title: 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.
abstract: In this study a new variant of type II von Willebrand disease is identified by multimeric analyses of increasing resolving power. Prior to multimeric analysis, the patient was misdiagnosed as carrying an undefined abnormality in platelet function because of his normal von Willebrand factor antigen (vWF:Ag) and low borderline ristocetin cofactor (Ricof) levels. Absence of the largest multimers from the patient's plasma and platelets was shown in a low-resolution system, but all the multimers were present in his relatives. An abnormality in the complex multimeric structure was demonstrated in both plasma and platelets with high-resolution agarose gels. The plasma of the proband and of several family members shows a broader central band with a minor, faster moving satellite band differing from the typical "triplet pattern" observed with normal plasma. Platelets show a "doublet" that runs with a mobility different from the "doublet" in normals. Therefore the proband may be either a homozygote or double heterozygote for this new abnormality. Treatment with desmopressin (DDAVP) on several occasions corrected the prolonged bleeding time of the patient only transiently. Factor VIII increased significantly, but vWF:Ag and Ricof responded poorly. We conclude that this vWF abnormality is different from those observed in the other variants (II A-G) previously described. Therefore the proposed designation for this new variant is type II H.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milano, Italy.
authors.forename: A B
authors.initials: AB
authors.lastname: Federici
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: R
authors.initials: R
authors.lastname: Lombardi
authors.forename: A
authors.initials: A
authors.lastname: Lattuada
authors.forename: M L
authors.initials: ML
authors.lastname: Colibretti
authors.forename: J A
authors.initials: JA
authors.lastname: Dent
authors.forename: T S
authors.initials: TS
authors.lastname: Zimmerman
mesh_terms: D000328:Adult; D000941:Antigens; D001760:Bleeding Time; D001792:Blood Platelets / Q000032:analysis*; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D005169:Factor VIII / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D012310:Ristocetin / Q000494:pharmacology; D014842:von Willebrand Diseases / Q000097:blood* / Q000188:drug therapy; D014841:von Willebrand Factor / Q000032:analysis* / Q000235:genetics* / Q000276:immunology
chemical_list: D000941:Antigens; D046911:Macromolecular Substances; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D012310:Ristocetin; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin