Transfusion and Gel Filtration Studies in von Willebrand's Disease

Kernoff, P. B. A.; Rizza, C. R.; Kaelin, A. C.

doi:10.1111/j.1365-2141.1974.tb00817.x

Cited by 28 publications

(11 citation statements)

References 19 publications

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“…These studies extend earlier findings on the transfusion response of subjects with vWD, human (8,(15)(16)(17)(18)(19) and swine (9,10,20,21 (20), but not tocorrect the bleeding time. Normal plasma infused in swine (9) …”

Section: Discussionsupporting

confidence: 77%

Macromolecular factor VIII complex: functional and structural heterogeneity observed in von Willebrand swine with transfusion.

Griggs¹,

Potter²,

McClanahan³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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The physiologic activities concerned with hemostasis and associated with the Factor VIII macromolecular complex were investigated in swine with von Willebrand's disease after infusions of cryoprecipitate, a lyophilized Factor VIII concentrate, or porcine serum. Immediately after each infusion the various activities, antihemophilic factor, von Willebrand platelet aggregating factor, and Factor VIII-related antigen, were elevated in approximate proportion to dose and the bleeding time was shortened. There was a late secondary rise in antihemophilic factor. During the period after infusion, there was a differential fall-off of the various activities, with the bleeding time effect lost first, followed by the von Willebrand platelet aggregating factor and then by the Factor VIIIrelated antigen. The plasma from swine with von Willebrand's disease late after infusion contained high levels of antihemophilic factor without other detectable activities of the complex. Antihemophilic factor, free of the other components, obtained from plasma from swine with von Willebrand's disease either before or late after infusion eluted from agarose gel columns both as high and lower molecular weight material, unlike normal antihemophilic factor, which had a high molecular weight. In contrast, on ultracentrifugation the antihemophilic factor in these plasmas sedimented slowly, even though chromatographically the plasmas contained both high and low molecular weight factor. All of the Factor VIII complex activities in normal porcine plasma sedimented rapidly. These studies demonstrate the heterogeneity of the Factor VIII complex and the apparent dependence of its chromatographic and sedimentation behavior on the functional activities associated with the complex."Factor VIII complex" refers to a macromolecular plasma protein complex that carries several biological functions needed for hemostasis (1). These functions are concerned with both fibrin clotting and platelet plug formation. Selective functional deficiencies of the Factor VIII complex occur in hemophilia A and in von Willebrand's disease (vWD). In severe hemophilia, only the antihemophilic factor (AHF) or Factor VIII coagulant activity is lacking. In severe vWD, AHF is greatly reduced or absent, but in addition, the other activities of the Factor VIII complex are lacking. These include: (a) the specific platelet aggregating factor (PAF) or von Willebrand factor (vWF), which in human beings requires ristocetin for its demonstration; (b) the Factor VIII-related antigen, which gives a precipitin reaction with antibody raised to the Factor VIII complex; (c) the bleeding time factor; and (d) a plasma factor, different from AHF, that on transfusion of subjects with vWD causes a delayed rise in AHF.In normal plasma and plasma concentrates, the AHF of the complex can be dissociated from the PAF/vWF (2) and the Factor VIII-related antigen (3) by an increase in the ionic strength (e.g., 0.25 M CaCd2), followed by gel chromatography.The isolated AHF is of apparent low molecular weig...

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Section: Discussionsupporting

confidence: 77%

Macromolecular factor VIII complex: functional and structural heterogeneity observed in von Willebrand swine with transfusion.

Griggs¹,

Potter²,

McClanahan³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…In this study also the t112 of the second phase of VIII:C seemed to be shorter (Table VI). The curves were so similar, however, that we feel that this difference is of no importance in comparison to the data reported by others for the half-disappearance time of VIII:C and VIIIR:Ag in transfused hemophiliacs (15)(16)(17). Analysis of the survival of VIIIR:Ag in the four transfused hemophiliacs in this study showed that in A.…”

Section: Discussionmentioning

confidence: 43%

“…In this way the biphasic nature of the disappearance curve was discovered. The early data showed some discordance, but more recent studies have shown that the t1/2s are in the range of about [12][13][14][15][16][17][18] h. The introduction of the quantitative assay for VIIIR:Ag using heterologous antisera (2) allowed the analysis of the disappearance of Factor VIII on the basis of VIIIR:Ag. It was then reported that this VIIIR:Ag decreased more slowly than VIII:C after transfusion of normal cryoprecipitate into hemophiliacs (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Survival of 125iodine-labeled Factor VIII in normals and patients with classic hemophilia. Observations on the heterogeneity of human Factor VIII.

Over¹,

Sixma²,

Bruïne³

et al. 1978

J. Clin. Invest.

100

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“…This effect is seen with cryoprecipitate [9] and plasma [10] and, perhaps most convincingly, with highpurity vWF concentrate [11], with hemophil iac plasma [10], and with serum [12], Lastly, in vitro studies reveal that the half-life of fac tor VIII is shortened in plasma with reduced vWF concentrations [13] and is extremely brief in the culture medium of cells expressing recombinant human factor VIII unless vWF is added to the medium [14]. This paper discusses a mathematical mod el of factor VIII kinetics based upon the pro posed factor VUI-stabilizing function of vWF binding.…”

Section: Introductionmentioning

confidence: 76%

A Mathematical Model of Coagulation Factor VIII Kinetics

Noe

1996

Pathophysiol Haemos Thromb

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It appears that the binding of coagulation factor VIII to von Willebrand factor in plasma stabilizes the otherwise highly labile factor VIII. A mathematical model of factor VIII kinetics has been developed based upon this proposed effect of factor VIII binding. The model’s kinetic parameter values have been estimated by fitting the model to data available in the medical literature. The model gives accurate quantitative predictions of the elevated steady-state concentrations of factor VIII in clinical conditions associated with the acute phase reaction and in pregnancy, the decreased steady-state concentrations of factor VIII in females heterozygous for hemophilia, the decreased steady-state concentrations of factor VIII in patients with type 1 (heterozygous) and type 3 (homozygous) von Willebrand disease, and the variable half-life of factor VIII in factor replacement therapy for hemophilia and von Willebrand disease.

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Transfusion and Gel Filtration Studies in von Willebrand's Disease

Cited by 28 publications

References 19 publications

Macromolecular factor VIII complex: functional and structural heterogeneity observed in von Willebrand swine with transfusion.

Macromolecular factor VIII complex: functional and structural heterogeneity observed in von Willebrand swine with transfusion.

Survival of 125iodine-labeled Factor VIII in normals and patients with classic hemophilia. Observations on the heterogeneity of human Factor VIII.

A Mathematical Model of Coagulation Factor VIII Kinetics

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