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67 Patienten mit 68 durch Streptokinasebehandlung eroffneten Arterien wurden bis zu sechs Jahren spater nachuntersucht. In zehn der 68 Falle (=15%) war ein Reverschlus noch wahrend des stationaren Aufenthaltes aufgetreten. Das verbleibende Patientenkollektiv mit definitiv eroffneten Gefasen gliederte sich in drei Gruppen: Patienten, bei denen eine Beurteilung der Gefasverhaltnisse moglich war (A), Patienten, die in der Zwischenzeit verstorben waren (B) und Patienten, bei denen aus technischen Grunden eine Ermittlung des Gefasstatus ausgeschlossen war (C). Folgende Ergebnisse wurden in der Gruppe A ermittelt

Ten patients with 13 stenoses in the pelvic area were treated with low doses of streptokinase (30 000 U/h) for 72 hours. A significant improvement in the degree of stenosis was obtained as shown by post-stenotic pressure values. Biochemically there was a marked plasminaemia with moderately low fibrinogen levels. Streptokinase treatment with low doses could form an alternative method of treatment in arterial stenoses.

Two-day treatment with activator (equimolar streptokinase-human plasminogen complex) was given to 26 patients. Indications were chronic arterial occlusion and stenosis of the lower-limb arteries (25 patients), and thrombosis of the subclavian veins. The onset of claudication had on average been 7.5 months previously, average walking distance 288 metres. Five occlusions of iliac arteries and three of femoral arteries were removed. In addition, stenosis of the aorta (one case), the iliac artery (ten cases) and femoral artery (one case) was partly removed. Occlusion of the axillary vein was also removed. Average duration of the successfully treated occlusions was 4.3 months. Those stenoses that responded to activator had the well-known morphological criteria for fibrinolysis. The walking distance of the patients increased from an average of 288 to 401 metres. Activator treatment was well tolerated. No serious, especially cerebral, complications occurred. The most striking laboratory finding was of circulating plasmin during the entire duration of the infusion.

Mit Hilfe eines Clot-Lysis-Tests war es moglich, Streptokinasekonzentrationen in Humanplasma quantitativ zu erfassen. Das Testsystem bestand aus Rinderfibrinogen, Rinderplasminogen, Human-Euglobulin, EDTA, Humanplasma (mit unbekanntem Streptokinaseanteil) und Thrombin.

Subcutaneous Defibrase R administration permits reliable and safe reduction of fibrinogen values throughout weeks and months, and their maintenance on any desired level. 12 patients suffering from arterial occlusion with rest pain and necrosis were subjected to subcutaneous Defibrase therapy. 4 of them developed resistance to treatment after 1, 3, 4, and 6 weeks, respectively, i.e. fibrinogen levels started to rise again despite Defibrase administration. Arwin R was administered subcutaneously in an attempt to produce another drop in fibrinogen, which was successful in 2, but failed in the other 2 patients.

Twelve patients (age 33-77 years, mean age 68.4 years) with peripheral vascular disease (PVD) stage III-IV received continuous intravenous infusions of 5 ng prostacyclin (PGI2)/kg/min and physiological saline for 7 days. The administration was randomized and double-blind with an interval of 7 days between the infusions. During PGI2 infusion systolic blood pressure fell significantly from 147.8 +/- 4.8 mm Hg to 140.6 +/- 4.0 mm Hg (P less than 0.01) and returned to 144.5 +/- 4.9 mm Hg post infusion. Transcutaneous pO2 (tcpO2) measured on the instep of the affected limb increased significantly by 8.9 +/- 3.8 Torr during PGI2 infusion and remained elevated during the subsequent week. A significant reduction of pain was observed from the 5th day of PGI2 infusion, lasting for at least the following observation period. Platelet cAMP increased from 18.8 +/- 1.5 pmol/10(8) platelets to 24.7 +/- 1.6 pmol/10(8) platelets on the 3rd day of PGI2 infusion (P less than 0.01). Spontaneous platelet aggregation was also significantly reduced during PGI2 infusion. However, 7 days after the infusion thromboxane B2 (TXB2) in plasma and spontaneous platelet aggregation significantly increased in comparison with the preinfusion values, indicating a rebound phenomenon. The clinical outcome was favorable in 9 of 12 patients, was unchanged in two patients, while progressing to limb amputation in one patient.

