Defective Fibrinolytic Response in Atherosclerotic Patients – Effect of lloprost and Its Possible Mechanism of Action

Abstract

SummaryPlasma fibrinolytic activity and tissue-type plasminogen activator (t-PA) were defective in response to venous stasis in five out of ten patients with peripheral occlusive artery disease. Discontinuous infusions of iloprost, a stable synthetic analogue of prostacyclin, restored a normal fibrinolytic response in all five patients but did not induce a parallel increase of plasma t-PA. These findings suggest that in addition to the possible benefits due to its vasodilatory and antiplatelet activity, iloprost may improve the fibrinolytic activity in patients with atherosclerotic disease, providing them with further antithrombotic protection. The profibrinolytic effect of iloprost seems not to depend on its ability to induce vascular t-PA release. Rather, it might be related to its inhibitory effect on PAI release from platelets, endothelial cells and/or hepatocytes. Venous occlusion test represents an easy diagnostic approach to fibrinolytic defects, even if related to arterial disease, and may help select patients who need therapeutic intervention.

Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

“…These results could not be explained only by the immediate short-lived vasodilatory action of iloprost. It is therefore generally thought that the additional positive effects of iloprost on platelets, endothelial cells and phagocytes [6][7][8][9][10][11][12], as well as on the cytokine production [14], may induce a sort of healing of the microvascular lesion responsible for Raynaud's phenomenon, and of its consequences in SSc.…”

“…The drug is a chemically stable derivative of prostacyclin, with a longer half-life and similar biological properties [5], including vasodilatation, inhibition of platelet aggregation [6], inhibition of leukocyte chemotaxis and adhesion to the endothelium [7,8], downregulation of adhesion molecules on phagocytes and endothelial cells [9,10], and enhanced fibrinolytic activity [11]. These actions can influence the pathophysiological mechanisms responsible for Raynaud's phenomenon in SSc, which include vasospasm, increased platelet activation, vascular endothelial damage, fibrotic intimal hyperplasia and luminal narrowing in the digital arteries [12].…”

Iloprost infusion decreases skeletal muscle ischemia-reperfusion injury

“…Prostacyclin and iloprost have also been shown to stimulate fibrinolysis, which may be a beneficial property in the setting of acute skeletal muscle ischemia. 17,18 Another potentially beneficial property of iloprost, which has been demonstrated in myocardial ischemia-reperfusion models and may potentially apply to skeletal muscle, involves membrane stabilization. Iloprost infusion in these models has 'led to decreased myocardial enzyme release and decreased relcase of membrane phospholipids after ischemia-reperfusion injury.m9…”

Decreased fibrinolytic activity in juvenile chronic arthritis.

“…The effect of high dose aspirin on the fibrinolytic system is controversial and depends on the experimental procedure and the assay used.12 13 In our patients it seems unlikely that fibrinolytic activity was reduced by non-steroidal antiinflammatory drug treatment because (a) the plasma fibrinolytic activity was measured in basal conditions-that is, not after venous occlusion, and such an assay is not affected by aspirin treatment'2; (b) the group of patients with systemic JCA had a much greater decrease in fibrinolytic activity than the poly-pauciarticular group, though all patients were treated with equivalent doses of these drugs.…”