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 ◽  
...  

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.

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 269-274 ◽  
Author(s):  
PM Mannucci ◽  
R Lombardi ◽  
AB Federici ◽  
JA Dent ◽  
TS Zimmerman ◽  
...  

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.


1993 ◽  
Vol 70 (02) ◽  
pp. 351-356 ◽  
Author(s):  
W A Fricke ◽  
M A Lamb ◽  
S C Rastogi

SummaryA multilaboratory collaborative study was undertaken to assess the feasibility of using a plasma standard for expressing the results of assays for the von Willebrand factor content of von Willebrand factor concentrates and of factor VIII concentrates. Thirteen laboratories tested six concentrates for von Willebrand factor antigen, ristocetin cofactor activity, and multimer content using the World Health Organization plasma standard for factor VIII/von Willebrand factor, 87/718, as a standard. Only a few assays were invalid because of nonparallelism or nonlinearity. Significant interlaboratory and interassay differences were found for both von Willebrand factor antigen and ristocetin cofactor activity. There was generally good agreement between the laboratories with respect to the multimer content in the preparations. With respect to assay validity, a plasma standard could be suitable for assaying concentrated preparations of von Willebrand factor.


Blood ◽  
1979 ◽  
Vol 54 (3) ◽  
pp. 600-606 ◽  
Author(s):  
D Meyer ◽  
D Frommel ◽  
MJ Larrieu ◽  
TS Zimmerman

Abstract A previously healthy elderly man with mucocutaneous bleeding was found to have a benign monoclonal IgG gammapathy associated with criteria for severe von Willebrand disease (Factor VIII procoagulant activity, Factor-VIII-related antigen, and ristocetin cofactor activity, less than 10% of normal). Associated qualitative abnormalities of factor VIII/von Willebrand factor were demonstrated by radiocrossed immunoelectrophoresis and immunoradiometric assay. The late clinical onset and negative family history are in favor of an acquired form of vWD. The monoclonal gammapathy and abnormalities of factor VIII/von Willebrand factor have been stable over a 10-yr period. No inhibitor to Factor VIII procoagulant activity, ristocetin cofactor activity, or Factor-VIII-related antigen could be demonstrated. Following transfusion of cryoprecipitate (with a normal cross immunoelectrophoretic pattern), there was a rapid removal of the large forms of Factor.-VIII-related antigen, paralleled by a decay of ristocetin cofactor activity. The transfusion study of this patient with acquired von Willebrand disease type II (variant of von Willebrand disease) serves to emphasize the relationship between polydispersity of Factor VIII/von Willebrand Factor and functional heterogeneity.


Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 180-184 ◽  
Author(s):  
Alessandra Casonato ◽  
Elena Pontara ◽  
Francesca Sartorello ◽  
Maria Grazia Cattini ◽  
Maria Teresa Sartori ◽  
...  

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.


Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1419-1420
Author(s):  
A Asakura ◽  
J Harrison ◽  
E Gomperts ◽  
C Abildgaard

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.


Author(s):  
А.Л. Берковский ◽  
Е.В. Сергеева ◽  
А.В. Суворов ◽  
К.Н. Иевская ◽  
Е.В. Анисимова

Введение. Фактор Виллебранда (ФВ) является важным компонентом системы гемостаза, и отклонение от нормы его содержания или состава вызывает развитие различных типов болезни Виллебранда. Определение ристоцетин-кофакторной активности ФВ (ФВ:РКФА) является особенно значимым при выявлении таких типов болезни Виллебранда как 2А, 2В и 2М, при которых содержание антигена ФВ находится в нормальных пределах, а ФВ:РКФА значительно снижена. Цель исследования: получение реагента для измерения ФВ:РКФА из концентратов тромбоцитов с длительным сроком хранения, обеспечивающего правильность диагностики. Материалы и методы. Функционально полноценные тромбоциты получали из донорских тромбоцитарных концентратов со сроком хранения 7–14 суток. Результаты. При создании реагента для измерений ФВ:РФКА нами был подобран метод отбора функционально полноценных донорских тромбоцитов для получения фиксированных формальдегидом клеток. На основе таких тромбоцитов был разработан реагент, позволяющий измерять ФВ:РКФА с использованием как агрегационного, так и агглютинационного метода. Выявлено соответствие результатов определения ФВ обоими методами с коэффициентом корреляции 0,96. Проведена оценка агрегационного метода измерения ФВ:РКФА по результатам участия в международной программе внешнего контроля качества UK NEQAS for Blood Coagulation (Великобритания). Заключение. Показано, что использование полученного из фиксированных тромбоцитов реагента позволяет правильно измерять ФВ:РКФА. Introduction. Von Willebrand factor (vWF) is an important component of hemostatic system and deviations from the norm of its content or composition are the cause of various types of von Willebrand disease development. Determination of ristocetin-cofactor activity of vWF (vWF:RCo) is particularly important for identifying 2A, 2B and 2M types of von Willebrand disease, in which the content of vWF antigen is within the normal range, and vWF:RCo signifi cantly reduced. Aim: to obtain a reagent for the measurement of vWF:RCo from platelet concentrates with a long shelf life, providing correct diagnostics. Materials and methods. Fully functional platelets were obtained from donor platelet concentrates with a shelf life of 7–14 days. Results. We discovered the method for selection of fully functional donor platelets to produce formaldehyde-fi xed cells. On the basis of these platelets we developed a reagent that allows to measure vWF:RCo using both aggregation and agglutination methods. The appropriateness was found between the results of vWF determination by both methods with a correlation coeffi cient 0.96. The aggregation method of measuring vWF:RCo was evaluated by a result of participation in the international program of external quality control UK NEQAS for Blood Coagulation (United Kingdom). Conclusion. It is shown that the use of a reagent obtained from fi xed platelets allows for the correct measurement of vWF:RCo.


Blood ◽  
1979 ◽  
Vol 54 (3) ◽  
pp. 600-606
Author(s):  
D Meyer ◽  
D Frommel ◽  
MJ Larrieu ◽  
TS Zimmerman

A previously healthy elderly man with mucocutaneous bleeding was found to have a benign monoclonal IgG gammapathy associated with criteria for severe von Willebrand disease (Factor VIII procoagulant activity, Factor-VIII-related antigen, and ristocetin cofactor activity, less than 10% of normal). Associated qualitative abnormalities of factor VIII/von Willebrand factor were demonstrated by radiocrossed immunoelectrophoresis and immunoradiometric assay. The late clinical onset and negative family history are in favor of an acquired form of vWD. The monoclonal gammapathy and abnormalities of factor VIII/von Willebrand factor have been stable over a 10-yr period. No inhibitor to Factor VIII procoagulant activity, ristocetin cofactor activity, or Factor-VIII-related antigen could be demonstrated. Following transfusion of cryoprecipitate (with a normal cross immunoelectrophoretic pattern), there was a rapid removal of the large forms of Factor.-VIII-related antigen, paralleled by a decay of ristocetin cofactor activity. The transfusion study of this patient with acquired von Willebrand disease type II (variant of von Willebrand disease) serves to emphasize the relationship between polydispersity of Factor VIII/von Willebrand Factor and functional heterogeneity.


Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1419-1420 ◽  
Author(s):  
A Asakura ◽  
J Harrison ◽  
E Gomperts ◽  
C Abildgaard

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.


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