Low-dose Intra-arterial Streptokinase Research Articles

A protocol for the safe treatment of acute lower limb ischaemia with intra-arterial streptokinase and surgery.

Over a 5-year period 70 patients, presenting with subacute ischaemia of the lower limb (more than 12 h), were treated with low-dose intra-arterial streptokinase. There were 72 infusions and effective lysis was achieved in 52 (72 per cent), with an average infusion time of 25 h. A total of 23 (32 per cent) also underwent percutaneous transluminal angioplasty when lysis showed an underlying stenosis, and a further 19 (26 per cent) required surgery to remove persistent stenosis, organized thrombus or atheromatous debris. Significant bleeding occurred in 4 patients (6 per cent) and 13 (18 per cent) underwent amputation. There were five deaths (7 per cent), one of which was directly related to the infusion, while three were due to myocardial infarction. All of the major complications occurred in the early part of the study and both the selection of patients and the technique of infusion were modified to improve safety. Complementary treatment by percutaneous transluminal angioplasty and surgery was used more frequently in the later part of the study. The technique is not recommended for the white leg of acute ischaemia (less than 12 h), or for lysis of clot in a retroperitoneal Dacron graft, but may be uniquely valuable to demonstrate the cause of subacute ischaemia.

Conservative management of asymptomatic popliteal aneurysm

Historical review shows that the treatment of popliteal aneurysm has developed by trial and error and there is disagreement about the proper management of the symptomless patient. In 1981 a policy of conservative management for asymptomatic popliteal aneurysm was adopted in this unit. Since that time we have also managed nine patients with thrombosed popliteal aneurysms by arteriography and low-dose intra-arterial streptokinase. Six patients treated within 72 h of occlusion achieved significant (70-100 per cent) lysis, but streptokinase was ineffective in those treated 10 or more days after the thrombosis. Of the six patients with significant lysis, three were treated by elective reconstruction and two by anticoagulation. One patient who had significant lysis died. Vascular patency of all five successfully treated limbs was maintained and no limb loss occurred in those who presented late and failed to achieve significant lysis. These results reinforce the view that thrombolysis is the treatment of choice for thrombosed popliteal aneurysms. The low complication rate for asymptomatic popliteal aneurysms and the advent of safe, effective thrombolysis indicate that operation for symptomless popliteal aneurysm is no longer required.

Thrombolytic therapy in the management of acute limb ischaemia

Acute limb ischaemia poses a threat to both the limb and life of a patient. Until recently, attempted revascularization by thromboembolectomy or vascular reconstruction held the best chance of limb salvage. Thrombolytic techniques afford an alternative method of management for this condition and are effective in selected patients. Low-dose intra-arterial streptokinase is the most established method of thrombolysis, although the recently developed tissue plasminogen activator offers a promising alternative. Intra-arterial thrombolysis is not an easy option, being labour intensive and requiring close co-operation between surgeon and radiologist. Thrombolytic and surgical techniques are not mutually exclusive but are best used to complement each other. Ideally patients with acute limb ischaemia should be managed by surgeons with knowledge of, and access to, optimal current surgical and non-surgical techniques.

Survey of the use of thrombolysis for acute limb ischaemia in the UK and Ireland

A total of 156 vascular surgeons from the UK and Ireland responded to a postal questionnaire on the use of thrombolysis in acute limb ischaemia. Almost half had used thrombolysis in the previous 12 months. Low dose intra-arterial streptokinase (89 per cent) was the regimen most frequently used, but 33 per cent had used intravenous streptokinase. Detailed results for 103 patients (limb salvage rate 60 per cent, amputation rate 35 per cent, mortality rate 5 per cent) were similar to those of previously published reports. Complications in most series were infrequent, but in the entire survey there were six bleeding-related deaths and one death from anaphylaxis. A total of 67 per cent of surgeons with working experience indicated that selected patients with acute arterial thromboses were most suitable for thrombolysis, particularly if there was no neurological deficit and no run-off for surgical bypass. Distal or late emboli and graft occlusions were regarded as appropriate by some surgeons. This study demonstrated that many vascular surgeons currently use thrombolysis, although sparingly and in selected cases. Patients with acute limb ischaemia should be managed by experienced vascular surgeons who are aware of the new therapeutic alternatives, an ideal supported by almost three-quarters of respondents to this survey.

Early results of low dose intra-arterial streptokinase therapy in acute and subacute lower limb arterial ischaemia.

