Regional Thrombolysis Research Articles

Combined regional thrombolysis and surgical thrombectomy for treatment of iliofemoral vein thrombosis

In at least half of patients with iliofemoral deep vein thrombosis post-thrombotic syndrome develops when only anticoagulant therapy is given. We combined thrombolysis, applied under ischemic conditions,with surgical thrombectomy to restore patency and valve function. The technique and the short-term and long-term results in 2 patient series are reported. A catheter was inserted into a foot vein of the thrombosed leg, and the limb was excluded from the circulation with a pneumatic cuff placed on the thigh with the patient under general anesthesia. Urokinase (0.5 million-3 million IU) and heparin were infused and allowed to act for 30 minutes while the pelvic axis was cleared with a Fogarty catheter through an inguinal venotomy. The external iliac vein was then clamped and the cuff removed. Thrombi that detached from the wall were flushed out with reactive hyperemia and squeezed out with manual leg compression. The blood was retrieved, washed, and transfused back into the patient. Various additional procedures were performed to secure outflow. Two patient series are reported: 1 with 12 consecutive patients and 1 with 21 patients who were successfully treated 6 to 10 years previously. Follow-up data were obtained for all patients after 1 year and for 18 of 21 patients after 6 to 10 years. Patency and valve function were assessed with duplex scanning or venography. Studies of blood coagulation and the kinetics of urokinase were performed in 5 additional patients. Vein patency and valve function were restored in all consecutive patients. At 1 year none of the 33 patients had had recurrence, and none showed clinical signs of post-thrombotic syndrome. At 6 to 10 years 3 of 18 patients had experienced another venous thromboembolism, but none in the treated leg. Sixteen legs were asymptomatic without compression therapy, and 2 had venous claudication. Coagulation studies showed a trace concentration of urokinase and a mild decrease in fibrinogen in the systemic circulation. The concentration of urokinase in blood collected from the treated leg was only 1% of that infused. Regional thrombolysis combined with surgical thrombectomy is relatively easy to perform and seems safe. Vein patency and valve function were restored, and post-thrombotic syndrome was prevented. Additional procedures to overcome pelvic vein obstructions were required in 11 of 33 patients (33%). The procedure should be tested against standard anticoagulation therapy in patients with acute iliofemoral thrombosis.

Rheolytic catheter and thrombolysis of dural venous sinus thrombosis: a case series.

The high morbidity and mortality rates associated with dural sinus thrombosis may be heightened by a delay in diagnosis, which necessitates prompt and effective treatment. Traditional treatment consists of the initiation of systemic anticoagulation with heparin and, more recently, regional thrombolysis with direct endovascular infusion of thrombolytic agents. We report our experience in a series of five patients in whom we accomplished mechanical clot lysis with the combination of a rheolytic device and balloon catheters. Five patients with dural sinus thrombosis were treated with a combination of pharmacological and mechanical thrombolysis with the 5-French Angiolet rheolytic catheter (Possis Medical, Minneapolis, MN) and balloon catheters. The success of the procedure was determined by resolution of or improvement in the patient's neurological examination results and imaging features. All five patients demonstrated immediate improvement as observed on imaging studies or in terms of neurological status. Three patients required more than one intervention, and all but one patient continued to improve after the final intervention. Two of the five patients continued to experience mild residual neurological deficits, and two patients experienced complete recovery. The fifth patient had a delayed recurrence of thrombosis that required multiple interventions, and the patient has significant neurological deficits. Navigation of the dural sinuses was possible in all patients with the use of a microcatheter and was possible to a variable degree with the rheolytic catheter. Known complications of the procedures included two pseudoaneurysms at the femoral puncture site. Mechanical clot lysis is a powerful technique for immediate restoration of antegrade venous flow in dural sinus thrombosis. In most patients, the superior sagittal sinuses and contralateral transverse sinuses could be accessed with the 5-French rheolytic catheter.

Recombinant Tissue Plasminogen Activator for the Treatment of Lower Extremity Peripheral Vascular Occlusive Disease

Regional thrombolysis in the recanalization of peripheral vascular occlusive disease is an increasingly accepted therapeutic modality. Efficacy and complication rate are major issues in thrombolytic therapy. This prospective study was undertaken to determine if locally delivered recombinant tissue plasminogen activator (r-TPA) is safe and effective in clot lysis at non-weight-adjusted doses. Twenty patients (undergoing 21 infusions) from two centers underwent fibrinolytic therapy with use of r-TPA, at a dose rate of 2 mg/h. The mean duration of arterial occlusion was 27.2 days (range, 1-117 days). Concomitant intravenous heparin anticoagulation was administered to all patients. A coaxial infusion delivery system was employed. Hematologic parameters and angiographic follow-up were evaluated at 4-hour intervals during thrombolytic infusion. The chosen maximum r-TPA dose of 40 mg could be extended at investigator discretion. Complete clot lysis was achieved in 18 of 21 (85.7%) infusions at a mean total dose of 38.9 mg (range, 8-84 mg). The mean infusion duration was 19.7 hours. In 16 of 19 (84.2%) infusions, in which the nadir fibrinogen level was recorded, it remained greater than 65% of baseline. Three of 21 (14.3%) infusions resulted in three major bleeding complications, one of which resulted in death. In this two-center trial, catheter-directed r-TPA infusion at 2 mg/h is effective for clot lysis. When combined with concomitant heparin administration, this treatment may result in an unacceptably high frequency of bleeding complications.

