Treatment of Deep Vein Thrombosis with Enoxaparin in Pediatric Cancer Patients Receiving Chemotherapy.

Abstract

Thrombosis is a known risk in pediatric patients with leukemia. This risk is increased when L-asparaginase is administered. However, children with cancer may have thrombotic complications similar to adults even in the absence of L-asparaginase. The risk may be related to the presence of central lines, surgery, immobilization, or inherited thrombophilia. Cancer in adult patients is also associated with an increased risk of thrombosis that may be related to the disease itself. Low molecular weight heparin such as enoxaparin has become widely used in adult patients with thrombosis. However, there is little data regarding the use of enoxaparin in children undergoing myelosuppressive therapy for malignancies. The purpose of this study was to review the utilization of low molecular weight heparin, enoxaparin (Lovenox), in children with cancer at our institution who had thrombosis while undergoing myelosuppressive chemotherapy. In particular we were interested in the efficacy of enoxaparin in these patients, and if these children were able to continue their chemotherapy without adjustment or interruption secondary to bleeding complications. We conducted a retrospective review from 1999 through April 1, 2004 which yielded seven patients with malignancies and a vascular thrombotic event. The age range was 4–17 years. Diagnosis include: B-precursor ALL (n=3), T-ALL, Hodgkin’s disease, Anaplastic large cell lymphoma, and rhabdomyosarcoma (n=1 each). Six patients developed a deep vein thrombus or clot of the vena cava. One of these 6 patients also had a pulmonary embolus. One patient presented with manifestations of a unilateral cerebral vascular accident without evidence of a DVT. U/S and CT/MRI were performed on patients when appropriate. All patients were screened for Protein C & S deficiency, ATIII deficiency, Factor V Leiden mutation, prothrombin 20210a mutation, and lupus anticoagulant. Treatment was enoxaparin, 1–1.5 mg/kg/dose twice daily to maintain a heparin anti-Xa level of 0.5-1.5 IU/mL. Once the clot had resolved, the enoxaparin was maintained daily for a total of 3–6 months of therapy. All patients had resolution of their thrombosis within 1–2 months of initiation of enoxaparin, and none required delays or dose-reduction of their chemotherapy regimens while on anti-coagulation. There were 10 documented occurences of thrombocytopenia (platelet count < 50,000) in 2 patients without bleeding complications. There was a minimum of 50 days of documented thrombocytopenia while on enoxaparin. We conclude that enoxaparin is effective and safe treatment for thrombotic complications in children undergoing cancer chemotherapy.

Feasibility and safety of delivering full‐dose anticoagulation therapy in children treated according to Dana‐Farber Cancer Institute acute lymphoblastic leukemia consortium therapy protocols

“…The response to ACT (52% CR, 29% PR and 19% ST) in our cohort was comparable to most studies in children with TE, including those with and without underlying cancer 10,13. In a study of 33 cancerpatients with deep vein thrombosis (DVT), Tousovska et al reported 67% CR and 33% PR/ST.…”

“…Many risk factors for the development of TE in this population are similar in the induction and consolidation phases, except for the amount of asparaginase exposure.There are limited data in the literature on treatment of TE in children with cancer who are on active treatment. Stine et al described the treatment course of seven pediatric cancer patients with TE 10. They did not observe any bleeding episodes, claiming that their treatment approach was safe.…”

Population Pharmacokinetics of Enoxaparin in Pediatric Patients

“…Enoxaparin is a low-molecular-weight heparin commonly used for the treatment and prophylaxis of thromboembolism in pediatric patients. 1-11 Despite widespread use, pharmacokinetic data to give dosing guidance in pediatrics is sparse. The dosing of enoxaparin in pediatrics has been extrapolated from adult data and subsequently refined through clinical experience.…”

Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study

“…Until recently, unfractionated heparin (UFH) followed by oral anticoagulation has been considered the initial anticoagulant regimen of choice for the treatment of VTE in children [1,3]. However, low-molecular-weight-heparin (LMWH) such as enoxaparin is increasingly used in the pediatric population [3][4][5][6][7][8][9][10][11][12][13][14]. Current knowledge demonstrates that therapy with LMWH is at least equally efficacious and safe as UFH in the prevention and treatment of VTE in adult patients [15].…”