scholarly journals von Willebrand Activity and Electrophoretic Mobility of Platelet Factor VIII Related Antigen in Patients with von Willebrand’s Disease

1977 ◽  
Author(s):  
Y. Sultan ◽  
J. Lamazière ◽  
P. Maisonneuve
Keyword(s):  
Factor Viii ◽  
Electrophoretic Mobility ◽  
Secondary Process ◽  
Functional Protein ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Number Of Patients ◽  
Von Willebrand

We have previously shown that patients with severe Von Willebrand’s disease (VWd), mainly homozygotes had no factor VIII related antigen (F VIIIRA) in their platelets as well as no Von Willebrand activity (F VIIIVW) as measured by the ristocetin cofactor assay. In all other patients with less severe form of the disease platelet F VIIIRA was detectable. In normal controls electrophoretic mobility of platelet F VIIIRA was found to be identical to the mobility of plasma VIII-RA either on the total platelet lysate or after isolation on sepharose 4B columns.In the present study F VIIIVW and the electrophoretic mobility of F VIIIRA were compared in platelet extracts and the plasma of a number of patients. Seven of the ten patients tested were genetic variants of vwd with very low ratio of F VIIIVW/F VIIIRA suggesting a non functional protein with an increased electrophoretic mobility : one group of patients showed abnormalities of plateletF VIIIRA identical to those found in the plasma. However another group showed a high ratio of F VIIIVW/F VIIIRA suggesting a more active protein than the one in patient’s plasma although the platelet F VIIIRA had an increased electrophoretic mobility. These results are the first example of a F VIIIRA with abnormal electrophoretic mobility associated to high F VIIIVW activity. The loss of F VIIIVW in the patient’s plasma would be a secondary process occuring after F VIIIRA is released in the circulation.

Factor VIII-Related Activities in Normal, Haemophilic and von Willebrand’s Disease Platelet Fractions

1978 ◽  
Vol 40 (02) ◽  
pp. 288-301 ◽  
Author(s):  
P Meucci ◽  
I R Peake ◽  
A L Bloom
Keyword(s):  
Factor Viii ◽  
Electrophoretic Mobility ◽  
Concanavalin A ◽  
Freezing And Thawing ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Normal Plasma ◽  
Significant Difference ◽  
Ristocetin Cofactor

SummaryFactor VIII-related activities have been studied in platelet fractions in order to try to reconcile the conflicting findings of other workers, and to extend the studies. In platelets from 16 normal subjects procoagulant factor VIII was not detected. The amount of factor VIII-related antigen (FVIIIR: AG) in the cytosol per mg of protein was about twice that in the membrane fraction and about ten times that in the debris fraction. There was no significant difference between the amount of FVIIIR: AG and ristocetin cofactor (RistCof) activity in each fraction. The findings in haemophilic platelets were similar. In von Willebrand’s disease (vWd) one serverely affected patient had no detectable factor VIII related activities in any platelet fraction. In 5 patients with intermediate vWd results were normal. In a further 5, with more prolonged bleeding times, no FVIIIR: RistCof was detected in platelets, despite a normal amount of FVIIIR: AG in the cytosol and debris. The electrophoretic mobility of cytosol FVIIIR: AG was increased in all normals and patients, while that in the membrane and debris fractions had normal mobility. Cytosol FVIIIR: AG eluted later than normal FVIIIR: AG on gel filtration on Sepharose 2B, and also showed reduced antibody binding in an immunoradiometric assay. Precipitation of FVIIIR: AG by concanavalin A was incomplete in all platelet fractions from normals, and even more reduced in vWd platelet fractions. The results suggest the possibility of two types of platelet FVIIIR: AG.A factor VIII-related antigen was shown to be associated with normal washed platelets by immunofluorescence techniques (Bloom et al. 1973). Since then, several studies have been reported on the localisation of factor VIII related antigen (FVIIIR: AG), factor VIII procoagulant activity (FVIII: C) and factor VIII related ristocetin cofactor activity (FVIIIR: RistCof) within the platelets. Initially, Howard et al. (1974) indicated that FVIIIR: AG was firmly bound to the platelet membrane, and noted that in lysed platelets the level of FVIIIR: AG as measured by electroimmunodiffusion was higher than that in whole platelet suspensions. However, further studies by Nachman and Jaffe (1975) showed that FVIIIR: AG was also present to a considerable extent in the granules, and they detected none in the platelet cytosol. Bouma and colleagues (1975) were, however, able to find FVIIIR: AG and FVIIIR: RistCof in the cytosol upon freezing and thawing platelets. This FVIIIR: AG had an electrophoretic mobility comparable to that of normal plasma. They also noted that platelets which were air dried apparently had a granular FVIIIR:AG localisation by immunfluorescence; however, intact platelets in suspension did not stain by this method.Recently Ruggeri et al. (1977) and Sultan et al. (1977) have also found FVIIIR: AG in the cytosol, and the former authors reported it to have increased electrophoretic mobility when compared to normal plasma FVIIIR:AG. Results concerning the localisation of FVIIIR: AG in normal platelets have thus been conflicting. Similarly, in the few reports available concerning platelet FVIIIR: AG in von Willibrand’s disease variable results have also been obtained (Ruggeri et al. 1977, Howard et al. 1974, Shearn et al. 1974 and Bouma et al. 1975).In this study we report on the localisation of factor VIII-related activities in normal, haemophilic and von Willebrand’s disease platelets using available standard techniques as well as precipitation of FVIIIR: AG with the plant lectin concanavalin A, a procedure which has been shown to detect abnormal forms of FVIIIR:AG in certain types of von Willebrand’s disease (Peake and Bloom 1977).

