A Revised Classification of von Willebrand Disease

A simplified phenotypic classification of von Willebrand disease is proposed that is based on differences in pathophysiology. Quantitative defects are divided into partial deficiency (type 1) and severe deficiency (type 3). Qualitative defects (type 2) are divided into four subcategories. Type 2A refers to variants with decreased platelet-dependent function associated with the loss of high-molecular weight VWF multimers. Type 2B refers to variants with increased affinity for platelet glycoprotein Ib. Type 2M refers to qualitatively abnormal variants with decreased platelet-dependent function not associated with the loss of high-molecular weight multimers. Type 2N refers to variants with decreased affinity for factor VIII. When recognized, mixed phenotypes caused by compound heterozygosity are indicated by separate classification of each allele. Standard amino acid and nucleotide numbering schemes are recommended for the description of mutations.

[1]  Z. Ruggeri.  Structure and function of von Willebrand factor: relationship to von Willebrand's disease. , 1991, Mayo Clinic proceedings.

[2]  C. Rizza,et al.  A Variant of Factor VIII Related Antigen , 1974 .

[3]  J. Delobel,et al.  A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction. , 1990 .

[4]  A. Federici,et al.  A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF). , 1986, Blood.

[5]  D. Mancuso,et al.  von Willebrand disease type B: a missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein Ib. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Ginsburg,et al.  Molecular characterization of a unique von Willebrand disease variant. A novel mutation affecting von Willebrand factor/factor VIII interaction. , 1991, The Journal of biological chemistry.

[7]  J. Batlle,et al.  Abnormal proteolytic degradation of von willebrand factor after desmopressin infusion in a new subtype of von willebrand disease (ID) , 1991, American journal of hematology.

[8]  P. Mannucci,et al.  Type II H von willebrand disease: New structural abnormality of plasma and platelet von willebrand factor in a patient with prolonged bleeding time and borderline levels of ristocetin cofactor activity , 1989, American journal of hematology.

[9]  P. Mannucci,et al.  Investigation of a case of subtype IIC von Willebrand disease: Characterization of the variability of this subtype , 1986, American journal of hematology.

[10]  I. Peake,et al.  Apparent ‘Dominant’ and ‘Recessive’ Inheritance of Von Willebrand’s Disease (VWD) Within the Same Kindreds, Possible Biochemical Mechanisms , 1979, Thrombosis and Haemostasis.

[11]  P. Mannucci,et al.  Clinical indications for desmopressin (DDAVP) in congenital and acquired von Willebrand disease. , 1991, Blood reviews.

[12]  Z. Ruggeri,et al.  Von Willebrand's disease. , 1976, Progress in hemostasis and thrombosis.

[13]  G. Mariani,et al.  Heterogeneity of type I von Willebrand disease: evidence for a subgroup with an abnormal von Willebrand factor. , 1985, Blood.

[14]  C. Rothschild,et al.  New variant of von Willebrand disease with defective binding to factor VIII. , 1989, Blood.

[15]  H. Weiss,et al.  Pseudo-von Willebrand's disease. An intrinsic platelet defect with aggregation by unmodified human factor VIII/von Willebrand factor and enhanced adsorption of its high-molecular-weight multimers. , 1982, The New England journal of medicine.

[16]  H. Weiss,et al.  A new von Willebrand variant (type I, New York): increased ristocetin- induced platelet aggregation and plasma von Willebrand factor containing the full range of multimers , 1986 .

[17]  J. Batlle,et al.  Further evidence for recessive inheritance of von willebrand disease with abnormal binding of von willebrand factor to factor VIII , 1992, American journal of hematology.

[18]  J. Lavergne,et al.  Multimeric structure of factor VIII/von Willebrand factor in von Willebrand's disease. , 1980, The Journal of laboratory and clinical medicine.

[19]  A. Bloom,et al.  Inherited variants of factor-VIII-related protein in von Willebrand's disease. , 1974, The New England journal of medicine.

[20]  J. Lazerson,et al.  A new variant of dominant type II von Willebrand's disease with aberrant multimeric pattern of factor VIII-related antigen (type IID). , 1984, Blood.

[21]  P. Mannucci,et al.  Multimeric composition of factor VIII/von Willebrand factor following administration of DDAVP: implications for pathophysiology and therapy of von Willebrand's disease subtypes , 1982 .

[22]  K. B. Thomas,et al.  Variant von Willebrand's disease type B--revisited. , 1982, Blood.

[23]  J. Ware,et al.  von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure. , 1993, The Journal of clinical investigation.

