<i>L</i>-Asparaginase in Acute Lymphoblastic Leukemia Treatment: The Role of Human Antithrombin III Concentrates in Regulating the Prothrombotic State Induced by Therapy

Abstract

It is well known that L-asparaginase (L-Ase) treatment may cause thrombotic events in patients with acute lymphoblastic leukemia (ALL). The mechanism of this effect is not well understood although a reduction in plasma antithrombin III (AT III) levels is observed. In our study, a group of patients treated with L-Ase received AT III concentrates as adjuvant treatment. This adjuvant treatment reduced the levels of plasma D-dimer and thrombin-antithrombin complex, which are considered as early markers of a hypercoagulability state. These preliminary data suggest that large randomized trials will have to be conducted to improve our understanding of the role of AT III concentrates in ALL therapy.

Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study

“…13,[22][23][24][25][26] Several studies have also evaluated the potential benefit of AT concentrates in children and adults with ALL. Most measured surrogate markers evaluating thrombin generation [27][28][29][30] and only one reported a lower incidence of thrombosis in patients treated with AT (0 events in 17 treated cases vs. 10 events in 37 patients not receiving AT, p=0.021). 21 Although none of our patients died from thrombosis, overall and diseasefree survival rates were decreased among the patients who had experienced a thrombotic event.…”

BSH Guideline: management of thrombotic and haemostatic issues in paediatric malignancy

“…Antithrombin concentrate (AT) can be shown to improve plasma markers of hypercoagulability in patients with ALL during periods of asparagine depletion (Gugliotta et al, 1990;Mazzuconi et al, 1994;Pogliani et al, 1995;Nowak-G€ ottl et al, 1996;Kuhle et al, 2006). However, published studies to date have failed to demonstrate a clear reduction in the incidence of VTE in this group of children (Mitchell et al, 2003b;Ranta et al, 2013).…”

Antithrombin Iii Supplementation in Childhood Acute Lymphoblastic Leukemia Treated With L-Asparaginase

“…In patients receiving AT concentrates after ASP administration, thrombin± antithrombin complex and D-dimer levels did not increase, while their levels increased in those without AT supplementation [6]. Thus, the supplementation of AT may be bene® cial in ALL patients with acquired AT de® ciency and hypercoagulable state.…”