DIAGNOSIS OF VON WILLEBRAND DISEASE IN ARGENTINA: A SINGLE INSTITUTION EXPERIENCE

KEMPFER AC; SANCHEZ-LUCEROS A, ; WOODS AI; BLANCO AN,; PAIVA J; LAZZARI MA

Annals of Blood

Ame publishing group

Año: 2017 vol. 2 p. 22 - 34

2521-361X

Background: von Willebrand disease (VWD) is the most common autosomal bleeding disorder, mostlyinherited as dominant trait. VWD is due to deficiency/abnormality of von Willebrand factor (VWF). Thetrue prevalence of VWD is unknown, but estimated as 0.1% to 1% of the general population.Methods: The bleeding score (BS) was used to evaluate the bleeding status of patients presenting atour institution. Laboratory analyses include: VWF:Ag, VWF:RCo, VWF:CB, multimeric pattern, VWFpropeptide, Desmopressin challenge test. Genotypic analysis comprises the study of specific exons of VWF,depending on the suspected variant.Results: We describe the main characteristics of our VWD population, including phenotypic andgenotypic methods used to achieve the diagnosis. From our 2,482 patients registered, quantitative variantsaccount for 83.2% of cases, and qualitative, 16.8% of cases. Platelet-type VWD (PT-VWD) was diagnosedin two patients and acquired von Willebrand syndrome (AVWS) in six. From quantitative variants, relativefrequencies are: possible type 1, 78.7%; type 1, 14.9%; type 1S, 1.5%; type 1C, 0.4%; type 3, 1.6%. Fromqualitative variants: 2M, 21.9%; 2B, 10.3%; 2A, 8.4%; 2N, 3.4%; patients currently without completediagnosis: 56%. Family history of bleeding: 64.7% of cases. Type 3, 2A and 2B VWD showed the highestmajor bleeding (MB) frequency. Genotypic diagnosis was reached in eight type 1C, 72 type 2M, 38 type2B, 30 type 2A, 14 type 2N, and two PT-VWD patients. Five de novo mutations were identified among52 families (9.61%): two mutations were associated with type 2B VWD (p.V1316M and p.S1310F), onemutation associated with type 1C (Vicenza) (p.R1205H) described in combination with p.R924Q, onedeletion associated to type 1 VWD according to the ISTH VWF database (p.Pro1648fs*45) in combinationwith p.R1426C resulting in a 2M phenotype and one mutation related to type 2A VWD (p.Y1542D). Sixpatients are under prophylactic treatment due to their severe bleeding: four are type 3 VWD, one type 2MVWD, and one, the patient with p.Pro1648fs*45 and p.R1426C.Conclusions: The wide heterogeneity of clinical symptoms and laboratory data from possible type 1VWD implies a risk for bleeding that becomes crucial in challenging situations. In our population, type 2Mwas found to be more frequent than the type 2A variant. DDAVP (1-deamino-8-D-arginine vasopressin)challenge test, VWF propeptide/antigen ratio and genotypic studies are useful tools for discriminatingcases representing difficult diagnoses such as type 2M versus type 1C VWD. Elevated propeptide ratio,the detection of antiphospholipid antibodies, platelet-associated antibodies or anti-VWF immunoglobulinsand negative genotypic screening is useful to discriminate inherited VWD from AVWS. Genotypic testingassisted discrimination between types 2B versus platelet-type-VWD and type 2N VWD versus mildhemophilia A