developing cardiovascular events in the following 10 years. We conclude that, in this cohort, PwH have a higher prevalence of SAH when compared with Brazilian men without haemophilia and about two-fifths have a high risk of developing a CVD event in the following 10 years.


Cardiovascular Diseases , Hemophilia A , Adult , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Cross-Sectional Studies , Female , Hemophilia A/blood , Hemophilia A/complications , Hemophilia A/epidemiology , Hemophilia A/physiopathology , Humans , Male , Middle Aged , Prevalence , Risk Factors
9.
Value Health ; 23(7): 862-869, 2020 07.
Article En | MEDLINE | ID: mdl-32762987

OBJECTIVE: To assess patient preferences for benefits and risks in hemophilia A treatment. METHODS: A systematic literature search and pretest interviews were conducted to determine the most patient-relevant endpoints in terms of effects, risks, and administration of hemophilia A treatments. A Best-Worst Scaling (BWS; Case 3 or multiprofile case) approach was applied in a structured questionnaire. Patients were surveyed by interviewers in a computer-assisted personal interview. Treatments in the choice scenarios comprised bleeding frequency per year, application type, risk of thromboembolic event risk, and inhibitor development. Each respondent answered 13 choice tasks, including 1 dominant task, comparing 3 treatment profiles. Data were analyzed using a mixed logit model (random-parameters logit). RESULTS: Data from 57 patients were used. The attributes "bleeding frequency per year" and "inhibitor development" had the greatest impact on respondents' choice decisions. Patients disliked being at risk of inhibitor development more than being at risk of thromboembolic events. The type of application, whether intravenous or subcutaneous, was of less importance for patients. There was a significant preference variation for all attributes. CONCLUSIONS: Patients value low frequency of bleeding per year and low risk of development of inhibitors the most. An increase of risk and frequency would significantly decrease the impact on choice decisions. The type of application does not seem to influence the choice decision very much compared with the other attributes. Regarding preference heterogeneity, further analysis is needed to identify subgroups among patients and their characteristics. This may help to adapt individually patient-tailored treatment alternatives for hemophilia A patients.


Choice Behavior , Decision Making , Hemophilia A/therapy , Patient Preference , Hemophilia A/physiopathology , Humans , Surveys and Questionnaires , Thromboembolism/epidemiology
10.
Haemophilia ; 26(4): 718-725, 2020 Jul.
Article En | MEDLINE | ID: mdl-32364278

INTRODUCTION: Historically persons with haemophilia (PWH) were not encouraged to participate in exercise due to the risk of bleeding and the lack of factor products available. This has now changed, and the availability of safe products allows PWH to be active and participate in sports. Studies have found that exercise has a positive effect on pain, joint health and movement with PWH. AIM: To record the amount and types of physical activity undertaken by a haemophilia population at a single treatment centre. METHODS: An observational cross-sectional study to assess physical activity and quality of life of all registered patients over the age of 18 at the Oxford Haemophilia and Thrombosis Centre. Participants were posted questionnaires including the International Physical activity Questionnaire (IPAQ), Haemophilia Activity List (HAL), EQ-5D-5L and asked to list their physical activities. RESULTS: A total of 256 questionnaires were sent, with a 40% response rate for severe and 28% for mild patients. 85% met the UK physical activity guidelines. Sedentary behaviour for an average weekday was 6.4 hours, and weekends were 5.3 hours. Joint disease and severity type influenced the amount of activity undertaken, together with values for HAL and EQ-5D-5L. Twenty two types of activities were listed. CONCLUSION: It is encouraging to see the amount of physical activity PWH participate in, however, time spent in a sedentary state needs monitoring. PWH want to be active and the challenge for caregivers is to find activities they can do and strategies to maintain participation.


