EFFECTS OF INTERMITTENT NAFAMOSTAT MESYLATE IN DIVIDED DOSES IN PATIENTS WITH DISSEMINATED INTRAVASCULAR COAGULATION OCCURRING WITH HEMATOPOIETIC MALIGNANCIES

In this uncontrolled, unblinded efficacy study, 33 patients with disse minated intravascular coagulation (DIG) or the prodromal stage (preDIC ) of the condition were treated with nafamostat mesylate (NM) administ ered intermittently to examine whether this regimen would be as effica cious as the standard regimen without causing an increase in drug toxi city. Efficacy was evaluated on the basis of the results of coagulatio n studies and on improvement in the DIC score, which was calculated by adding the points of the underlying diseases, clinical symptoms, prot hrombin ratio, fibrinogen, and fibrin degradation product (FDP)-E frac tion, A score of 3 points was categorized as preDIC, and 4 or more as DIG. In Japan, the FDP-E fraction is often measured as a substitute fo r FDP because the value of the FDP-E fraction changes in a wider range and shows more sensitive responses than FDP, NM is usually given by 2 4-hour continuous administration; in this study, NM was infused interm ittently at a daily dose of 90 to 150 mg intravenously to avoid hyperk alemia, Each infusion lasted 4 hours, and the interval between adminis trations was 2.95 +/- 0.19 hours, After 7 days of treatment, the mean DIC score decreased significantly from 3.9 +/- 0.1 to 2.0 +/- 0.2 (P < 0.001); after 14 days of treatment, the score was 2.0 +/- 0.2 (P < 0. 001); at the end of treatment, the score was 1.3 +/- 0.2 (P < 0.001), The improvement in clinical symptoms was considered to be excellent in 8 of 33 patients and good in 16, for an efficacy rate of 72.7% (24 of 33), Although the mean serum potassium level increased significantly, no patient developed hyperkalemia. The administration of NM in interm ittent divided doses was found to be highly effective in the treatment of DIC in patients with the hemopoietic malignancies.