Observational studies suggest that short term infusion of prostacyclin (PGI 2 ) may be of rapid and prolonged benefit in peripheral arterial disease. 10 patients with peripheral arterial disease received 72 hour intravenous infusions of PGI 2 and saline alone. The administration was randomized and single blind and 7 days separated the infusions. Calf muscle blood flow did not alter during PGI 2 or control infusions. Reactive hyperaemia improved slightly after PGI 2 but not significantly more so than after the control infusion. Leg pain improved during both infusions, but more so during PGI 2 infusion. Systolic pressure in the cubital, posterior tibial and dorsal pedal arteries was unaltered by PGI 2 infusion. Both the inhibition of spontaneous platelet aggregability and the aggregation response to ADP had returned to baseline 72 hours after PGI 2 , although platelet adhesion remained impaired. Coagulation, fibrinolysis and apparent viscosity were unaltered by PGI 2 infusion. Healing of ischaemic ulcers was not observed within 7 days of either infusion. However, within 8 weeks, 6 patients had undergone ulcer healing and 3 had progressed to amputation.

21 patients (aged 28-81 years) with recent subarachnoid hemorrhage (10 saccular aneurysms, 3 arteriovenous angiomas, 8 normal angiograms) were continuously infused with tranexamic acid at a dosage of 5 g daily for up to 14 days. Therapy was surveyed by daily measurement of the available plasminogen activity (aPl) with the chromogenic substrate S-2251 and by a modified bioassay, whereby the concentration of tranexamic acid was determined thrombelastographically and expressed as antifibrinolytic equivalent. In addition, a battery of blood coagulation tests was performed daily. 5 patients died, 1 after postoperative stroke, 3 as a result of general complications during intensive care treatment, but only 1 due to rebleeding. 4 patients were successfully operated during the first week, 1 patient after 2 weeks. aPl fell from 99.2% (SEM 3.0%, n = 21) before treatment to 72.9% (SEM 3.5%, n = 21) after 24 h and to the therapeutic level between 50 and 60% from day 2 on. The mean steady state of the antifibrinolytic equivalent corresponded to about 150 micrograms/ml of tranexamic acid during infusion. Intra- and interindividual changes were relatively small for aPl, when compared with the antifibrinolytic equivalent measured by the bioassay. In 2 elderly patients tranexamic acid infusion had to be terminated because of clinical and laboratory signs of disseminated intravascular coagulation, whereby aPl fell below the therapeutic range, elucidating that this method is a sensitive indicator for a hypercoagulable state and useful for the surveillance of therapy with antifibrinoltic agents.

