Coagulation and fibrinolysis in children with acute lymphoblastic leukaemia 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 given 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-05-92-protocol, [cylophosphamide]/methotrexate/ASP ([CYC]/MTX/ASP) and high dose arabinoside/ASP (HIDAC/ASP). In 33 children with acute lymphoblastic leukaemia the following parameters were determined: plasminogen-activator-inhibitor-1, plasminogen, antiplasmin, protein C, antithrombin, modified antithrombin, prothrombin-fragments 1+2 and thrombin-antithrombin-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 (median 65% NHP) compared to the HTDAC/ASP-combination (median 105% NHP) (p=0.01). The other parameters showed the characteristic changes after ASP-therapy. None of our patients developed any clinical signs of thrombosis, even though two patients showed four altered coagulation parameters on the same day. This shows, that the coexistance of indwelling catheters plus four decreased coagulation parameters does not necessarily imply the development of thrombosis. We conclude that the parameters measured in this study do not sufficiently predict the development of thrombosis.