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


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.
Castaman
G
G
Department of Hematology, S. Bortolo Hospital, Vicenza, Italy.
Rodeghiero
F
F
Tosetto
A
A
Cappelletti
A
A
Baudo
F
F
Eikenboom
J C J
JC
Federici
A B
AB
Lethagen
S
S
Linari
S
S
Lusher
J
J
Nishino
M
M
Petrini
P
P
Srivastava
A
A
Ungerstedt
J S
JS
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005169:Factor VIII / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D011795:Surveys and Questionnaires; D014148:Tranexamic Acid / Q000494:pharmacology; D014842:von Willebrand Diseases / Q000097:blood* / Q000235:genetics*; D014841:von Willebrand Factor / Q000096:biosynthesis / Q000235:genetics*
D014841:von Willebrand Factor; D014148:Tranexamic Acid; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin