scholarly journals Type IIA von Willebrand disease with apparent recessive inheritance

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1419-1420
Author(s):  
A Asakura ◽  
J Harrison ◽  
E Gomperts ◽  
C Abildgaard
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Recessive Trait ◽  
Bleeding Tendency ◽  
Von Willebrand Factor Antigen ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor ◽  
Limited Change

Type IIA von Willebrand's Disease (vWD) is the most common type II variant, and all reported cases (56 individuals in 26 families) have had autosomal dominant inheritance. An eight-year-old female with an increased bleeding tendency since infancy was found to have laboratory values typical of type IIA vWD, but her parents and siblings were asymptomatic. With the exception of uniformly decreased levels of ristocetin cofactor in relation to von Willebrand factor antigen, the results of family studies were normal including the presence of large multimeric forms of von Willebrand factor antigen. These findings are consistent with the propositus having the homozygous state of an autosomal recessive trait. Desmopressin infusion in the propositus was followed by a significant increase of factor VIII coagulant and von Willebrand factor antigen but a limited change in ristocetin cofactor with no development of large multimers.

scholarly journals Type IIA von Willebrand disease with apparent recessive inheritance

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1419-1420 ◽  
Author(s):  
A Asakura ◽  
J Harrison ◽  
E Gomperts ◽  
C Abildgaard
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Recessive Trait ◽  
Bleeding Tendency ◽  
Von Willebrand Factor Antigen ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor ◽  
Limited Change

Abstract Type IIA von Willebrand's Disease (vWD) is the most common type II variant, and all reported cases (56 individuals in 26 families) have had autosomal dominant inheritance. An eight-year-old female with an increased bleeding tendency since infancy was found to have laboratory values typical of type IIA vWD, but her parents and siblings were asymptomatic. With the exception of uniformly decreased levels of ristocetin cofactor in relation to von Willebrand factor antigen, the results of family studies were normal including the presence of large multimeric forms of von Willebrand factor antigen. These findings are consistent with the propositus having the homozygous state of an autosomal recessive trait. Desmopressin infusion in the propositus was followed by a significant increase of factor VIII coagulant and von Willebrand factor antigen but a limited change in ristocetin cofactor with no development of large multimers.

scholarly journals A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF)

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 269-274 ◽  
Author(s):  
PM Mannucci ◽  
R Lombardi ◽  
AB Federici ◽  
JA Dent ◽  
TS Zimmerman ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Normal Plasma ◽  
Von Willebrand Factor Antigen ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

Abstract A patient with a lifelong bleeding disorder was diagnosed as having Type II von Willebrand disease. The larger multimers of von Willebrand factor were absent from her plasma but present in platelets. A high- resolution electrophoretic technique was used to study the complex structure of individual von Willebrand factor multimers. In normal plasma, each multimer could be resolved into five bands: a more intense central one and four less intense, two moving faster and two slower than the central band. In normal platelets, each multimer could also be resolved into five bands. The central one had a mobility similar to that in plasma, whereas the four satellite bands had a mobility that differed from that of the corresponding plasma bands. In the patient, platelet von Willebrand factor antigen content and ristocetin cofactor activity were normal, and von Willebrand factor showed the same structure of individual multimers as seen in normal platelets. On the other hand, plasma von Willebrand factor antigen and ristocetin cofactor activity were decreased, and the structure of individual von Willebrand factor multimers was different from that of normal plasma and similar to that seen in normal and patient's platelets. After infusion of 1-deamino-8-D-arginine vasopressin, the largest von Willebrand factor multimers, as well as new satellite bands with a mobility similar to those in normal plasma, appeared in the patient plasma, and the levels of von Willebrand factor antigen and ristocetin cofactor activity became normal. Yet no relevant change in the prolonged bleeding time was observed. This new variant of von Willebrand disease, therefore, is characterized by the presence of a dysfunctional von Willebrand factor molecule that exhibits unique structural abnormalities in plasma but appears to be normal in platelets. The designation of Type IIF is proposed for this type of von Willebrand disease in accordance with the terminology that has been previously used.

scholarly journals A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF)

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 269-274
Author(s):  
PM Mannucci ◽  
R Lombardi ◽  
AB Federici ◽  
JA Dent ◽  
TS Zimmerman ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Normal Plasma ◽  
Von Willebrand Factor Antigen ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

A patient with a lifelong bleeding disorder was diagnosed as having Type II von Willebrand disease. The larger multimers of von Willebrand factor were absent from her plasma but present in platelets. A high- resolution electrophoretic technique was used to study the complex structure of individual von Willebrand factor multimers. In normal plasma, each multimer could be resolved into five bands: a more intense central one and four less intense, two moving faster and two slower than the central band. In normal platelets, each multimer could also be resolved into five bands. The central one had a mobility similar to that in plasma, whereas the four satellite bands had a mobility that differed from that of the corresponding plasma bands. In the patient, platelet von Willebrand factor antigen content and ristocetin cofactor activity were normal, and von Willebrand factor showed the same structure of individual multimers as seen in normal platelets. On the other hand, plasma von Willebrand factor antigen and ristocetin cofactor activity were decreased, and the structure of individual von Willebrand factor multimers was different from that of normal plasma and similar to that seen in normal and patient's platelets. After infusion of 1-deamino-8-D-arginine vasopressin, the largest von Willebrand factor multimers, as well as new satellite bands with a mobility similar to those in normal plasma, appeared in the patient plasma, and the levels of von Willebrand factor antigen and ristocetin cofactor activity became normal. Yet no relevant change in the prolonged bleeding time was observed. This new variant of von Willebrand disease, therefore, is characterized by the presence of a dysfunctional von Willebrand factor molecule that exhibits unique structural abnormalities in plasma but appears to be normal in platelets. The designation of Type IIF is proposed for this type of von Willebrand disease in accordance with the terminology that has been previously used.

Reduced von Willebrand factor survival in type Vicenza von Willebrand disease

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 180-184 ◽  
Author(s):  
Alessandra Casonato ◽  
Elena Pontara ◽  
Francesca Sartorello ◽  
Maria Grazia Cattini ◽  
Maria Teresa Sartori ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Bleeding Tendency ◽  
Normal Platelet ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity ◽  
Original Type

Type Vicenza variant of von Willebrand disease (VWD) is characterized by a low plasma von Willebrand factor (VWF) level and supranormal VWF multimers. Two candidate mutations, G2470A and G3864A at exons 17 and 27, respectively, of the VWF gene were recently reported to be present in this disorder. Four additional families, originating from northeast Italy, with both mutations of type Vicenza VWD are now described. Like the original type Vicenza subjects, they showed a mild bleeding tendency and a significant decrease in plasma VWF antigen level and ristocetin cofactor activity but normal platelet VWF content. Unlike the original patients, ristocetin-induced platelet aggregation was found to be normal. Larger than normal VWF multimers were also demonstrated in the plasma. Desmopressin (DDAVP) administration increased factor VIII (FVIII) and VWF plasma levels, with the appearance of even larger multimers. However, these forms, and all VWF oligomers, disappeared rapidly from the circulation. The half-life of VWF antigen release and of elimination was significantly shorter than that in healthy counterparts, so that at 4 hours after DDAVP administration, VWF antigen levels were close to baseline. Similar behavior was demonstrated by VWF ristocetin cofactor activity and FVIII. According to these findings, it is presumed that the low plasma VWF levels of type Vicenza VWD are mainly attributed to reduced survival of the VWF molecule, which, on the other hand, is normally synthesized. In addition, because normal VWF-platelet GPIb interaction was observed before or after DDAVP administration, it is proposed that type Vicenza VWD not be considered a 2M subtype.

scholarly journals A diagnosis of von Willebrand disease despite normal test results for factor VIII and von Willebrand factor antigen and activity

2019 ◽  
Vol 94 (12) ◽  
pp. 1425-1432 ◽  
Author(s):  
Penelope Motum ◽  
Sarah Just ◽  
Diane Zebeljan ◽  
Catherine Nicholls ◽  
Geoffrey Kershaw ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Test Results ◽  
Von Willebrand Factor Antigen ◽  
Normal Test ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

scholarly journals Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2433-2436
Author(s):  
PM Mannucci ◽  
A Lattuada ◽  
G Castaman ◽  
R Lombardi ◽  
ML Colibretti ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Gene Deletion ◽  
Von Willebrand Disease ◽  
Low Levels ◽  
Genetically Determined ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Severe Type ◽  
Factor Antigen ◽  
Ristocetin Cofactor

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.

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