Abstract 543

Background:

Type 2 A and 2 M von Willebrand Disease (VWD) are both characterized by the presence of a dysfunctional von Willebrand factor (VWF) and a variable bleeding tendency. The bleeding incidence and possible clinical differences between these two types have never been investigated prospectively in a large number of patients.

Aims and design of the study:

To investigate clinical history and determinants of bleeding in a cohort of patients (pts) with type 2 A and M VWD characterized by mutations over 24 months of follow-up.

Patients and Methods:

10 families with type 2 A VWD (47 patients) and 15 with type 2 M (58 patients) with type 2 M VWD were diagnosed according to the recommendations of the ISTH-SSC subcommittee on VWF and prospectively followed-up from April 2007 to March 2009. Bleeding score (BS) was calculated in all the patients at enrollment by the administration of the same questionnaire tested in type 1 VWD. In case of VWF:RCo levels < 10 U/dL, all patients were tested with a more sensitive ELISA assay to calculate ratios between VWF:RCo and VWF:Ag. VWF mutations were identified in all the patients.

Results:

The 105 patients were characterized by the following mutations: type 2 A R202W/R1583Q 1 pt, S1506L 11 pts, S1543F 1 pt, R1596W 3 pts, V1607D 8 pts, I1628T 1 pt, G1629R 1 pt, G1631D 9 pts, V1665E 8 pts, Q2520P 2 pts, multiple changes 1 pt. Type 2 M: L1278P 6 pts, R1315L 3 pts, R1315C 9 pts, Y1321C 9 pts, L1361W 4 pts, R1374H 23 pts, C1927/c.8155+6C>T 1 pt, c.3831del-3 3 pts. The table summarizes the main demographic and laboratory characteristics. All the patients had a VWF:RCo/VWF:Ag ratio <0.6. The mean BS and VWF:Ag were significantly higher in type 2 A (P < 0.01). No correlation between VWF:RCo levels and the severity of BS was observed.

M/FAge,yr(range)BS*(range)FVIII:C(U/dL)VWF:Ag*(U/dL)VWF:RCo(U/dL)
Type 2 A (n=47) 25/22 47 (13–87) 10.6 ± 5.7 (3 – 26) 54 ± 54 45 ± 45 9.8 ± 9.6 
Type 2 M (n=58) 34/24 49 (19–96) 7.5 ± 5.6 (1 – 28) 48 ± 19 26 ± 14 8 ± 3.8 
M/FAge,yr(range)BS*(range)FVIII:C(U/dL)VWF:Ag*(U/dL)VWF:RCo(U/dL)
Type 2 A (n=47) 25/22 47 (13–87) 10.6 ± 5.7 (3 – 26) 54 ± 54 45 ± 45 9.8 ± 9.6 
Type 2 M (n=58) 34/24 49 (19–96) 7.5 ± 5.6 (1 – 28) 48 ± 19 26 ± 14 8 ± 3.8 
*

P < 0.01

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During follow-up, the bleeding episodes in patients with type 2 M and R1374H or R1315C mutations were very few and mild while they were recurrent and severe in those with type 2 A and V1665E or G1631D mutations, the only laboratory difference being the lack of high molecular weight multimers in type 2 A VWD. Furthermore, 44 gastrointestinal bleeding episodes occurred in 15 patients with type 2 A (range 1–7) compared to 8 episodes in 2 patients with type 2 M (range 2–6). Older age was strongly related to the risk of recurrence of this type of bleeding.

Conclusions:

Bleeding tendency in type 2 A VWD is higher than that of type 2 M VWD and it is not related to the reduction of FVIII:C and VWF activity. The risk of gastrointestinal bleeding is greater in type 2 A and might be related to the lack of high molecular weight multimers and older age. Further analysis are required to evaluate the definite impact of some mutations on the different bleeding tendency.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
bleeding diathesis, von willebrand disease, brachial plexus neuritis, hemorrhage, follow-up, gastrointestinal bleeding, hemorrhagic episodes, von willebrand factor, enzyme-linked immunosorbent assay, recurrence risk

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Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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