PO634-TUE Relationship between bleeding tendency and the affected domain with mutations responsible of VWD2M phenotype

WOODS AI; KEMPFER AC; PAIVA-PALOMINO J; BLANCO A; CHUIT R; CASINELLI MM; SÁNCHEZ LUCEROS A; LAZZARI MA

Toronto

Congreso; XXV Congress of the International Society on Thrombosis and Haemostasis and 61st Annual SSC Meeting.; 2015

International Society on Thrombosis and Haemostasis

Background: Type 2M von Willebrand disease (VWD2M) is characterized by VWF:RCo/VWF:Ag < 0.6, and normal multimers. Mutations (Mt) are mainly in the A1 domain (A1), and, in a minor extent, in the A2. Variable bleeding tendency is common in patients (P) Aims: To correlate bleeding tendency with Mt location within affected members (AFM) in families (F), and determine the Mt penetrance and VWD prevalence (Pr) within F with ≥ 2 generations (G). Methods: Bleeding score (BS), major bleeding (MB), bleeding time (BT) (min), factor VIII (FVIII) and VWF (IU/dL), propeptide/VWF:Ag (VWFpp ratio). We selected 9F; n = 66; AFM=44 (66.6%) Results: A1 Mt: F = 5 (n = 28); AFM=20. Diagnosis age: females (fem): median (md)=17 yr; males: md=11 yr. P with MB=30%. P with abnormal BS=66.6%; fem=72.7%; males=57%. p.F1293C: 1F; n = 2; 1G; AFM=100%; p.R1374C: 3F; n = 20; 2 and 3G; AFM=70% p.A1437T: 1F; n = 6; 3G; AFM=66.6%. BT=9.2 SD4; FVIII=51 SD23; VWF:Ag=26 SD11; VWF:RCo=7.2 SD4.5; VWFpp=2.7 SD 0.6. Pr=69.2%, wit no differences between Mt. A2 Mt: F = 4 (n = 38), AFM=24. Diagnosis age: fem: md=20 yr; males: md=12 yr. P with MB=41.6%. P with abnormal BS=66.6%; fem=82%; males=54%. p.L1503P: 1F; n = 4; 3G; AFM=50%; p.E1549K: 1F; n = 28; 4G; AFM=64.3%; p.R1564W: 1F; n = 2; 1G; AFM=50%; p.I1628T: 1F; n = 4; 2G; AFM=75%. BT=8.2 SD 3.3; FVIII=55 SD 22; VWF:Ag=59 SD 21; VWF:RCo=7.9 SD 6.5; VWFpp=1.5 SD 0.7. Pr=63.8%, with no differences within Mt Conclusion: P from A1 group Mt showed low VWF:Ag and high VWFpp ratio (p = 0.000 respectively) suggesting shortened VWF survival; so, it is important to make the VWFpp in P, in order to know ifuse of low purity blood concentrates is required. Despite the shorterVWF survival, these P did not show more severe clinical symptoms than those from A2 group. In A2 group there were more P with MB, but not significant (P=ns; RR=1.2). BT, FVIII, and VWF:RCo did not show Differences between A1 and A2 group P. Both A1 and A2 Mt were present in all G, showing complete penetrance, making mandatory the family study. Prevalence of VWD2M in A1 group is higher, but not significant.