Antithrombin supplementation did not impact the incidence of pegylated asparaginase-induced venous thromboembolism in adults with acute lymphoblastic leukemia

Chen, Jason; Ngo, Dat; Aldoss, Ibrahim; Shayani, Sepideh; Tsai, Ni‐Chun; Pullarkat, Vinod

doi:10.1080/10428194.2018.1519811

Cited by 19 publications

(8 citation statements)

References 23 publications

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“…99 In contrast, a recently published single center retrospective study of adult patients with ALL who received pegaspargase showed there was no significant decrease in thrombotic events in patients who received AT replacement. 100 In the CAPELAL trial, adults received AT if their measured level was <60%. The rate of thrombosis in AT-treated vs. non-AT treated patients was 5% vs. 12% (P ¼ 0.04).…”

Section: Thrombosismentioning

confidence: 99%

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management

Bade

Patzke

et al. 2019

J Oncol Pharm Pract

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The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.

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Section: Thrombosismentioning

confidence: 99%

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management

Bade

Patzke

et al. 2019

J Oncol Pharm Pract

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“…Capped ATIII dosing (maximum 2000 units) was implemented as a pilot study with peak monitoring to ensure that patients achieved an adequate response. The threshold for ATIII administration was defined at less than 70%, and ATIII was checked twice weekly in patients receiving enoxaparin anticoagulation during periods of exposure to Erwinia asparaginase or pegaspargase . An algorithm was developed to guide response to post‐ATIII infusion peak levels (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…The five doses shown for BMI ≥ 35 kg/m 2 are representative of a single patient with a BMI of 39 kg/m 2 , the largest patient included receiving enoxaparin anticoagulation during periods of exposure to Erwinia asparaginase or pegaspargase. 3,7,8 An algorithm was developed to guide response to post-ATIII infusion peak levels (Figure 1 Peak ATIII levels were obtained in 9 of 11 patients. Two patients who received capped ATIII dosing without peak levels are included in the cost-savings analysis, but not the efficacy analysis.…”

Section: Resultsmentioning

confidence: 99%

Capped antithrombin III dosing is cost effective in the management of asparaginase‐associated thrombosis

Young

Sawyer

Jenkins

et al. 2019

Pediatric Blood & Cancer

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Asparaginase therapy induces a transient antithrombin III (ATIII) deficiency, which contributes to the risk of asparaginase‐induced thrombosis. At Cincinnati Children's Hospital Medical Center, management of asparaginase‐induced thrombosis includes ATIII supplementation during therapeutic anticoagulation with enoxaparin. Due to the expense associated with ATIII, a capped dosing approach for ATIII was evaluated in this population. Peak ATIII levels were obtained following capped doses to evaluate response. In this pilot evaluation, 11 patients received a total of 138 capped doses for a total cost savings of $803 782. This pilot evaluation represents the first reported analysis of capped ATIII dosing in oncology patients.

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“…No randomized clinical trials have been conducted in adults to assess the efficacy of routine antithrombin repletion. In a single‐institution retrospective analysis of adults receiving PEGylated asparaginase, the VTE rates were similar among 47 patients who were monitored for antithrombin deficiency with scheduled repletion compared with 28 patient who did not receive antithrombin monitoring or repletion (17% versus 11%, P = .52), but there were imbalances in pharmacologic thromboprophylaxis administration . By comparison, in a single‐institution retrospective study that included patients receiving either PEGylated or native L‐asparaginase, there were no VTE recorded among the 30 patients who received scheduled antithrombin repletion compared with 5 VTE among the 15 patients who did not receive repletion ( P < .001) .…”

Section: Antithrombin Monitoring and Repletionmentioning

confidence: 98%

“…In the majority of studies, the threshold for antithrombin repletion was either 50% to 60% (with a threshold of 70% in two studies). There were fewer VTE in the antithrombin cohorts in all but one study, yielding an overall summary risk ratio of 0.40 (95% CI, 0.19‐0.81) by a random effects model . Notably, the estimated approximate cost of a course of antithrombin repletion typically is between $12 000 and $35 000 dollars in the United States …”

Section: Antithrombin Monitoring and Repletionmentioning

confidence: 99%

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

Zwicker

Wang

DeAngelo

et al. 2020

Journal of Thrombosis and Haemostasis

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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.

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Antithrombin supplementation did not impact the incidence of pegylated asparaginase-induced venous thromboembolism in adults with acute lymphoblastic leukemia

Cited by 19 publications

References 23 publications

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management

Capped antithrombin III dosing is cost effective in the management of asparaginase‐associated thrombosis

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

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