The prevention and management of asparaginase‐related venous thromboembolism in adults: Guidance from the SSC on Hemostasis and Malignancy of the ISTH

Abstract

Venous thromboembolism is a common complication of asparaginase-based chemotherapy regimens for the treatment of acute lymphoblastic leukemia. Thrombosis associated with asparaginase administration poses a number of specific and often clinically challenging management decisions. This review provides guidance on the prevention and treatment of thrombosis associated with asparaginase in adults including discussions on antithrombin repletion, pharmacologic thromboprophylaxis, cerebral venous thrombosis, and therapeutic anticoagulation. K E Y W O R D S acute lymphoblastic leukemia, anticoagulation, antithrombin, asparaginase, cerebral venous thrombosis, venous thromboembolism The guidance statements included in this document are similar to those in other guidance documents and are predicated on the following premises: For each of the clinical situations, our guidance statements are applicable to an average adult patient with venous thromboembolism (VTE) associated with asparaginase therapy during the course of therapy for acute lymphoblastic leukemia (ALL).We anticipate that there will be clinical circumstances for which our guidance statements do not apply. As for all cases, our statements may provide guidance but do not replace clinical judgement for the management of individual patients.• The wording "we recommend" reflects a strong guidance statement with strong consensus among the authors, whereby the clinician should consider adopting the practice in a majority of cases.

Management of hemostatic complications in acute leukemia: Guidance from the SSC of the ISTH

“…For each of the topics, guidance statements were generated following review of published literature and are based on consensus opinion of the authors. Thrombotic complications applicable to acute leukemia have been addressed in previous SSC guidance documents that include the management of thrombosis in cancer patients with thrombocytopenia 1 and those associated with L‐asparaginase 2 …”

“…LMWH thromboprophylaxis was suggested throughout induction therapy with L-asparaginase in patients without severe thrombocytopenia (ie, platelet count <30 × 10 9 /L) or concern for hemorrhage. 2 Studies have consistently shown a reduction of fibrinogen levels with L-asparaginase treatment. 56,57 Hypofibrinogenemia can result in abnormal coagulation assays, but its effects on hemorrhagic or thrombotic outcomes are conflicting.…”

“…been reviewed in a recent ISTH guidance document. 2 In that guidance document, it was suggested that AT concentrates be administered for levels <50% to 60% to a target level of 80% to 120%. LMWH thromboprophylaxis was suggested throughout induction therapy with L-asparaginase in patients without severe thrombocytopenia (ie, platelet count <30 × 10 9 /L) or concern for hemorrhage.…”

“…Thrombotic complications applicable to acute leukemia have been addressed in previous SSC guidance documents that include the management of thrombosis in cancer patients with thrombocytopenia 1 and those associated with L-asparaginase. 2…”

Incidence of Venous Thrombosis After Peg-Asparaginase in Adolescent and Young Adults with Acute Lymphoblastic Leukemia

“…In addition, the use of AT concentrates to prevent VTE in peg-asparaginase-treated patients is also controversial. The recently published International Society of Thrombosis and Hemostasis SSC (NC, USA) guidance document suggests monitoring of AT level as well as repletion during peg-asparaginase therapy in the adult population after the literature showed a 60% risk reduction in VTE when implementing such strategies [ 32 ]. Whether the AYA population can benefit from a similar approach warrants further investigation.…”