Thirty-two patients with acute and subacute limb-threatening peripheral arterial ischaemia were treated with low dose intra-arterial streptokinase infusions. The mean duration of infusion was 38 h. Six patients developed pericatheter thrombosis and two had distal embolization of fragments of thrombus but in all cases these responded to repositioning the catheter and continuing the infusion. Five patients developed groin haematomata and in three of these there was evidence of a systemic fibrinolytic effect from the streptokinase with plasma fibrinogen reduced below 1 g/l. The most serious complication was perforation of the popliteal and tibial arteries which occurred on two occasions and required cessation of the infusion. Twenty-two patients (69 per cent) achieved limb salvage, eight (25 per cent) suffered a major amputation and two (6 per cent) died. The outcome was not related to the site, nature or duration of the arterial occlusion but patients with loss of sensation or paralysis of the affected limb were significantly less likely to obtain limb salvage (P = 0.001). For occlusions greater than 30 cm in length a new technique was used where the thrombus was lysed from distal to proximal in short lengths by gradual catheter withdrawal. This was successful in five out of six cases. Low dose intra-arterial streptokinase has been confirmed as an effective, relatively safe method of treatment in recent arterial ischaemia and can be recommended in situations where the results of surgery may not be favourable. In particular, patients with arterial thromboses and no distal run-off, distal and late arterial emboli, thrombosed popliteal aneurysms and patients after a failed embolectomy, have all been shown to respond to thrombolytic therapy with intra-arterial streptokinase.

Post-traumatic axillary artery thrombosis dissolution with low-dose intra-arterial streptokinase

This case demonstrates an unusual complication of clavicular fracture. We feel that at the time of injury a large force depressed the distal clavicle causing momentary compression to the axillary artery resulting in injury to, or around the wall of the artery. This led to secondary thrombosis within the lumen. Intra-arterial thrombolytic therapy was used to avoid arterial surgery in this difficult situation. Case report A healthy 35-year-old man sustained a distally displaced fracture of the right clavicle when struck by a swinging crane on a North Sea oil platform. This was treated by standard non-operative management. Two weeks later he became aware of cold Angers, numbness, pain and weakness in his right forearm and hand and presented to a trauma clinic, where symptoms were attributed to a brachial plexus neurapraxia and treated expectantly. Increased weakness was noted (Grade 415 MRC grading in each muscle group) z weeks later and the right bra&al, radial and ulnar pulses were absent. In addition, he had impaired sensation on the lateral aspect of his arm. After admission to a medical ward, arteriography revealed a 5-cm occlusion of the axillary artery with poor collateral circulation. A 5G arterial catheter was advanced into the thrombus via the right femoral approach under fluoroscopic control (Figure ~a). Streptokinase was infused via the catheter at 5000units/h, but concomitant herapin was not used. The prothrombin time (PT), kaolin-cephalin clotting time (KCCT) and platelets all remained normal. The fibrin degradation products (FDPs) and fibrinogen titres were monitored 4 hourly. The patient was checked regularly for clinical evidence of bleeding and arteriography was used to assess clot lysis. Observed changes in fibrinogen titres and FDPs did not necessitate an alteration in infusion rate. At 36 h after starting the infusion there was increasing pain in the arm secondary to reperfusion. At 48 h arteriography demonstrated some clot lysis. The catheter was advanced further into the clot. At 98 h the pain had resolved and the artery had become patent, but with some residual thrombus. The infusion was maintained until 108 h when the fibrinogen titres and FDP levels were no longer acceptable. Arteriography at this time revealed no thrombus, but showed a residual stenosis which was subsequently treated by translurninal angioplasty (Figure lb). Full power and sensation returned to the arm, with easily palpable radial and ulnar pulses.

Fibrinolytic therapy for infra-inguinal synthetic graft occlusions

The results of infra-inguinal graft fibrinolysis are variable, and the true success rates are frequently disguised by the inclusion of patients receiving adjunctive surgery, such as surgical thrombectomy, anastomosis revision and graft extension. Follow-up is sparse. As part of a larger prospective study, we have offered fibrinolysis using streptokinase to 10 patients with occluded infra-inguinal synthetic grafts. In one patient the graft could not be entered with a catheter. The remaining nine patients received local low-dose intra-arterial streptokinase. Six patients experienced complete lysis and were discharged with functioning grafts. Significant stenoses were dilated by transluminal angioplasty. The median graft patency duration was 7 months. Two patients have since required above-knee amputations. Our results using transluminal angioplasty are comparable to those results where adjunctive surgery has been used to treat underlying anastomotic stenoses. Further research into graft anastomotic stenosis management is indicated.

Late results of local thrombolytic treatment of peripheral arterial occlusions.

