Coagulation abnormality as a complication of L-asparaginase therapy in childhood lymphoblastic leukemia
Keywords:
L-asparaginase, childhood ALL, coagulation, bleeding
Abstract
Background Bleeding, one of the most common symptoms ofacute leukemia in untreated patients, is mostly due to thrombocy-
topenia as a result of myeloinvasion by leukemic cells. Neverthe-
less, a further contributory factor for the additional hemorrhagic
complication during intensive chemotherapy is the myelosuppressive
effect of most active drugs. L-asparaginase, one of the cytostatics
used during remission induction therapy for childhood of acute
lymphoblastic leukemia (ALL), is widely reported to impair the he-
mostatic system.
Objective To determine the influence of shorter courses of L-as-
paraginase (L-Ase) on some of the hemostatic parameters in the
treatment of childhood ALL.
Methods A prospective analytical study was carried out in the
Department of Child Health, Cipto Mangunkusumo Hospital Jakarta
from July 1, 1999 to June 30, 2001 on newly diagnosed ALL pa-
tients with normal liver function tests treated according to our na-
tional ALL protocol which one of its composition contained 6 in-
stead of 9 injections of L-asparaginase.
Results All of 30 children with ALL included in the study, experi-
enced prolongation of prothrombin time (PT), activated partial
thromboplastin time (aPTT), and decreased fibrinogen concentra-
tion, markedly during the administration of L-asparaginase. How-
ever, none of the patients had additional hemorrhage or evidence
of disseminated intravascular coagulation (DIC).
Conclusion The use of shorter courses of L-asparaginase, 6 in-
jections, in the remission induction chemotherapy of childhood ALL
in our department may reduce the blood clotting factors without
further hemorrhage complication or evidence of DIC
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Hematol 1989;32:20-3.
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vincristine and prednisone therapy in lymphoblastic
leukemia. Cancer 1975;35:144-7.
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fibrinogen survival using autologous I-fibrinogen. Blood
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Hematol 1986;22:391-401.
2. Homans AC, Rybak ME, Baglini RL, Tiarks C, Steiner
ME, Forman EN. Effect of L-asparaginase administra-
tion on coagulation and platelet function in children
with leukemia. J Clin Oncol 1987;5:811-7.
3. Ramsay NK, Coccia PF, Krivit W, Nesbit ME, Edson JR.
The effect of L-asparaginase on plasma coagulation fac-
tors in acute lymphoblastic leukemia. Cancer 1977;40:
1398-401.
4. Sills RH, Nelson DA, Stockman JA. L-asparaginase-in-
duced coagulopathy during therapy of acute lympho-
blastic leukemia. Med Pediatr Oncol 1978;4:311-3.
5. Gralnick HR, Henderson E. Hypofibrinogenemia and
coagulation factor deficiencies with L-asparaginase treat-
ment. Cancer 1971;27:1313-20.
6. Priest JR, Ramsay NK, Latchaw RE, Lockman LA,
Hasegawa DK, Coates TD, et al. Thrombotic and hem-
orrhagic strokes complicating early therapy for childhood
acute lymphoblastic leukemia. Cancer 1980;46:1548-54.
7. Priest JR,Ramsay NK, Bennett AJ, Krivit W, Edson JR.
The effect of L-asparaginase on antithrombin, plasmi-
nogen, and plasma coagulation during therapy for acute
lymphoblastic leukemia. J Pediatr 1982;100:984-9.
8. Barrowcliffe TW, Kirkwood TB, Rizza CR. Alumunium
hydroxide adsorption and factor VIII clotting assays. Lan-
cet 1980;1:820.
9. Gralnick HR, Abrell E. Studies of the procoagulant
and fibrinolytic activity of promyelocytes in acute
promyelocitic leukemia. Br J Hematol 1973;24:89-99.
10. Gralnick HR, Sultan C. Annotation: Acute promyelocytic
leukemia, haemorrhagic manifestation and morphologic
criteria. Br J Hematol 1975;29:373-6.
11. Anderson N, Lokich JJ, Tullis JL. L-asparaginase effect
on antithrombin-III levels. Med Pediatr Oncol
1979;7:335-40.
12. Buchanan GR, Holtkamp CA. Reduced antithrombin
III levels during L-asparaginase therapy. Med Pediatr
Oncol 1980;8:7-14.
13. Vellenga E, Mulder NH, Nieweg HO. Antithrombin III
deficiency during asparaginase therapy. Lancet
1980;1:649-50.
14. Barbui T, Finazzi G, Falanga A. The management of
bleeding and thrombosis in leukemia. In: Henderson ES,
Lister TA, Greaves MF, editors. Leukemia: 6th ed. Phila-
delphia: Saunders, 1996. p. 291-300.
15. Pui CH, Jackson CW, Chesney CM, Lyles SA, Bowman
WP, Abrowictch M, et al. Sequential changes in platelet
function and coagulation in leukemic children treated
with L-asparaginase, prednisone, and vincristine. J Clin
Oncol 1983;1:380-5.
16. Vellenga E, Kluft C, Mulder NH, Wijngaards G,
Nieweg HO. The influence of L-asparaginase therapy
on the fibrinolytic system. Br J Haematol 1984;57:
247-54.
17. Gatot D, Windiastuti E, Abdulsalam M, Munthe BG.
Treatment of Childhood Acute Lymphoblastic Leu-
kemia. The Jakarta Experience. Presented at the 17 th
Asia Pacific Cancer Conference, Bali; 2003 Octo-
ber 8-11.
18. Jaffe N, Traggis L, Das WC, Das L, Moloney, Hann HW,
Kim BS, et al. L-asparaginase in the treatment of neo-
plastic diseases in children. Cancer Res 1971;31:942-8.
19. Land VJ, Sutow WW, Fernbach DJ, Lane DM, Williams
TE. Toxicity of L-asparaginase in children in advanced
leukemia. Cancer 1972;30:339-43.
20. Pui CH, Chesney CM, Bergum PW, Jackson CW,
Rappaport SI. Lack of pathogenic role of protein C and
S in thrombosis associated with asparaginase-pred-
nisone-vincristine therapy for leukemia. Br J Haematol
1986;64:283-90.
21. Saito M, Asakura H, Jokaji H, Uotani C, Kumabashiri I,
Ito K, et al. Changes in hemostatic and fibrinolytic pro-
teins in patients receiving L-asparaginase therapy. Am J
Hematol 1989;32:20-3.
22. Al-Mondhiry H. Hypofibrinogenemia associated with
vincristine and prednisone therapy in lymphoblastic
leukemia. Cancer 1975;35:144-7.
23. Betticole RE, Himelstein ES, Oettgen HF, Clifford GO.
Hypofibrinogenemia due to L-asparaginase: Studies on
fibrinogen survival using autologous I-fibrinogen. Blood
1970;35:195-200.
Published
2016-10-18
How to Cite
1.
Gatot D, Pringgardini K, Suradi R. Coagulation abnormality as a complication of L-asparaginase therapy in childhood lymphoblastic leukemia. PI [Internet]. 18Oct.2016 [cited 20Apr.2024];46(1):46-0. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/854
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Received 2016-10-10
Accepted 2016-10-10
Published 2016-10-18
Accepted 2016-10-10
Published 2016-10-18
