scholarly journals Haemophilia and Joint Disease: Pathophysiology, Evaluation, and Management

2011 ◽  
Vol 1 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Karin Knobe ◽  
Erik Berntorp
Keyword(s):  
Joint Disease ◽  
Clotting Factor ◽  
Recurrent Bleeding ◽  
Effective Prevention ◽  
Haemophilic Arthropathy ◽  
Chronic Synovitis ◽  
Bleeding Episodes ◽  
End Stage ◽  
Clotting Factor Concentrates

In patients with haemophilia, regular replacement therapy with clotting factor concentrates (prophylaxis) is effective in preventing recurrent bleeding episodes into joints and muscles. However, despite this success, intra-articular and intramuscular bleeding is still a major clinical manifestation of the disease. Bleeding most commonly occurs in the knees, elbows, and ankles, and is often evident from early childhood. The pathogenesis of haemophilic arthropathy is multifactorial, with changes occurring in the synovium, bone, cartilage, and blood vessels. Recurrent joint bleeding causes synovial proliferation and inflammation (haemophilic synovitis) that contribute to end-stage degeneration (haemophilic arthropathy); with pain and limitation of motion severely affecting patients’ quality of life. If joint bleeding is not treated adequately, it tends to recur, resulting in a vicious cycle that must be broken to prevent the development of chronic synovitis and degenerative arthritis. Effective prevention and management of haemophilic arthropathy includes the use of early, aggressive prophylaxis with factor replacement therapies, as well as elective procedures, including restorative physical therapy, analgesia, aspiration, synovectomy, and orthopaedic surgery. Optimal treatment of patients with haemophilia requires a multidisciplinary team comprising a haematologist, physiotherapist, orthopaedic practitioner, rehabilitation physician, occupational therapist, psychologist, social workers, and nurses.

scholarly journals Prevention of the Musculoskeletal Complications of Hemophilia

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
E. C. Rodriguez-Merchan
Keyword(s):  
Prophylactic Treatment ◽  
Cost Effective ◽  
Venous Access ◽  
Joint Disease ◽  
Clotting Factor ◽  
Hemophilic Arthropathy ◽  
Chronic Synovitis ◽  
Clotting Factor Concentrates ◽  
Venous Access Devices

Hemophilia is an inherited disorder of clotting factor deficiencies resulting in musculoskeletal bleeding, including hemarthroses, leading to musculoskeletal complications. The articular problems of hemophiliac patients begin in infancy. These include: recurrent hemarthroses, chronic synovitis, flexion deformities, hypertrophy of the growth epiphyses, damage to the articular cartilage, and hemophilic arthropathy. The most commonly affected joints are the ankle, the knee, and the elbow. Hematologic prophylactic treatment from ages 2 to 18 years could avoid the development of hemophilic arthropathy if the concentration of the patient's deficient factor is prevented from falling below 1% of normal. Hemarthroses can be prevented by the administration of clotting factor concentrates (prophylaxis). However, high costs and the need for venous access devices in younger children continue to complicate recommendations for universal prophylaxis. Prevention of joint arthropathy needs to focus on prevention of hemarthroses through prophylaxis, identifying early joint disease through the optimal use of cost-effective imaging modalities and the validation of serological markers of joint arthropathy. Screening for effects on bone health and optimal management of pain to improve quality of life are, likewise, important issues. Major hemarthrosis and chronic hemophilic synovitis should be treated aggressively to prevent hemophilic arthropathy.

scholarly journals How I use bypassing therapy for prophylaxis in patients with hemophilia A and inhibitors

Blood ◽  
2015 ◽  
Vol 126 (2) ◽  
pp. 153-159 ◽  
Author(s):  
Cindy A. Leissinger ◽  
Tammuella Singleton ◽  
Rebecca Kruse-Jarres
Keyword(s):  
Physical Disability ◽  
Hemophilia A ◽  
Joint Disease ◽  
Clotting Factor ◽  
On Demand ◽  
Increased Risk ◽  
Related Quality ◽  
Health Related ◽  
Bleeding Episodes

