Supervisors info:
Κοκόρη Στυλιανή, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Τσιριγώτης Παναγιώτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή ΕΚΠΑ
Γρουζή Ελισάβετ, Αιματολόγος, Συντονίστρια Διευθύντρια Νοσοκομειακής Υπηρεσίας Αιμοδοσίας- Αντικαρκινικού-Ογκολογικού Γ. Ν .Α « Ο Άγιος Σάββας»
Summary:
The term thrombotic microangiopathy includes rare diseases which result in thrombosis in microcirculation due to endothelial injury. These lesions decrease the oxygenation of tissues such us kidneys, brain, lungs and gastrointestinal system. Most important clinical syndromes of thrombotic microangiopathies are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), whose pathophysiologic mechanisms are different. In TTP there is deficiency in ADAMTS13 enzyme, which leads to accumulation of ultra-large vWF (ULVWF) multimers, inducing platelet clumping and thrombosis in microcirculation. Typical hemolytic uremic syndrome (HUS) is caused by shiga toxin which is produced by E. Coli (serotype O157:H7 or O104:H4) and cause endothelial injury, while atypical HUS is provoked by dysregulation of the alternative pathway of complement system, causing its uncontrolled activation, which leads to injury in endothelium and red blood cells. These lesions are responsible for hemolysis, activation and accumulation of the platelets. The term secondary HUS is used to describe HUS which coexist with a disease or a situation such us pregnancy, certain cytotoxic drugs, autoimmunity, transplantation, cancer, or infection. There is a predisposition for HUS in people with mutations in complement regulatory proteins such us factor H, factor Ι, MCP/CD46, thrombomodulin, factor B and C3, as well as, in the existence of autoantibodies against factor Η. Mutations in diacylglycerol kinase-epsilon (DGKE) and cobalamin C defficiency are rare hereditary diseases which can present with relapsing HUS.
The treatment of thrombotic microangiopathies includes therapy of the underlying condition/disease, as well as, supportive therapy. Plasmapheresis is the therapy of choice for TTP, while eculizumab, a humanized, anti-C5 monoclonal antibody which targets at uncontrolled activation of complement system in atypical HUS.
