Epsilon-Aminocaproic Acid Inhibits the Activity of Factor VIII Inhibitors in Patients with Severe Haemophilia A in vivo and in vitro

2000 ◽  
Vol 103 (2) ◽  
pp. 67-72 ◽  
Author(s):  
Kanjaksha Ghosh ◽  
Shrimati Shetty ◽  
Anil Pathare ◽  
Dipika Mohanty
Keyword(s):  
Factor Viii ◽  
Aminocaproic Acid ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Epsilon Aminocaproic Acid

The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

1993 ◽  
Vol 69 (01) ◽  
pp. 021-024 ◽  
Author(s):  
Shawn Tinlin ◽  
Sandra Webster ◽  
Alan R Giles
Keyword(s):  
Factor Viii ◽  
Canine Model ◽  
Significant Inhibition ◽  
Human Condition ◽  
Haemophilia A ◽  
Variable Expression ◽  
The Family ◽  
Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

Molecular Weight of Human Plasma Factor VIII.

1979 ◽  
Author(s):  
P.A. Bolhuis ◽  
J.J. Sixma
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
Gel Filtration ◽  
Aminocaproic Acid ◽  
Disulfide Bridge ◽  
Iodoacetic Acid ◽  
Plasma Factor ◽  
Barbital Buffer

Recently it has been postulated that native plasma factor VIII is of low molecular weight. We have investigated the molecular weight of VIII: C by agarose chromatography. Factor VIII: C was eluting at the void volume under the following conditions. 1) Blood anticoagulated with 10mM benzamidine 10mM ε-aminocaproic acid and diisopropyl-fluoro-phosphate. Gelchromatography was performed with 10mM benzamidine, 10mM ε-aminocaproic acid and huuman albumin 40 mg/ml) in Michaelisbuffer at 37° in the presence or absence of 2mM Ca2+. 2) Heparin plasma 4U/ml) and elution in barbital buffer, 3) citrated plasma in michaelisbuffer, 4 As (3). but after prevention of disulfide bridge formation by collection of the blood into 5mM iodoacetic acid, 10mM N-ethylmaleimide or ImM p-chloromercuriphenylsulphonic acid. Similar elution patterns were obtained with factor VIII purified from cryoprecipitate. Upon reduction the molecular weight of both purified and plasma factor VIII decreased and the lowest molecular weight form with measurable coagulant activity was about 480.000. Incubation at high ionic strength (0.25M CaCl2) resulted in dissociation and the activity was associated with a molecular weight of 50 - 100.000. Gel filtration at pH 6.0 also resuited in retardation of factor VIII on agarose columns. The data suggests that the in vivo molecular weight of factor VIII is 1-2x106 and that alterations are due to changes in the in vitro conditions.

Determining the approximate factor VIII level of patients with severe haemophilia A on emicizumab using in vivo global haemostasis assays

Haemophilia ◽  
2021 ◽  
Author(s):  
Hande Kizilocak ◽  
Elizabeth Marquez‐Casas ◽  
Jemily Malvar ◽  
Roxana Carmona ◽  
Guy Young
Keyword(s):  
Factor Viii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Factor Viii Level ◽  
Viii Level

DDAVP Factor VIII Concentrate and its Properties in VIVO and in VITRO

1979 ◽  
Author(s):  
I-M. Nilsson ◽  
M. Mikaelsson ◽  
H. Vilhardt ◽  
B. Wiechel
Keyword(s):  
Factor Viii ◽  
Blood Donors ◽  
In Vivo Studies ◽  
Severe Haemophilia ◽  
Plasma Pool ◽  
Factor Viii Concentrates ◽  
Qualitative Effect ◽  
Fraction I

DDAVP fraction I-0 was prepared from a plasma pool derived from 80 blood donors who had received DDAVP and tranexamic acid. A control fraction I-0 was prepared from a plasma pool from the same group of blood donors under identical conditions except for the drug treatment.The DDAVP plasma pool as well as the DDAVP fraction I-0 contained 2-3 times as much VIII:C as the controls. VIIIR:Ag increased to a lesser extent. No difference in stability of VIII:C was seen. In vivo studies showed that infusion of the DDAVP fraction I-0 to 3 patients with severe haemophilia A caused a 2-3 times higher increase in VIII:C than after infusion of the same volume of the control fraction I-0. No difference in disappearance rate of VIII:C was seen.Both factor VIII concentrates normalised the defect in VWD.It is concluded that administration of DDAVP to blood donors prior to collection of blood increases the content of VIII:C in the ensuing factor VIII concentrate and secondly that such stimulation has no demonstrable qualitative effect on the factor VIII obtained.

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

Management of Haemophilia in Sweden

1976 ◽  
Vol 35 (03) ◽  
pp. 510-521 ◽  
Author(s):  
Inga Marie Nilsson
Keyword(s):  
Factor Viii ◽  
Total Population ◽  
Age Groups ◽  
Factor Ix ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Haemophilia B ◽  
Human Fraction ◽  
Mild Haemophilia

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.

Acquired Haemophilia: Functional Study of Antibodies to Factor VIII

1981 ◽  
Vol 45 (03) ◽  
pp. 285-289 ◽  
Author(s):  
J P Allain ◽  
A Gaillandre ◽  
D Frommel
Keyword(s):  
Factor Viii ◽  
Functional Study ◽  
Factor Viii Inhibitor ◽  
Acquired Haemophilia ◽  
Viii Inhibitor ◽  
Kinetics Of ◽  
Antibody Function ◽  
Native Plasma

SummaryFactor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.

The Natural Course of Defibrination Syndrome Caused by Echis Colorata Venom in Man

1974 ◽  
Vol 31 (03) ◽  
pp. 420-428 ◽  
Author(s):  
M Fainaru ◽  
S Eisenberg ◽  
N Manny ◽  
C Hershko
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Major Bleeding ◽  
Renal Damage ◽  
Specific Treatment ◽  
Natural Course ◽  
Factor V ◽  
Thrombocyte Count

SummaryThe natural course of defibrination syndrome caused by Echis colorata venom (ECV) in five patients is reported. All patients developed afibrinogenemia within six hours after the bite. Concomitantly a depression in factor V was recorded. Factor VIII and thrombocyte count in blood were normal in most patients. In the light of the known effects of ECV on blood coagulation in vivo and in vitro it is concluded that the afibrinogenemia is due to intravascular clotting.Four patients had transient renal damage, manifested by oliguria, azotemia, albuminuria and cylindruria, ascribed to microthrombi in the renal glomeruli.After the bite, the natural course was benign, no major bleeding was observed, and all signs of coagulopathy reverted to normal within 7 days. Therefore we recommend no specific treatment for this condition. In the case of heavily bleeding patients, administration of antiserum against ECV and/or heparin should be considered.

Comparison of the Actions of Thrombin and the Thrombin-Like Venom Enzymes Ancrod and Batroxobin

1976 ◽  
Vol 36 (01) ◽  
pp. 009-013 ◽  
Author(s):  
D. L Aronson
Keyword(s):  
Factor Viii ◽  
Fibrinopeptide A ◽  
Enzymic Reaction

SummaryThrombin acts on several coagulant proteins to produce products with physiologic, pharmacologic and pathologic potential. The most sensitive thrombin substrate seems to be factor VIII. Some thrombin dependent reactions studied in vitro and proposed as control reactions seem too insensitive to the action of thrombin to be of in vivo significance.The only enzymic reaction the thrombin-like venom enzymes, Ancrod and Batroxobin, have in common with thrombin is the removal of fibrinopeptide A.

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