Exercise/physiology , Exercise/psychology , Hemophilia A/therapy , Hemorrhage/prevention & control , Adult , Aged , Cross-Sectional Studies , Hemophilia A/complications , Hemophilia A/physiopathology , Hemorrhage/etiology , Humans , Joint Diseases/complications , Joint Diseases/diagnosis , Joint Diseases/prevention & control , Male , Middle Aged , Outcome Assessment, Health Care , Quality of Life , Sedentary Behavior , Severity of Illness Index , Surveys and Questionnaires/statistics & numerical data , United Kingdom/epidemiology
11.
Haemophilia ; 26(4): 726-734, 2020 Jul.
Article En | MEDLINE | ID: mdl-32364326

INTRODUCTION: Patients with haemophilia (PwH) often prefer shod walking over barefoot walking as footwear offers ankle joint stability and comfort during gait. Yet, the biomechanical mechanisms contributing to the latter remain poorly understood. AIM: To explore the effect of shoes on the biomechanical functioning of the ankle and foot complex in PwH with and without haemophilic ankle arthropathy and to determine the amount of ankle joint loading during shod walking. METHODS: We analysed data of PwH without haemophilic ankle arthropathy (n = 5) and PwH with severe haemophilic ankle arthropathy (n = 17) and a control group (n = 17). During 3D gait analysis, a four-segment kinetic foot model was used to calculate kinematic and kinetic parameters of the ankle, Chopart, Lisfranc and first metatarsophalangeal (MTP 1) joints during both barefoot and shod walking. RESULTS: We found a significantly greater ankle joint power generation during shod walking compared to barefoot walking in PwH with severe haemophilic ankle arthropathy (P < .001). Chopart joint biomechanics were significantly lowered in all three groups during shod walking compared to barefoot walking. During shod walking, the ankle joint load was significantly lowered in both PwH groups (P = .039 and P = .002), but not in the control group (P = .952). CONCLUSION: Explorations in this study uncover a tendency that shoes alter the biomechanical functioning of the ankle and foot complex in PwH and simultaneously lower the ankle joint load during walking.


Biomechanical Phenomena/physiology , Hemophilia A/physiopathology , Joint Diseases/physiopathology , Shoes/adverse effects , Walking/physiology , Adult , Ankle Joint/diagnostic imaging , Ankle Joint/physiopathology , Case-Control Studies , Cross-Sectional Studies , Foot Joints/diagnostic imaging , Foot Joints/physiopathology , Gait Analysis/methods , Hemophilia A/complications , Humans , Joint Diseases/diagnostic imaging , Joint Diseases/etiology , Magnetic Resonance Imaging/methods , Middle Aged
12.
Medicine (Baltimore) ; 99(9): e19339, 2020 Feb.
Article En | MEDLINE | ID: mdl-32118768

Ageing people with hemophilia (PWH) have a higher prevalence of hypertension than the general population. This study aimed to determine whether macroscopic hematuria was associated with hypertension in PWH in a post hoc analysis using data from a cross-sectional study conducted by the ADVANCE Working Group (the H3 study), which included PWH ≥ 40 years of age. Data from 16 contributing centers, located in 13 European countries and Israel, were analyzed using logistic regression models. Of 532 recruited PWH in the H3 study, 117 had hypertension and a positive family history of hypertension (hypertension FH+), 75 had hypertension and a negative family history of hypertension (hypertension FH-), 290 had no diagnosis of hypertension, and the remaining 50 had missing hypertension data. Logistic regressions showed that macroscopic hematuria was associated with hypertension FH+, both in the univariate (OR = 1.84 [1.17-2.90], P = .01) and in the multivariate model (OR = 1.80 [1.03-3.16], P = .04). Macroscopic hematuria was not associated with hypertension FH-. Moreover, in a multivariate logistic regression the odds of hypertension FH+ were increased with the number of macroscopic hematuria episodes. The association between macroscopic hematuria and hypertension was significant for PWH with a family history of hypertension.


