Bleeding score and fibrinolysis after DDAVP in possible type 1 VWD patients

WOODS AI; S¨¢NCHEZ LUCEROS A; BLANCO AN; MESCHENGIESER SS; LAZZARI MA

Amsterdam

Congreso; XXIV Congresss of the International Society on Thrombosis and Haemostasis; 2013

International Society on Thrombosis and Haemostasis

Background: VWD is rarely associated with spontaneous bleeding, but may result in a possibly severe bleeding after a haemostatic challenge such as trauma, delivery or surgery. Nevertheless, incomplete VWD penetrance and low specificity of the bleeding symptoms make type 1VWD a diagnostic challenge, especially in the subjects with low VWF (30?50 IU/dl) and mild bleeding symptoms who are currently diagnosed as low VWF or possible type 1 VWD. DDAVP is the main treatment in most of VWD pts, although the enhanced response of fibrinolytic could add a bleeding risk factor in these pts. In addition of the VWF, DDAVP also produces the release of fibrinolytic activators from the endothelial cells. Fibrinolytic activity is evaluated by euglobulins lysis time (ELT). Aims: Our purpose was to evaluate the changes in plasmatic fibrinolytic activity induced by DDAVP infusion, and to correlate these changes with the bleeding score (BSS), in 471 possible type 1 VWD adult pts (358 females, 113 males). Methods: BSS was calculated. Blood samples were drawn before (B), and after 1 (1 h) and 2 (2 h) the DDAVP infusion (i.v. 0.3 lg/kg). ELT was done in each sample. Pts were grouped according to gender and the BSS being higher or lower than 5for females, and higher or lower than 3 males. Difference (DIF) between ELT-1 h and 2 h vs. before was calculated. Results: Females: BSS low (n=276): ELT-B=190.6 SD 91.6 min; 1h=73.3 SD34.8 min; DIF=3.08 SD1.6 min; 2h=93.1 SD46.4 min; DIF = 2.3 SD0.9.BSS high (n=84): ELT-B =177.7SD65.7 min (P=0.23); 1h=63.9 SD28.5 min (P=0.025); DIF=3.5 SD1.5 min (P=0.03);2h=85.1 SD29.6 min (P=0.137); DIF=2.3SD0.7 (P=1). Males: BSS low (n=95): ELT-B= 177.1SD72.5 min; 1h=78.6 SD44.9 min; DIF=2.7 SD1.3 min; 2h=89.4SD46.6 min; DIF=2.3SD1.4. BSS high (n=18): ELT-B=168.9 SD67.5 min (P=0.661); 1 h =67.5 SD39.1 min (P=0.329); DIF=3.1 SD1.9 min (P=0.238); 2h=89.3 SD43.2 min (0.993); DIF=2.0 SD0.8 (P=0.38). Conclusions: In females with a high BSS there was a significantly higher fibrinolytic activity in the first h post DDAVP. In contrast, there were no differences in males. Given these results, it is possible to consider that some enhanced fibrinolytic activity associated with pathophysiological stress situations, could be influencing the severity of the clinical profile observed in possible type 1 VWD patients. Gender-related differences in endothelial response to stimuli such as stress or drugs (DDAVP) could explain both the differences found in the fibrinolytic activity, and the clinical expression of VWD in women.