Thrombosis Complications in Pediatric Acute Lymphoblastic Leukemia: Risk Factors, Management, and Prevention: Is There Any Role for Pharmacologic Prophylaxis?

Abstract

Pediatric acute lymphoblastic leukemia (ALL) has achieved close to 90% cure rates through extensive collaborative and integrative molecular research, clinical studies, and advances in supportive care. Despite this high achievement, venous thromboembolic complications (VTE) remain one of the most common and potentially preventable therapy-associated adverse events in ALL. The majority of thromboses events involve the upper central venous system which is related to the use and location of central venous catheters (CVC). The reported rates of symptomatic and asymptomatic CVC-related VTE range from 2.6 to 36.7% and 5.9 to 43%, respectively. Thrombosis can negatively impact not only disease-free survival [e.g., therapy delays and/or interruption, omission of chemotherapy agents (e.g., asparaginase therapy)] but also can result in long-term adverse effects that can impair the quality of life of ALL survivors (e.g., post-thrombotic syndrome, central nervous system (CNS)-thrombosis related complications: seizures, neurocognitive deficits). In this review, will discuss thrombosis pathophysiology in pediatric ALL, risk factors, treatment, and prevention strategies. In addition, the recently published clinical efficacy and safety of direct oral anticoagulants (DOACs) use in thrombosis treatment, and their potential role in primary/secondary thrombosis prevention in pediatric patients with ALL will be discussed. Future clinical trials involving the use of these novel oral anticoagulants should be studied in ALL not only for primary thrombosis prevention but also in the treatment of thrombosis and its secondary prevention. These future research findings could potentially extrapolate to VTE prevention strategies in other pediatric cancer diagnoses and children considered at high risk for VTE.

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

“…CNS thrombosis has an important place in terms of symptomatic thromboembolic complications in patients with ALL 3,8 . Most studies investigating cases of thrombosis in patients with leukemia include data on cerebral sinus vein thrombosis (CSVT) because it is more common than arterial thrombosis 2,9 . Data on the frequency of arterial thrombosis are limited.…”

“…3,8 Most studies investigating cases of thrombosis in patients with leukemia include data on cerebral sinus vein thrombosis (CSVT) because it is more common than arterial thrombosis. 2,9 Data on the frequency of arterial thrombosis are limited. In a meta-analysis by Caruso et al, the incidence of CNS thrombosis was reported in 49 patients out of 1752 pediatric patients with leukemia (2.49%).…”

“…11 The role of genetic thrombophilia in cancer-related thrombosis is controversial. 2 It has been reported that the risk of thrombosis increases in the presence of additional prothrombotic risks in patients with malignancy and that patients should be screened for these risk factors and necessary precautions should be taken. 2,21,22 Activated protein C resistance is the most frequent coagulation abnormality associated with CVT.…”

“…Although thrombosis is relatively rare in the pediatric age group, it is reported that the frequency in the pediatric population is increased 1 . The diagnoses of leukemia and lymphoma are known as independent risk factors in patients with thrombosis, in which venous thromboembolism is predominant 2 . The estimated incidence of thrombosis in patients with leukemia has been reported in a fairly wide range, 5%–70% 3 .…”

“…1 The diagnoses of leukemia and lymphoma are known as independent risk factors in patients with thrombosis, in which venous thromboembolism is predominant. 2 The estimated incidence of thrombosis in patients with leukemia has been reported in a fairly wide range, 5%-70%. 3 In the study of Caruso et al, in which 1752 ALL (acute lymphoblastic leukemia) patients were evaluated, the incidence of thrombosis was reported as 5.2%, and more than half of those cases (53.8%) were central nervous system (CNS) thrombosis.…”