PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “FACTOR VIII”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed2001

Structure of a factor VIII C2 domain-immunoglobulin G4kappa Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII.

The development of an immune response to infused factor VIII is a complication affecting many patients with hemophilia A. Inhibitor antibodies bind to antigenic determinants on the factor VIII molecule and block its procoagulant activity. A patient-derived inhibitory immunoglobulin G4kappa antibody (BO2C11) produced by an immortalized memory B-lymphocyte cell line interferes with the binding of factor VIII to phospholipid surfaces and to von Willebrand factor. The structure of a Fab fragment derived from this antibody complexed with the factor VIII C2 domain was determined at 2.0 A resolution. The Fab interacts with solvent-exposed basic and hydrophobic side chains that form a membrane-association surface of factor VIII. This atomic resolution structure suggests a variety of amino acid substitutions in the C2 domain of factor VIII that might prevent the binding of anti-C2 inhibitor antibodies without significantly compromising the procoagulant functions of factor VIII.

Antibodies, Monoclonal↗
PubMed1993

In vitro evaluation of factor VIII--bypassing activity of activated prothrombin complex concentrate, prothrombin complex concentrate, and factor VIIa in the plasma of patients with factor VIII inhibitors: thrombin generation test in the presence of collagen-activated platelets.

Clinical efficacy of plasma-derived products with factor VIII--bypassing activity in patients with factor VIII inhibitors is difficult to evaluate. It is also difficult to predict efficacy by coagulation assay. A test of thrombin generation in defibrinated plasma and in the presence of activated platelets was used to test the bypassing activity of the most currently used products (activated prothrombin complex concentrate from various origins, prothrombin complex concentrate, and factor VIIa). The bypassing activity was evaluated in the absence and presence of tissue factor. In plasma with inhibitor, activated prothrombin complex concentrate elicited dose-dependent thrombin formation, whereas prothrombin complex concentrate and factor VIIa induced only minimal thrombin activity. Addition of tissue factor in the assay elicited thrombin generation in the presence of factor VIIa and prothrombin complex concentrate and allowed additional thrombin formation in the presence of activated prothrombin complex concentrate. Although it is hazardous to extend results of in vitro testing to clinical efficacy, our study sheds some light on the mechanism of action of the various substances used to treat bleeding episodes in patients with factor VIII inhibitors.

Blood Coagulation Factors↗
PubMed1977

Interaction of factor VIII antigen in hemophilic plasmas with human antibodies to factor VIII.

By utilizing a simple modification of previous immunological assays, we have demonstrated that most, if not all, hemophilic plasmas contain antigen reactive with human antibodies directed against Factor VIII procoagulant activity (VIIIc). Antibodies developing in a nonhemophiliac patient and in a hemophiliac patient gave similar results. The VIIIc antigen so identified was removed from hemophilic plasmas with immobilized rabbit antibody which reacted with normal VIIIc and von Willebrand's disease antigen. These data suggest that there are greater antigenic similarities between normal and hemophilic Factor VIII than previously thought.

Antigen-Antibody Reactions↗
PubMed1999

Identification of a factor VIII peptide, residues 2315-2330, which neutralizes human factor VIII C2 inhibitor alloantibodies: requirement of Cys2326 and Glu2327 for maximum effect.

Factor VIII (FVIII) inhibitor alloantibodies react with combinations of the A2, C2 and A3-C1 domains of the FVIII molecule. Some inhibitors block binding of FVIII to both von Willebrand factor (VWF) and phospholipid, and recognize a C2 domain epitope which overlaps both binding sites. In order to determine the essential binding regions for alloantibodies inhibitory for FVIII activity, we have performed inhibitor neutralization assays and competitive inhibition assays using 10 overlapping synthetic peptides spanning the carboxy-terminal region of the C2 domain (residues 2288-2332). We found one peptide (2315-2330, L9) which neutralized the anti-FVIII activity of four out of five different C2 alloantibodies by 50%, 39%, 47% and 57%, respectively. Neutralization of these alloantibodies by recombinant C2 domain (residues 2173-2332) was 68%, 50%, 59%, 86% and >95%, respectively. The inhibitor which was not neutralized by L9 peptide and reacted by immunoblotting with peptide 2218-2307, did not prevent binding of FVIII to VWF and only partially inhibited binding of FVIII to phosphatidylserine. Mutants of the L9 peptide were prepared in which each residue from 2315-2330 was sequentially substituted by glycine. Inhibitor neutralization experiments using these peptides demonstrated that Arg2320 and Cys2326 or Glu2327 are important for the effect of L9 peptide, since their substitution by glycine reduced its neutralizing effect by 60% to >90%, suggesting that they are crucial for formation of the one of the C2 inhibitor epitopes.