scholarly journals A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity

Blood ◽  
1982 ◽  
Vol 60 (1) ◽  
pp. 201-207 ◽  
Author(s):  
RR Montgomery ◽  
WE Hathaway ◽  
J Johnson ◽  
L Jacobson ◽  
W Muntean
Keyword(s):  
Factor Viii ◽  
Functional Activity ◽  
Type I ◽  
Two Stage ◽  
Functional Abnormality ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
New Variant ◽  
Von Willebrand

Reports on variants of von Willebrand's disease are numerous, but many of these are based on tests that will show marked fluctuations with time and tests that might not be similar in affected family members. This report describes 8 patients with a new variant of von Willebrand';s disease in which there is a normal APTT, slightly reduced one-stage factor VIII:C assay (VIII:C-1), and a drastically reduced two- stage factor VIII:C assay (VIII:C-2). The VIII:C in this variant is more readily adsorbed to AI(OH)3. This variability in VIII:C assays and excessive adsorption to AI(OH)3 are corrected by the addition of either hemophilic plasma or hemophilic factor-VIII-related antigen. This variant is stable with restudy on multiple occasions and is inherited in a stable fashion in three generations of one family. The multimeric structure of the VIIIR:Ag appears normal, although the concentration is moderately reduced. The differences in functional activity, the adsorption to AI(OH)3, and the differences between functional and antigenic (VIII:C Ag) assays of VIII:C support that this is a functional abnormality of type I von Willebrand's disease.

Immunologie Studies in von Willebrand’s Disease

1976 ◽  
Vol 35 (01) ◽  
pp. 110-119 ◽  
Author(s):  
Y Sultan ◽  
J Simeon ◽  
P Maisonneuve ◽  
J. P Caen
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
The Other ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Short Period ◽  
Von Willebrand ◽  
Immunologic Properties

SummaryTwo patients with a severe von Willebrand’s disease characterized by no detectable factor VIII related antigen in their plasma received transfusions of cryoprecipitate. The bleeding time was corrected for a short period of time and returned to its pretransfusional value although the other parameters of the disease were still corrected. Electrophoretic and immunologic properties of factor VIII related antigen infused were determined serially after transfusion. Modifications of these properties occurred progressively after transfusion. The half disappearance time of F. VIIIR. A. was determined and found to be considerably shorter than in hemophilic recipients. This study suggests an alteration in vivo of F. VIIIR. A. infused into von Willebrand recipients.

scholarly journals A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity

Blood ◽  
1982 ◽  
Vol 60 (1) ◽  
pp. 201-207 ◽  
Author(s):  
RR Montgomery ◽  
WE Hathaway ◽  
J Johnson ◽  
L Jacobson ◽  
W Muntean
Keyword(s):  
Factor Viii ◽  
Functional Activity ◽  
Type I ◽  
Two Stage ◽  
Functional Abnormality ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
New Variant ◽  
Von Willebrand

