scholarly journals Immunologic Studies of Antihemophilic Factor (AHF, Factor VIII) II. Properties of Cross-reacting Material

Blood ◽  
1970 ◽  
Vol 35 (6) ◽  
pp. 809-820 ◽  
Author(s):  
LEON W. HOYER ◽  
ROBERT T. BRECKENRIDGE
Keyword(s):  
Calcium Phosphate ◽  
Physical Properties ◽  
Factor Viii ◽  
Barium Sulfate ◽  
Genetic Variant ◽  
Hemophilia A ◽  
Procoagulant Activity ◽  
Normal Plasma ◽  
Fraction I ◽  
Antihemophilic Factor

Abstract Patients with a genetic variant of hemophilia A have in their plasmas material which has antigenic characteristics similar to those of antihemophilic factor (AHF). The physical properties of the biologically inactive cross-reacting material (CRM) are like those of AHF from normal plasma. The CRM is concentrated in Cohn fraction I and in cryoprecipitates and is not adsorbed from plasma by calcium phosphate or barium sulfate. It is inactivated by heating to 56° for 30 minutes. The CRM is less sensitive to thrombin inactivation than AHF and is recovered in serum. The similar properties of AHF and CRM support the hypothesis that patients with this genetic variant of hemophilia A synthesize a material similar to AHF but lacking procoagulant activity.

scholarly journals Immunologic Studies of Antihemophilic Factor (AHF, Factor VIII): Cross-Reacting Material in a Genetic Variant of Hemophilia A

Blood ◽  
1968 ◽  
Vol 32 (6) ◽  
pp. 962-971 ◽  
Author(s):  
LEON W. HOYER ◽  
ROBERT T. BRECKENRIDGE
Keyword(s):  
Factor Viii ◽  
Genetic Variant ◽  
Hemophilia A ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Antihemophilic Factor

Abstract Immunologic studies have identified two genetically distinct types of hemophilia A. While a majority of patients apparently fail to synthesize AHF, a variant has been recognized in which a nonfunctional but antigenically cross-reacting AHF-like protein is present. Plasmas from two of twenty-seven families with hemophilia A have a cross-reacting material which inactivates an anticoagulant to AHF. Nonfunctional cross-reacting material was not present in plasmas from six patients with von Willebrand’s disease.

Investigations on the Nature of Hemophilia A

1963 ◽  
Vol 09 (01) ◽  
pp. 030-052 ◽  
Author(s):  
Eberhard Mammen
Keyword(s):  
Factor Viii ◽  
Human Plasma ◽  
Barium Sulfate ◽  
Freeze Drying ◽  
Room Temperature ◽  
Hemophilia A ◽  
Normal Human Plasma ◽  
Normal Human ◽  
And Storage ◽  
Prothrombin Activation

SummaryIn this paper an inhibitor is described that is found in hemophilic plasma and serum different from any till now described inhibitor. The inhibitor only inhibits prothrombin activation in the “intrinsic clotting systems”. This inhibitor is probably not present in normal human plasma or serum. It is destroyed by ether and freeze drying, is labile to acid and storage at room temperature. It is stable upon dialysis and has not been adsorbed on barium sulfate, aluminum hydroxide or kaolin. It precipitates at 50% v/v saturation with alcohol. The nature of this inhibitor seems to be a protein or lipoprotein.Factor VIII was isolated from hemophilic plasma. The amount isolated was the same as from normal plasma and the activity properties were not different. Hemophiliacs have normal amounts of factor VIII.

Comparative Investigations on Factor VIII Assays

1975 ◽  
Author(s):  
R. Pflugshaupt ◽  
S. Moser ◽  
K. Züger ◽  
R. Bütler
Keyword(s):  
Factor Viii ◽  
High Activity ◽  
Hemophilia A ◽  
Statistical Evaluation ◽  
Two Stage ◽  
One Stage ◽  
Normal Plasma ◽  
Calibration Curves ◽  
Factor Viii Concentrates

Six one stage methods and one two stage method were tested for precision and reproducibility. With each method twenty calibration curves of normal plasma and two lots of Factor VIII concentrates were established. Statistical evaluation revealed only minor differences. Neither one of the methods was optimal for both the physiological-pathological region and the region of high activity preparations.Three selected methods were tested in vivo for accuracy: nine patients with hemophilia A were treated with equal amounts of Factor VIII concentrates or kryoprecipitates respectively. The methods showed different activities for preparations as well as for patient’s plasma. The discrepancy between measured and expected recovery differed for each method.

