Schematics of the principal pathways of APL cell interactions with the hemostatic system, which can be affected by ATRA. APL cell expresses: (a) cellular procoagulants (TF and CP) that activate the clotting cascade; ATRA decreases the expression of both TF and CP, thus reducing the procoagulant activity; (b) fibrinolysis proteins (u-PA, t-PA, PAI) and receptor (u-PAR); ATRA increases both plasminogen activators and inhibitors, resulting in unchanged or reduced fibrinolytic activity; (c) nonspecific proteases, including granule elastase, that proteolyze fibrinogen/fibrin and other coagulation factors; ATRA does not affect this cellular mechanism; and (d) cytokines, including IL-1β and TNF-α, that induce the endothelium thrombogenicity; ATRA increases the production of cytokines.