Erwinia- and E. coli-derived L-asparaginase have similar effects on hemostasis. Pilot study in 10 patients with acute lymphoblastic leukemia.
BACKGROUND
L-asparaginase (L-ase) affects the synthesis of several hemostatic factors, including the naturally occurring clotting inhibitors antithrombin III, protein C and S, and thromboembolic events are a well-recognized complication of the hypercoagulable state resulting from this treatment. Recently, in addition to the widely used E. Coli-derived L-ase, a new L-ase derived from Erwinia Carotovora has been introduced into clinical studies. This formulation seems to have lesser side-effects, but data on its effects on the hemostatic system are very limited. We report here the hemostatic changes observed in 10 adult patients with acute lymphoblastic leukemia (ALL) treated with Erwinia- or with E. Coli-derived L-ase.


RESULTS
The decreases (percentages of basal level) of antithrombin III, protein C and plasminogen (functional assays) were similar in both groups of patients (about 50% of the basal value 6 or 8 days after starting L-ase) and so were the number of instances in which the level of these proteins fell below 70% of normal. On the contrary, the fibrinogen level (PT-derived method) was less severely decreased by Erwinia L-ase (34% of basal value for E. Coli L-ase versus 58% for Erwinia L-ase; P = 0.048) and there were more instances in which the fibrinogen level was less than 100 mg/dL than with E. Coli L-ase (40% versus 16%; P = 0.051). Thrombin-AT-III complexes (ELISA) showed similar pattern during both treatments. Two patients treated with Erwinia L-ase had moderate hyperglycemia, requiring insulin treatment but not L-ase discontinuation. No allergic reaction or pancreatitis was observed. A patient in the Erwinia L-ase-treated group developed deep venous thrombosis on day 7 after the start of L-ase and was treated with subcutaneous heparin (12,500 U x 2/day), with prompt improvement.


CONCLUSIONS
This study shows that the two L-ase formulations have similar effects on hemostasis. Patients treated with Erwinia L-ase may develop thrombotic symptoms, as already reported for E. Coli-L-ase.
Castaman
G
G
Department of Hematology, San Bortolo Hospital, Vicenza, Italy.
Rodeghiero
F
F
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004885:Erwinia / Q000201:enzymology*; D004926:Escherichia coli / Q000201:enzymology*; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use; D007527:Isoenzymes / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D011241:Prednisone / Q000627:therapeutic use; D013924:Thrombophlebitis / Q000139:chemically induced*; D014750:Vincristine / Q000627:therapeutic use
D001426:Bacterial Proteins; D007527:Isoenzymes; D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone; D015255:Idarubicin