Sucrose Formulated Recombinant Human Antihemophilic Factor VIII Is Safe and Efficacious for Treatment of Hemophilia A in Home Therapy

2000 ◽  
Vol 83 (06) ◽  
pp. 811-816 ◽  
Author(s):  
E. Gorina ◽  
E. Kellermann ◽  
E. Vosburgh ◽  
T. C. Abshire ◽  
H.-H. Brackmann ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
De Novo ◽  
Pharmacokinetic Profile ◽  
Full Length ◽  
Home Therapy ◽  
Safety And Efficacy ◽  
Previously Treated Patients ◽  
New Formulation ◽  
Antihemophilic Factor

SummaryTo add an increased level of safety to antihemophilic factor replacement therapy, a full-length, recombinant Factor VIII (rFVIII) product has been developed without human-derived plasma proteins during purification and formulation and using an additional solvent/detergent viral inactivation step. This first clinical trial of a sucrose-formulated full-length rFVIII (rFVIII-FS) was conducted in previously treated patients (≥100 prior exposure days) with severe (<2% FVIII) hemophilia A in North America (NA) and Europe (EU). Pharmacokinetic profiles for rFVIII-FS were compared with those of currently licensed rFVIII product (Kogenate®) in 35 patients. Safety and efficacy during home therapy were evaluated in 71 patients. The new formulation displayed a pharmacokinetic profile similar to that of rFVIII. Patients on home therapy received a cumulative total of 11,867 exposure days, 12,546 infusions, and 22,443,694 IU of rFVIII-FS. Of 2585 bleeds, 93.5% were treated with 1-2 infusions and 80.5% of responses were rated as excellent or good. No evidence of de novo inhibitor formation was observed. Only 0.27% of infusions were associated with any drugrelated adverse event. Except for an episode of intermittent chest pain with palpitations which ceased after treatment with analgesics, associated adverse events were mild or moderate. Overall, rFVIII-FS provided excellent hemostatic control, was well-tolerated, and caused no significant adverse effects, thus demonstrating safety and efficacy for treatment of bleeds in patients with hemophilia A.

Studies on the Enzymatic Activity of the Antihemophilic Factor (Factor VIII)

1967 ◽  
Vol 17 (01/02) ◽  
pp. 188-193 ◽  
Author(s):  
S van Creveld ◽  
I. A Mochtar ◽  
C. N Pascha
Keyword(s):  
Enzymatic Activity ◽  
Factor Viii ◽  
Esterase Activity ◽  
Barium Sulphate ◽  
Screening Tests ◽  
Normal Human ◽  
The Stability ◽  
Fraction I ◽  
Antihemophilic Factor ◽  
Esterase Activities

SummaryPreparations of normal human antihemophilic factor (AHF, factor VIII) obtained by continuous free electrophoresis in the “Elphor” apparatus, were investigated for enzymatic activity on various substrates. A number of enzymatic activities could be excluded by screening tests, performed with fraction I of Cohn. In some preparations esterase-activity was demonstrable on the substrates benzoyl-arginyl-ethylester (BAEE) and on glycerol tributyrate. There was, however, no correlation between these esterase-activities and the AHF-activity in the preparations. Moreover, the stability of the esterase at 4° C was much greater than the stability of the AHF-activity. We therefore assume that the AHF has no enzymatic activity on these substrates under the conditions of the tests. Attempts to activate AHF by calcium, magnesium or serum, were unsuccessful. Both esterase-activities were also present in fraction I of Cohn prepared from normal human citrated or resin plasma. The esterase-activity on BAEE is removed from resin plasma by adsorption to barium sulphate. The esterase-activity on glycerol tributyrate is not adsorbed.

Chromatography of Antihemophilic Factor on Diaminoalkane- and Aminoalkane-Derivatized Sepharose

1982 ◽  
Vol 47 (02) ◽  
pp. 124-127 ◽  
Author(s):  
J-J Morgenthaler
Keyword(s):  
Ionic Strength ◽  
Ethylene Glycol ◽  
Factor Viii ◽  
Homologous Series ◽  
Procoagulant Activity ◽  
Antihemophilic Factor

SummaryAntihemophilic factor was chromatographed on a homologous series of diaminoalkane- and aminoalkane-modified Sepharose beads. Both factor VIII procoagulant activity (VIII:C) and protein are retarded on these columns when compared to their elution on a column made of unmodified Sepharose. Longer chains bind VIII:C and protein more tightly than shorter chains. No bound activity could be eluted with ethylene glycol. Increasing ionic strength eluted VIII:C and protein from aminoalkane- as well as from alkane-Sepharose. It seems likely that hydrophobic, rather than ionic forces, are responsible for the binding of VIII:C to the latter carriers.

scholarly journals The Binding of Bovine Factor VIII of Human Platelets

1977 ◽  
Author(s):  
Edward P. Kirby ◽  
Sha May Tang
Keyword(s):  
Factor Viii ◽  
Evans Blue ◽  
Sodium Iodide ◽  
Dextran Sulfate ◽  
Human Platelets ◽  
Procoagulant Activity ◽  
Human Fibrinogen ◽  
Total Binding ◽  
Antihemophilic Factor ◽  
Bovine Factor