One hundred thirty-four patients, in whom acute and subacute arterial occlusions of lower limbs were treated with low dose intraarterial streptokinase, were observed for periods of up to five years. Primary recanalization of occluded vessels was achieved in 66 patients, but in the remaining 68 patients recanalization was not observed. In 45% of the patients with successful thrombolytic treatment, percutaneous dilatation (PTA) of remnant stenosis was performed. In patients with successful recanalization the reocclusion rate was greatest in the first year (17.4%); the first two weeks after therapy were most critical in this respect. The reocclusion rate during the succeeding years ranged from 4% to 9% per year. The cumulative patency rate after five years was 63.4%. Late results were better in patients in whom more proximal vascular segments were affected. The preservation of vessel patency was highly dependent on the severity and extent of the previous atherosclerotic process and especially on the state of peripheral (runoff) arteries. Presence of diabetes mellitus increased the reocclusion rate of recanalized vessels. Of the patients with unsuccessful recanalization, only 5 reported some symptomatic improvement during the observation period, 39 (57%) needed immediate amputation, and an additional 8 (4.7%) were amputated later on. Considering the fact that all patients were previously refused for bypass surgery owing to unsuitable runoff vessels or bad general condition, the long-term results were surprisingly good, suggesting that thrombolytic treatment, combined in remnant stenosis with PTA, was an efficient method in patients with acute or subacute arterial occlusions.

Acute Peripheral Arterial Ischemia: A Prospective Evaluation of Differential Management with Surgery or Thrombolysis

In this three year prospective study of 177 patients with acute peripheral arterial ischemia those subjects with acute iliofemoral emboli or ischemia with a neurosensory deficit had urgent operations. The remainder included patients less likely to have limb salvage after surgery and who therefore were treated with thrombolytic therapy. This was done in three open studies of intravenous, acylated, plasminogen-streptokinase activator complex, low dose intraarterial streptokinase and intraarterial tissue-plasminogen activator (t-PA). The overall outcome after 30 days of thrombolytic therapy was limb salvage (55%), amputation (15%), and death (30%). The severity of the presenting ischemia was the most important prognostic indicator. In patients with a neurosensory deficit, limb salvage after either embolectomy or surgical reconstruction (59%) was more likely than after thrombolysis (31%). In patients without a neurosensory deficit, limb salvage after thrombolysis (68%) was better, though not significantly, than after surgery (53%). Local intraarterial thrombolysis with either streptokinase or t-PA produced an encouraging 66% limb salvage in 59 cases. In management of acute peripheral arterial occlusions an approach based on the severity of ischemia is optimal, with urgent surgery for patients with a neurosensory deficit and intraarterial thrombolytic therapy reserved as an alternative in selected cases with stable ischemia.

Treatment of peripheral arterial obstruction with streptokinase: results in arterial vs graft occlusions

A retrospective study of the efficacy of local low-dose intraarterial streptokinase for the treatment of peripheral arterial occlusion was performed in 60 cases. The results of treatment of occlusion of native arterial and arterial graft occlusions were compared. Twenty-two (73%) of 30 cases of arterial occlusion showed complete or partial angiographic resolution, compared with 16 (53%) of 30 cases of arterial graft occlusion. Ten (71%) of 14 patients with venous arterial grafts were successfully treated vs only six (38%) of 16 patients with prosthetic arterial grafts. These results suggest that streptokinase is an effective fibrinolytic agent for the treatment of arterial occlusion and arterial graft occlusion. Its effectiveness in arterial graft obstruction is comparatively low, although patients with venous grafts respond much more favorably than those with synthetic conduits.

Low dose intra-arterial streptokinase and acylated plasminogen-streptokinase activator complex: A retrospective review of two thrombolytic regimes in recent peripheral arterial ischaemia

Thrombolytic therapy was used for 57 patients with acute and sub-acute lower limb arterial ischaemia. In the first 34 patients a new thrombolytic agent, acylated plasminogen-streptokinase complex (BRL 26921) was assessed. Following this, 23 patients received low dose intra-arterial streptokinase. The two thrombolytic regimes have been analysed retrospectively. There were differences observed between the two groups in the type of patients treated and in the severity of limb ischaemia. Of the patients receiving BRL 26921, five (15%) had complete, and three (9%) partial lysis of the occluding thrombus. Serious bleeding occurred in six (18%) and minor bleeding in ten (29%) patients. After 30 days, twelve patients (35%) had limb salvage and eleven (32%) had died. Fifteen patients (65%) receiving intra-arterial streptokinase had lysis of the occluding thrombus. Minor bleeding was observed in three patients (13%). After 30 days, 15 (65%) had limb salvage and three (13%) had died. Patients receiving BRL 26921 had a significantly greater reduction in plasma fibrinogen and plasminogen concentrations during treatment which may have accounted for the bleeding complications. At the dose used, BRL 26921 had no demonstrable fibrinogen sparing effect. Improved lysis rates with fewer bleeding complications might be achieved by reducing the dose of BRL 26921. Low dose intra-arterial streptokinase has been confirmed as a safe, effective method of thrombolysis in recent peripheral arterial ischaemia.

