The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic...

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Acute lymphoblastic leukaemia (ALL) treatment increasingly uses L-asparaginase (L-Asp) in adults.
• L-Asp therapy disrupts haemostatic and anticoagulant balance, primarily causing thrombosis.
• Acquired antithrombin (AT) deficiency is known, but other protein depletions complicate thrombosis mechanisms.

Purpose of the Study:

• To define the precise mechanism of thrombosis associated with L-Asp therapy.
• To evaluate the role of antithrombin (AT) concentrates in managing L-Asp-induced thrombosis.
• To address the lack of evidence-based guidelines for prevention and management strategies.

Main Methods:

• Review of clinical data and in vitro coagulation assays in patients receiving L-Asp.
• Analysis of haemostatic and anticoagulant protein levels during L-Asp therapy.
• Assessment of the efficacy of AT concentrates in thrombotic event management.

Main Results:

• In vitro coagulation assays are often prolonged, but thrombosis is the main clinical concern.
• L-Asp therapy leads to acquired deficiency in AT and other haemostatic proteins.
• Limited evidence supports the use of AT concentrates for prevention or treatment.

Conclusions:

• The exact mechanism of thrombosis in L-Asp-treated patients requires further definition.
• Current management of thrombotic events relies on AT-dependent anticoagulants despite AT depletion.
• Evidence-based guidelines for AT concentrate use in L-Asp-associated thrombosis are lacking.