Von Willebrand Factor Fragment in Type IIA von Willebrand’s Disease: Demonstration of Two Different Forms of Fragments

1987 ◽  
Vol 17 (4) ◽  
pp. 182-188 ◽  
Author(s):  
Hoyu Takahashi ◽  
Tsuneyasu Tsukada ◽  
Wataru Tatewaki ◽  
Masaharu Hanano ◽  
Masayoshi Sanada ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Von Willebrand ◽  
Willebrand Factor

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

1986 ◽  
Vol 55 (03) ◽  
pp. 338-341 ◽  
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.

Von Willebrand’s Disease caused by Compound Heterozygosity for a Substitution Mutation (T1156M) in the D3 Domain of the Von Willebrand Factor and a Stop Mutation (Q2470X)

2002 ◽  
Vol 88 (09) ◽  
pp. 421-426 ◽  
Author(s):  
Stefan Lethagen ◽  
Christina Isaksson ◽  
Charlotta Schaedel ◽  
Lars Holmberg
Keyword(s):  
Von Willebrand Factor ◽  
Null Allele ◽  
Dependent Manner ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Stop Mutation ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryHereditary defects of the von Willebrand factor (VWF) gene cause von Willebrand’s disease (VWD) which shows great variability dependent on the nature and location of the mutation. We here describe the characteristics of a substitution of methionine for threonine 1156 in the D3 domain of the VWF, i.e. the domain involved in the intracellular multimerization of pro-VWF dimers. A VWD patient with severe symptoms was a compound heterozygote for the T1156M mutation and a null allele (Q2470X) on the other chromosome. This led to marked reduction of plasma VWF concentration to about 0.05 U/ml and an abnormality of VWF multimers as in type 2A VWD. Expression in vitro of the mutation demonstrated that 1156M-VWF is secreted from COS-7 cells in a much reduced amount and lacking large multimers. When coexpressed with normal VWF 1156M-VWF decreased the secretion of normal VWF in a dose-dependent manner, the secreted VWF showing all the multimers. Two relatives of the propositus were single heterozygotes for the T1156M mutation and were either asymptomatic or had the manifestations of mild type 1 VWD. The expression data and studies of platelet VWF indicate that the T1156M mutation results in intracellular retention of VWF rather than impaired synthesis. Three other members of the family were heterozygotes for the Q2470X mutation and demonstrated the variable expressivity of a null allele.

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 von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 668-672 ◽  
Author(s):  
L Holmberg ◽  
E Berntorp ◽  
M Donner ◽  
IM Nilsson
Keyword(s):  
Von Willebrand Factor ◽  
Platelet Rich Plasma ◽  
Severe Bleeding ◽  
Molecular Defect ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Coagulant Activity ◽  
The One ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract In eight members of one family, platelets in platelet-rich plasma aggregated at much lower ristocetin concentrations than normal. Ivy bleeding time was variously prolonged, and von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity, and factor VIII coagulant activity were decreased. Most of the affected members had had slight to rather severe bleeding symptoms. Platelet-type von Willebrand's disease (vWD) could be ruled out. All multimers of vWF:Ag were found in plasma as well as platelets. Administration of 1-desamino- 8-D-arginine vasopressin (DDAVP) to the propositus did not cause thrombocytopenia, and platelet-poor plasma obtained immediately after did not aggregate normal platelets. The molecular defect in this family, inherited as an autosomal dominant, resembles the one in type IIB because of the response to ristocetin but differs from IIB because all vWF:Ag multimers are present in plasma and the response to DDAVP is atypical. We conclude that this family has a new subtype of vWD and propose that structural as well as functional criteria should be used for a proper classification of vWD.

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 Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 654-661 ◽  
Author(s):  
IR Peake ◽  
MB Liddell ◽  
P Moodie ◽  
G Standen ◽  
DJ Mancuso ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Ecori Fragment ◽  
Compound Heterozygous ◽  
Recessive Trait ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Type Iii ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Severe Type

Abstract Southern blotting was performed with cDNA probes for the human von Willebrand factor (vWF) gene on six patients with severe type III von Willebrand's disease (vWD). A partial deletion in the 3′ end of the vWF gene was demonstrated in one individual whose parents were related and who had an alloantibody inhibitor to vWF. A resulting novel 2.0- kilobase (kb) EcoRI fragment was used for carrier detection within the patient's family, and seven carriers of this recessive trait were identified. Of the six tested, five had normal or only slightly reduced levels of vWF antigen, but with generally higher levels of factor VIII. The sixth carrier had moderately severe vWD and it is proposed that this patient is heterozygous for the defective vWF gene and a second recessive vWF defect. The novel 2.0-kb EcoRI restriction fragment was cloned and sequenced, and compared with that of the corresponding normal 4.2-kb EcoRI fragment that includes exons 41 and 42 of the vWF gene. A deletion of 2,320 base pairs (bp) which included exon 42, was identified and a novel 182-bp insert was found between the breakpoints. This insert was detected by polymerase chain reaction amplification both in the patient's DNA and in his carrier relatives.

Sign in / Sign up

Export Citation Format

Share Document