Properties of the Platelet Retention (von Willebrand) Factor and Its Similarity to the Antihemophilic Factor (AHF)

Abstract The abnormal retention of platelets in glass-bead filters in von Willebrand’s disease was corrected by a fraction of normal cryoprecipitate that eluted, along with antihemophilic factor (AHF), in the void volume after chromatography on Bio-Gel 5 M. This platelet retention factor had an apparent molecular weight in excess of 5 x 106, was also present in hemophilic cryoprecipitate, but was not detectable in the void volume fractions of cryoprecipitate prepared from the plasma of a patient with von Willebrand’s disease. The adsorptive and thermal stability properties of the retention (von Willebrand) factor were similar to those of AHF. Platelet retention is the result of a complex interaction between red cells, platelets, and the von Willebrand factor, and it is suggested that the activity of the latter factor may be associated with the same high molecular weight protein that possesses coagulant (AHF) activity in normal subjects but that lacks this activity in hemophiliacs. The deficiency of this protein in von Willebrand’s disease may account for the hemostatic defect in this disorder.

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The In Vitro Association of Antihemophilic Factor and von Willebrand Factor

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657311 ◽

1983 ◽

Vol 49 (01) ◽

pp. 037-041 ◽

Cited By ~ 23

Author(s):

M B Zucker ◽

M E Soberano ◽

A J Johnson ◽

A J Fulton ◽

S Kowalski ◽

...

Keyword(s):

Von Willebrand Factor ◽

Ion Concentration ◽

Void Volume ◽

Gel Chromatography ◽

Clotting Factors ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Von Willebrand ◽

Willebrand Factor ◽

Antihemophilic Factor

SummaryConsiderable evidence, including results of gel chromatography, indicates that antihemophilic factor (AHF; factor VIII: C) is associated with von Willebrand factor (vWF; factor VIIIR: RC or VTIIR: Ag) in citrated plasma. The present study was undertaken to determine whether these factors are also associated in plasma with a physiologic calcium ion concentration, or in an artificial medium using purified antihemophilic factor and plasma as a source of vWF. When fresh BaS04-treated native normal plasma was passed through a column of Sepharose CL-4B that was equilibrated and eluted with fresh BaS04-treated plasma from a patient with severe von Willebrand’s disease, the AHF and vWF activities were found in the void volume. Thus, AHF remains associated with vWF on gel chromatography in the presence of physiological concentrations of all plasma constituents except the vitamin-K-dependent clotting factors. On the other hand, when to 200,000 X purified “vWF-free” AHF was chromatographed in buffered 4% albumin with 2 mM CaCl2, virtually all of it appeared in the included volume of the column with an apparent molecular weight between that of fibrinogen or factor V (340,000) and gamma globulin (160,000). The combination of the “vWF-free” AHF with the vWF in plasma was studied by adding the AHF to BaS04-treated plasma from normal subjects or patients with severe hemophilia or von Willebrand’s disease and chromatographing the mixture. The AHF activity appeared in the void volume in an amount that was inversely related to the ratio of the AHF to vWF activity. Thus, with 1-12 U of AHF per unit of vWF, virtually all of the AHF eluted in the void volume, with 30 and 500 units of AHF per unit of vWF, only about 50% and 10% of the AHF, respectively, eluted in the void volume, and in the absence of vWF, none of the AHF activity eluted in the void volume.

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Heterogeneity of the Factor VIII/Von Willebrand Factor Protein in Von Willebrand’s Disease

10.1055/s-0039-1680467 ◽

1977 ◽

Author(s):

H. R. Gralnick ◽

Y. Sultan ◽

B. S. Coller

Keyword(s):

Molecular Weight ◽

Factor Viii ◽

Von Willebrand Factor ◽

Apparent Molecular Weight ◽

Total Carbohydrate ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Parallel Reduction ◽

Von Willebrand ◽

Willebrand Factor

The recent advent of techniques to purify the factor VIII/von Willebrand factor (f.VIII/vWf) protein from plasma to quantitate the f.VIII/vWf protein and to measure the vWf (plasma ristocetin cofactor) have greatly added to our understanding of von Willebrand’s disease (vWd). The initial studies of antigen, procoagulant and vWf levels revealed a parallel reduction in all three activities in vWd suggesting a quantitative deficiency of the f. VIII/vWf protein and its biologic activities.Recent studies, however, have suggested three major forms of vWd. The first group of patients have a quantitative defect with a parallel reduction of the f.VIII/vWf protein and of the antigen, vWf and procoagulant activities. The second group of patients appear to have a qualitative defect of the f.VIII/vWf protein. These individuals have normal levels of the antigen and procoagulant activity; however, the vWf activity is reduced or absent. The third group of patients have a combination of a qualitative and quantitative deficiency. These variants resemble both previous groups in that there are reduced levels of the antigen, procoagulant and vWf activities but usually greater reduction of the vWf activity.Three major defects of the f.VIII/vWf protein have been recognized in vWd: 1) decreased plasma concentration of the f. VIII/vWf protein, 2) the apparent molecular weight of the protein is reduced and/or the largest molecular weight polymers are absent, and 3) there is a partial or total carbohydrate deficiency. For the f.VIII/vWf protein to express vWf activity, it must be of a minimal molecular size and have a specific carbohydrate content and/or sequence.

