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The effect of L-asparaginase on antithrombin, plasminogen, and plasma coagulation during therapy for acute
Insights
L-asparaginase chemotherapy in children with acute lymphoblastic leukemia alters hemostatic function, decreasing key clotting factors and increasing clotting times. These changes may explain observed thrombosis and hemorrhage risks.
Area of Science:
- Hematology
- Pediatric Oncology
- Pharmacology
Background:
- Acute lymphoblastic leukemia (ALL) is a common childhood cancer.
- Chemotherapy regimens, including L-asparaginase, vincristine, and prednisone, are used for ALL remission induction.
- L-asparaginase is known to affect protein synthesis and coagulation factors.
Purpose of the Study:
- To sequentially evaluate the impact of L-asparaginase, vincristine, and prednisone combination chemotherapy on hemostatic function in children with ALL.
- To investigate the relationship between chemotherapy-induced hemostatic changes and the risk of bleeding or clotting events.
Main Methods:
- Sequential blood sampling in 12 children undergoing ALL remission induction therapy.
- Measurement of plasma concentrations of antithrombin, plasminogen, and fibrinogen.
- Assessment of plasma clotting times: prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT).
- Monitoring of platelet counts and Factor V levels throughout the treatment period.
Main Results:
- L-asparaginase therapy led to progressive decreases in antithrombin, plasminogen, and fibrinogen.
- Significant increases in PT, PTT, and TT were observed during L-asparaginase treatment.
- Platelet counts increased as bone marrow remission was achieved.
- Factor V levels showed a steady increase, potentially linked to vincristine or prednisone.
Conclusions:
- Combination chemotherapy for ALL, particularly L-asparaginase, induces significant hemostatic abnormalities.
- These coagulation alterations, including reduced clotting factors and prolonged clotting times, may underlie the increased incidence of thrombosis and hemorrhage reported with L-asparaginase therapy.
- Further research is warranted to manage these hemostatic risks in pediatric ALL patients.
Abstract:
Hemostatic function was studied sequentially in 12 children receiving L-asparaginase, vincristine, and prednisone as remission induction chemotherapy for acute lymphoblastic leukemia. The three-week period of L-asparaginase therapy was characterized by progressive decreases in plasma antithrombin, plasminogen, and fibrinogen concentrations, and by progressive increases in plasma clotting times (prothrombin time, partial thromboplastin time, thrombin time). Platelet counts rose rapidly during the third and fourth weeks of therapy as bone marrow remission was achieved. Factor V levels increased steadily during a five-week period, perhaps related to vincristine or prednisone therapy. Recent reports of thrombosis and hemorrhage in children and adults receiving L-asparaginase may be explained by this complex set of abnormalities in coagulation and coagulation control.