Thrombo-occlusive Events Research Articles

Reduction in thrombus formation by placement of endovascular stents at endarterectomy sites in baboon carotid arteries.

Although antithrombotic therapies with aspirin, dipyridamole, and heparin have decreased thrombo-occlusive events, they have not abolished these complications. Endovascular mechanical support, first reported by Dotter in 1969, has been proposed as a means to reduce both acute and chronic vessel closure by providing a supporting framework for the disrupted and sometimes dissected arterial wall. To determine the effects of placing self-expanding stainless steel wire endoprostheses on the accumulation of thrombus at sites of carotid artery endarterectomy we measured platelet deposition continuously for 90 minutes and at 24 and 48 hours by gamma camera imaging of autologous 111In-labeled platelets in six stented and nonstented endarterectomized baboons that received heparin but no antiplatelet agents. At nonstented endarterectomy sites 5.36 +/- 1.25 x 10(8), 4.78 +/- 0.98 x 10(8), and 4.55 +/- 0.81 x 10(8) platelets per cm were deposited at 30, 60, and 90 minutes, respectively. In contrast, stented endarterectomy sites accumulated 0.99 +/- 0.31 x 10(8), 0.66 +/- 0.33 x 10(8), and 0.80 +/- 0.36 x 10(8) platelets per cm at 30 minutes (p = 0.02), 60 minutes (p = 0.004), and 90 minutes (p = 0.002), respectively. Platelet deposition remained reduced at 24 and 48 hours in stented endarterectomized carotid arteries (ECAs) when assessed as a ratio between net radioactivity in the endarterectomized region versus whole blood radioactivity (p = 0.006 and p = 0.009, respectively). Both stented and nonstented ECAs remained patent acutely, although two of six nonstented ECAs occluded by 30 days. By comparison 11 of 14 nonstented ECAs remained patent in another group of control animals. Scanning electron microscopy of control and stented arteries at 30 days demonstrated equivalently confluent endothelium. We postulate that endovascular stents reduce the thrombogenic effects of flap formation, tearing, dissection, and vasospasm in ECAs.

Thrombolytic therapy for noncoronary diseases

Thrombolytic therapy has been used fairly extensively in the management of acute proximal deep-vein thrombophlebitis of the extremities, acute pulmonary embolism, and acute peripheral arterial thrombosis and embolism in addition to acute thrombotic coronary events. In the presence of acceptable indications and a favorable benefit to risk ratio, this form of therapy, when successful, has served as a useful adjunct in the management of these disorders. In deep-vein thrombophlebitis, lysis of the thrombus before permanent pathological changes (eg, organization, scarring) have occurred can prevent venous valvular dysfunction and postural venous hypertension and its complications, especially the postphlebitic syndrome. In the more severe forms of acute pulmonary embolism, thrombolytic therapy, when applied early after symptom onset, decreases morbidity and is likely to prevent a chronic increase in pulmonary vascular resistance and persistent pulmonary hypertension. In peripheral arterial thrombo-occlusive events, early restoration of flow through thrombolysis has been shown to limit ischemic damage and serve as a useful supplement to angioplasty or surgery. Thrombolytic therapy has been used less extensively in acute strokes. Here the danger of reperfusion causing bleeding into a softened area of brain undergoing infarction has slowed its evaluation for this disorder; its application to stroke remains experimental.

Non-enzymatic glycation of antithrombin III in vitro

Non-enzymatic glycation of antithrombin III (AT-III) has been proposed as a significant contributor to the increased incidence of thrombo-occlusive events in diabetics. AT-III, isolated from normal human plasma by means of heparin affinity and ion-exchange chromatography, was incubated with 0–0.5 M glucose in neutral phosphate buffer at 37°C. The extent of non-enzymatic glycation could be monitored by uptake of radioactivity as well as by binding to a phenylboronate affinity resin, which effectively retards AT-III containing ketoamine-linked glucose. Non-enzymatically glycated AT-III (approx. 1 mol glucose/mol protein) bound heparin nearly as efficiently as non-glycated AT-III. The two AT-III preparations were equally active in inhibiting thrombin cleavage of chromogenic substrate. Following incubation with [ 14C]glucose, structural analyses of cyanogen-bromide-cleaved peptides of enzymatically glycated AT-III showed that the [ 14C]glucose adducts were distributed over many sites on the molecule. This lack of specificity contrasts with the restrcted sites of modification on hemoglobin, albumin and ribonuclease A, and explains why non-enzymatic glycation of AT-III has little if any effect on its function.