Thrombotic and Hemorrhagic Complications in the Treatment of Acute Lymphoblastic Leukemia with L-Asparaginase

GM Galstyan, OA Polevodova, AV Bazhenov, VV Troitskaya, OA Gavrilina, DG Gitel’zon, AE Vasil’ev, EN Parovichnikova

National Medical Hematology Research Center, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Gennadii Martinovich Galstyan, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(916)488-50-73; e-mail: gengalst@gmail.com

For citation: Galstyan GM, Polevodova OA, Bazhenov AV, et al. Thrombotic and Hemorrhagic Complications in the Treatment of Acute Lymphoblastic Leukemia with L-Asparaginase. Clinical oncohematology. 2018;11(1):89-99.

DOI: 10.21320/2500-2139-2018-11-1-89-99


ABSTRACT

The article provides a literature review on the use of the L-asparaginase (ASP) in acute lymphoblastic leukemia (ALL) and describes two clinical cases. During the treatment with ASP as part of remission induction therapy thrombotic and hemorrhagic complications in the central nervous system were registered. In both cases these complications were associated with reduced plasma levels of antithrombin III (АТ), hypofibrinogenemia and thrombocytopenia. The risk factors for thrombohemorrhagic complications in ALL patients during ASP treatment are reviewed including combined ASP + anthracycline therapy, oral contraceptives, glucocorticosteroids, thrombophilia and the presence of central venous catheter (CVC). Possible mechanisms of thrombosis as well as the timing of its occurrence and possible localisation are discussed. The article considers different strategies for prevention and treatment of thrombotic and hemorrhagic complications in ALL patients receiving ASP. In all ALL patients receiving ASP plasma levels of fibrinogen and AT should be assessed before treatment initiation, on day 3 after the injection and further every 5 to 7 days within a period of 3 weeks after the injection. Novel oral anticoagulants are not dependent on blood AT levels and may be used for prevention and treatment of thrombotic and hemorrhagic complications associated with ASP intake. Finally, recommendations for the correction of AT levels and hypofibrinogenemia are given.

Keywords: L-asparaginase, thrombosis, thromboelastography, antithrombin III, hypofibrinogenemia, thrombocytopenia, novel oral anticoagulants.

Received: August 16, 2017

Accepted: October 27, 2017

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