Peripheral arterial occlusive disease: conservative treatment of intermittent claudication.

Intermittent claudication is the principal symptom in stage II of peripheral arterial occlusive disease. As this is a multilocular manifestation of atherosclerosis, a distinction must be drawn between treatment of the underlying disease with consideration of the individual risk factors and improvement and abolition of the intermittent claudication. Various therapeutic principles exist, and drug therapy is the subject of controversial discussion. On the basis of eight controlled, randomized studies, it was demonstrated that in comparison with placebo a statistically significant increase in the pain-free walking distance can be achieved by oral drug administration within 3-6 months. This drug therapy should be considered for those patients with intermittent claudication who cannot undergo revascularization, angioplasty, or walking training.

Intravenous prostaglandin E1 versus pentoxifylline therapy in chronic arterial occlusive disease--a controlled randomised multicenter study.

In a controlled multicenter study 70 patients with chronic arterial occlusive disease stage IV according to Fontaine's classification were randomised to treatment with prostaglandin E1 (PGE1) or pentoxifylline (PX), administered over 4 weeks. Parameters of effectiveness were the reduction of analgesics, the relief of rest pain according to an analogue scale, the improvement of the ulceration according to an ulcer score and the healing of necrotic area. The results show that both forms of treatment produced a significant reduction in analgesic consumption and rest pain. Moreover in both groups a significant reduction of the ulcer score and healing of the necrotic area were observed. Side effects occurred in six patients of the PGE1-group and in ten patients of the PX-group, which required premature discontinuation of treatment in four patients of the PX-group. The study also demonstrated that PGE1 is more effective in the treatment of severe arterial occlusive disease than PX. With respect to the analgesic consumption, the reduction of ulcer score and the healing of necrotic area a significant difference was found in favour of PGE1. In accordance the six months follow-up examinations showed a marked deterioration in the PX-group opposed to the PGE1-group. The intravenous application of PGE1 over a period of 4 weeks in patients with severe arterial occlusive disease seems to be an effective therapeutical principle.

Systemic fibrinolytic activity and inhibitor levels during treatment of deep vein thrombosis with urokinase and streptokinase.

In a prospective, randomized trial 33 patients with deep vein thrombosis were treated either with 2,200 or 1,100 IU/kg/h urokinase or with 100,000 IU/h streptokinase for at least 6 days. While streptokinase was given continuously, urokinase was administered intermittently (12 hr urokinase alternating with 12 hr heparin). Urokinase treatment resulted in a dose-dependent fibrinolytic state with shortening of the euglobulin clot lysis time, easily demonstrable amidolytic activity and moderate decrease of plasminogen. At the end of each urokinase-free interval the fibrinolytic activity had mostly faded, but was reproducibly elicited again by each new urokinase administration. Streptokinase immediately evoked the customary, intense fibrinolytic state, which progressively tapered off as plasminogen fell to 1% of its pretreatment concentration. In all treatment groups alpha-2-antiplasmin dropped to approximately 40% of its initial value during the first 12 hr with a further decrease to about 20% after 6 days. alpha-2-macroglobulin fell only moderately with either urokinase regimen, whereas it decreased progressively to 45% under streptokinase. While the fibrinolytic activity decreased under streptokinase over the 6-day infusion period, it appeared to increase with each successive urokinase infusion particularly with 1100 IU/kg/h. Thus the final euglobulin clot lysis times and the final fibrinogen concentrations were similar in all three treatment groups on the sixth day.

Controlled multicenter pilot study of urokinase- heparin and streptokinase in deep vein thrombosis.

Thirty-three patients with acute iliofemoral thrombosis were randomly assigned to three treatment groups in a pilot dose-ranging study of thrombolytic therapy in deep vein thrombosis. One group received tissue culture urokinase in a dose of 2,200 I.U./kg/hr, and a second group in a dose of 1,100 I.U./kg/hr following a loading dose of 4,400 I.U./kg given in ten min. Urokinase was administered for 12 hr periods, alternating with 12 hr periods of heparin. A third group received an initial dose of 250,000 I.U. of streptokinase in 20 min, followed by 100,000 I.U./hr. Treatment of all patients continued for three days. At the end of this period little improvement, evaluated by "blinded" interpretation of pre- and post-treatment phlebograms, was found in five out of ten of the higher-dose urokinase patients, seven out of eleven of lower-dosage urokinase patients, and six out of ten of streptokinase patients. Optional treatment for another three days showed little further improvement of urokinase-patients and moderate further improvement in the streptokinase-patients. Neither of the 2 dosage schemes at intermittent application of urokinase appeared to be advantageous. Urokinase treated patients experienced fewer adverse reactions.

[Deep venous thrombosis: streptokinase treatment with adaptation of the maintenance dosage]. / Tiefe Venenthrombosen: Streptokinase-Behandlung mit anagepasster Erhaltungsdosis.

Prolonged infusion of streptokinase at the customary dose of 100 000 u/h results in undesired plasminogen depletion in many patients. This can be avoided by adaptation of the streptokinase maintenance dose to the presumed rate of plasminogen synthesis of each individual patient. The practicability of this approach was tested in 52 patients who had streptokinase therapy of 3 to 9 days duration for deep vein thrombosis. Twice daily measurements of thrombin time and fibrinogen concentration were performed for immediate clinical surveyance and dosage adjustments. These led to a change from the original 100 000 u/h in most patients: in 65% the dose was reduced and in 10% it was increased. By this measure excessive plasminogen depletion was avoided in 88% of the patients. In them the final maintenance dose ranged from 40 000 to 150 000 u/h. Side effects were similar to those reported for the standard dosage scheme, and clinical results were good with a phlebographic success rate of 91% in recent and 65% in subacute or chronic deep vein thrombosis.

[Urokinase therapy of deep vein thrombosis (author's transl)]. / Die Behandlung tiefer Venenthrombosen mit Urokinase.

30 patients with deep vein thrombosis were treated with a combination of urokinase and heparin. Clinically relevant improvement was achieved in 2/3 of them with appr. 40,000 IU/h (1,000,000 IU/d) urokinase administered over a period of several days. This indicates that urokinase at this dosage offers a valuable alternative or supplementation to fibrinolytic therapy with streptokinase. With the dosage employed, routine blood coagulation tests are only minimally affected, although a strong enhancement of fibrinolytic activity can be demonstrated by the euglobulin clot lysis time. Plasminogen depletion - as is usually observed with streptokinase therapy - does not occur. Urokinase is well tolerated and there is only a very moderate bleeding tendency. The cost per day of urokinase therapy at the dosage employed is approximately twice that of customary streptokinase therapy.