Antithrombotic drugs in peripheral obliterative arterial diseases.

In the natural history of patients with peripheral obliterative arterial disease (POAD) the prognosis of the complaint "intermittent claudication" is relatively good and the amputation rate is presently only about 3%. However, POAD patients carry a high risk of cardiovascular events and their cumultative mortality rate within 10 years is as high as 40-50%. Atherothrombotic events in the coronary and, less frequently, cerebral arteries are by far the first cause of death and disability in these patients. The rationale for antithrombotic drugs in the treatment of POAD lies in the pivotal role of platelet activation and thrombin formation in the evolution of the atherothrombotic lesions, but also in the effect of some of these drugs on the regulation of microcirculatory responses. In acute thrombotic arterial occlusion, Heparin is the "first application" drug, especially in support of interventional revascularisation procedures. Regional thrombolysis often coupled with angioplasty (PTA), or systemic thrombolysis, are effective in revascularisation of especially infrainguinal-supra popliteal occlusions. However, controlled clinical trials are needed. In chronic POAD, intermittent claudication can be improved with a rational walking exercise programme, but, besides pentoxyphilline, especially ticlopidine significantly adds to the benefits of exercise. Regarding districtual progression of atherothrombosis and especially cardiovascular events, both aspirin and ticlopidine have been shown effective in single studies or meta-analyses. In a recent observational study of pooled data the cumulative endpoint including myocardial infarction, stroke and vascular death was reduced by 25 +/- 10% in the generality of patients treated with antiplatelet drugs. Finally, in critical limbs ischemia (CLI), some prostanoid compounds as Iloprost and Prostaglandin E1 favourably influence rest pain and ulcer healing, but less evidence is available on their effects on hard events as amputation and death. In conclusion, following the general indication to "be conservative" in the treatment of these patients, it seems clear that antithrombotic drugs have become by far a key medication in all different phases of POAD.

Regional Thrombolysis for Peripheral Arterial Occlusions: Initial Procedure of Choice?

Five cases, representative of our larger series, are described in which grafts and lower extremities of patients with peripheral arterial occlusions were salvaged by thrombolytic therapy with catheter-directed intra-arterial urokinase. These patients were poor surgical candidates due to serious medical problems in addition to their occlusions. Intra-arterial fibrinolysis restored arterial flow and revealed lesions suitable for percutaneous angioplasty, making surgical intervention unnecessary. As vascular surgeons and interventionalists, the authors believe that thrombolysis is underutilized in patients with lysable occlusions.

Accelerated thrombolysis using pulsed intra-thrombus recombinant human tissue type plasminogen activator (rt-PA)

The efficacy of regional thrombolysis for treating leg ischaemia is well established, but the duration of infusion and the frequent complications remain major disadvantages. By delivering recombinant human tissue type plasminogen activator (rt-PA) as pulsed intra-thrombus 5-mg aliquots combined with catheter manipulation to maintain an intra-thrombus location, the average time taken to achieve thrombolysis in 20 consecutive patients with infra-aortic occlusions was 109 min. Immediate thrombolysis was achieved in every case. Pulsed delivery of high dose rt-PA significantly accelerates thrombolysis, decreases dose and reduces costs.

Cerebral ischemia in children and young adults

Cerebral ischemia is very rare in children and young adults. There can be a multitude of causes; in many cases etiology remains undetermined. We report here on 7 cases, 11 to 25 years of age. Pathogenetic factors (lupus erythematodes, endocarditis, fibromuscular dysplasia) and risk factors (cigarette smoking, oral contraceptives) were found in 5 patients whereas in 2 cases the etiology was not determinable. Three patients were treated with low weight dextrans, two patients received prostaglandin E1, and in 2 cases regional thrombolysis was performed. Three female patients died, two with occlusions of the rostral part of the basilar artery and one with an occlusion of the carotid artery and lupus erythematodes as the primary disease. Long-term observations of the surviving patients showed good recovery from neurological deficits. Prognosis quoad sanationem seems better in this age group than in elderly patients.

Ulnar artery aneurysm complicated by distal embolization: Management with regional thrombolysis and resection

We report the first use of preoperative regional thrombolysis followed by resection and primary anastomosis performed for distal embolization that complicated ulnar artery aneurysm. This treatment scheme may be applicable to other situations in which distal emboli complicate the management of arterial lesions.