Laboratory diagnosis and molecular basis of mild von Willebrand disease type 1.
Mild type 1 von Willebrand disease (VWD) is characterized by low to variable penetrance of bleeding, a high (increased) prevalence of blood group O, von Willebrand factor (VWF) values around and above 30% with normal ratios of VWF:ristocetin cofactor activity (RCo)/VWF:antigen (Ag), VWF:collagen binding (CB)/VWF:Ag and factor VIII (FVIII):coagulant activity (C)/VWF:Ag. Within this group of patients, the combination of the C1584 mutation and blood group O is rather frequent. Patients with mild VWD type 1 present good/normal responses of FVIII:C and VWF parameters to desmopressin (DDAVP). With the exclusion of dominant VWD type Vicenza, type 1/2E, recessive 2N and dominant 2M, missense mutations in patients with mild VWD type 1 with normal multimers are mainly located in the regulatory sequence region, the D1/D2 propeptide region, the D' VWF-FVIII binding site region and the D4, B1-B3 and C1-C2 domains but rarely in the D3, A1 or A2 domain. A new category of either dominant or recessive mild VWD type 1 due to mutations in the D4, B1-B3 and C1-C2 domains of the VWF gene consists of two groups: one group with mild VWD with normal VWF multimers and a second group with mild/moderate VWD with smeary multimer pattern.
Michiels
Jan Jacques
JJ
Hemostasis and Thrombosis Research Center, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium. postbus@goodheartcenter.demon.nl
Berneman
Zwi
Z
Gadisseur
Alain
A
van der Planken
Marc
M
Schroyens
Wilfried
W
van Vliet
Huub H D M
HH
D000017:ABO Blood-Group System / Q000235:genetics; D001760:Bleeding Time; D018389:Codon, Nonsense; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005799:Genes, Dominant; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D010974:Platelet Aggregation / Q000187:drug effects; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012310:Ristocetin / Q000494:pharmacology; D014842:von Willebrand Diseases / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014841:von Willebrand Factor / Q000032:analysis / Q000737:chemistry / Q000235:genetics*
D000017:ABO Blood-Group System; D018389:Codon, Nonsense; D014841:von Willebrand Factor; D012310:Ristocetin; D003894:Deamino Arginine Vasopressin