Abstract Inhibitor development poses a significant challenge in the management of hemophilia because once an inhibitor is present, bleeding episodes can no longer be treated with standard clotting factor replacement therapy. Consequently, patients with inhibitors are at increased risk for difficult-to-control bleeding and complications, particularly arthropathy and physical disability. Three clinical trials in patients with inhibitors have demonstrated that prophylaxis with a bypassing agent reduces joint and other types of bleeding and improves health-related quality of life compared with on-demand bypassing therapy. In hemophilia patients without inhibitors, the initiation of prophylaxis with factor (F) VIII or FIX prior to the onset of recurrent hemarthroses can prevent the development of joint disease. Whether this is also true for bypassing agent prophylaxis remains to be determined.

scholarly journals Musculoskeletal treatment in haemophilia

2019 ◽  
Vol 4 (6) ◽  
pp. 230-239 ◽  
Author(s):  
Bülent Atilla ◽  
Hande Güney-Deniz
Keyword(s):  
Musculoskeletal System ◽  
Clotting Factor ◽  
Salvage Procedure ◽  
Acute Bleeding ◽  
Surgical Interventions ◽  
Bleeding Episodes ◽  
Clotting Factor Concentrates ◽  
Uncontrolled Bleeding ◽  
Normal Status

Haemophilia is a group of coagulation disorders inherited in an X-linked recessive pattern. Nearly three-quarters of all haemorrhages in haemophilia occur in the musculoskeletal system, usually in the large muscles and joints of the lower extremity. While prevention of bleeding with active prophylaxis is the recommended optimal therapy for severe haemophilia, there are many patients suffering from musculoskeletal system complications subsequent to uncontrolled bleeding. Recombinant clotting factor concentrates led to home treatment of acute bleeding episodes as well as allowing for minor and major surgical interventions. Avoiding of further complications by radiosynoviorthesis is the first-line recommendation, and arthroplasty is regarded as the effective salvage procedure for patients presenting with severe disability. Physiotherapy and rehabilitation in haemophilia patients are important to return the normal status of joint motion, to regain the muscle strength, to obtain the optimal functional levels and to improve patients’ quality of life.Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180068

Azidothymidine (AZT) in the Treatment of Symptomatic HIV-1-Infected Hemophiliacs

1990 ◽  
Vol 64 (01) ◽  
pp. 108-112 ◽  
Author(s):  
S Eichinger ◽  
I Pabinger ◽  
H Hartl ◽  
C Stain ◽  
S Mayerhofer ◽  
...  
Keyword(s):  
Risk Groups ◽  
Clotting Factor ◽  
Bleeding Tendency ◽  
Probability Of Survival ◽  
Immunodeficiency Virus ◽  
Progression Of Disease ◽  
Bleeding Episodes ◽  
Clotting Factor Concentrates ◽  
Dose Dependent ◽  
Hiv 1

SummaryTwenty-one immunodeficiency virus 1 (HIV 1)-positive hemophilic patients were treated with Azidothymidine (AZT) for symptomatic HIV infection. The median observation period was 20.5 months.At 25 months the probability of survival was 82%, the probability of progression of disease from CDC III or IV C2 to IV C1 (AIDS) was 20% in patients on continuous AZT treatment and 50% in patients with intermption of treatment. Three patients developed severe leukopenia and 3 patients severe anemii during AZT treatment. In 1 patient a dose-dependent striking increase of transaminases during AZT treatment was observed. In 7 patients treatment was intermpted, in 1 patient because of anemia, in 1 because of pruritus and in 5 patients because of noncompliance.No signiticant changes in the consumption of clotting factor concentrates and number of bleeding episodes before and during AZT treatment were noted.We conclude, that both hematological and non-hematological side effects of AZT in HIV 1-infected hemophilic patientr ur. comparable to those seen in other risk groups . AzT does not increase the bleeding tendency in this patient group.