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Stabilization of the Antihemophilic Factor (VIII :AHF) by the Von Willebrand Factor (VIII :VWF): A Possible Model for Von Willebrand’s Disease

10.1055/s-0039-1680356 ◽

1977 ◽

Author(s):

H. J. Weiss ◽

I. I. Sussman ◽

L. W. Hoyer

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Crossed Immunoelectrophoresis ◽

Factor Viii Antigen ◽

Von Willebrand ◽

Willebrand Factor ◽

Antihemophilic Factor

When compared with VIII:AHF in normal citrated plasmas, VIII:AHF activity showed increased lability at 37°C in the ‘late’ post-transfusion plasmas (VIII:AHF≫VIII:VWF) of a patient with von Willebrand’s disease, but not in the ‘early’ post-transfusion plasmas in which VIII:AHF~VIII:VWF. VIII:AHF was also labile in the baseline plasmas of 3 patients with von Willebrand’s disease in whom VIII:AHF≫VIII:VWF. In two of these patients the mobility of Factor VIII antigen (on crossed Immunoelectrophoresis) was increased. (VIII:AHF was not excessively labile in 4 other patients in whom VIII :AHF~VIII:VWF). In all of the above cases, VIII:AHF was stabilized by the addition of either purified von Willebrand factor or plasmas of patients with hemophilia, but not by plasmas of patients with severe von Willebrand’s disease. Thus, VIII:VWF may serve to stabilize VIII:AHF and this might explain the post-transfusion findings in von Willebrand’s disease.

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Current Knowledge of the AHF-Like Antigen

10.1055/s-0039-1689461 ◽

1975 ◽

Author(s):

Dominique Meyer

Keyword(s):

Molecular Weight ◽

Factor Viii ◽

Von Willebrand Factor ◽

Hemophilia A ◽

Factor Activity ◽

Factor Viii Activity ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Von Willebrand ◽

Willebrand Factor

Factor VIII and von Willebrand Factor activities are associated with a high molecular weight protein which can be isolated from plasma and may be studied by immunological methods. Homologous antibodies to Factor VIII are directed towards the active site of the Factor VIII molecule; they do not neutralize Willebrand Factor activity and do not precipitate with normal plasma. The use of such antibodies has allowed the distinction between Hemophilia A+ and A-. Specific precipitation of Factor VIII antibodies using polyethylene glycol will be reported, allowing typing of heavy and light chains of purified antibodies. Heterologous antisera prepared in rabbits against purified human Factor VIII complex neutralize Factor VIII and von Willebrand Factor activities and precipitate with AHF-like antigen. Estimation of this antigen in plasma has allowed (1) the differenciation of the molecular abnormalities in Hemophilia A and classical von Willebrand’s disease; (2) the comparison between normal and Hemophilic AHF-like antigen; (3) the detection of carriers of Hemophilia A; (4) the study of variants of von Willebrand’s disease; (5) the demonstration of this antigen in platelets and in endothelial cells. Factor VIII activity and AHF-like antigen are probably separate entities, circulating as a complex in normal plasma, as suggested by the following experiments: transfusion studies in von Willebrand’s disease; immuno-adsorption studies; comparison of Factor VIII complex in cryoprecipitate and supernatant; and dissociation in high salt buffer, demonstrating that Factor VIII includes two biologically linked but distinct fragments, of high (HMW) and low (LMW) molecular weight. The non functional HMW subunit, controlled by an autosomal locus, is identified by the presence of AHF-like antigen and Willebrand Factor activity. The LMW subunit, product of an X-chromosome locus, does not contain AHF-like antigen, but it carries Factor VIII activity, as demonstrated by the following facts: inactivation by both human and rabbit antibodies to Factor VIII; transient activation by thrombin; obtention of antisera which specifically inactivate Factor VIII.

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In vivo interaction of von Willebrand factor with platelets following cryoprecipitate transfusion in platelet-type von Willebrand's disease

Blood ◽

10.1182/blood.v63.1.226.bloodjournal631226 ◽

1984 ◽

Vol 63 (1) ◽

pp. 226-230

Author(s):

JL Miller ◽

BD Boselli ◽

JM Kupinski

Keyword(s):

Molecular Weight ◽

Von Willebrand Factor ◽

Platelet Rich Plasma ◽

Platelet Factor ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Von Willebrand ◽

Willebrand Factor

Previous studies performed in vitro have indicated that platelets from patients with platelet-type von Willebrand's disease (vWD) have receptors for von Willebrand factor (vWF) already exposed on their surfaces and that the addition of purified vWF or cryoprecipitate to patient platelet-rich plasma under stirring conditions is capable of inducing platelet aggregation and secretion. The present work reports the results of the transfusion of cryoprecipitate in a patient with platelet-type vWD. It is shown that, while factor VIII-related antigen and ristocetin cofactor activities maintain elevated levels for up to 12 hr following transfusion, the highest molecular weight vWF multimers decline rapidly. The platelet count also declines, followed in turn by a rise in the plasma level of platelet factor 4. Shortening of the bleeding time occurs only very transiently. The results of this study provide direct evidence that, in patients with platelet-type vWD, an abnormal interaction of their platelets with plasma vWF occurs in vivo, resulting in the absence of high molecular weight vWF multimers, low platelet counts, and impaired hemostasis that are characteristic of this disease.