[24]  P. Mannucci,et al.  Pharmacokinetics of Monoclonally-Purified and Recombinant Factor VIII in Patients with Severe von Willebrand Disease , 1993, Thrombosis and Haemostasis.

[25]  P. Mannucci,et al.  A variant of von Willebrand's disease characterized by recessive inheritance and missing triplet structure of von Willebrand factor multimers , 1983 .

[26]  D. Ginsburg,et al.  Impaired intracellular transport produced by a subset of type IIA von Willebrand disease mutations. , 1992, The Journal of biological chemistry.

[27]  N E Morton,et al.  International system for human gene nomenclature (1979) ISGN (1979). , 1979, Cytogenetics and cell genetics.

[28]  R. Elston,et al.  Genetics of classic von Willebrand's disease. I. Phenotypic variation within families. , 1979, Blood.

[29]  F. Bernardi,et al.  A de novo and heterozygous gene deletion causing a variant of von Willebrand disease. , 1990, Blood.

[30]  Z. Ruggeri,et al.  Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE). , 1986, The Journal of clinical investigation.

[31]  B. Bahnak,et al.  The human gene for von Willebrand factor. Identification of repetitive Alu sequences 5' to the transcription initiation site. , 1988, Biochemical and biophysical research communications.

[32]  L. Berkowitz,et al.  DDAVP for type IIB von Willebrand disease [letter] , 1989 .

[33]  H. Gralnick,et al.  A variant of type II von willebrand disease with an abnormal triplet structure and discordant effects of protease inhibitors on plasma and platelet von willebrand factor structure , 1987, American journal of hematology.

[34]  P. Kyrle,et al.  IIB von Willebrand's disease: pathogenetic and therapeutic studies , 1988, British journal of haematology.

[35]  A. Parquet‐Gernez,et al.  Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling , 1990, British journal of haematology.

[36]  Z. Ruggeri,et al.  von Willebrand factor and von Willebrand disease. , 1987, Blood.

[37]  A. Castella,et al.  Platelet-type von Willebrand's disease: characterization of a new bleeding disorder , 1982 .

[38]  A. Girolami,et al.  1-Desamino-8-D-Arginine Vasopressin (DDAVP) Infusion in Type IIB von Willebrand’s Disease: Shortening of Bleeding Time and Induction of a Variable Pseudothrombocytopenia , 1990, Thrombosis and Haemostasis.

[39]  P. Mannucci,et al.  A new variant of von Willebrand disease (type II I) with a normal degree of proteolytic cleavage of von Willebrand factor. , 1992, Thrombosis research.

[40]  I. Nilsson,et al.  Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in Type IIB von Willebrand's disease. , 1983, The New England journal of medicine.

[41]  D. Bonthron,et al.  The human von Willebrand factor gene. Structure of the 5' region. , 1988, European journal of biochemistry.

[42]  Z. Ruggeri,et al.  Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation , 1985 .

[43]  J. Batlle,et al.  von willebrand disease type IIC with different abnormalities of von willebrand factor in the same sibship , 1986, American journal of hematology.

[44]  I. Nilsson,et al.  Genetic Variants of von Willebrand's Disease , 1972, British medical journal.

[45]  J. Scott,et al.  Abnormal binding of factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. , 1991, The Journal of biological chemistry.

[46]  F. Hill,et al.  Investigation of a kindred with a new autosomal dominantly inherited variant type von Willebrand's disease (possible type IID). , 1985, Journal of clinical pathology.

[47]  N. Ciavarella,et al.  High-resolution analysis of von Willebrand factor multimeric composition defines a new variant of type I von Willebrand disease with aberrant structure but presence of all size multimers (type IC). , 1985, Blood.

[48]  J. Batlle,et al.  Multimeric pattern discrepancy between platelet and plasma von Willebrand factor in type IIC von Willebrand disease , 1986, American journal of hematology.

[49]  P. Mannucci,et al.  Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand's disease. , 1980, The New England journal of medicine.

[50]  H. Weiss,et al.  Heterogeneous abnormalities in the multimeric structure, antigenic properties, and plasma-platelet content of factor VIII/von Willebrand factor in subtypes of classic (type I) and variant (type IIA) von Willebrand's disease. , 1983, The Journal of laboratory and clinical medicine.

[51]  Z. Ruggeri,et al.  Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC). , 1982, The Journal of clinical investigation.

[52]  E. Tuddenham,et al.  Von Willebrand factor multimer patterns in von Willebrand's disease , 1983, British journal of haematology.