Effectiveness and Safety of Primary Thromboprophylaxis in Children with Cancer: A Systematic Review of the Literature and Network Meta-Analysis

Abstract

Thromboembolism (TE) is a well-recognized complication of pediatric cancer and can lead to mortality and excess morbidity. There is conflicting evidence about the effectiveness and safety of thromboprophylaxis in children. We conducted a systematic literature review and network meta-analysis of primary pharmacological thromboprophylaxis in children and adolescents (0–21 years) with cancer. The primary outcomes were objectively proven TE and major bleeding. The network meta-analysis included comparisons of multiple alternatives simultaneously: antithrombin (AT) replacement, low molecular weight heparin (LMWH), vitamin K antagonists (VKAs), and standard of care (SOC) defined as no thromboprophylaxis or low-dose heparin for catheter patency. Six articles describing 1,318 patients were included (mean age: 6.7 years, 56.7% male). Acute lymphoblastic leukemia was the underlying diagnosis in 97.5% of patients. All studies were considered at moderate or high risk of bias. LMWH was the only agent associated with lower odds of TE compared with SOC (odds ratio [OR]: 0.23, 95% confidence interval [CI]: 0.06–0.81). No statistically significant difference was detected between other thromboprophylaxis modalities and SOC. Tau2 and I 2 suggested a high degree of heterogeneity. No statistically significant differences in the odds of major bleeding were found between AT replacement, LMWH, VKA, and SOC. Current evidence suggests that low-dose LMWH is effective and safe to prevent TE in children with cancer but is insufficient to conclude if AT replacement or VKA are effective thromboprophylaxis options. Further research, notably randomized controlled trials enrolling children with diverse types of cancer, is crucially needed.

Thrombosis is associated with worse survival in children with acute lymphoblastic leukemia: A report from CYP‐C

“…Understanding the impact of TE on cancer outcomes is important to reduce the incidence of death and relapse. Thromboprophylaxis modalities are available to prevent cancer‐associated thrombosis and appear to be safe and effective, 45,46 but compliance and clinical implementation remain challenging. If thromboprophylaxis also led to improved survival outcomes in children with ALL, it would provide a strong impetus for its integration in clinical care.…”

Thrombosis and Haemostasis 2019 Editor's Choice Papers

“…[38][39][40][41][42][43][44][45] Because the risk of bleeding might be more important in children than in the general population, it is crucial to assess safety and efficacy of thromboprophylaxis specifically in children. In this context, the efforts from Pelland-Marcotte et al 46 to systematically review the effectiveness and safety of primary thromboprophylaxis in children with cancer in a network meta-analysis study were most welcome. Low molecular weight heparin was found to be the only effective and safe option to prevent thromboembolism in paediatric cancer highlighting the need for more studies focusing on thromboprophylaxis in children.…”

Chemotherapy Increases Stroke: Fact or Fiction?

“…Cancer is associated with an increased risk of thromboembolic events (TEEs). [1][2][3][4][5][6] The underlying mechanisms of cancer-associated thrombosis are complex because many factors can contribute to TEE, including site and stage of the cancer, type of treatment, such as chemotherapy, and patient characteristics, such as age (►Fig. 1).…”