scholarly journals Von Willebrand's disease in the German shepherd dog : clinical communication

2000 ◽  
Vol 71 (2) ◽  
Author(s):  
R.G. Lobetti ◽  
T. Dippenaar
Keyword(s):  
Factor Viii ◽  
Type I ◽  
Type Ii ◽  
German Shepherd ◽  
Excessive Bleeding ◽  
Von Willebrand's Disease ◽  
Clinical Communication ◽  
Von Willebrand’S Disease ◽  
German Shepherd Dog ◽  
Von Willebrand’S Factor

Two litters of Germanshepherd dogs were evaluated for a haemorrhagic tendency that was characterised by excessive bleeding from the umbilicus at birth, haemorrhage and haematoma formation at vaccination, excessive bruising, and lameness due to haemarthrosis. Platelet counts, clotting times and Von Willebrand's factor (VWF) assays were assessed in all dogs. Factor VIII determination was performed in 1 puppy and its parents. Based on the clotting times and VWF assay, 6 puppies (4 male and 2 female) showed type I Von Willebrand's disease (VWD), 5 (4 male and 1 female) possible type II VWD, and 4 were unaffected. One puppy with possible type II VWD had very low factor VIII activity; its sire had a normal factor activity, whereas the dam was in the low-normal range. This article reports type I and possible type II VWD in 2 related litters of German shepherd dogs, the latter being rare in German shepherd dogs.

scholarly journals Multiple Molecular Forms of Factor VIII Antigen in Normal Individuals and Von Willebrand’s Disease Patients

1977 ◽  
Author(s):  
T. S. Zimmerman ◽  
J. R. Kimball ◽  
T. S. Edgington ◽  
C. F. Abildgaard
Keyword(s):  
Factor Viii ◽  
Small Sample ◽  
Molecular Forms ◽  
Type I ◽  
Type Ii ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Multiple Molecular Forms ◽  
Normal Individuals ◽  
Factor Viii Antigen

Factor VIII antigen is present in normal individuals in multiple molecular forms which can be separated according to size. The intermediate and larger forms preferentially bind to platelets in the presence of ristocetin. In order to evaluate the possibility that Factor VIII antigen forms of large size may be an artifact of in vitro aggregation, we have ultracentrifuged plasma on a 20% sucrose cushion at 37°C for 10 min at 254,000 xg (peak). The rate of clearing of Factor VIII antigen was compared to that of IgM, fibrinogen, IgG, α1-antitrypsin and the S rate calculated to be between 15 and 18. These results indicate that Factor VIII-related antigen forms of high S exist even when plasma is maintained at physiological temperature and analyzed with minimal delay, suggesting that these large molecular forms also exist as such in vivo.Two types of von Willebrand’s disease (vWd) have been identified according to size of Factor VIII antigen forms present in plasma. In Type I all forms of Factor VIII antigen are present but are decreased in quantity. In Type II large forms are missing and smaller forms are present in normal or increased quantities. Factor VIII antigen was isolated from plasma of one patient with Type I and two patients with Type II vWd by counter Immunoelectrophoresis. The Factor VIII antigen was then reduced and electrophoresed on SDS-containing polyacrylamide gels. The presence of carbohydrate was evaluated by staining with perchloric acid-Schiff’s reagent (PAS). The 210,000 MW Factor VIII antigen subunit from each patient was PAS-positive. Though subtle changes in carbohydrate content or composition could not be evaluated by this technique, a total defect of glycosylation is unlikely in this small sample of vWd patients.

scholarly journals Multiple Molecular forms of Factor VIII Antigen in Normal Individuals and von Willebrand’s Disease Patients

1977 ◽  
Author(s):  
T. Zimmerman ◽  
J. Kimball ◽  
T. Edgington ◽  
C. Abildgaard
Keyword(s):  
Factor Viii ◽  
Molecular Forms ◽  
Type I ◽  
Type Ii ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Multiple Molecular Forms ◽  
Normal Individuals ◽  
Factor Viii Antigen