Hematuria/etiology , Hemophilia A/complications , Hypertension/complications , Adult , Aged , Aged, 80 and over , Aging , Cross-Sectional Studies , Female , Hematuria/epidemiology , Hematuria/physiopathology , Hemophilia A/epidemiology , Hemophilia A/physiopathology , Humans , Hypertension/epidemiology , Hypertension/physiopathology , Israel/epidemiology , Logistic Models , Male , Middle Aged , Risk Factors
13.
Expert Opin Investig Drugs ; 29(3): 295-301, 2020 Mar.
Article En | MEDLINE | ID: mdl-32008381

Introduction: Hemophilia A and B are congenital bleeding disorders. The current standard management of patients with severe hemophilia is prophylaxis which is given intravenously two or three times weekly; however, this is associated with a significant burden on the quality of life of the patient. The main attempts to improve the management of hemophilia is hence through the development of a new generation of products with properties facilitating prophylaxis and/or a better control of bleeding.Areas covered: This review describes the preclinical and phase 1/2 studies investigating the innovative products for the management of hemophilia patients with or without coagulation factor inhibitors.Expert opinion: Numerous innovative therapeutics, including factor concentrates and non-clotting factor-based therapies with extended half-life, are under clinical investigation. Among replacement therapies for hemophilia A, the results from phase 1/2 studies indicate that the most interesting products are those bioengineered using XTEN fusion technology. The anti-tissue factor pathway inhibitor antibody concizumab is the most innovative and interesting agent among non-clotting factor products. If the results of ongoing trials confirm the preliminary positive results, these promising agents will provide further improvements in the management and quality of life of patients with hemophilia.


Antibodies, Monoclonal, Humanized/therapeutic use , Hemophilia A/drug therapy , Animals , Antibodies, Monoclonal, Humanized/pharmacology , Drug Development , Drugs, Investigational/pharmacokinetics , Drugs, Investigational/pharmacology , Hemophilia A/physiopathology , Humans , Quality of Life , Severity of Illness Index
14.
Expert Opin Investig Drugs ; 29(3): 303-309, 2020 Mar.
Article En | MEDLINE | ID: mdl-31990229

Introduction: Primary prophylaxis with FVIII is the therapeutic regimen of choice in severe hemophilia A; it reduces joint bleeding and associated chronic damage and helps prevent fatal bleeds. However, the high frequency of intravenous injections is a significant challenge for the optimal implementation of prophylaxis, particularly in children and adolescents. Novel therapeutic approaches have been developed to overcome this challenge. FVIII products with an extended plasma half-life can reduce the number of intravenous injections in the frame of prophylaxis regimens and can yield higher trough plasma levels of FVIII. The goal is to avoid all spontaneous bleeding episodes (zero events).Areas covered: This article reviews the benefits offered by the currently licensed extended half-life products and examines limitations, unmet needs, and knowledge gaps.Expert opinion: FVIII replacement remains the standard of care in patients with hemophilia A; however, there have been advances in novel treatment approaches. Non-factor products such as emicizumab offer a promising alternative that warrants more real-life experience and a direct comparison with FVIII replacement.


Antibodies, Bispecific/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Factor VIII/therapeutic use , Hemophilia A/prevention & control , Adolescent , Animals , Child , Half-Life , Hemophilia A/physiopathology , Humans , Severity of Illness Index
15.
Article En | MEDLINE | ID: mdl-33396748

There is a broad range of factor products approved in Germany for haemophilia A treatment. Since the introduction of recombinant coagulation factor VIII (FVIII) products in the 1990s, there has been substantial debate whether there is a difference in inhibitor incidence between single FVIII products or product classes. Neither haemophilia registries nor clinical studies, including a randomised controlled clinical trial, provided a consistent and definite answer. The reasons were mainly related to methodological challenges in conducting controlled studies in a rare disease. In this analysis, the most relevant epidemiological challenges and main problems were examined, including study bias, potential overlap of individual studies and advanced development of therapy and methods in the course of time. Meta-analyses on two levels showed that therapies using recombinant products resulted in different event rates when compared to plasma-derived products. These results are accompanied by substantial study heterogeneity evidenced by Cochran's Q tests. Only three studies have been identified that meet the standards of current clinical guidance. To finally resolve this ongoing and disputable safety issue of replacement therapy, collaboration among registry owners, academia and regulators must be fostered.


