scholarly journals A Delphi Consensus Approach for Difficult-to-Treat Patients with Severe Hemophilia A without Inhibitors

2021 ◽  
Vol Volume 12 ◽  
pp. 913-928
Author(s):  
Sreenivas P Veeranki ◽  
Priti Pednekar ◽  
Marlon Graf ◽  
Rifat Tuly ◽  
Michael Recht ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Severe Hemophilia ◽  
Consensus Approach ◽  
Delphi Consensus

T Lymphocyte Proliferative Responses Induced by Recombinant Factor VIII in Hemophilia A Patients with Inhibitors

1996 ◽  
Vol 76 (01) ◽  
pp. 017-022 ◽  
Author(s):  
Sylvia T Singer ◽  
Joseph E Addiego ◽  
Donald C Reason ◽  
Alexander H Lucas
Keyword(s):  
T Lymphocytes ◽  
Factor Viii ◽  
Cellular Proliferation ◽  
Mononuclear Cells ◽  
Hemophilia A ◽  
Normal Subjects ◽  
Normal Male ◽  
Cell Fractionation ◽  
Severe Hemophilia ◽  
Human Factor Viii

SummaryIn this study we sought to determine whether factor VUI-reactive T lymphocytes were present in hemophilia A patients with inhibitor antibodies. Peripheral blood mononuclear cells (MNC) were obtained from 12 severe hemophilia A patients having high titer inhibitors, 4 severe hemophilia A patients without inhibitors and 5 normal male subjects. B cell-depleted MNC were cultured in serum-free medium in the absence or presence of 2 µg of recombinant human factor VIII (rFVIII) per ml, and cellular proliferation was assessed after 5 days of culture by measuring 3H-thymidine incorporation. rFVIII induced marked cellular proliferation in cultures of 4 of 12 inhibitor-positive hemophilia patients: fold increase over background (stimulation index, SI) of 7.8 to 23.3. The remaining 8 inhibitor-positive patients, the 4 hemophilia patients without inhibitors and the 5 normal subjects, all had lower proliferative responses to rFVIII, SI range = 1.6 to 6.0. As a group, the inhibitor-positive subjects had significantly higher proliferative responses to rFVIII than did the inhibitor-negative and normal subjects (p < 0.05 by t-test). Cell fractionation experiments showed that T lymphocytes were the rFVIII-responsive cell type, and that monocytes were required for T cell proliferation. Thus, rFVIII-reactive T lymphocytes are present in the peripheral circulation of some inhibitor-positive hemophilia A patients. These T cells may recognize FVIII in an antigen-specific manner and play a central role in the regulation of inhibitor antibody production

Dose Requirement for Replacement Therapy in Hemophilia A

1979 ◽  
Vol 42 (03) ◽  
pp. 825-831 ◽  
Author(s):  
Jean-Pierre Allain
Keyword(s):  
Clinical Effect ◽  
Hemophilia A ◽  
Clinical Results ◽  
Severe Hemophilia ◽  
Dose Requirement ◽  
Viii Level ◽  
The Relationship ◽  
In Vivo Recovery ◽  
Different Doses

SummaryIn order to determine the correlation between different doses of F. VIII and their clinical effect,. 70 children with severe hemophilia A were studied after treatment with single doses of cryoprecipitate. The relationship between plasma F. VIII levels or doses calculated in u/ kg of body weight and clinical results followed an exponential curve. Plasma F. VIII levels of 0.35 and 0.53 u/ml corresponded to 95 and 99% satisfactory treatment, respectively. Similar clinical results were obtained with 20 and 31 u/kg. When the in vivo recovery of F. VIII after lyophilized cryoprecipitate was 0.015 u/ml for each u/kg injected, plasma F. VIII levels of 0.30 and 0.47 u/ml respectively were achieved. Since home treatment is largely based on single infusions of F. VIII, it is suggested that moderate and severe hemorrhages be treated with a dose which will provide a plasma F. VIII level of 0.5 u/ml.

