Combined dihydroergotamine and heparin prophylaxis of postoperative deep vein thrombosis: proposed mechanism of action.
The cause of postoperative DVT is considered to be changes in blood coagulation, stasis of blood within the veins, and injury to the vein wall. The coagulation changes have been investigated and documented and involve platelet activation, stimulation of the coagulation cascade, and blunting of endogenous fibrinolytic activity. Stasis has been objectively identified by retention of contrast material in soleal sinuses and marked changes in venous flow velocity in patients in the supine position and in those under general anesthesia. Vein wall injury is more controversial, but has been shown to be directly related to venodilation. Such dilation of veins occurs in response to operative trauma, hence venous endothelial damage most likely plays a part in the milieu responsible for postoperative DVT. The prophylaxis provided by the combination of dihydroergotamine and heparin appears to affect each of the three limbs of Virchow's triad. Heparin achieves its prophylactic benefit by activating antithrombin III. Activated antithrombin III affects numerous sites in the coagulation cascade. It has been shown that 1 micrograms of antithrombin III inhibits the formation of 1 unit of thrombin; however, in the presence of heparin, 1 micrograms of activated antithrombin III inhibits 750 units of thrombin. Dihydroergotamine increases venous smooth muscle tone without affecting arteriolar smooth muscle. Hence, it has the effect of preventing stasis without increasing blood pressure. It also affects the platelet membrane, prostaglandin synthesis, and blood distribution, although these findings need to be elucidated. The combination of dihydroergotamine and heparin seems to have a synergistic prophylactic effect in preventing postoperative DVT. Heparin modifies the coagulation changes, whereas dihydroergotamine minimizes stasis and potentially prevents the endothelial damage caused by excessive operative venodilation. Such a combination of effects can explain the synergistic prophylactic efficacy found when dihydroergotamine and heparin were employed in combination in the multicenter trial [42].
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D004087:Dihydroergotamine / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations / Q000627:therapeutic use; D004357:Drug Synergism; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight; D006801:Humans; D007601:Jugular Veins / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control; D013924:Thrombophlebitis / Q000209:etiology / Q000517:prevention & control*
D004338:Drug Combinations; D006495:Heparin, Low-Molecular-Weight; C031388:heparin-dihydergot; D004087:Dihydroergotamine; D000990:Antithrombin III; D006493:Heparin