Hemophilia A , Germany/epidemiology , Hemophilia A/drug therapy , Hemophilia A/epidemiology , Hemophilia A/physiopathology , Humans , Incidence , Rare Diseases/epidemiology , Registries/statistics & numerical data
16.
Acta Biotheor ; 68(1): 21-43, 2020 Mar.
Article En | MEDLINE | ID: mdl-31853681

Correct interpretation of the data from integral laboratory tests, including Thrombin Generation Test (TGT), requires biochemistry-based mathematical models of blood coagulation. The purpose of this study is to describe the experimental TGT data from healthy donors and hemophilia A (HA) and B (HB) patients. We derive a simplified ODE model and apply it to analyze the TGT data from healthy donors and HA/HB patients with in vitro added tissue factor pathway inhibitor (TFPI) antibody. This model allows the characterization of hemophilia patients in the space of three most important model parameters. The proposed approach may provide a new quantitative tool for the analysis of experimental TGT. Also, it gives a reduced model of coagulation verified against clinical data to be used in future theoretical large-scale modeling of thrombosis in flow.


Blood Coagulation , Hemophilia A/physiopathology , Models, Theoretical , Thrombin/metabolism , Family Characteristics , Hemophilia A/diagnosis , Humans , Reagent Kits, Diagnostic
17.
BMJ Open ; 9(12): e032891, 2019 12 02.
Article En | MEDLINE | ID: mdl-31796490

INTRODUCTION: Haemophilia A is an X linked inherited bleeding disorder, caused by a decrease in coagulation factor VIII. Persons with haemophilia experience repeated musculoskeletal bleeding, which can lead to decreased range of motion, irreversible joint damage, low bone mineral density (BMD), and are at greater risk for osteoporosis. Women heterozygous for this mutation, also known as haemophilia A carriers, can have bleeding symptoms and even experience joint bleeding evidenced by radiological soft tissue and osteochondral changes. The prevalence of low BMD as a risk factor for osteoporosis has never been evaluated in carriers of haemophilia, and given the recent findings which suggest subclinical musculoskeletal bleeding in carrier women, we hypothesise that they too are at risk of impaired bone health. METHODS AND ANALYSIS: This is a national multicentre prospective matched-cohort study to compare BMD T-scores among symptomatic haemophilia A carriers, 50 years of age or older, with age-matched and body mass index-matched non-carriers (1:1). A total of 40 symptomatic carriers and 40 matched non-carriers will be recruited from St. Michael's Hospital, Kingston General Hospital in Ontario, Canada and Foothills Medical Centre in Alberta, Canada. Multivariable linear regression models will be used to estimate the effect of haemophilia carriership on BMD T-scores, adjusting for age, body mass index and other relevant covariates. ETHICS AND DISSEMINATION: The protocol was designed and will be conducted in compliance with applicable laws, rules and regulations. Research ethics approval was obtained from St. Michael's Hospital, Foothills Medical Centre, and Kingston General Hospital. Findings will be presented at international venues such as the American Society of Haematology and the World Federation of Haemophilia World Congress. The authors of this study will seek publication in journals such as Blood, Journal of Thrombosis and Haemostasis, American Journal ofHematology and British Journal ofHaematology.


Bone Diseases, Metabolic , Hemophilia A , Hemorrhage , Osteoporosis , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/epidemiology , Bone Diseases, Metabolic/etiology , Cohort Studies , Factor VIII/genetics , Female , Hemophilia A/diagnosis , Hemophilia A/epidemiology , Hemophilia A/genetics , Hemophilia A/physiopathology , Hemorrhage/complications , Hemorrhage/epidemiology , Heterozygote , Humans , Male , Middle Aged , Osteoporosis/diagnosis , Osteoporosis/epidemiology , Osteoporosis/etiology , Research Design , Risk Assessment/methods , Risk Factors , Sex Factors , Symptom Assessment/methods
18.
Rev Med Chil ; 147(5): 568-573, 2019 May.
Article Es | MEDLINE | ID: mdl-31859888

BACKGROUND: In patients with hemophilia, radionuclide synoviorthesis, or the intra-articular injection of a radionuclide to decrease the synovial hypertrophy tissue, aims to decrease or avoid hemarthrosis. AIM: To evaluate the effectiveness of radionuclide synoviorthesis in hemophilia. MATERIAL AND METHODS: Observational retrospective study of the evolution of 107 male patients aged 3 to 54 years who were subjected to radionuclide synoviorthesis between 2007 and 2015. RESULTS: Of 164 treated joints, in 65% treatment was successful, (defined as zero to two hemarthroses and absence of synovitis during the follow up period), in 17% it was partially successful (defined as two or less hemarthroses, but persistence of the synovitis) and failed in 18% of the procedures. No important complications were recorded. CONCLUSIONS: Radionuclide synoviorthesis has an overall 82% success rate, is minimally invasive, can be used at any age and is inexpensive We recommend its implementation in Chilean hemophilia treatment centers.


