Coagulation endothelial cell products

The procoagulant factors produced by endothelial cells are the coagulation factors von Willebrand factor (WF), F-V, F-VIII, tissue factor (TF), and plasminogen activator inhibitor (PAI), which blocks the activators u-PA and t-PA and counteracts fibrinolysis (G21, FI6). It has been shown that under the influence of complement activation (C9), in response to endotoxin in vitro (C24), in experimental E. coli sepsis in baboons (D30), and after stimulation with TNF (Al, N6), endothelial cells up-regulate the expression of TF, down-regulate TM and inhibit the production of t-PA and PAF. Thus, the balance may shift in the procoagulant direction with a large excess of PAI-1. 

Cardiovascular effects of prostaglandins are more complex. The coagulation system is clearly modulated by platelet-derived thromboxanes, which have procoagulation effects and the anticoagulative effects of endothelial cell-derived prostacyclin. Thromboxanes are clearly COX-1 derived because platelets do not express COX-2. The source of endothelial cell prostacyclin production is less clear with both enzymes expressed and mixed opinions on the relative contribution of the two enzymes. Recent results with Vioxx, a selective COX-2 inhibitor, imply a modest effect on myocardial infarction rate in patients taking the compound but do not define whether this is caused by a change in ratio simply by a lack of platelet effect or that inhibition of endothelial cell prostacyclin also skews the pro- and anticoagulant ratio. 

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