Tissue factor activity (TFA) of 10(8) leukemia cells was measured in 82 patients with acute nonlymphoid leukemia by the clotting method. The TFA bore a significant correlation to the development of disseminated intravascular coagulation (DIC) in these cases. Mean TFA value with standard deviation (SD) was 8.3 +/- 6.3 U in 48 cases with DIC, which was significantly higher than 0.3 +/- 4.2 U in 34 cases without DIC. Whereas Mean TFA in non-M3 was 0.9 +/- 6.3 U which was significantly lower than 37.2 +/- 2.3 U in M3, some non-M3 showed TFA as high as M3 and were complicated by DIC. In heparin treatment, dosage of heparin could not be controlled by either APTT or AcCT but was controlled by the extent of TFA of leukemia cells. Retrospective analysis of clinical features revealed that 97000X + 9000 units/day (X = logarithm value of TFA) of heparin is an adequate dosage for the successful treatment of DIC when TFA of leukemia cells is 0.8 U or more.

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.

SummaryIncubation of human umbilical vein endothelial cells with one of the following compounds: endotoxin, recombinant interleukin-1β, recombinant tumor necrosis factor α, allogenic lymphocyte subpopulations or phorbol ester resulted in significant induction of tissue factor synthesis. Diacylglycerol had the same effect and also enhanced synergistically the induction caused by endotoxin and interleukin-1β. Two different inhibitors of protein kinase C, H7 and sphingosine, inhibited tissue factor synthesis at concentrations which did not depress protein synthesis in general, suggesting that protein kinase C is involved in the processes leading to tissue factor synthesis. Cells down-regulated for the tissue factor response to TPA responded essentially normally to endotoxin and interleukin-1 with regard to tissue factor synthesis.

SummaryHuman umbilical vein endothelial cells (HUVEC) are inducible for tissue factor (TF) activity in culture. Based on experiments using ECGF (4–20 µg/ml) with heparin (90 µg/ml), we obtained the followingresults: 1) In confluent HUVEC cultures, ECGF had essentially no influence on the levels of inducible TF. 2) In growing HUVEC cultures, ECGF reduced the TF response shortly after seeding but full response was regained when cells were kept confluent for 2–3 days. 3) Although secondary cultures responded best to TF induction in the absence of ECGF, the response was essentially equal over at least 8 passages in the prcgcncc of ECGF 1) Of total cellular TF induced in HUVEC, about 25% was available on the surface, and less than 4% was released with theshed plasma membrane vesicles. The proportion of total TF a>ctivity available on the surface of mtact cells wasnot influenced by the presence of ECGF 5) T½, for the decay of TF activity induced was 8.3—9.5 h, whereas in HUVEC when protein synthesis was blocked afterIF induction a T½ of about 30 h was found.

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