Hemarthrosis/therapy , Hemophilia A/therapy , Radioisotopes/administration & dosage , Rhenium/therapeutic use , Synovitis/therapy , Yttrium Radioisotopes/therapeutic use , Adolescent , Adult , Child , Child, Preschool , Hemarthrosis/diagnostic imaging , Hemarthrosis/physiopathology , Hemophilia A/physiopathology , Humans , Injections, Intra-Articular , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Synovitis/diagnostic imaging , Synovitis/physiopathology , Time Factors , Treatment Outcome , Young Adult
19.
Haemophilia ; 25(6): 928-937, 2019 Nov.
Article En | MEDLINE | ID: mdl-31667968

INTRODUCTION: There is considerable evidence to indicate that exercise can have a positive impact on the treatment of people with haemophilia (PWH). However, there is a requirement for in-depth and comprehensive studies. AIM: This study aimed to analyse the evidence regarding the effects of exercise in PWH through an umbrella review of existing systematic reviews and meta-analyses. The secondary objective was to analyse the quality of the evidence. METHODS: This umbrella review followed the PRISMA guidelines and was documented in the PROSPERO registry (CRD42019140785). We searched the PubMed, Web of Science, SPORTDiscus, Scopus, CINAHL and Cochrane Library databases. The methodological quality of the systematic reviews was assessed using AMSTAR 2. RESULTS: Out of a total of 1030 systematic reviews, 10 fulfilled the criteria. Only one study was classified as high quality, and half of the selected studies were classified as low or critically low quality according to AMSTAR 2. Furthermore, most reviews investigated the effects of strength training and aquatic training, with positive results associated with low adverse events. Range of motion, strength and pain were the most investigated variables. All reviews showed overlapping studies. CONCLUSION: Exercise is an effective way to treat haemophilia and has a low incidence of related adverse events. However, caution is needed in the interpretation of the results due to half of the selected reviews showed low or critically low quality and only one have high quality.


Exercise , Hemophilia A/physiopathology , Hemophilia B/physiopathology , Humans
20.
Article En | MEDLINE | ID: mdl-31614706

Physical activity (PA) is highly beneficial for people with haemophilia (PWH), however, studies that objectively monitor the PA in this population are scarce. This study aimed to monitor the daily PA and analyse its evolution over time in a cohort of PWH using a commercial activity tracker. In addition, this work analyses the relationship between PA levels, demographics, and joint health status, as well as the acceptance and adherence to the activity tracker. Twenty-six PWH were asked to wear a Fitbit Charge HR for 13 weeks. According to the steps/day in the first week, data were divided into two groups: Active Group (AG; ≥10,000 steps/day) and Non-Active Group (NAG; <10,000 steps/day). Correlations between PA and patient characteristics were studied using the Pearson coefficient. Participants' user experience was analysed with a questionnaire. The 10,000 steps/day was reached by 57.7% of participants, with 12,603 (1525) and 7495 (1626) being the mean steps/day of the AG and NAG, respectively. In general, no significant variations (p > 0.05) in PA levels or adherence to wristband were produced. Only the correlation between very active minutes and arthropathy was significant (r = -0.40, p = 0.045). Results of the questionnaire showed a high level of satisfaction. In summary, PWH are able to comply with the PA recommendations, and the Fitbit wristband is a valid tool for a continuous and long-term monitoring of PA. However, by itself, the use of a wristband is not enough motivation to increase PA levels.


Exercise , Fitness Trackers , Hemophilia A/physiopathology , Adult , Female , Humans , Male , Middle Aged , Monitoring, Physiologic/methods , Motivation , Patient Compliance , Surveys and Questionnaires
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