Abstract
Two patients developed clinical features of intracranial bleeding—which were confirmed by computerized axial tomograms—during their induction therapy for acute lymphocytic leukemia. Coagulation studies showed clotting abnormalities including severe hypofibrinogenemia. These findings most probably were related to the effect of L-asparaginase which was part of the treatment protocol. Central nervous system leukemia, intrathecal chemotherapy, cranial irradiation, extreme leukocytosis, or thrombopenia at the time of diagnosis or day of stroke did not appear to be predisposing factors in these cases.
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Benett JM, Catovsky D, Daniel MT, et al. (1976) Proposals for the classification of the acute leukaemias. Br. J Haematol 33:451
Broome JD (1968) Studies on the mechanism of tumor inhibition by L-asparaginase. J Exp Med 127:1058
Brozovic M (1977) Physiological mechanism in coagulation and fibrinolysis. Br Med Bull 33:231
Buchanan GR, Holtkamp CA (1980) Reduced antithrombin III levels during L-asparaginase therapy. Med Ped Oncol 8:7
Cairo MS, Lazarus K, Gilmore RL, Baehner RL (1980) Intracranial hemorrhage and focal seizures secondary to use of L-asparaginase during induction therapy of acute lymphocytic leukemia. J Pediatr 97:829
Conard J, Durand J, Feger J, Samama M (1973) Acquired abnormal antithrombin III in L-asparaginase treated patients? In: IVth International Congress of thrombosis and hemostasis, Vienna, p 228 (abstr 193)
David RB, Hadfield MG, Vines FS, Mauer HM (1975) Dural sinus occlusion in leukemia. Pediatrics 56:793
Dearth JC, Fountain KS, Smithson WA, Burgert EO, Gilchrist GS (1978) Extreme leukemic leukocytosis (blast crisis) in childhood. Mayo Clin Proc 53:207
Deutsch E, Fischer M, Frischauf H, Nonetz N, Kechner K, Pesendorfer F, Stych H, Weissmann A (1970) Blood coagulation changes under L-asparaginase therapy. In: Grundmann E, Oettgen HF (eds) Recent results in cancer research. vol 33. New York, Springer, p 331
Egeberg O (1965) Inherited antithrombin deficiency causing thrombophilia. Thrombos Diathes Hemorrh 13:516
Fritz R, et al. (1959) The association of fatal intracranial hemorrhage and blast crisis in patients with acute leukemia. N Engl J Med 261:59
Gadner H, Riehm H (1977) Veränderungen der Hämostase während der Induktionstherapie akuter lymphoblastischer Leukämien im Kindesalter. Klin Paediat (Buech Paediat) 78:130
Haskell CM, Connellos GP, Leventhal BG, Carbon PP, Block JB, Serpick AA, Selawry OS (1969) L-asparaginase. Therapeutic and toxic effects in patients with neoplastic disease. N Engl J Med 281:1028
Kauffmann RH, Veltkamp JJ, Van Tilburg NH, Van Es LA (1978) Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome. Am J Med 65:607
Land VJ, Sutow WW, Fernbach DJ, Lane DM, Williams TE (1972) Toxicity of L-asparaginase in children with advanced leukemia. Cancer 30:339
Lau SO, Bock GH, Edson JR, Michael AF (1980) Sagittal sinus thrombosis in the nephrotic syndrome. J Pediatr 97:948
Lockman LA, Mastri A, Priest JR, Nesbit M (1980) Dural venous sinus thrombosis in acute lymphoblastic leukemia. Pediatrics 66:943
Marciniak E, Farley CH, De Simone PA (1974) Familial thrombosis due to antithrombin III deficiency. Blood 43:219
Montgomery R, Natelson SG (1977) Afibrinogenemia with intracerebral hematoma. Am J Dis Child 131:555
Oettgen HF, Stephenson PA, Schwartz MK, Leeper RD, Fallal L, Tan CC, Clarkson BD, Golbey RB, Krakoff IH, Karnovsky DA, Murphy ML, Burchenal JH (1970) Toxicity E. coli L-asparaginase in man. Cancer 25:253
Ortega J, Nesbit M, Donaldson M, Hittle R, Weiner J, Karon M, Hammond D (1977) L-asparaginase, vincristine and prednisone for induction of first remission in acute lymphocytic leukemia. Cancer Res 37:535
Paton RC, Douglas AS (1976) Mechanism of thrombotic disease. In: Ioachim HL (ed) Pathobiology annual, vol 6. Appleton-Century-Crofts, New York, pp 59–93
Pierce M (1962) Neurological complications in acute leukemia in children. Pediatr Clin North Am 9:425
Pochedly C (1975) Neurological manifestations in leukemia I. NY State J Med 75:575
Priest JR, Ramsey NKC, Latchaw RE, Lockman LA, Hasegawa DK, Coates TD, Coccia PF, Edson JG, Nesbit ME, Krivit W (1980) Thrombotic and hemorrhagic strokes complicating early therapy for childhood acute lymphoblastic leukemia. Cancer 46:1548
Ramsay NKC, Coccia PF, Krivit W, Nesbit ME, Edson JR (1977) The effect of L-asparaginase of plasma coagulation factors in acute lymphoblastic leukemia. Cancer 40:1398
Riehm HJ, Gadner H, Henze G, Langermann H-J, Odenwald E (1980) The Berlin childhood acute lymphoblastic leukemia therapy study, 1970–1976. Am J Pediatr Hematol/Oncol 2:299
Sills RH, Nelson DA, Stockmann JA III (1978) L-asparaginase coagulopathy during therapy for acute lymphocytic leukemia. Med Pediatr Oncol 4:311
Wada JK, Patch MJ, McGehee WG (1979) Low levels of antithrombin III (AT III) due to L-asparaginase. Blood 54 (suppl 1):308a
Whitecar JP, Bodey GP, Harris JE, Freireich EJ (1970) L-asparaginase. N Engl J Med 282:732
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Urban, C., Sager, W.D. Intracranial bleeding during therapy with L-asparaginase in childhood acute lymphocytic leukemia. Eur J Pediatr 137, 323–327 (1981). https://doi.org/10.1007/BF00443266
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DOI: https://doi.org/10.1007/BF00443266