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.

The Spectrum of von Willebrand’s Disease

1967 ◽  
Vol 18 (01/02) ◽  
pp. 040-056 ◽  
Author(s):  
E. J Walter Bowie ◽  
P Didisheim ◽  
J. H Thompson ◽  
C. A Owen
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Severe Bleeding ◽  
Platelet Adhesiveness ◽  
Platelet Activity ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
The Third ◽  
Generation Test

SummaryPatients (from 5 kindreds) with variants of von Willebrand’s disease are described. In one kindred the depression of factor VIII was moderate (20 to 40% of normal) and transfusion of 500 ml of normal plasma led to an increase higher than anticipated and to an almost normal level of factor VIII 17 to 24 hrs later. This represents the usual type of von Willebrand’s disease.In the second kindred the concentration of factor VIII was less than 2 % of normal in the son and daughter, who had severe bleeding and hemarthroses.The third kindred was characterized by reduction of factor VIII and a long bleeding time as well as by a serum defect in the thromboplastin-generation test comparable to that seen in patients with hemophilia B, yet with normal levels of factors IX, X, and VII. The severity of the serum defect, the positive result with the Rumpel-Leede test, and the reduced platelet activity in the thromboplastin-generation test are all compatible with the diagnosis of thrombopathy or ‘‘thrombopathic hemophilia.” In two other kindreds, one patient had a long bleeding time and normal levels of factor VIII and another had a normal bleeding time and decrease of factor VIII. The last patient had the type of response to transfusion usually seen in von Willebrand’s disease.In four kindreds, platelet adhesiveness in vivo was found to be strikingly abnormal (virtually absent).It would appear, therefore, that von Willebrand’s disease forms a spectrum, and whether the kindreds reported simply reflect variations of a single genetic disease state or represent separate entities will be answered only by clarification of the underlying etiology of that disease.

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.

scholarly journals Multimeric composition of factor VIII/von Willebrand factor following administration of DDAVP: implications for pathophysiology and therapy of von Willebrand's disease subtypes

Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1272-1278 ◽  
Author(s):  
ZM Ruggeri ◽  
PM Mannucci ◽  
R Lombardi ◽  
AB Federici ◽  
TS Zimmerman
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Resting State ◽  
Bleeding Time ◽  
Type I ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Plasma Factor ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract We have studied the modifications in the multimeric composition of plasma factor VIII/von Willebrand factor and the bleeding time response following administration of 1-Deamino-[8-D-arginine]-Vasopressin (DDAVP) to patients with different subtypes of von Willebrand's disease. In type I, all multimers were present in plasma in the resting state, though they were decreased in concentration. Administration of DDAVP resulted in an increased concentration of these forms as well as the appearance of larger forms than were previously present. There was concomitant correction of the bleeding time. In type IIA, large multimers were absent in the resting state, and although DDAVP induced an average threefold increase in the plasma concentration of factor VIII/von Willebrand factor, the larger multimers did not appear and the bleeding time, although shortened, was not corrected. In contrast, the larger multimers that were also absent from type IIB plasma in the resting state rapidly appeared following DDAVP administration. However, their appearance was transitory and the bleeding time, as in IIA patients, was shortened but not corrected. The characteristic multimeric composition of platelet factor VIII/von Willebrand factor in given subtypes predicted the alteration in plasma factor VIII/von Willebrand factor induced by DDAVP. These studies provide evidence that the different subtypes of von Willebrand's disease represent distinct abnormalities of factor VIII/von Willebrand factor. They also suggest that complete hemostatic correction following DDAVP can be routinely expected only in type I von Willebrand's disease, and only if factor VIII/von Willebrand factor can be raised to normal levels.

Factor VIII synthesis: hepatic and renal allografts in swine with von Willebrand's disease

1976 ◽  
Vol 230 (5) ◽  
pp. 1342-1348 ◽  
Author(s):  
WP Webster ◽  
SR Mandel ◽  
LE Strike ◽  
GD Penick ◽  
TR Griggs ◽  
...  
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Normal Liver ◽  
Normal Kidney ◽  
Von Willebrand's Disease ◽  
Renal Allografts ◽  
Von Willebrand’S Disease ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Transplantation Experiments

Transplantation experiments were utilized to study the possible sites of synthesis of von Willebrand factor (vWF) and factor VIII (F VIII) activities. Three normal kidney and two normal liver allografts were implanted into five swine with von Willebrand's disease (vWD) that survived for 1,6, and 7, and 4 and 9 days, respectively. The correction of the multiple hemostatic defects of vWD by organ transplantation was evaluated using the F VIII procoagulant activity, bleeding time, and platelet aggregating factor (PAF) levels; i.e., vWF levels. Normal kidney allografts produced no changes in the bleeding times or increases in F VIII or PAF. Transfusions for surgical hemostasis produced transient increases in F VIII and PAF. In animals receiving normal liver allografts, the levels of F VIII exceeded 100%, PAF was increased, and sustained correction of the bleeding time and maintenance of hemostasis was observed. These data suggest that the kidney is incapable of synthesizing either the vWF or the F VIII and that cells contained in the liver, possibly the endothelial cells, are one of the sites of synthesis of these factors.