Case report: Popliteal artery perforation during low dose intra-arterial streptokinase infusion

There has been a recent increase in the use of low dose intra-arterial streptokinase infusion for the management of patients with acute peripheral arterial occlusions. Though serious complications using this technique occur less frequently than when using systemic thrombolytic therapy, a case is reported where the catheter used to infuse streptokinase perforated the popliteal artery 36 hours after the infusion commenced. The use of softer arterial catheters and restriction of patient movement where possible may prevent the recurrence of this previously unreported hazard.

Low-dose intra-arterial streptokinase: Benefit versus risk

Twenty-six unselected patients presenting with acute arterial ischaemia of a limb were treated with low-dose intra-arterial streptokinase under the joint care of a radiologist and a vascular surgeon. The results are reported and complications described. It is suggested that co-operative radiological and surgical management is essential and a shortened protocol for the safer administration of the drug is suggested.

The systemic fibrinolytic effect of low-dose intraarterial streptokinase: observations in 12 patients. Work in progress.

The systemic hematological effects of low-dose intraarterial streptokinase were studied in 12 patients with angiographic evidence of thrombosis. Streptokinase was administered at 5,000 U/hr; this rate was increased in the absence of clinical response or a systemic effect, which was defined as a thrombin time greater than twice that of the control time and/or a fibrinogen concentration less than 30% that of the control concentration. Eight patients experienced a systemic effect with final infusion rates of 7,500 to 20,000 U/hr over 20 to 72 hours, while 4 patients had no evidence of a systemic effect at 5,000 to 10,000 U/hr over 18 to 138 hours. A systemic effect could not be predicted based on infusion rates or durations, and the presence of a systemic effect was not predictive of hemorrhagic complications or thrombolytic effect in our small series. These results suggest that a systemic effect is frequently encountered with this form of therapy and is of uncertain clinical relevance.

Intraarterial streptokinase infusion for acute popliteal and tibial artery occlusion

Eight consecutive patients with acute thrombotic or embolic occlusion of the popliteal or tibial artery were treated with low-dose intraarterial streptokinase followed by arterial reconstructive surgery where appropriate. Three patients had acute thrombosis of a popliteal aneurysm with limbthreatening ischemia. All three were relieved of their acute ischemia by streptokinase infusion accompanied by lysis of clots in the popliteal artery outflow tract. Each patient then underwent elective popliteal aneurysm bypass. Four patients had acute embolic popliteal or tibial artery occlusion. Each was relieved of ischemic symptoms. One required surgery to remove residual clot. One patient with thrombosis of the tibioperoneal trunk did not have a decrease in symptoms with streptokinase infusion, but did experience sufficient outflow tract thrombolysis to permit construction of a tibial bypass with resultant restoration of normal circulation. Low-dose intraarterial streptokinase may be the treatment of choice for selected patients who present with thrombosis of a popliteal aneurysm with tibial vessel involvement or with embolic popliteal or tibial artery occlusion.

Segmental renal artery emboli treated with low-dose intra-arterial streptokinase

Herein we describe a sixty-one-year-old man with unilateral segmental renal artery emboli treated with renal intra-arterial streptokinase infusion. The initial infusion rate was 9,000 units1hr. which was decreased to 5,000 units/hr. over the next six hours. Periodic arteriography demonstrated progressive lysis and virtual complete resolution after fifty-two hours of infusion. Intravenous pyelogram (IVP) six weeks later showed almost complete return of function compared with IVP obtained six years earlier. We have demonstrated successful clot lysis at an infusion rate of 5,000 units/hr., compared with reported rates of 25,000 units/hr. and without the frequently utilized initial large intravenous bolus. Such low-dose streptokinase infusion should, theoretically, limit the incidence of recognized dose-related complications and permit its use in clinical settings where higher dosages are contraindicated. Intra-arterial streptokinase therapy seems particularly suitable for the high surgical risk patient and in arterial lesions not amenable to surgery. The availability of this potentially efficacious therapy suggests that aggressive diagnostic studies be pursued early in patients suspected of having an acute renal arterial embolus.