The role of the physiotherapist in the management of people with haemophilia: defining the new normal

2020 ◽  
Vol 81 (8) ◽  
pp. 1-8
Author(s):  
AJ Wells ◽  
D Stephensen
Keyword(s):  
Physical Activity ◽  
Recurrent Bleeding ◽  
Significant Shift ◽  
New Era ◽  
Assessment And Treatment ◽  
Bleeding Episodes ◽  
New Treatments ◽  
Improve Health

Physiotherapists aim to maximise quality of life and movement potential within the spheres of promotion, prevention, treatment/intervention and rehabilitation. Haemophilia care is witnessing a significant shift towards a new era of potentially life-changing treatments which offer a future of minimal or no bleeds for people with haemophilia. As such, physiotherapy intervention should be more proactive rather than reactive to treat and rehabilitate recurrent bleeding episodes. The role of the physiotherapist within the multidisciplinary team includes the differential diagnosis of musculoskeletal bleeding, supporting and encouraging higher levels of physical activity, rehabilitation to maximise physical potential and capabilities, assessment and treatment of non-bleed-related musculoskeletal issues, managing comorbidities and falls risk, and improving the longitudinal surveillance of musculoskeletal health. Encouraging and supporting people with haemophilia to become more active will improve wellbeing and improve health and health outcomes, and physical activity is becoming one of the most important outcomes for people with haemophilia. Recommendations on the best way to accurately capture these data are vital to ensure the full health benefits of new treatments for people with haemophilia are clear.

Chronic morbidities of premature newborns

2013 ◽  
Vol 154 (38) ◽  
pp. 1498-1511 ◽  
Author(s):  
György Balla ◽  
Miklós Szabó
Keyword(s):  
Quality Of Life ◽  
Periventricular Leukomalacia ◽  
Organ Damage ◽  
Detailed Knowledge ◽  
Effective Prevention ◽  
Premature Newborns ◽  
Vascular Growth ◽  
Common Risk Factors ◽  
End Stage

The most important chronic morbidities of premature newborns, deeply influencing quality of life, are retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage and periventricular leukomalacia. Since the rate of premature birth has not decreased in recent years in Hungary, and treatments of these end stage disorders are extremely difficult, prevention gains tremendous significance. Effective prevention is based on detailed knowledge of the pathophysiological mechanisms of these special diseases having multifactorial nature sharing several common risk factors, and one is the pathological angiogenesis. This sensitive system is affected by several stress situations which are the consequences of prematurity leading to abnormal vascular growth. After birth, relative hyperoxia, compared to intrauterine life, and decreasing concentrations of vascular growth factors result in vascular injury, moreover, may cause vessel apoptosis. The consequence of this phenomenon is the activation of hypoxia responsible genes resulting in robust pathological neovascularization and organ damage during the later phase. Saving normal angiogenesis and inhibiting reactive neovascularization may lead to better quality of life in these premature infants. Orv. Hetil., 2013, 154, 1498–1511.

scholarly journals Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens

Blood ◽  
2015 ◽  
Vol 125 (13) ◽  
pp. 2038-2044 ◽  
Author(s):  
Johannes Oldenburg
Keyword(s):  
Treatment Strategies ◽  
Coagulation Factor ◽  
Pharmacokinetic Profile ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Joint Disease ◽  
System Level ◽  
Clotting Factor ◽  
Individualization Of Therapy ◽  
Clotting Factor Concentrates

Abstract Prophylactic application of clotting factor concentrates is the basis of modern treatment of severe hemophilia A. In children, the early start of prophylaxis as primary or secondary prophylaxis has become the gold standard in most countries with adequate resources. In adults, prophylaxis is reasonably continued when started as primary or secondary prophylaxis in childhood to maintain healthy joint function. Initial data support that adult patients with already existing advanced joint arthropathy benefit from tertiary prophylaxis with significantly lowered number of bleeds, almost complete absence of target joints, and less time off from work. Current prophylactic regimens, although very effective, do not completely prevent joint disease in a long-term perspective. Joint arthropathy in primary prophylaxis develops over many years, sometimes over a decade or even longer time periods. The ankle joints are the first and most severely affected joints in those patients and thus may serve in outcome assessment as an indicator of early joint arthropathy when followed by ultrasound or magnetic resonance imaging. Optimized outcome and best use of available resources is expected from individualization of therapy regimens, which comprises the individual’s bleeding pattern, condition of the musculoskeletal system, level of physical activity and the pharmacokinetic profile of the substituted coagulation factor, and most recently includes novel products with extended half-lives.