Abstract Reports on variants of von Willebrand's disease are numerous, but many of these are based on tests that will show marked fluctuations with time and tests that might not be similar in affected family members. This report describes 8 patients with a new variant of von Willebrand';s disease in which there is a normal APTT, slightly reduced one-stage factor VIII:C assay (VIII:C-1), and a drastically reduced two- stage factor VIII:C assay (VIII:C-2). The VIII:C in this variant is more readily adsorbed to AI(OH)3. This variability in VIII:C assays and excessive adsorption to AI(OH)3 are corrected by the addition of either hemophilic plasma or hemophilic factor-VIII-related antigen. This variant is stable with restudy on multiple occasions and is inherited in a stable fashion in three generations of one family. The multimeric structure of the VIIIR:Ag appears normal, although the concentration is moderately reduced. The differences in functional activity, the adsorption to AI(OH)3, and the differences between functional and antigenic (VIII:C Ag) assays of VIII:C support that this is a functional abnormality of type I von Willebrand's disease.

A Simple Enzyme-Immunoassay (EIA) Test for Factor VIII-Related Antigen (VIIIAGN)

1979 ◽  
Vol 42 (03) ◽  
pp. 848-854 ◽  
Author(s):  
Paul M Ness ◽  
Herbert A Perkins
Keyword(s):  
Factor Viii ◽  
Enzyme Immunoassay ◽  
Hemophilia A ◽  
Single Sample ◽  
Healthy Controls ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Increased Sensitivity

SummaryAn enzyme immunoassay (EIA) system has been developed to measure factor VIII- related antigen (VIIIAGN). This assay gives similar results to the commonly used Laurell electroimmunodiffusion (EID) assay for VIIIAGN as shown by comparison of both techniques with samples from healthy controls, patients with hemophilia A, and patients with von Willebrand’s disease. The assay also has a greater precision than the EID technique as demonstrated by multiple assays of aliquots of a single sample. The use of this EIA test for VIIIAGN is simple and employs inexpensive reagents and equipment. The use of expensive antisera is minimized. EIA for VIIIAGN has the advantage of increased sensitivity compared to Laurell EIA.

scholarly journals Characterization of the defect of the factor VIII/von Willebrand factor protein in von Willebrand's disease

Blood ◽  
1982 ◽  
Vol 59 (3) ◽  
pp. 542-548 ◽  
Author(s):  
HR Gralnick ◽  
MC Cregger ◽  
SB Williams
Keyword(s):  
Sialic Acid ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Platelet Rich Plasma ◽  
Molecular Forms ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Platelet Receptor ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The factor VIII/von Willebrand factor (f.VIII/vWf) protein was purified from the plasma of a patient with von Willebrand's disease (vWd). The patient had all of the classic laboratory findings of vWd except for the ristocetin-induced platelet aggregation of his own platelet-rich plasma. The disease has been documented in three generations. Comparison of the purified normal and vWd f.VIIi/vWf protein revealed several abnormalities, including decreased concentration of f.VIII/vWf antigen; decreased specific vWf activity; absence of the larger molecular forms of the f.VIII/vWf protein; carbohydrate deficiencies affecting the sialic acid, penultimate galactose and N- acetylglucosamine moieties; and decreased binding of the f.VIII/vWf protein to its platelet receptor. These studies indicate the multiplicity of biochemical and functional abnormalities associated with the f.VIII/vWf protein in vWd. f.VIII/vWf protein to normal f.VIII/vWf protein that had been treated with 2-mercaptoethanol (2-ME) to reduce the multimer size and then treated with specific exoglycosidases to remove the sialic acid and penultimate galactose residues revealed similar biologic properties.

scholarly journals DDAVP in type IIa von Willebrand's disease

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 465-468 ◽  
Author(s):  
HR Gralnick ◽  
SB Williams ◽  
LP McKeown ◽  
ME Rick ◽  
P Maisonneuve ◽  
...  
Keyword(s):  
Factor Viii ◽  
Protease Inhibitors ◽  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Time Period ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

