ADAMTS13 in arterial thrombosis

The aim of this thesis was to study the role of ADAMTS13 in arterial thrombosis, a disease that comprises both environmental and genetic factors. We determined ADAMTS13 in ischemic stroke patients and controls. Also in a study of myocardial infarction, stroke and peripheral arterial disease patients, ADAMTS13 was determined. In all studies we found lower levels of ADAMTS13 in patients compared with controls. Moreover, patients with lower levels of ADAMTS13 had also higher OR’s than controls. Polymorphisms in the ADAMTS13 gene, studied in arterial thrombosis patients, were not of influence on the levels nor on the risk of arterial thrombosis. A polymorphism in the Von Willebrand Factor gene was studied in arterial thrombosis. The frequency of the rare allele was very low. Furthermore ADAMTS13 was studied in other conditions associated with thrombotic complications, such as meningococcal sepsis and liver cirrhosis. In children with meningococcal sepsis the levels of ADAMTS13 were strongly reduced and levels of VWF were strongly elevated. Liver cirrhosis is often accompanied by alterations in the haemostatic system. In our group of liver cirrhosis patients we found highly elevated VWF and a large variation in levels of ADAMTS13. No clear explanation for this variation was found yet. At least we studied several assays in TTP patients and liver cirrhosis patients. We concluded that for TTP patients all assays were suitable. Overall we can conclude that ADAMTS13 plays an important role in arterial thrombosis, especially in coronary heart disease patients. However, these results were form case-controle studies and need to be further studied in prospective studies.

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