scholarly journals Gene therapy for haemophilia: a very modern success story

2015 ◽  
Vol 2 (2) ◽  
pp. 26-28
Author(s):  
Amit Nathwani
Keyword(s):  
Gene Therapy ◽  
Clotting Factor ◽  
Haemophilia A ◽  
Single Administration ◽  
Success Story ◽  
Spontaneous Bleeding ◽  
Bleeding Episodes ◽  
Paradigm Shifting

Abstract AAV-mediated gene therapy has the potential to be paradigm shifting as a treatment for haemophilia. A single administration of AAV vector can result in safe and consistent long-term expression of transgene (>5 years), reduction in spontaneous bleeding episodes, reduction in clotting factor usage and an improvement in quality of life. There is huge commercial interest in this approach, with the expectation that an AAV gene therapy product for haemophilia B will be licensed by 2020.

scholarly journals How do we optimally utilize factor concentrates in persons with hemophilia?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 206-214
Author(s):  
Ming Y. Lim
Keyword(s):  
Standard Of Care ◽  
Clotting Factor ◽  
World Federation ◽  
Musculoskeletal Health ◽  
Related Factors ◽  
Tailored Approach ◽  
Individualized Management ◽  
Clotting Factor Concentrates ◽  
Factor Concentrate

Abstract The current mainstay of therapy for hemophilia is to replace the deficient clotting factor with the intravenous administration of exogenous clotting factor concentrates. Prophylaxis factor replacement therapy is now considered the standard of care in both pediatric and adult patients with hemophilia with a severe phenotype to protect musculoskeletal health and improve quality of life. Heterogeneity in bleeding presentation among patients with hemophilia due to genetic, environmental, and treatment-related factors has been well described. Accordingly, the World Federation of Hemophilia recommends an individualized prophylaxis regimen that considers the factors mentioned above to meet the clinical needs of the patient, which can vary over time. This review focuses on the practical points of choosing the type of factor concentrate, dose, and interval while evaluating appropriate target trough factor levels and bleeding triggers such as level of physical activity and joint status. We also discuss the use of a pharmacokinetics assessment and its incorporation in the clinic for a tailored approach toward individualized management. Overall, adopting an individualized prophylaxis regimen leads to an optimal utilization of factor concentrates with maximum efficacy and minimum waste.

HCV quasispecies evolution: association with progression to end-stage liver disease in hemophiliacs infected with HCV or HCV/HIV

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 533-541 ◽  
Author(s):  
Hongxing Qin ◽  
Norah J. Shire ◽  
Erica D. Keenan ◽  
Susan D. Rouster ◽  
M. Elaine Eyster ◽  
...  
Keyword(s):  
Liver Disease ◽  
Clotting Factor ◽  
Progression Rate ◽  
Bleeding Disorders ◽  
The Core ◽  
End Stage Liver Disease ◽  
End Stage ◽  
Clotting Factor Concentrates ◽  
Quasispecies Evolution ◽  
Over Time

AbstractPatients with inherited bleeding disorders who received clotting factor concentrates before 1987 have high rates of hepatitis C virus (HCV) or HCV/HIV infection. We evaluated HCV quasispecies evolution in longitudinally collected specimens comparing those from patients with progression to end-stage liver disease (ESLD; cases) to those with compensated chronic hepatitis (controls). Plasma samples were obtained from the National Cancer Institute Multicenter Hemophilia Cohort Study. Controls were matched for age, sex, infection duration, and presence/absence of HIV. Samples from early infection were compared to those obtained after onset of ESLD in the cases. The first hypervariable (HVR1) and core proteincoding regions were amplified, subcloned, and sequenced. Complexity and diversity were determined. More than 700 sub-clones from 10 pairs of patients (8 with HIV) followed over approximately 9.3 years were evaluated. HVR1 complexity narrowed over time in the cases, whereas it increased in controls (P = .01). Similar trends were observed for diversity within HVR1 and the core region (P = .04). HCV-infected patients with inherited bleeding disorders undergo quasispecies evolution over time. Evolution patterns differ for progressors and nonprogressors. Further understanding of these mechanisms may help identify factors related to progression rate and treatment response.

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