Update on the role of the complement system in the pathogenesis of thrombotic microangiopathies

Abstract

(Full text is available at http://www.manu.edu.mk/prilozi). In thrombotic microangiopathies (TMA) pathological changes of the small vessels are present, which lead to ischaemia of the affected tissues, low platelet-count and intravascular haemolytic anaemia with fragmentocytes. Two main clinical syndromes belong to the group of TMAs: the haemolytic uraemic syndrome (HUS) with kidney failure, mainly affecting children, and the thrombotic thrombocytopenic purpura (TTP), starting primarily in adulthood. HUS can be clinically classified into two forms: typical and atypical HUS, the latter being caused by defective regulation of the complement system. However, acccording to recent studies, complement activation is also present in other TMAs. Complement activation products (C3a, C5a, MAC) are able to activate endothelial cells, which results in loss of their antiinflammatory and antithrombotic potential. Activation of the complement system can also lead to direct activation of platelets and granulocytes. The consequent endothelial damage and thrombosis forms the pathological basis of the TMAs. Exploring the exact pathogenetic role of the complement system in these diseases makes the development of new therapeutic methods possible. Key words: TMA, aHUS, D+ HUS, TTP, complement system, endothelial cell activation.