Proposed pharmacologic actions of defibrotide. Factors involved in coagulation are depicted in yellow, factors released from endothelial cells are in the green area, factors involved in endothelial cell activation are in the orange area, and factors involved in platelet activation are in the purple area. Yellow circle with red center, inhibition, increase (+) or decrease (–); green arrow, activation; red arrow, production. cAMP, cyclic adenosine monophosphate; CysLT, cysteinyl leukotriene; FPA, fibrinogen peptide A; ICAM, intracellular adhesion molecule; IL-6, interleukin 6; LFA1, leukocyte function-associated antigen 1; LTB4, antileukotriene B4; MHC, major histocompatibility complex; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; NO, nitric oxide; NOS, nitric oxide synthase; PAI-1, plasminogen activator inhibitor-1; PAF, platelet-activating factor; PGE₂, prostaglandin E2; PGI₂, prostaglandin I2; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin; TNFα, tumor necrosis factor-α; TXA₂, thromboxane A2; VEGF, vascular endothelial growth factor. Reprinted from Pescador et al²  with permission.