Amino Acid Sequence↗
PubMed1979

Preparation of stable intermediate-purity factor VIII concentrate with a note on high-purity factor VIII.

Cryoprecipitate prepared by a rapid thawing technique was pooled in batches of 600--720 donor units and washed with ice-cold Tris-citrate-NaCl solution. After dissolving at 37 degrees C, it was adsorbed with Al(OH)3 and kaolin, and cleared by centrifugation. The supernatant, diluted with 5% dextrose was passed repeatedly through a bed of Celite, filtered through a 293 mm X 0.3 micrometer membrane disc and lyophilized. Typical composition was 15 U . ml-1 factor VII, and 40 mg . ml-1 protein with a yield of 300 U/l of starting plasma. The crude factor VIII concentrate was also a suitable material for preparation of high-purity factor VIII by controlled pore glass chromatography.

Blood Donors↗
PubMedDate not supplied

Near normoglycemia for 1 year has no effect on platelet reactivity, factor VIII, and von Willebrand factor in insulin-dependent diabetes mellitus: a controlled trial.

The impact of prolonged near-normoglycemia on platelet reactivity (spontaneous and induced platelet aggregation), factor VIII, and von Willebrand factor in patients with insulin-dependent diabetes mellitus (IDDM) was evaluated in a prospective, randomized, controlled clinical trial. Twenty IDDM patients with no or only minor clinical signs of microvascular disease were randomly assigned to 1 year of continuous subcutaneous insulin infusion (CSII) or unchanged conventional insulin treatment (CIT). Hemoglobin A1c declined during the 12 month observation period from 7.3 +/- 1.2% to 6.4 +/- 0.9% (2p less than 0.01) in the CSII group, while this measure of glycemic control was unchanged in the CIT group: 7.2 +/- 1.1% vs 8.0 +/- 1.6% (NS). Platelet reactivity, factor VIII, and von Willebrand factor concentrations were identical in the two groups at entry into the study, and no significant changes in these variables were seen in either group. Thus, the present results do not support the concept of increased platelet reactivity following CSII treatment.

Adult↗
PubMedDate not supplied

Impact of factor VIII deficiency on clotting factor utilization in the United States.

In a study of 1,551 hemophiliacs over a 4-year period of time, factor VIII utilization was assessed. It is clear that factor VIII usage is a function of severity of disease and therapeutic program. The average amount of factor VIII used per patient was 39,880 U/year. Patients selected for home care, use significantly more than those patients not on home care. As much as 101,000 U/year are used by a small number of patients on prophylaxis. These data can be used in predicting source plasma requirements for annual national use as well as costs.

Blood Donors↗
PubMed1989

Anti-A in factor VIII concentrate: a cause of severe hemolysis in a patient with acquired factor VIII:C antibodies.

The authors report a case of acute macrohematuria in a patient with spontaneously acquired antibodies against factor VIII:C. Severe hemolysis was observed under factor VIII concentrate therapy. In 4 batches of the factor VIII concentrate high titers up to 1:512 of 'immune' anti-A were found. Clotting factor preparations used for replacement therapy, therefore, should be investigated for iso-antibodies, at least in situations where an intensive infusion therapy is required.

ABO Blood-Group System↗
PubMed1990

Disappearance of factor VIII antibodies upon frequent administration of factor VIII.

20 haemophilia patients known to have antibodies against F VIII for at least more than three years were treated on a regular base with 25 U/kg b.w. F VIII every other day. All 5 patients with previous maximal anti F VIII antibody levels between 5 and 60 BU/ml showed a decrease of antibody level and normal F VIII recovery within 1-2 months. From 12 patients with previous antibody levels above 60 BU/ml, 8 showed a disappearance of antibodies within 2-26 months. In 3 patients in whom no previous highest inhibitor level was known, one was treated successfully. Another group of 6 young patients in whom an inhibitor against F VIII had just (less than 3 months) developed, was treated with F VIII as soon as an inhibitor was detected. The dose infused was 25 U/kg b.w. F VIII twice weekly. In 5 patients this regimen was successful within 1-7 months. In the 6th patient the dosage was increased to every other day. One year after the beginning of therapy no inhibitor was detectable. So our results show that regular administration of F VIII in intermediate or low dose can lead to rapid disappearance of anti F VIII antibodies especially in patients with moderate inhibitor levels.

Autoantibodies↗