Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease: an international, multicenter study

Abstract

Summary. Objectives: We undertook an international, multicenter study to describe the clinical picture and to estimate the bleeding risk in a group of obligatory carriers of type 3 von Willebrand disease (VWD). Patients and methods: Obligatory carriers (OC) of type 3 VWD were identified by the presence of offspring with type 3 VWD or by being an offspring of a type 3 patient. Normal controls were age-and sex-matched with the obligatory carriers. A physician-administered standardized questionnaire was used to evaluate hemorrhagic symptoms at presentation. A score system ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) was used to quantitate bleeding manifestations. Odds ratios were computed for each symptom. Results: Ten centers participated to the study, enrolling a total of 35 type 3 VWD families, with 70 OC. A total of 215 normal controls and 42 OC for type 1 VWD were also included. About 40% of type 3 OC had at least one bleeding symptom compared to 23% of normal controls and 81.8% of type 1 OC (P < 0.0001 by chi-squared test), showing that type 3 OC clearly represent a distinct population from type 1 OC. The clinical situations associated with an increase of bleeding risk in type 3 OC were epistaxis [odds ratio 3.6; 90% confidence intervals (CI) 1.84-21.5], cutaneous bleeding (odds ratio 5.5; 90% CI 2.5-14.1) and postsurgical bleeding (odds ratio 16.3; 90% CI 4.5-59). The severity of bleeding score correlated with the degree of factor (F) VIII reduction in plasma. Conclusions: OC for type 3 VWD represent a distinctive population from type 1 OC. These patients, however, present with more frequent bleeding symptoms in comparison to normal controls, especially in case of significantly low FVIII. Desmopressin and/or tranexamic acid might be useful to prevent or treat bleeding in these cases.

The bleeding score predicts clinical outcomes and replacement therapy in adults with von Willebrand disease

“…[10][11][12][13] Usually, the bleeding history is an essential criterion for the diagnosis of inherited bleeding disorders, including VWD. [14][15][16][17] A bleeding score (BS) based upon bleeding symptoms and calculated using the questionnaire proposed by Tosetto et al 18 was used to confirm diagnosis in a large cohort of European families with type 1 VWD 19 and was subsequently applied with some modifications to other clinical studies on VWD. 20,21 More recently, in a limited number of patients with some VWD types (1, 2A, 2B, 2M), attempts were made to use the BS not only for diagnostic purposes but also to evaluate the patients' tendency to bleed.…”

Management of Inherited Bleeding Disorders in Pregnancy

“…However, successful management of delivery with DDAVP has been described in VWD Vicenza despite the basal factor VIII/VWF not rising significantly in pregnancy. 109 In type 2B VWD, a transient thrombocytopenia occurs frequently after DDAVP administration and the therapeutic response is poor, therefore, it is not usually recommended for type 2B. 110 In type 2N VWD, the abnormal binding of factor VIII to VWF shortens the response.…”

Optimizing treatment of von Willebrand disease by using phenotypic and molecular data

“…These minimal criteria stem from the results of several recent international studies [17][18][19][20] and were explored using a Bayesian approach in type 1 VWD. 21 For the definition of significant bleeding, the overall bleeding tendency of the patient may be more useful than the presence of a single severe symptom.…”