The benefit of
asparaginase for treating acute lymphoid leukaemia (ALL) has been well established. Native
asparaginase derives from Escherichia coli (
colaspase) or Erwinia chrysanthemi (crisantaspase); in a third preparation,
colaspase is pegylated. Depletion of
asparagine leads to decreased synthesis of procoagulant,
anticoagulant, and fibrinolytic
proteins, with resultant
hypercoagulability and greater risk of
venous thromboembolism (VTE).
Colaspase and crisantaspase are not dose-equivalent, with crisantaspase displaying haemostatic toxicity only at dosages much higher and administered more frequently than those of
colaspase. Cerebral
venous thrombosis and
pulmonary embolism are two life-endangering manifestations that occur during treatment with
asparaginase particularly in children and in adults with ALL, respectively. Approximately one-third of
VTEs are located in the upper extremities and are central venous line-related. Other risk factors are longer duration of
asparaginase treatment and concomitant use of
prednisone,
anthracyclines, and
oral contraceptives. The risk associated with inherited
thrombophilia is uncertain but is clearly enhanced by other risk factors or by the use of
prednisone. VTE prevention with fresh frozen plasma is not recommended; the efficacy of
antithrombin (AT) concentrates has occasionally been reported, but these reports should be confirmed by proper studies, and AT should not be routinely employed. Therapeutic or prophylactic
heparin doses are only partially effective, and direct
thrombin or
factor Xa inhibitors could play significant roles in the near future.