Abstract 5320 Von Willebrand factor (vWF) is a large multimeric glycoprotein that plays an important role as a co-factor in platelet adhesion and aggregation and as the circulating carrier for factor VIII; increased vWF levels, and the persistence of unprocessed ultra-large vWF multimers (ULVWF) that are hyperactive to binding GPIb-IX-V complex with high-strength bonds, precipitate platelet clumping in arterioles and capillaries, causing platelet aggregation and thrombotic microangiopathy resulting in tissue ischemia with an increased risk of CAD and stroke. vWF is the major ligand binding the subunit of trombospondin, P-selectin, collagen and SLAM family (signaling lymphocytic activation molecule), mediates platelet translocation, tethering and rolling under high shear stress and adhesion. The activity of VWF is modulated by ADAMTS-13 a Zn2+/Ca2+ dependent metalloprotease that cleaves vWF to smaller and less active forms at the tyr842/met843 within the A2 domain, and cleaves the tyr 1605/met 1606; this mechanism reduces the molecular weight and platelet-tethering function of vWF to the sub endothelium at high shear stress. ADAMTS-13 levels also correlate positively with cholesterol, triglycerides and body mass index (BMI). In addition, we have observed a negative association with fibrinogen, C-reactive protein, and ion trasport K+dependent Na+/Ca2+ exchange (SLC24A3); the phosphorylation of tyrosine 1605 and threonine/serine kinase inhibitors have negative effects on integrin GPIIb-IIIa that showed decrease expression. In patients with a level of ADAMTS-13 below 38%, the presence of ultra large vWF multimers is high and the relative risk of ischemic heart disease was 18.2% (95% CI, 0.8 to 4.2), and the relative risk of stroke was 11.5 % (95% CI, 0.6 to 3.9). We investigated the relation between the low activity of ADAMTS-13 and AMI or stroke; we measured VWF and ADAMTS-13 antigen levels in 16 patients with AMI, in 10 patients with stroke, and in 16 control subjects. We demonstrated that vWF levels are significantly higher in patients with AMI or stroke, while a severe decrease of ADAMTS-13 activity augments the risk of cardiovascular disease, and cerebral ischemia; measurement of both VWF and ADAMTS-13 may provide a good indicator for the likelihood of AMI and stroke. Disclosures: No relevant conflicts of interest to declare.