Effect of disease and chemotherapy on hemostasis in children with acute lymphoid leukemia.
OBJECTIVE
We sought to determine the effect of disease and combination chemotherapy on the hemostatic system in children with acute lymphoid leukemia (ALL).


METHODS
We conducted a prospective study of children newly diagnosed with ALL. Plasma samples were obtained at four time points: at diagnosis before therapy, 5 days after administration of L-asparaginase alone, after the remission induction program, and at completion of the consolidation phase. Plasma levels of 21 hemostatic proteins were measured. The amount of thrombin generated following activation with an APTT reagent was quantitated.


RESULTS
At diagnosis there were significant elevations in factors VIII, IX, von Willebrand, alpha 2-macroglobulin and protein S. In contrast, there were significant reductions in protein C, prekallikrein, and factors XIIIA and XIIIS. L-asparaginase treatment alone decreased concentrations of 11 proteins, with antithrombin III being affected to the greatest extent. After multiagent chemotherapy, not including L-asparaginase, concentrations of most proteins increased to or above baseline. At completion of consolidation therapy, which included weekly L-asparaginase administration, concentrations of most proteins were decreased compared with baseline values. The amount of thrombin generated following activation with an APTT reagent was similar to adults.


CONCLUSIONS
Plasma concentrations of coagulation proteins are affected by disease (ALL) alone and by combination chemotherapy with or without L-asparaginase. There is no impairment of in vitro capacity to generate thrombin. L-asparaginase alone caused a decrease in almost all proteins; however, ATIII was affected to the greatest extent.
Mitchell
L G
LG
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Halton
J M
JM
Vegh
P A
PA
Barr
R D
RD
Venneri
T
T
Pai
K M
KM
Andrew
M E
ME
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000990:Antithrombin III / Q000032:analysis; D001215:Asparaginase / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D006487:Hemostasis; D006801:Humans; D007223:Infant; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy; D011446:Prospective Studies; D013917:Thrombin / Q000096:biosynthesis
D001779:Blood Coagulation Factors; D000990:Antithrombin III; D013917:Thrombin; D001215:Asparaginase