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.

scholarly journals Clotting factor concentrate switching and inhibitor development in hemophilia A

Blood ◽  
2012 ◽  
Vol 120 (4) ◽  
pp. 720-727 ◽  
Author(s):  
Alfonso Iorio ◽  
Paolo Puccetti ◽  
Mike Makris
Keyword(s):  
Clotting Factor ◽  
Controlled Study ◽  
Control Group ◽  
Inhibitor Development ◽  
Factor Viii Concentrates ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Clotting Factor Concentrates ◽  
Study Designs ◽  
Factor Concentrate

The development of alloantibodies or inhibitors is the most serious complication a patient with severe hemophilia can experience from treatment with clotting factor concentrates. Although common in previously untreated patients, inhibitor development is rare in multiply exposed, well-tolerized patients. There has been a nonevidence-based reluctance to change concentrate because of a perceived greater inhibitor risk after the switch, even though most patients are now likely to be using a concentrate on which they did not begin. Inhibitors in previously treated patients are observed in approximately 2 per 1000 patient/years, which makes it difficult to study and compare rates among different products. Because the baseline inhibitor risk in previously treated patients may vary over time, it is important to compare the risk in patients switching to a new product with that in a parallel control group of nonswitching patients or within a case-controlled study. The study designs imposed by regulators are suboptimal in detecting immunogenicity signals. The issue of immunogenicity of new products is likely to gain more relevance in the near future, with a call for effective postmarketing surveillance studies for all of the new engineered factor VIII concentrates with prolonged half-lives that are likely to enter clinical practice.

Systematic Review of Randomized Controlled Trials of Prophylactic Clotting Factor Concentrate in Hemophilia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3114-3114
Author(s):  
Kent Stobart ◽  
Alfonso Iorio
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Hemophilia A ◽  
Clotting Factor ◽  
Control Group ◽  
Controlled Trials ◽  
Pharmacokinetic Data ◽  
Randomized Controlled ◽  
Clotting Factor Concentrates ◽  
Factor Concentrate

Abstract Introduction: One of the current approaches to managing persons with hemophilia entails the use of prophylactic treatment with clotting factor concentrates (CFC) to prevent bleeds and bleeding related complications. However, this process is not practiced in all countries, or is based on the synthesis of evidence from data of all trials. Objective: To conduct a systematic review/meta-analysis (SR/MA) regarding the effectiveness of clotting factor concentrate prophylaxis in the management of people with hemophilia A or B. Methods: We conducted a SR of all randomized controlled trials (RCTs) that studied the effect of prophylactic CFCs in people with hemophilia A or B. We searched all major electronic databases (MEDLINE, LILACS, EMBASE, and the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Controlled Trials Register) as well as performing handsearches of journals and relevant meeting abstract books. We included RCTs that that compared the use of prophylactic CFCs to a control group. Results: We identified 29 studies, of which four (including 37 participants) were eligible for inclusion. Three studies evaluated hemophilia A; one showed a decrease in frequency of joint bleeds with prophylaxis compared to placebo (non-physiological dose), with a rate difference (RD) −10.80 (95% confidence interval (CI) −16.33 to −5.27) bleeds per year. The remaining two studies evaluating hemophilia A compared two prophylaxis regimens, one study showed no difference in joint bleed frequency, RD −5.04 (95%CI −17.02 to 6.94) bleeds per year and another failed to demonstrate an advantage of factor VIII dosing based on individual pharmacokinetic data over the standard prophylaxis regimen with RD −0.14 (95% CI −1.34 to 1.05) bleeds per year. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, RD −3.30 (95% CI −5.50 to − 1.10) bleeds per year. Conclusion: There is insufficient evidence to determine whether prophylactic clotting factor concentrates decrease bleeding and bleeding-related complications in hemophilia A or B, compared to placebo, on-demand treatment, or prophylaxis based on pharmacokinetic data from individuals. Well-designed RCTs are needed to assess the effectiveness of prophylactic clotting factor concentrates.