Highly purified bovine Factor VIII (FVIII) was iodinated by the lactoperoxidase method. Subsequent chromatography on agarose and extensive dialysis against sodium iodide solutions was required to remove non-covalently bound 1-125 which adhered tightly to FVIII. Iodination destroyed the procoagulant activity (Antihemophilic Factor-AHF) of FVIII, but did not affect its Platelet Aggregating Factor (PAF) activity. Binding to human platelets was determined by incubating radio!abelled FVIII with formalin-treated platelets, centrifuging, and measuring both bound and free radioactivity. Results obtained by this method were much more precise than those obtained by measuring disappearance of unlabelled AHF, PAF, or FVIII-related antigen from the supernatant, although the estimates of total binding obtained were comparable. Binding of FVIII to formal in-treated platelets was approximately the same as to unfixed platelets, and the binding could be saturated by adding an excess of unlabelled FVIII. Maximal binding occurred within 1-2 minutes at 37° and binding could be blocked by dextran sulfate, Evans Blue or other inhibitors of FVIII-induced platelet agglutination. Treatment of platelets with trypsin inhibited binding of labelled F-VIII. Binding was not affected by the presence of plasma, or high levels of purified human fibrinogen or FVIII.

High Frequency of Low Plasma Haptoglobin Values Found in Hemophilia A Patients on Prophylactic Treatment with Factor VIII Concentrates - A Sign of Hemolysis?

1981 ◽  
Vol 46 (02) ◽  
pp. 554-557 ◽  
Author(s):  
Nils Egberg ◽  
Margareta Blombäck
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
High Frequency ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Factor Viii Concentrates ◽  
Fraction I ◽  
Elevated Lactate ◽  
Elevated Lactate Dehydrogenase ◽  
Plasma Haptoglobin

SummaryLow plasma haptoglobin values have been observed in hemophilia A patients on regular prophylactic treatment with factor VIII concentrates. Two of 3 patients treated with fraction I-0 (Kabi) and 7 of 11 patients treated with high-purity concentrates (Hyland) had low haptoglobin values. Four of 8 patients who were treated with high-purity concentrates prescreened for a low content of anti-A and anti-B immunoglobulins still showed low haptoglobin levels. Unexpectedly, 2 patients of blood group 0 showed low haptoglobin values. The presence of irregular erythrocyte alloantibodies and/or other contaminants of the concentrates might thus also be a cause of hemolysis resulting in an increased consumption of haptoglobin.Elevated lactate dehydrogenase levels were also frequent. No correlations were found between albumin, aspartate or alanine aminotransferase levels and haptoglobin levels.

Factor VIII Ise (R2159C) in a Patient with Mild Hemophilia A, an Abnormal Factor VIII with Retention of Function but Modification of C2 Epitopes

1997 ◽  
Vol 77 (05) ◽  
pp. 0862-0867 ◽  
Author(s):  
Hiroshi Suzuki ◽  
Midori Shima ◽  
Morio Arai ◽  
Kazuhiko Kagawa ◽  
Katuyuki Fukutake ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Factor Viii ◽  
Missense Mutation ◽  
Hemophilia A ◽  
Sscp Analysis ◽  
C2 Domain ◽  
Factor Viii Activity ◽  
Normal Plasma ◽  
Factor Viii Antigen

SummaryWe found a patient with mild hemophilia A who had no detectable factor VIII antigen (FVIII:Ag), as shown by two-site ELISA using inhibitor alloantibodies (TK). We then analyzed A2, A2/B, and C2 antigen of the patient's DDAVP-induced FVIII using several anti-FVIII monoclonal antibodies. Factor VIII activity (FVIII : C) was increased from 12 to 42 Uldl by the administration of DDAVP. The DDAVPinduced increases in the A2 and A2/B antigens were 40 and 36 Uldl, respectively. However, the increase in the C2 antigen was only 7.5 Uldl. SSCP analysis and subsequent sequencing demonstrated an Arg to Cys transition at codon 2159. The anti-FVII1:C titer of monoclonal antibody, NMC-VIII15 which recognized the C2 domain, against normal plasma was 450 Bethesda Ulmg of IgG. However, the titer against DDAVP-treated patient's plasma was only 15 Bethesda Ulmg. We also tested DDAVP-induced increase in the FVIII : Ag in another mild hemophilia A patient with the same mutation at Arg2159. Increase in his C2 antigen levels was only 19% of those in the A2 and A2/B antigen. We designate this abnormal FVIII as FVIII Ise. Our results show that a missense mutation at Arg2159 to Cys modifies the antigenicity of the C2 domain.

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