Abnormality of Separate Subunits of Factor Viii ?

Bennett, Enid

doi:10.1016/s0140-6736(73)91455-4

Cited by 5 publications

(2 citation statements)

References 12 publications

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“…(35), and thus presumably the carrier protein, are administered. Although these data are not complete they suggest that the carrier molecule may be the material which stimulates the appearance of factor VIII activity in these patients after transfusion.…”

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confidence: 99%

The Defect in Hemophilic and von Willebrand's Disease Plasmas Studied by a Recombination Technique

Cooper¹,

Wagner²

1974

J. Clin. Invest.

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A B S T R A C T Factor VIII in preparations from normal plasma is a large glycoprotein of greater than 2 million molecular weight which elutes in the exclusion volume of 4% agarose gels at an ionic strength of 0.15. Recent studies have demonstrated that the factor VIII in canine and bovine plasma is a macromolecular complex composed of a large inert carrier protein and a noncovalently bound small fragment which contains the procoagulant active site. This complex is dissociable in 0.25 M CaCl2, and conditions for its recombination have been reported. The present study reports the dissociation characteristics of normal human factor VIII preparations in 0.25 M CaCla and the ability to achieve quantitative recombination of the dissociated fragments of normal human and bovine factor VIII after the removal of Ca'. The recombination technique was used to characterize further the defect in hemophilia and von Willebrand's disease. Void volume preparations from human hemophilia A-, canine hemophilia A, and human von Willebrand's plasma, with no factor VIII procoagulant activity, were mixed with the small active fragment prepared from the normal plasma of their respective species. Chromatography of the three mixtures in agarose gel showed that the fractions from the human hemophilic plasmas contained a molecule that bound the small active normal fragment, but neither the fractions from canine hemophilia A plasmas nor the fractions from the human von Willebrand's plasmas demonstrated evidence of such material. These data suggest that there is present in human hemophilia A plasma a normal functional carrier molecule which is absent or nonfunctional in the plasma of hemophilic dogs and humans with von Willebrand's disease.

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confidence: 99%

The Defect in Hemophilic and von Willebrand's Disease Plasmas Studied by a Recombination Technique

Cooper¹,

Wagner²

1974

J. Clin. Invest.

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“…As chromosome activation or inactivation is presumed to be a random phenomenon one would expect a proportion of carriers to show only small excesses of antigen over clot-promoting material insufficient to remove them from the normal range, thus accounting for the detection failures. These findings have now been widely confirmed though detection rates have varied depending on the precise techniques used (Denson, 1973 ;Bennett, 1973b;Prentice & Forbes, 1973). The techniques have been extended and applied to a group of women, the childless daughters of known carriers, each of whom had thus an even chance of being a carrier herself on genetic grounds.…”

Section: Implications Of Current Findingsfor Haemophilia and Von Willmentioning

confidence: 95%