Factor VIII antigen is present in normal individuals in multiple molecular forms which can be separated according to size. The smaller forms have little or no ristocetin co-factor activity. In order to evaluate the possibility that Factor VIII antigen forms of large size may be an artifact of in vitro aggregation, we have ultracentrifuged plasma on a 20% sucrose cushion at 37 C for 10 min at 254,000 xg (peak). The rate of clearing of Factor VIII antigen was compared to that of other plasma proteins. The results indicate that Factor VIII-related antigen forms of high S exist even when plasma is maintained at physiological temperature and analyzed with minimal delay, suggesting that these larger molecular forms also exist as such in vivo.In von Willebrand’s disease (vWd) all forms of Factor VIII antigen may be present but decreased in quantity (Type I) or large forms may be missing with smaller forms present in normal or increased quantities (Type II). Factor VIII antigen was isolated from plasma of three patients with Type I and three patients with Type II vWd by counter immunoelectrophoresis. The Factor VIII antigen was then reduced and electrophoresed on SDS-containing Polyacrylamide gels. The presence of carbohydrate was evaluated by staining with perchloric acid-Schiff’s reagent (PAS). The 210,000 MW Factor VIII antigen subunit from each patient was PAS-positive. Though subtle changes in carbohydrate content or composition could not be evaluated by this technique, a total defect of glycosylation is unlikely in this sample of vWd patients.

Gel Filtration Patterns of Factor VIII Coagulant Antigen and Factor VIII Related Antigen in Normal and von Willebrand’s Disease

1983 ◽  
Vol 50 (02) ◽  
pp. 509-512
Author(s):  
Juan Chediak ◽  
Ian Peake ◽  
Arthur Bloom
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
Gel Filtration ◽  
Low Molecular Weight ◽  
Type I ◽  
Type Ii ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Coagulant Activity

SummaryGel filtration (sepharose 2B CL) patterns of factor VIII coagulant antigen (VIIIC :Ag) and factor VIII related antigen (VIIIR: Ag) were obtained using normal plasma and plasma from patients with von Willebrand’s disease. The latter group consisted of five individuals with normal mobility of factor VIIIR :Ag on cross-immunoelectrophoresis (Type I) and five others with abnormal (increased) mobility (Type II). Results showed that the elution of VIIIC: Ag was delayed in those subjects whose ratio of VIIIR :Ag to VIIIC :Ag was reduced. It has previously been reported that VIIIR :Ag exerts a stabilizing influence on the coagulant activity of factor VIII (VIII: C); our data suggests that when VIIIR :Ag is deficient, abnormal (low molecular weight) forms of VIIIC: Ag circulate.

Effect Of DDAVP In Patients With Von Willebrand’s Disease And Hemophilia A

1981 ◽  
Author(s):  
A I Warrier ◽  
C Hillman ◽  
J M Lusher
Keyword(s):  
Side Effects ◽  
Factor Viii ◽  
Hemophilia A ◽  
Blood Components ◽  
Excessive Bleeding ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Crossed Immunoelectrophoresis ◽  
Transient Improvement ◽  
The U.S