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.

Serial Changes in the Coagulation System Following Clotting Factor Concentrate Infusion

1975 ◽  
Vol 34 (02) ◽  
pp. 475-482 ◽  
Author(s):  
F. E Preston ◽  
D. A Winfield ◽  
R. G Malia ◽  
E. K Blackburn
Keyword(s):  
Liver Disease ◽  
Factor Viii ◽  
Antithrombin Iii ◽  
Fibrinogen Level ◽  
Plasma Fibrinogen ◽  
Coagulation System ◽  
Clotting Factor ◽  
Plasma Fibrinogen Level ◽  
Clotting Factor Concentrates ◽  
Factor Concentrate

SummaryVarious parameters of the coagulation system have been monitored in patients with Christmas disease following the infusion of clotting factor concentrates. Significant reduction of clotting factor VIII and serum antithrombin III were observed in each of the five studies, whilst the plasma fibrinogen level fell in four subjects. The induced abnormalities were shortlived and there were no clinical sequelae. Further studies are required to assess the effects of similar concentrates in patients with liver disease.

CD4+ Counts before and after Switching to Monoclonal High-Purity Factor VIII Concentrate in HIV-Infected Haemophilic Patients

1994 ◽  
Vol 72 (02) ◽  
pp. 214-217 ◽  
Author(s):  
Caroline Sabin ◽  
John Pasi ◽  
Andrew Phillips ◽  
Jonathan Elford ◽  
George Janossy ◽  
...  
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
Strong Association ◽  
Cd4 Count ◽  
Clotting Factor ◽  
Randomised Trials ◽  
Before And After ◽  
Clotting Factor Concentrates ◽  
Factor Concentrate

SummaryAllogenic proteins that contaminate intermediate purity clotting factor concentrates may activate the immune system of HIV-infected haemophilic patients. In 37 haemophilic patients infected with HIV who had originally been treated with intermediate purity factor VIII concentrate and then changed to monoclonally-purified high purity factor VIII concentrate the rates of CD4+ decline (109/1 per year) were 0.06 before and 0.02 after a switch to high purity products (p = 0.01). The median follow-up of patients after the switch to high purity products was 1.7 years (range 0.2 to 3 years). This significant change in the rate of CD4 decline was independent of the starting CD4 count, age and antiretroviral therapy. This result is consistent with those from randomised trials of the introduction of high-purity concentrate. Given the strong association between the CD4+ count and survival, treatment with high purity rather than intermediate purity clotting factor concentrate may confer a survival benefit for HIV-infected haemophilic patients.

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

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.

Antibody to Hepatitis G Mrus after a Vapour-Heated Factor Vlll Goncentrate

1990 ◽  
Vol 64 (02) ◽  
pp. 232-234 ◽  
Author(s):  
P M Mannucci ◽  
A R Zanetti ◽  
M Colombo ◽  
A Chistolini ◽  
R De Biasi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B ◽  
Factor Viii ◽  
Alanine Aminotransferase ◽  
Household Contact ◽  
Clotting Factor ◽  
Double Infection ◽  
Marked Elevation ◽  
Clotting Factor Concentrates

SummaryTo evaluate whether or not clotting factor concentrates exposed to virucidal procedures transmitted hepatitis C, sera obtained in 1984–1986 from 27 previously untreated hemophiliacs infused with a vapour-heated factor VIII concentrate were tested retrospectively for the antibody to the hepatitis C virus (anti- HCV). A 2-year-old hemophiliac, negative for anti-HCV before administration of concentrate, seroconverted at week 12 and remained anti-HCV positive thereafter. Both his parents were anti-HCV negative and he had no other household contact. The patient had also become HBsAg positive at week 8 and had at the same time a marked elevation of alanine aminotransferase. His double infection with the hepatitis B and C viruses indicates that hot vapour was not completely effective in inactivating these viruses.

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.

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