SummaryUsing clotting assay and radioimmunoassay (RIA), tissue factor activity (TFA) and TF related antigen (TFR:AG) were determined in an extracellular culture medium of HL-60 cells. After 12 h incubation, TFA and TFR:AG in the medium with endotoxin (EDX: 1 μg/ml) reached maximums which were 1.8 and 2.1 times greater than those in the medium without EDX, respectively. In the leukemic cells of 10 patients with acute nonlymphoid leukemia (ANLL), TFR:AG showed a significant correlation with TFA (p <0.01). On day 1 of the induction chemotherapy, TFR:AG in the 7 patients with DIC significantly increased to 288.9 ± 153.1 ng/ml (p <0.01), whereas no increase in TFR: AG was recognized in the 3 patients without DIC. These results suggest that TF may be released from leukemic cells into the culture medium or blood stream, and that this may correlate with the development of DIC.

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Tissue factor activity (TFA) of leukemic cells (1 x 10(8) cells/mL) was measured in 44 patients with acute nonlymphoid leukemia (ANLL) by the one-stage assay using factor-IX deficient plasma (OSA-dIX) and two-stage assay (TSA). According to the preventative heparin dose schedule based on the TFA measured by the TSA, all disseminated intravascular coagulation (DIC) was controlled successfully. The procedure of the TSA was too complicated for clinical use, and its minimal measurable value was 125 units (U)/L of TFA. The OSA-dIX was simpler in its procedure and sensitive enough to measure accurately a TFA quantity as small as 30 U/L with high reproducibility. In 20 ANLL patients with 125 U/L or more of TFA measured by both assays, there was a significant relationship between their logarithms of TFA (r = 0.93, P less than 0.01). These results suggested that DIC complication in ANLL patients would be controlled successfully by the administration of heparin dosage based on the TFA measured by the OSA-dIX.

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From the retrospective analysis of correlation between the activity of tissue factor (TFA) of leukemia cells (LC) and DIC complication in patients with acute leukemia, we have already reported an adequate dose schedule of heparin treatment for DIC can be calculated in accordance with the TFA of LC To evaluate this dose schedule, the prospective analysis was designed. Prior to the remission induction chemotherapy, TFA of LC obtained from 67 patients with leukemia (ANLL: M1;5, M2;22, M;34, M4;8, M5;4, M6;3, CML-BC: 11) was measured by Nemerson's two-stage method reported previously. Regardless of DIC complication, continuous heaprin therapy with 0, 15,000 or 9,700X + 9,000 units/day (X: logarithm value of TFA) was started with chemotherapy in patinet with 0, 0.8−4.1 U or >4.1 U of TFA, respectively. The complete remission and significant decrease of LC were achieved in 16 patients with ANLL and 5 patients with CML-BC, respectively. In 20 patients whose LC had 0.8 U of TFA or more (group A), 15 and 1 patients were complicated by DIC before and after start of the chmotherapy, respectively. DIC was improved in all of these patients. Other 4 patients were not complicated by DIC. There was no major bleeding due to heparin administration. In 47 patients whose LC had less than 0.8 U of TFA (group B), 40 patients were not complicated by DIC throughout the observation period. Remaining 4 and 3 patients were complicated by DIC before and after start of the chemotherapy, respectively. Among these patients, only one, whose DIC was due primarily to endotoxinemia, failed in control of the DIC. Consequently, in 67 patients subjected to this study, only one patient died of complicated DIC, although 17 patients (group A:4, group B:13) died of various causes other than DIC during the observation periods. These results suggest that our dose schedule of heparin is appropriate for both prevention and treatment of DIC complication in leukemia patients.