COAGULATION AND FIBRINOLYSIS IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA TREATED ACCORDING TO THE COALL-05-92-PROTOCOL

The etiology of thrombo-embolic events after therapy with asparaginase (ASP) is not fully understood. To investigate if cytotoxic drugs give n in combination with asparaginase (ASP) have an additional effect on the coagulation system, a detailed analysis of coagulation factors was performed. Therefore, we investigated two combinations of the COALL-0 5-92-protocol, [cylophosphamide]/methotrexate/ASP ([CYC]/MTX/ASP) and high dose arabinoside/ASP (HIDAC/ASP). In 33 children with acute lymph oblastic leukaemia the following parameters were determined: plasminog en-activator-inhibitor-1, plasminogen, antiplasmin, protein C, antithr ombin, modified antithrombin, prothrombin-fragments 1+2 and thrombin-a ntithrombin-complex. All children had an indwelling catheter. The most distinctive result of this investigation is that plasminogen shows a deeper and longer lasting decrease in the [CYC]/MTX/ASP-combination (m edian 65% NHP) compared to the HTDAC/ASP-combination (median 105% NHP) (p=0.01). The other parameters showed the characteristic changes afte r ASP-therapy. None of our patients developed any clinical signs of th rombosis, even though two patients showed four altered coagulation par ameters on the same day. This shows, that the coexistance of indwellin g catheters plus four decreased coagulation parameters does not necess arily imply the development of thrombosis. We conclude that the parame ters measured in this study do not sufficiently predict the developmen t of thrombosis.