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In vivo interaction of von Willebrand factor with platelets following cryoprecipitate transfusion in platelet-type von Willebrand's disease

Blood ◽

10.1182/blood.v63.1.226.226 ◽

1984 ◽

Vol 63 (1) ◽

pp. 226-230 ◽

Cited By ~ 14

Author(s):

JL Miller ◽

BD Boselli ◽

JM Kupinski

Keyword(s):

Molecular Weight ◽

Von Willebrand Factor ◽

Platelet Rich Plasma ◽

Platelet Factor ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Von Willebrand ◽

Willebrand Factor

Abstract Previous studies performed in vitro have indicated that platelets from patients with platelet-type von Willebrand's disease (vWD) have receptors for von Willebrand factor (vWF) already exposed on their surfaces and that the addition of purified vWF or cryoprecipitate to patient platelet-rich plasma under stirring conditions is capable of inducing platelet aggregation and secretion. The present work reports the results of the transfusion of cryoprecipitate in a patient with platelet-type vWD. It is shown that, while factor VIII-related antigen and ristocetin cofactor activities maintain elevated levels for up to 12 hr following transfusion, the highest molecular weight vWF multimers decline rapidly. The platelet count also declines, followed in turn by a rise in the plasma level of platelet factor 4. Shortening of the bleeding time occurs only very transiently. The results of this study provide direct evidence that, in patients with platelet-type vWD, an abnormal interaction of their platelets with plasma vWF occurs in vivo, resulting in the absence of high molecular weight vWF multimers, low platelet counts, and impaired hemostasis that are characteristic of this disease.

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Spinal Cord Stimulator Placement in a Patient with Type 2 von Willebrand’s Disease

Pain Management Case Reports ◽

10.36076/pmcr.2018/2/153 ◽

2018 ◽

pp. 153-155

Author(s):

Scott Masson

Keyword(s):

Spinal Cord ◽

Von Willebrand Factor ◽

Pain Syndrome ◽

Von Willebrand Disease ◽

Spinal Cord Stimulator ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Von Willebrand ◽

Willebrand Factor ◽

Antihemophilic Factor

We present a case of a 76-year-old female with a history of lumbar post-laminectomy pain syndrome and Type II von Willebrand’s disease who underwent successful implantation of a spinal cord stimulator. A consultation with the patient’s hematologist was obtained, and antihemophilic factor/von Willebrand factor complex was administered immediately prior to insertion and removal of trial leads. After reporting greater than 90% pain relief, the patient then underwent permanent implantation with administration of antihemophilic factor/von Willebrand factor complex prior to placement. The epidural space was entered atraumatically, and lead placement was uneventful with minimal resistance met. Leads were tunneled to her right gluteal region, where a pocket was created for her generator. She continues to report good relief without neurological signs of epidural hematoma nearly 6 months post-procedure. Key words: von Willebrand disease, high-frequency spinal cord stimulator, post-laminectomy pain syndrome

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Further Studies on Aggregation of Platelet-Type von Willebrand’s Disease Platelets by Human von Willebrand Factor

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661559 ◽

1986 ◽

Vol 55 (03) ◽

pp. 338-341 ◽

Cited By ~ 7

Author(s):

H Takahashi ◽

W Tatewaki ◽

M Hanano ◽

R Nagayama ◽

A Shibata

Keyword(s):

Von Willebrand Factor ◽

Ricinus Communis ◽

Divalent Cations ◽

Peanut Agglutinin ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Ricinus Communis Agglutinin ◽

Von Willebrand ◽

Induced Aggregation ◽

Willebrand Factor

SummaryPlatelet-type von Willebrand’s disease (vWD) is a bleeding disorder characterized by a heightened interaction between platelets and von Willebrand factor (vWF) as the result of an intrinsic platelet abnormality (probably in GPIb). Platelet aggregability was nearly normal in response to thrombin, wheat germ agglutinin and Ricinus communis agglutinin in this disorder. Unmodified platelets showed no aggregation upon the addition of peanut agglutinin. Partially purified human vWF induced little aggregation of washed patient platelets, but the aggregation was greatly enhanced in the presence of plasma devoid of vWF. Monoclonal antibodies directed against GPIb and GPIIb/IIIa as well as EDTA completely inhibited vWF-induced aggregation. These results indicate that human vWF induces aggregation of platelet-type vWD platelets in the presence of divalent cations and some plasma cofactor(s), and that both GPIb and GPIIb/IIIa are involved in this aggregation.

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