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.

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

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.

scholarly journals Functional Properties and in Vivo Survival of Normal and Asialo Human Factor VIII/VON Willebrand Protein

1977 ◽  
Author(s):  
J.M. Sodetz ◽  
S.V. Pizzo ◽  
P.A. McKee
Keyword(s):  
Sialic Acid ◽  
Factor Viii ◽  
Cross Reactivity ◽  
Molecular Defect ◽  
Survival Times ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Human Factor Viii ◽  
Von Willebrand

Recent evidence suggests that the molecular defect in von Willebrand’s disease resides in the carbohydrate moiety of Factor VIII/von Willebrand factor (FVIII/vWF). In light of this, we have examined and compared certain properties of normal and asialo FVIII/vWF. Purified human FVIII/ vWF was desialylated using a protease-free neuraminidase. At various incubation times, sialic acid released, ristocetin-induced platelet aggregating activity(RPA) and procoagulant activity (PCA) were measured. RPA decreased with increasing amounts of sialic acid released. When completely desialylated (>95%), only 35±10% of the initial RPA was retained. In contrast, PCA remained constant with up to 80-85% sialic acid removed. Normal and asialo FVIII/vWF displayed similar immunological cross-reactivity to normal FVIII/vWF rabbit anti-sera. However, immuno-electrophoretic results clearly indicated a reduced anodic mobility for asialo FVIII/vWF relative to normal. Normal and asialo FVIII/vWF were then radiolabeled with 125I, infused in rabbits and the circulatory survival times measured. Asialo FVIII/vWF was cleared from circulation at a rate 50-fold greater than that observed for normal FVIII/vWF. This clearance was accompanied by quantitative appearance of radioactivity in the liver. In addition, simultaneous infusion of human asialo α1-acid glycoprotein, a protein known to bind to hepatic asialoglycoprotein receptors, competitively inhibited asialo FVIII/vWF clearance. These results indicate that desialylation of FVIII/vWF does not alter PCA, decreases RPA and, as observed with other plasma asialoglycoproteins, facilitates its rapid hepatic clearance. Understanding these properties of asialo FVIII/vWF represents an important initial step towards defining a possible carbohydrate defect as a cause for von Willebrand’s disease.

scholarly journals The heterogeneity of type IIA von Willebrand's disease: studies with protease inhibitors

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1207-1212 ◽  
Author(s):  
J Batlle ◽  
MF Lopez Fernandez ◽  
M Campos ◽  
B Justica ◽  
C Berges ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Relative Proportion ◽  
Clinical Expression ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Time Correction ◽  
Von Willebrand ◽  
Willebrand Factor

The absence of large von Willebrand factor (vWF) multimers from plasma is a characteristic of Type IIA von Willebrand's disease (vWD) and is thought to contribute to the clinical expression of this disorder. Recently, three IIA patients have been reported in whom intermediate and large multimers could be restored if blood were collected in 5 mm EDTA, 6 mmol/L N-ethylmaleimide, and 1 mmol/L leupeptin. This suggested that absence of large multimers resulted from in vitro proteolysis. We have now collected blood from ten Type IIA vWD patients in these inhibitors but were not able to detect large multimers in the plasma of any of them. In addition, intermediate-sized multimers were reduced or completely absent in all. The inclusion of inhibitors in the citrate anticoagulant, as compared to citrate alone, was found to increase the relative proportion of intermediate multimers in some patients but had no effect in others, and in none did it restore large multimers to plasma. The results with platelet vWF were more varied. Four patients showed an absence or decrease of large multimers, whereas in seven patients large multimers were present. When compared with citrate anticoagulant alone, the inclusion of inhibitors in the anticoagulant had little or no effect on the platelet multimeric pattern. 1-Deamino-8- D-Arginine Vasopressin (DDAVP) was administered to six patients from five families. Two patients from one family showed complete correction and a third patient showed almost complete correction of her bleeding time. Two patients showed minimal correction and one showed no detectable correction. An increase in multimer size after DDAVP tended to be associated with correction of the bleeding time. However, in no case did the largest multimers appear in plasma even in patients with complete bleeding time correction. The presence or absence of inhibitors in the anticoagulant had little or no effect on the multimeric pattern after DDAVP. These results indicate that Type IIA vWD is a heterogeneous disorder in which absence of largest and intermediate multimers is an in vivo phenomenon.

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.

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