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.

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.

Effect of Plasma and Platelet Concentrate Infusions on Factor VIII, Platelet Adhesiveness, and Bleeding Time in Bleeder Swine

1972 ◽  
Vol 28 (03) ◽  
pp. 431-439
Author(s):  
C. N Cornell ◽  
R. G Cooper ◽  
M. E Muhrer ◽  
S Garb
Keyword(s):  
Beneficial Effect ◽  
Factor Viii ◽  
Bleeding Time ◽  
Platelet Concentrate ◽  
Platelet Adhesiveness ◽  
Normal Range ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Platelet Infusion

SummaryBleeder swine are characterized by a prolonged bleeding time, decreased factor VIII levels or reduced platelet adhesiveness or both, and a factor VIII response to infusion of plasma or serum similar to that described in von Willebrand’s disease. In this study the factor VIII response of bleeder swine infused with fresh non-glass-contact pig plasma was similar to that reported in previous experiments after infusion of plasma that was frozen and stored for a variable period of time before use or was not free of glass contact. There was no beneficial effect on platelet adhesiveness. Following platelet concentrate infusion, there was no sustained normalization of platelet adhesiveness, although elevations into the normal range occurred at varying intervals after platelet infusion in two of three pigs investigated. Infusion of factor VIII-deficient plasma from a canine hemophiliac elicited a factor VIII response similar to that described in von Willebrand’s disease patients infused with plasma from factor VIII-deficient human hemophiliacs. In none of these experiments was there any apparent correction of the bleeding time.

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.

Studies on a Variant of Factor VIII Resulting in ’von Willebrand’s Disease»

1975 ◽  
Author(s):  
F. G. H. Hill ◽  
M. C. K. Chan ◽  
R. M. Hardisty
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time

A variant of von Willebrand’s disease in a 14-year-old girl is described, characterised by a prolonged bleeding time and defective ristocetin aggregation (VIIIWF 6%), with VIIIRAg 70-110% and VIIIC 40-60%. The electrophorotic mobility of her VIIIRAg in agarose at pH 9.2 was intermediate between normal VIIIRAg and that of the patient of Kernoff et al, (1), and identical with that of Case 4 of Peake et al. (2). Further characteristics of the factor VIII molecule in this patient’s plasma and platelets will be presented, including antigenic, physicochemical and functional propeertis.1. Kernoff, P. B. A. et al. (1974). Brit. J. Haemat. 26, 435.2. Peake, I. R. et al. (1974). N. Engl. J. Med. 291, 113.

Variant von Willebrand’s Disease

1980 ◽  
Vol 43 (01) ◽  
pp. 002-005 ◽  
Author(s):  
David Green ◽  
K J Philip
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Excessive Bleeding ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Crossed Immunoelectrophoresis ◽  
The Family ◽  
History Of ◽  
Autosomal Dominance ◽  
Ristocetin Cofactor

Summary30 members of an Illinois kindred were studied with a battery of haemostatic tests including the template bleeding time, platelet retention by glass beads (PRGB), measurement of activities related to factor VIII, and crossed-immunoelectrophoresis (CIEP). 9 family members had a history of excessive bleeding, and all 9 had prolonged bleeding times and increased migration of their factor VIII-related antigen (VIIIR:Ag) on CIEP. Of the other tests performed, the VIII: Ristocetin Cofactor and the PRGB showed the best correlation with the bleeding time. 3 subjects who were not bleeders, but who came from a branch of the family where there were several affected members, also had an abnormal VIIIR: Ag. The pattern of inheritance of the altered VIIIR: Ag in this family was one of autosomal dominance with full penetrance. The CIEP is a valuable screening test for the detection of variant von Willebrand’s disease and the recognition of silent heterozygotes.

Increased Activity of “Anti-Willebrand Factor” in Diabetic Plasma

1964 ◽  
Vol 11 (01) ◽  
pp. 027-037 ◽  
Author(s):  
A. E Ödegaard ◽  
B. A Skalhegg ◽  
A. J Hellem
Keyword(s):  
Platelet Adhesiveness ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Platelet Reaction ◽  
Willebrand Factor ◽  
Increased Activity

SummaryIn a group of 25 patients with insulin-treated diabetes mellitus a marked increase in the ADP-induced platelet adhesiveness was demonstrated. This phenomenon was due to a plasmatic factor. In vitro-plasma from these patients restored the decreased ADP-induced platelet adhesiveness in von Willebrand’s disease.The factor was also effective in vivo, since transfusion of 450 ml diabetic plasma to a patient with von Willebrand’s disease normalized the decreased platelet adhesiveness and shortened the prolonged bleeding time. The role of this factor in the ADP platelet reaction as a cofactor together with calcium is stressed.

Evaluation of the Cuticle Bleeding Time in Canine Haemophilia A

1986 ◽  
Vol 55 (01) ◽  
pp. 070-073 ◽  
Author(s):  
M I M Pijnappels ◽  
E Briët ◽  
G Th van der Zwet ◽  
R Huisden ◽  
N H van Tilburg ◽  
...  
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Severe Bleeding ◽  
Suitable Model ◽  
Haemophilia A ◽  
Bleeding Tendency ◽  
The Central Nervous System ◽  
Time Test ◽  
Labrador Retrievers

SummaryIn this paper we describe our clinical experience and results with the cuticle bleeding time test in a colony of cross-bred Labrador retrievers with severe haemophilia A. The dogs have a severe bleeding tendency with a high incidence of fatal haemorrhages in the central nervous system. Homozygous females appeared to be especially prone to this lethal complication. Factor VIII recovery and half-life determinations yielded results similar to the data from human studies. The cuticle bleeding time proved to be a good measure of the coagulation defect. The prolongation of the bleeding time could be completely abolished by administration of 10 to 15 units of canine factor VIII per kg body weight. We conclude that the cuticle bleeding time in canine haemophilia provides us with a suitable model for the in vivo study of new therapeutic materials.

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.

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