TISSUE FACTOR (TF) AND UROKINASE PLASMINOGEN-ACTIVATOR RECEPTOR (UPAR) AND BLEEDING COMPLICATIONS IN LEUKEMIC PATIENTS

Tissue factor (TF) and urokinase receptor (uPAR) are key cellular rece ptors triggering, respectively, coagulation and fibrinolysis. Bleed in g complications among leukemic patients have been related to an abnorm al expression of TF by blast cells and/or to an abnormal fibrinolytic response. In this study the expression of TF and uPAR has been assesse d in 18 acute non-lymphoblastic and 8 lymphoblastic leukemic blast cel ls using several methodological approaches. TF mRNA was evaluated by i n situ hybridization and TF and uPAR antigen were evaluated immunologi cally in cell lysates and on the cell surface by flow cytometry. In ad dition, TF-procoagulant activity was measured in coagulation-based ass ays. The reliability of these methods was corroborated in six leukemic cell lines of different lineages and states of maturation. Disseminat ed intravascular coagulation was detected in two M(3) leukemia patient s whose blast cells expressed high amounts of TF. Hyperfibrinolysis wa s detected in one M(1) and two M(2) patients, whose blast cells displa yed a high content of uPAR antigen, but no TF. Furthermore, M(5) leuke mia blast cells expressed both TF and uPAR, although no hemostatic def ects or bleeding complications were detected in these patients. Taken together, although a limited number of patients was included in this s tudy, these data suggest that in leukemia patients exhibiting bleeding , either TF or uPAR are expressed by their blast cells. However, the p resence of these receptors does not necessarily imply the existence of a hemostatic disorder.