Effect of glucocorticoids, E. coli- and Erwinia L-asparaginase on hemostatic proteins in children with acute lymphoblastic leukemia

Abstract

Our results indicate that GC and E. coli L-asparaginase, in particular, induce hemostatic alterations which have implications on our understanding of thrombotic and hemorrhagic events during the treatment of ALL in children.

Changes in hypercoagulability by asparaginase: a randomized study between two asparaginases

“…A remarkable shortening of the APTT most likely due to a rise in factor VIII and IX, together with a progressive hypofibrinogenemia and a significant rise in both the ATIII and protein C activities, were responsible for an unstable balance between coagulation and bleeding factors before L-asparaginase was added to the treatment. All these changes could probably be attributed to the use of prednisone [25,26]. We did not find an additional effect of L-asparaginase on the coagulation proteins that are involved in fibrin formation [11].…”

“…The administration of L-asparaginase, either generated from native E. coli or from Erwinia chrysanthemi, does not lead to a further increase or any decrease in the levels of TAT and F1þ2. As prednisone therapy continues during the second part of ALL induction treatment the raised levels of F1þ2 and TAT might be attributed to the concomitant use of corticosteroids [25]. Considering that the half-lives of F1þ2 and TAT are respectively 90 and 3 min and that both parameters were taken at the same time for each investigation, we conclude that thrombin generation is not clearly influenced by the administration of L-asparaginase in the way it was given in this study.…”

The evaluation of protein Z levels of children with acute lymphoblastic leukaemia during induction therapy

“…Mall et al [9] showed that AT and PC levels are increased at the end of the first week after monotherapy with steroids in ALL patients treated according to ALL BFM-95 protocol. This only shows the effect of prednisone on protein Z.…”

“…Many of the protocols use corticosteroids, L-asparaginase (L-ASP), anthracyclines, vincristine and intrathecal methotrexate during induction therapy [5][6][7][8]. In cases with ALL, although many studies investigated the effects of steroid and L-ASP administration on levels of the coagulation proteins such as protein S, protein C (PC) and antithrombin (AT), to our knowledge, protein Z levels have not been investigated in any study yet [9,10]. In cases with ALL, although many studies investigated the effects of steroid and L-ASP administration on levels of the coagulation proteins such as protein S, protein C (PC) and antithrombin (AT), to our knowledge, protein Z levels have not been investigated in any study yet [9,10].…”

Von Willebrand Factor and Factor VIII Levels in Egyptian Children With Newly Diagnosed Acute Lymphoblastic Leukemia in Relation to Peripheral Blast Cells and Steroid Therapy

“…3,4 Increased levels of VWF:Ag in children at the time of diagnosis of acute lymphoblastic leukemia (ALL) has been reported with a lot of variability in the response of VWF:Ag levels following therapy. [5][6][7][8] It is postulated that peripheral lymphoblasts activate the endothelium and lead to elevation of VWF:Ag. The endothelial activation and VWF:Ag then lead to thrombin activation and elevation in parameters of thrombin generation resulting in the inducement of prothrombotic state seen in children with ALL.…”