Common Genetic Variants in ABO and CLEC4M Modulate the Pharmacokinetics of Recombinant FVIII in Severe Hemophilia A Patients

2020 ◽  
Vol 120 (10) ◽  
pp. 1395-1406 ◽  
Author(s):  
Iris Garcia-Martínez ◽  
Nina Borràs ◽  
Marta Martorell ◽  
Rafael Parra ◽  
Carme Altisent ◽  
...  
Keyword(s):  
Blood Group ◽  
Half Life ◽  
Robust Regression ◽  
Hemophilia A ◽  
Illumina Miseq ◽  
Activity Levels ◽  
Severe Hemophilia ◽  
Single Nucleotide Variants ◽  
Common Genetic Variants ◽  
Recombinant Fviii

AbstractThe pharmacokinetic (PK) response of severe hemophilia A (HA) patients to infused factor VIII (FVIII) shows substantial variability. Several environmental and genetic factors are associated with changes in FVIII plasma levels and infused FVIII PK. Based on the hypothesis that factors influencing endogenous FVIII can affect FVIII PK, the contribution of single-nucleotide variants (SNVs) in candidate genes was investigated in 51 severe HA patients. The effects of blood group, F8 variant type, von Willebrand factor antigen and activity levels, age, and weight were also explored. The myPKFiT device was used to estimate individual PK parameters, and SNVs and clinically reportable F8 variants were simultaneously analyzed in an Illumina MiSeq instrument, using the microfluidics-based Fluidigm Access Array system. The contribution of SNVs to FVIII half-life and clearance was addressed by robust regression modeling, taking into account other modulators. In line with previous studies, we provide robust evidence that age, body weight, and blood group, as well as SNVs in ABO and CLEC4M, participate in the variability of FVIII PK in HA patients. Main results: each copy of the rs7853989 (ABO) allele increases FVIII half-life by 1.4 hours (p = 0.0131) and decreases clearance by 0.5 mL/h/kg (p = 5.57E-03), whereas each additional rs868875 (CLEC4M) allele reduces FVIII half-life by 1.1 hours (p = 2.90E-05) and increases clearance by 0.3 mL/h/kg (p = 1.01E-03). These results contribute to advancing efforts to improve FVIII replacement therapies by adjusting to each patient's PK profile based on pharmacogenomic data. This personalized medicine will decrease the burden of treatment and maximize the benefits obtained.

scholarly journals Third‐degree atrioventricular block and pacemaker implantation in a man with severe hemophilia A: A case report

2021 ◽  
Vol 37 (2) ◽  
pp. 460-461
Author(s):  
Ricardo Mesquita Camelo ◽  
Bruna Pontes Duarte ◽  
Antônio Macedo do Nascimento ◽  
Ana Maria Vanderlei
Keyword(s):  
Case Report ◽  
Atrioventricular Block ◽  
Hemophilia A ◽  
Pacemaker Implantation ◽  
Severe Hemophilia ◽  
Third Degree Atrioventricular Block

Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6367-6370 ◽  
Author(s):  
Charles R.M. Hay ◽  
Ben Palmer ◽  
Elizabeth Chalmers ◽  
Ri Liesner ◽  
Rhona Maclean ◽  
...  
Keyword(s):  
United Kingdom ◽  
Factor Viii ◽  
Hemophilia A ◽  
Interquartile Range ◽  
Severe Hemophilia ◽  
The United Kingdom ◽  
Potential Risk Factors ◽  
History Of ◽  
Previously Treated Patients ◽  
Adjusted Incidence

Abstract The age-adjusted incidence of new factor VIII inhibitors was analyzed in all United Kingdom patients with severe hemophilia A between 1990 and 2009. Three hundred fifteen new inhibitors were reported to the National Hemophilia Database in 2528 patients with severe hemophilia who were followed up for a median (interquartile range) of 12 (4-19) years. One hundred sixty (51%) of these arose in patients ≥ 5 years of age after a median (interquartile range) of 6 (4-11) years' follow-up. The incidence of new inhibitors was 64.29 per 1000 treatment-years in patients < 5 years of age and 5.31 per 1000 treatment-years at age 10-49 years, rising significantly (P = .01) to 10.49 per 1000 treatment-years in patients more than 60 years of age. Factor VIII inhibitors arise in patients with hemophilia A throughout life with a bimodal risk, being greatest in early childhood and in old age. HIV was associated with significantly fewer new inhibitors. The inhibitor incidence rate ratio in HIV-seropositive patients was 0.32 times that observed in HIV-seronegative patients (P < .001). Further study is required to explore the natural history of later-onset factor VIII inhibitors and to investigate other potential risk factors for inhibitor development in previously treated patients.

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