Evaluation of ADAMTS-13 Activity and VWF:Ag Levels in Patients with Ischemic Stroke.

Background: The role of von Willebrand factor cleaving protease (ADAMTS-13) in the pathogenesis of ischemic stroke is still undefined. ADAMTS-13 cleaves ultra-large multimers of von Willebrand factor (ULVWF), and is believed to regulate the size thus the activity of VWF, especially on sites of high shear stress. By assuming the hypothesis, that a deficiency of ADAMTS-13 influences the thrombotic tendency such as intravascular aggregation and platelet thrombus formation, we analysed adult patients with onset of cerebral ischemia.

Methods and Patients: 158 unrelated patients (female:89 /male:69) with an objectively confirmed ischemic stroke (n=126) or TIA (n=32), median age at first onset:42 years (range:17–71 years), and 82 healthy subjects, median age:28 years (range:16–52 years), were studied. In our study group we analysed on the one hand 95 patients (pts) with early onset of stroke/TIA <45 years (median age:32 years), and on the other hand 63 elderly pts >45 years (median age:54 years). None of the pts enrolled had overt evidence of autoimmune or malignancy disease. ADAMTS13 was measured with an assay based on the positive correlation between multimeric size and Ristocetin Cofactor activity of the VWF.

Results: In our population the ADAMTS-13 activity was in median 95% (range= 40–185%) significantly higher than 91% (range=52–150%) among controls (p=0.002; OR 0.54). In the subgroup analysis we found no statistical differences in the mean ADAMTS-13 activities among pts with early onser (99% vs 91%; p=0.76, OR 0.93), and among pts with onset at age 45 years as compared to healthy controls (88% vs 91%; p=0.30, OR 1.25). Furthermore, we found statistical differences in the mean VWF:Ag levels among all pts as compared to healthy controls (135% vs 110%; p=0.01, OR 0.63), and in the elderly pts (140% vs 110%; p=0.01, OR 1.63). The young pts showed no statistical differences in the mean VWF:Ag levels compared with the control group (127% vs 110%; p=0.98, OR 0.99).

Conclusion: The results from this study show that higher levels of ADAMTS-13 activity and VWF:Ag as compared to healthy controls are associated with ischemic stroke/TIA. Only in the elderly pts we observed a tendency to a negative association between ADAMTS-13 and VWF (lower ADAMTS-13 levels and higher levels of VWF:Ag). It may be, that higher ADAMTS-13 levels have a relevance to prevent thrombotic events.

Further studies are needed to confirm whether the relationship between VWF and ADAMTS-13 plays an additional role in the pathogenesis on the onset of ischemic stroke.