Pegasparaginase treatment alters thrombin generation by modulating the protein C and S system in acute lymphoblastic leukaemia/lymphoma.

Paediatric patients with acute lymphoblastic leukaemia/lymphoma treated with pegasparaginase are at an increased risk of thrombosis. We evaluated changes in thrombin generation in the presence and absence of thrombomodulin using paired plasma samples collected from paediatric patients treated with pegasparaginase. Postpegasparaginase samples were significantly less sensitive to reductions in thrombin generation in the presence of thrombomodulin compared with prepegasparaginase, suggesting reduced protein C and S activity. This corresponded to a significant decrease in protein C and protein S antigen. Alterations in the protein C and S pathway may contribute to the increased risk of thrombosis in patients treated with pegasparaginase.