European investigators have reported on the efficacy of l-deamino-9-D-arginine vasopressin (DDAVP) in von Willebrand’s disease (vWD) and mild hemophilia A. We have thus evaluated the effects of a single intranasal dose of DDAVP (200ugm of the more dilute form available in the U.S.), in 12 individuals with vWD and in 4 with moderate hemophilia A. Crossed immunoelectrophoresis of VIII: RAg demonstrated normal electrophoretic mobility in each of the vWD subjects. Components of the factor VIII system (VIII: C, VIII: RAg, VIII: R Cof.) were assayed pre - and 90 and 180 minutes post- DDAVP. Each of 11 subjects with mild or moderate vWD had an increase in VIII: C activity (avg. 2X increase), 8 of 11 had an increase in VIII: R Cof, and 9 of 11 had an increase in VIII: RAg. The twelfth vWD subject, who had severe vWD, had no rise in any of these components. Of 4 vWD subjects who had pre- and post-DDAVP template bleeding times (BT) performed, the only one who had a prolonged baseline BT showed a normal BT 90 minutes post-DDAVP. One vWD subject, in whom we had documented an increase in all F. VIII components after DDAVP, later underwent dental extractions 90 minutes after DDAVP. No excessive bleeding was noted. Four individuals with moderate hemophilia A (baseline VIII: C values of 0.02-0.10 u/ml) were also studied. Three had a rise in all components of the factor VIII system post-DDAVP while the fourth did not. No undesirable side effects were noted in any of the 16 subjects who received DDAVP. We conclude that even the more dilute form of DDAVP available in the U.S., when given intranasally, results in transient improvement in selected individuals with vWD or moderate hemophilia A. This drug thus warrants further study as an alternative to blood components in the management of vWD, as well as in mild and moderate hemophilia A.

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.

scholarly journals The complex multimeric composition of factor VIII/von Willebrand factor

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1140-1143 ◽  
Author(s):  
ZM Ruggeri ◽  
TS Zimmerman
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Sodium Dodecyl ◽  
Factor Vii ◽  
Buffer System ◽  
Type I ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Von Willebrand ◽  
Willebrand Factor

We have analyzed the multimeric structure of factor VIII/von Willebrand factor in plasma by sodium dodecyl sulfate electrophoresis using gels of varying porosity and a discontinuous buffer system. Factor VIII/von Willebrand factor bands were identified by reaction with 125I-labeled affinity-purified antibody and subsequent autoradiography. In 1% agarose gels, normal plasma displayed a series of sharply defined oligomers. However, increasing the agarose concentration to 2.0% or utilizing mixtures of 0.8% agarose--1.75% acrylamide revealed two bands of lesser intensity interposed between the major bands. When the acrylamide concentration in the gels was increased to 2.5%, bands with a faster mobility than IgM and fibronectin were now evident. Type IIA von Willebrand's disease showed not only an absence of the larger multimers but also a relative increase in several of the newly identified bands as compared to type IIB, type I, and normal. These studies suggest that factor VII/von Willebrand factor in IIA von Willebrand's disease is structurally different from that in other forms of the disorder. They also indicate that the multimeric composition of factor VII/von Willebrand factor is more complex than can be explained by simple linear polymerization of a single protomer.

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.

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 A new variant of dominant type II von Willebrand's disease with aberrant multimeric pattern of factor VIII-related antigen (type IID)

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1369-1371
Author(s):  
S Kinoshita ◽  
J Harrison ◽  
J Lazerson ◽  
CF Abildgaard
Keyword(s):  
Factor Viii ◽  
Band Pattern ◽  
Variant Form ◽  
Type Ii ◽  
Laboratory Findings ◽  
Von Willebrand's Disease ◽  
Dominant Type ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
New Variant

A new type II variant form of von Willebrand's disease has been recognized in a mother and daughter who have bleeding manifestations typical of von Willebrand's disease. Laboratory findings include consistently prolonged bleeding times, with normal levels of factor VIII procoagulant and antigen, but decreased ristocetin cofactor activity. Electrophoresis in SDS 1.5% agarose gel and reaction with 125I-labeled anti-factor VIII-related antigen rabbit IgG, followed by autoradiography, revealed that both plasma and platelets lack the large multimers of factor VIII-related antigen. In 2.5% gel, the propositus plasma lacked the normal “triplet” pattern. In 3.0% gel, a 5-band pattern was observed in normal, type IIA, and type IIB plasma, whereas type IIC plasma revealed a 2-band pattern. The patient's plasma revealed a 4-band pattern distinctly different from normal or other type II variants. We suggest that this new variant be labeled type IID, until a more appropriate nomenclature is developed.

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