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Atherosclerosis complicated by thromboembolism is the main cause of obstructive arterial disease in the legs. Two studies from West Germany suggest that antiplatelet drugs may slow the progress of atherosclerosis in leg arteries and prevent occlusive thrombosis under some circumstances. The same agents may also reduce the risk of rethrombosis after successful vascular repair in the femoropopliteal region; in one trial, aspirin decreased the incidence of reocclusion after thromboendarterectomy and, in another, the combination of aspirin and dipyridamole was effective after bypass with synthetic material. Antithrombotic drugs are used in most centers after percutaneous transluminal angioplasty, but there is no definite evidence for their need. Thus, it appears that in contrast to cardiac and cerebrovascular disease, few efforts have been made to determine the true value of antithrombotic therapy in peripheral arterial disease. The management of acute thromboembolism in the legs requires a multidisciplinary approach. Depending on the type (embolic or thrombotic), length and localization of the arterial occlusion, surgical (embolectomy, thromboendarterectomy, peripheral bypass surgery) or nonsurgical (systemic fibrinolysis or local thrombolytic therapy with or without balloon angioplasty) treatment is preferred. The importance of nonsurgical therapeutic approaches may become even greater in elderly patients with a poor operative risk. This review discusses the available therapeutic modalities in acute and chronic peripheral thromboembolic arterial disease.

Coronary thrombolysis is at present intensively investigated in the treatment of acute myocardial infarction. One line of research focuses on the development of new, fibrin-specific agents which might induce more clot-selective thrombolysis than streptokinase and urokinase. Clot-selective thrombolytic agents preferentially activate fibrin-bound plasminogen and, thereby, minimize the generation of free circulating plasmin which is responsible for the hemostatic breakdown and bleeding risk. Intravenous administration of fibrin-specific thrombolytic agents has two major advantages over intracoronary administration: firstly, infusion is more easily and widely applicable and secondly, therapy may be initiated more rapidly, which is important for the early restoration of nutritional blood flow and salvage of functional myocardial tissue. Three clot-selective thrombolytic agents are presently investigated for coronary thrombolysis. Impressive reopening rates have been reported with acylated streptokinase-plasminogen complex, but unfortunately, its use was associated with extensive systemic fibrinolytic activation and bleeding complications. Pro-urokinase, the single chain precursor of urokinase, exhibited intrinsic, fibrin-specific thrombolytic activity in vitro and in animal models but no human trials have yet been reported. At present, the largest clinical experience has been obtained with tissue-type plasminogen activator (t-PA). After small-scale pilot studies with t-PA obtained from cell culture media, larger clinical trials have now been performed using t-PA obtained by recombinant DNA technology (rt-PA). In the first study, intravenous infusion of rt-PA in patients with acute myocardial infarction yielded a recanalization rate of about 75% without clinically relevant systemic activation of the fibrinolytic system in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Three laboratory methods for monitoring heparin treatment have been compared using 63 plasma samples: the thrombin time, the activated partial thromboplastin time, and the measurement of the heparin concentration using a chromogenic substrate. A good correlation was found between the methods. However, the intensity of anticoagulation was identical in only 27 of the 63 samples (43%) when the thrombin time and the activated partial thromboplastin time were compared. Fully discordant results were recorded for four samples (6%). The thrombin time was found to be more closely related to the plasma heparin concentration than was the activated partial thromboplastin time. Both antithrombin-III activity and immunologic levels were lower in the group with strong heparinization. It is suggested that the thrombin time is a good and safe method for monitoring heparin treatment.

We report a case of acute thrombosis of the common femoral artery which occurred on the tenth day of postoperative prophylactic heparin therapy. Platelet count was 14,000/mm3 at the time of the acute event. Cessation of heparin administration resulted in progressive normalization of the platelet count. Iliofemoral thrombectomy, followed by popliteal thromboembolectomy, allowed successful recanalization of the occluded arteries, after failure of local thrombolysis with low-dose streptokinase. The pathogenesis, diagnosis and treatment of heparin-induced thrombocytopenia associated with thromboembolic complications are discussed.