Abstract 1-D-Amino(8-D-arginine)-vasopressin (DDAVP) infusion in three patients with type IIa von Willebrand's disease (vWD) resulted in a normalization of the factor VIII coagulant, factor VIII-related antigen, and von Willebrand factor (vWF) (ristocetin cofactor) activities and the bleeding time. The normalization of these hemostatic parameters persisted for four hours. Over the same time period there was a marked increase in the quantity of the vWF multimers when blood was collected in the presence of protease inhibitors. The vWF multimers present were even larger than the normal. When blood was collected in the absence of protease inhibitors, a smaller increase in the plasma vWF multimers was observed and fewer of the intermediate and larger vWF multimers were seen; multimers larger than those present in normal plasma were not visualized. The platelet vWF multimers and activities did not change with or without inhibitors. These studies suggest that there is a subgroup of patients with type IIa vWD who respond to DDAVP with complete normalization of their hemostatic abnormalities and whose vWF is sensitive to proteolysis.

A Multidisciplinary Approach To Hemophilia At A New Regional Center; How Effective Is It?

1981 ◽  
Author(s):  
W A Andes ◽  
W B Smith ◽  
K Wulff ◽  
K Ohene-Frempong ◽  
A Sonis ◽  
...  
Keyword(s):  
Factor Viii ◽  
Replacement Therapy ◽  
Carrier Status ◽  
Home Therapy ◽  
Von Willebrand's Disease ◽  
Factor Xi Deficiency ◽  
Von Willebrand’S Disease ◽  
Regional Center ◽  
Number Of Patients ◽  
One Year

This study reports data on 74 patients initially evaluated for bleeding disorders at a one year-old hemophilia center. These patients represent a majority of 100 patients currently using any replacement therapy in the state’s hemophilia program. Thirty-five percent of the patients were self-referred, 45% professional-referred, and 20% came to the center through advice from the state NHF Chapter. Diagnoses established were factor VIII deficiency (65%), Christmas disease (19%), von Willebrand’s disease (10%), factor XI deficiency (1 patient), and severe carrier status for factor VIII (6%). Factor VIII inhibitors were found in 7 patients. Several patients did not know their deficient factor, most did not know their inhibitor status, and only 2 patients knew that they had inhibitors. Approximately 50% of the patients were receiving adequate replacement therapy prior to being seen. Care in 5 patients has not improved after their center visit (1 died, 1 is retarded, 2 resist advice or therapy in a rural area, and 1 generally rejects therapy for bleeding for her severe von Willebrand’s disease). Home therapy was available to 32% of patients when initially seen, and 21% more went on home therapy later. A startling number of patients (20% of all) required replacement therapy for untreated bleeds which began within 12 hours prior to a center visit, although 86% of the patients travelled by auto to the visit. Data on 68 patients suggests that they spend an average of $6,500 per year on factor concentrate. Since the immediate family averaged 5.3 persons and the mean income was only $12,500, the burden of the disease was great. Although at least 30% of patients are receiving improved care since their initial center visit, several patients do not yet avail themselves of resources available in this region. Only long-term, even relentless efforts will correct some less than optimal aspects of therapy and such efforts are being made.

scholarly journals A Syndrome of Platelet-release Abnormality and Mild Hemophilia

Blood ◽  
1974 ◽  
Vol 43 (6) ◽  
pp. 821-830 ◽  
Author(s):  
Carolyn Chesney ◽  
Robert W. Colman ◽  
Liberto Pechet
Keyword(s):  
Factor Viii ◽  
Gel Filtration ◽  
Base Line ◽  
Clot Retraction ◽  
Presumptive Diagnosis ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Normal Platelet ◽  
Viii Level

Abstract Two families were studied because of a hemorrhagic tendency. The presumptive diagnosis of von Willebrand’s disease was suggested by low factor VIII levels (7.5%-33%), prolonged template Ivy bleeding time (9.5-17 min), low platelet adhesiveness (0%-8%), normal platelet factor 3, and normal clot retraction. Further studies, however, showed abnormal platelet aggregation with ADP, epinephrine, and collagen, and deficient release of platelet antiheparin activity and 14C serotonin. Patients’ platelets, rendered free of plasma by gel filtration, continued to show abnormal aggregation when resuspended in normal plasma. Plasma from the patients contained greater than 200% factor VIII by immunologic assay. The patients’ coagulant factor VIII level returned to base line within 24 hr after plasma or cryoprecipitate transfusions. Unlike von Willebrand’s disease, management of these patients required both platelets and cryoprecipitate to prevent bleeding.

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