Venous Thrombosis in Children with Acute Lymphoblastic Leukemia Treated on DCOG ALL-9 and ALL-10 Protocols: The Effect of Fresh Frozen Plasma

Abstract

Background Venous thromboembolism (VTE) is an important complication for treatment of acute lymphoblastic leukemia (ALL) in children. Especially, ALL treatment, with therapeutics such as asparaginase and steroids, increases the thrombotic risk by reduction in procoagulant and anticoagulant proteins. Replacement of deficient natural anticoagulants by administration of fresh frozen plasma (FFP) may have a preventive effect on the occurrence of VTE. Methods We retrospectively analyzed all consecutive children (≤18 years) with ALL, treated on the Dutch Childhood Oncology Group (DCOG) ALL-9 and ALL-10 protocols at the Emma Children's Hospital Academic Medical Center between February 1997 and January 2012, to study the effect of FFP on VTE incidence, antithrombin and fibrinogen plasma levels, and VTE risk factors. Results In total, 18/205 patients developed VTE (8.8%; 95% confidence interval [CI]: 4.9–12.7%). In all patients, VTE occurred after asparaginase administration. In total, 82/205 patients (40%) received FFP. FFP supplementation did not prevent VTE or alter plasma levels of antithrombin or fibrinogen. In the multivariate analysis, VTE occurred significantly more frequently in children ≥12 years (odds ratio [OR]: 3.89; 95% CI: 1.29–11.73) and treated according to the ALL-10 protocol (OR: 3.71; 95% CI: 1.13–12.17). Conclusion FFP supplementation does not seem to be beneficial in the prevention of VTE in pediatric ALL patients. In addition, age ≥12 years and treatment according to the DCOG ALL-10 protocol with intensive and prolonged administration of asparaginase in combination with prednisone are risk factors. There is a need for effective preventive strategies in ALL patients at high risk for VTE.

Risk factors for the development of hospital-acquired pediatric venous thromboembolism—Dealing with potentially causal and confounding risk factors using a directed acyclic graph (DAG) analysis

“…Adult studies showed that prophylactic anticoagulation could be safely administered without increasing the number or severity of bleeding events, resulting in a reduction in VTE’s cumulative incidence [ 24 ] in ALL patients. Hence, VTE prophylaxis [ 25 ] or protein replacement with fresh frozen plasma [ 26 ] has recently been proposed in patients with ALL during the induction period with pediatric clinical trials ongoing. In our study, prophylactic anticoagulation in ALL was not employed.…”

Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study

“…In the literature, it has been reported that treatment with LMWH for a minimum of 3 months and until L‐asparaginase therapy is over with major radiologic improvement seems to be effective and feasible 31 . It is thought to have a positive prophylactic effect 32 . New oral anticoagulants (NOACs) such as rivaroxaban can be used in some thromboembolic disorders.…”

“…31 It is thought to have a positive prophylactic effect. 32 New oral anticoagulants (NOACs) such as rivaroxaban can be used in some thromboembolic disorders. Results of the EINSTEIN-Jr CVT study showed that rivaroxaban is effective and safe in pediatric CVT.…”

Risk Factors for the Development of Hospital-Acquired Pediatric Venous Thromboembolism: Dealing With Potentially Causal and Confounding Risk Factors Using Directed Acyclic Graph (Dag) Analysis

“…Adult studies showed that prophylactic anticoagulation could be safely administered without increasing the number or severity of bleeding events, resulting in a reduction in the cumulative incidence of VTE(24) in ALL patients. Hence, VTE prophylaxis(25) or protein replacement with fresh frozen plasma(26) has recently been proposed in patients with ALL during the induction period with pediatric clinical trials ongoing. In our study, prophylactic anticoagulation in ALL was not employed.…”