Thrombosis and acute lymphoblastic leukaemia

Abstract

Summary Venous thrombosis is more frequent in patients treated for acute lymphoblastic leukaemia (ALL) than other malignancies and has distinctive causes, clinical features and remedies. The reported incidence varies from 1% to 36%, depending on the chemotherapy protocol and whether the reported cases are symptomatic or detected on screening radiography. The risk is thought to arise from increased thrombin generation at diagnosis combined with reduced thrombin inhibitory capacity due to depletion of circulating anti‐thrombin (AT) by asparaginase. A number of patient and treatment variables have been reported to influence the risk of thrombosis including hereditary thrombophilia, early insertion of central venous catheters and exposure to a combination of steroids and asparaginase during induction. Erwinia asparaginase is associated with a lower risk of thrombosis compared with Escherichia coli asparaginase. The majority of symptomatic thromboses are related to central venous catheters and involve the upper venous system. Central nervous system thrombosis involving the cerebral venous sinuses is a unique feature of asparaginase‐related thrombosis and is reported to occur in 1–3% of patients. Conclusive evidence to support the use of anti‐coagulant treatment or AT concentrates for primary prevention is lacking, as is evidence for the efficacy of AT concentrates in the management of established thrombosis. Preventative strategies are hampered by conflicting data on factors that would enable identification of those at highest risk of thrombosis.

Intensified chemotherapy inspired by a pediatric regimen combined with allogeneic transplantation in adult patients with acute lymphoblastic leukemia up to the age of 40

“…That difference might be explained by the contributory role of active leukemia, steroids and asparaginase to a pro-thrombotic state and a higher risk for thrombo-embolic events. 22,23 Our definition of feasibility included the completion of chemotherapy within a predefined strict time schedule. Excessive delay in treatment was observed in only five patients, indicating that a disciplinary, dose-dense approach is feasible in adult patients with ALL.…”

Personal practice: How we manage the risk of bleeding and thrombosis in children and young adults with acute lymphoblastic leukaemia

“…The risks are highest in the first few weeks of treatment when the haemostatic abnormalities are at their worst (Caruso et al, 2006;Qureshi et al, 2010). These have been comprehensively described elsewhere (Mitchell et al, 1995;Payne & Vora, 2007) and we don't intend to recapitulate them here. Instead our intention is to describe the nature and frequency of the problems and how they may best be managed by addressing practice-based questions.…”

Thrombose coronaire distale compliquant une leucémie aiguë lymphoblastique traitée par asparaginase

“…Les thromboses veineuses profondes (TVP) sont des complications plus fréquentes lors du traitement par asparaginase. L'incidence des TVP varie de 1,7 à 36,7 % [3]. Les TVP surviennent après une moyenne de quatre injections [4].…”

“…Les TVP surviennent après une moyenne de quatre injections [4]. Les facteurs de risque sont la leucémie, les traitements (asparaginase et corticothéra-pie), les cathéters centraux et la thrombophilie [3,5]. Les TVP siègent sur cathéter, aux membres inférieurs (35 %) et supé-rieurs (25 %), au poumon (15 %) et au cerveau (25 %) [4].…”

“…Les TVP siègent sur cathéter, aux membres inférieurs (35 %) et supé-rieurs (25 %), au poumon (15 %) et au cerveau (25 %) [4]. Dans l'étude PARKAA, quatre thromboses siègent dans l'oreillette droite [3]. L'asparaginase entraîne un déficit en asparagine intracellulaire induisant la mort cellulaire des cellules lymphoblastiques humaines.…”