Twenty patients (67.2 ± 12.3 yrs; aged 39-86 yrs, 10 males, 10 females) with stage IV of peripheral obliterative arterial disease received at random either a) BM 13.177, a thromboxane receptor antagonist, at a dose of 6 g/24 hrs for 7 days i.v., followed by oral treatment of 6.4 g/day in four doses for 2 weeks and a subsequent placebo week, or b) placebo alone with the same protocol. The clinical course was followed by measurement of blood pressure (by Riva-Rocci on the left brachial artery and by Doppler of the ankle artries), blood flow at restand after 3 min of tourniquet ischemia (by venous occlusion plethysmography), TcpCf2 at the wrist of the affected limb, and by subjective estimation of pain with visual analog scale before, at the end of the infusion period, as well as on day 7 and 14 of oral treatment, and 7 days after treatment while patients of both groups were on placebo. In addition spontaneous platelet aggregation by PAT III, induced platelet aggregation in whole blood by collagen and in PRP by ADP at different doses on the same days were measured on the same days as described above.Results: BM 13.177 completely inhibited aggregation in whole blood induced by collagen 0.3 (ig/ml, however one week after treatment a rebound phenomenon was observed with 16.0 ± 3.8 OHM compared to pretreatment value of 11.0 ± 3.8 OHM (p < 0.01). At a higher dose of 1.2 |ig/ml the same inhibiting effect on platelet aggregation was observed. Spontaneous platelet aggregation as measured by PAT III was evident in only 2/10 pat. pre-treatment, was abolished in all patients on i.v. BM 13.177, returned in 1/10 pat. during oral treatment, but in 4/10 pat. on day 7 after treatment, while being on placebo, again indicating a rebound phenomenon (p < 0.03) ADP induced platelet aggregation was not significantly affected by BM 13.177. In the placebo group, too, no significant differences were observable between the different treatment regimens. Clinical data did not show any significant alteration in either verum or placebo group during the six week period, indicating no benificial effect of thromboxane receptor antagonists in advanced stages of peripheral obliterative arterial disease, although platelet inhibiting effects were clearly demonstable.

10 patients with claudication pain, but without rest pain or necrosis, were treated for 3 weeks with Defibrase (R) ∗∗ , a snake-venom enzyme designed for clinical use in defibrinogenation therapy. Treatment was monitored by fibrinogen determination according to CLAUSS. Average fibrinogen values of around 60 mg% were obtained by daily Defibrase administration. Another 10 patients were given placebo treatment. Each patient was allocated at random to the respective group. The results, as assessed by determining the walking distance, the poststenotic systolic pressure, and the pressure gradient along the occlusion, failed to show any significant difference in the two groups treated with either defibrinogenating measures or placebo.

A most common complication of acute ischemic stroke is deep vein thrombosis (DVT), preferentially of the paralytic limb. Without prophylactic therapy an incidence of 33%–70% has been reported, according to the method used for detection, i.e., clinical symptomatology, phlebography, or 125I-fibrinogen scanning, the latter being most sensitive [1–4].

Controlled double-blind studies have shown, that the antifibrinolytic agent tranexamic acid significantly reduces both the mortality and the rate of rebleeding from a fresh ruptured subarachnoid aneurysm (1–3). KASTE and RAMSAY (4) did not observe this favourable result in a Finnish study. Rebleeding of a subarachnoid aneurysm occurs most often during the initial two weeks, i.e. at a time, where mortality is highest. Therefore, antifibrinolytic therapy is often carried out as a pre-operative procedure in order to overcome this critical period. While fibrinolytic activation is rarely observed in the blood after subarachnoid hemorrhage, it is generally seen in the cerebrospinal fluid. Here, raised concentration of fibrin degradation products indicate enhanced fibrinolytic activity, which may be responsible for a dissolution of the peri-aneurysmal fibrin plug and subsequent rebleeding. Tranexamic acid crosses the blood-brain barrier and inhibits the activation of plasminogen to plasmin.

435 arterial occlusions were treated with streptokinase over a period of 3 days. A continuous streptokinase regimen with a maintenance dose of 100 000 u SK/h was administered. The successful removal of femoral obstructions was possible in 8.9%. A complete dissolution of the iliac thrombus masses had been achieved in 19%. 41 aortic occlusions were treated. The treatment was capable of removing the aortic obstructions in 24%. It became evident that there was a close relationship between the average occlusion time and the respective clearance rate. Por example, in patients undergoing lysis treatment during the very first two weeks after femoral occlusion, clearance was established in 75% and best lytic results were achieved if the history of iliac occlusion was well below 3 months duration. The relationship of vessel clearance rate and walking distance showed, that on the average there was no lengthening in walking distance where treatment had failed (no vessel clearance obtained). On the other hand, a significant average rise in walking distance from initially 325 up to 800 meters (p < 0.05) was seen when vessels clearance had been recorded.