The various therapeutic modalities in deep venous thrombosis of the lower limbs (surgical thrombectomy, thrombolysis, anticoagulation, bed rest) are discussed with special reference to developments in the last ten years (new generation of thrombolytics, introduction of INR to express prothrombin time). Tentative therapeutic guidelines are proposed.

Human factor VIII has been dissociated into fragment VIII-C and fragment VIII-AG in the presence of calcium chloride (0.25 M). After removing the calcium, recombination of the molecule is obtained. Fragment VIII-C can be activated by thrombin in a similar manner to the coagulant activity of whole factor VIII. This activation is calcium-dependent. In rabbits immunized against purified F VIII, VIII-C and VIII-AG specific antisera against these three entities were obtained.

Treatment of arterial stenoses by the Simpson atherectomy catheter is carried out by resecting the atheroma. A rotating cutter housed in a cylindrical chamber with a lateral opening is applied against the arterial wall by a low-pressure balloon. Several cuts are made until a large enough diameter of arterial lumen is obtained. We report the results in the first 6 patients treated by this technique using 7F and 9F catheters. All had short (less than 2 cm) and narrow (greater than or equal to 70%) stenoses of iliac, superficial femoral or popliteal arteries. To reduce the stenoses to 30% or less, 4 to 11 cuts were necessary. Histological study of the fragments was performed. The result was inadequate in the only case of stenotic iliac artery and we proceeded with balloon dilatation. The small fragments obtained in this particular case were very hard and calcified. 4 patients with claudication (superficial femoral or popliteal stenosis) were asymptomatic after treatment, whereas one patient suffering from Burger's disease with acral necrotic lesions did not benefit from the procedure in spite of a good morphological result. No complication was encountered. This efficient technique is especially indicated in short segmental stenoses of femoro-popliteal or possibly iliac arteries. It avoids the usual intimal cracks associated with balloon angioplasty and produces a smooth surface whose long term benefit has still to be demonstrated.

Since monitoring of oral anticoagulation (OA) by prothrombin time (PT) is a source of standardization difficulties, the authors have tested another approach. 107 patients under long term OA were monitored by both PT and a colorimetric factor X assay (in vitro activation of factor X with RVV and assessment of amidolytic activity towards S-2222). The PT values were between 10 and 34% (therapeutic range 15--25%), and factor X levels were between 10 and 44% (therapeutic range 16--24%). The correlation between the two methods was highly significant (r = 0.65, p less than 0.001). In 68% of the patients the two tests gave the same information (55 subjects were adequately, 16 insufficiently and 2 over-anticoagulated). For a slightly broader therapeutic range (PT 15--30%, corresponding to 16--28% factor X) concordant information was obtained in 82% of the patients. During stable OA, PT and factor X assay gave very similar information. An advantage of the latter method is the possibility of automation, while a disadvantage is its insensitivity to factor VII.

Two local cold provocation tests were carried out in 25 healthy volunteers and in 14 patients with Raynaud's disease, using finger systolic pressure (FSP) and digital blood flow measurements. Mean FSP was significantly lower in Raynaud's patients compared to healthy volunteers at 15 degrees C and 10 degrees C (cuff temperature). Maximal digital flow (at skin temperature of 38 degrees C) was slightly though not significantly lower in Raynaud's patients as compared to normals (27 +/- 3 versus 36 +/- 4 ml/100 ml/min). Upon cooling, statistical significance was reached starting from finger skin temperature of 24 degrees C. Overlap between the two groups was considerable but only 1 out of 13 patients with Raynaud's disease had both tests normal. Ten of the patients participated in a double-blind cross-over trial with naftidrofuryl (200 mg t.i.d.) versus placebo. Significant (p less than 0.05) subjective improvement was noted after 6 weeks with naftidrofuryl but this was not necessarily substantiated by an increased digital flow or pressure in the test situation.