Thrombolysis of clotted hemodialysis grafts with tissue-type plasminogen activator

PURPOSE: To evaluate prospectively the efficacy of treating thrombosed hemodialysis arteriovenous polytetrafluoroethylene (PTFE) grafts using tissue-type plasminogen activator (tPA) and percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: Forty-two sequential thrombosed PTFE dialysis grafts in 33 patients presented for declotting. All 42 grafts were treated with a modified lysis and PTA technique with use of 2 mg tPA and 3,000-5,000 U heparin in a total volume of 5 mL, administered into the graft via an angiocatheter. The elapsed time from tPA injection until completion was recorded. Prospective data collection included demographic information, technical details of the procedure, immediate outcomes, complications, and patency rates. RESULTS: Technical success, defined as complete graft recanalization with a palpable thrill after treatment plus successful hemodialysis, was achieved in all cases, except five. These five cases were deliberate graft closures due to inadequacy of the outflow veins to support an arteriovenous graft after successful lysis. Mean lysis time was 40.8 minutes and mean room procedure time after the lysis period was 65.4 minutes. Eight procedure-related complications occurred (two major and six minor). The follow-up period was 4-241 days, with an estimated mean of 157 days. The 30-day and 90-day primary patency rates were 57% and 50%, respectively. CONCLUSIONS: Treatment of thrombosed PTFE dialysis grafts with use of 2 mg tPA and 3,000 U of heparin is safe and effective. Use of this modified lysis and PTA technique allows an expeditious procedure in the angiography suite. However, this technique precludes imaging of the outflow veins before treatment, so that grafts entering diffusely diseased veins may need to be closed after successful lysis.     

Prolonged binding of radiolabeled recombinant tissue-type plasminogen activator after angioplasty and enclosed thrombolysis of the femoropopliteal arteries.

The authors measured the binding of indium-111-labeled recombinant tissue-type plasminogen activator (rt-PA) within the recanalized femoropopliteal segment after percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis. In patients with long occlusions (n = 3), 91 micrograms of rt-PA was bound 1 hour after the procedure, and the half-time of the final washout curve averaged 114 hours. After PTA in patients with multiple stenoses (n = 6), 45 micrograms of rt-PA was bound, and the half-time averaged 32 hours. These values were significantly smaller than those in patients with occlusions (P < .01). In patients with a single stenosis (n = 4), 19 micrograms of rt-PA was bound, and the half-time averaged 5 hours. These values were significantly smaller than those in patients with multiple stenoses (P < .01). The progressive accumulation of rt-PA at the sites of PTA therapy is most likely related to increasing presence of fibrin with increasing lesion severity. Fibrin accumulation may be partly responsible for early failures after PTA in extensive lesions. Removal of this fibrin with enclosed thrombolysis might improve patency.     

Original report. Pulse-spray thrombolysis of thrombosed hemodialysis grafts with tissue plasminogen activator

OBJECTIVE: The purpose of this study was to evaluate pulse-spray pharmacomechanical thrombolysis with the use of tissue plasminogen activator in the recanalization of thrombosed hemodialysis access grafts. CONCLUSION: Pulse-spray pharmacomechanical thrombolysis with tissue plasminogen activator is an effective method for percutaneous recanalization of thrombosed hemodialysis access grafts with results similar to other percutaneous techniques.     

Comparison of urokinase and tissue plasminogen activator for thrombolysis in rats

Microvascular thrombosis in free flap and replantation surgery may be amenable to thrombolytic therapy. A blinded, controlled, preliminary study in rats compared urokinase (UK) and tissue plasminogen activator (t-PA) on thrombolytic efficacy, systemic fibrinolytic effect, and reocclusion. Bilateral femoral vein clots were induced in 38 rats. Local infusion of UK, t-PA, or saline was performed. Fibrinogen levels were drawn from one group. A second group was evaluated for reocclusion up to one month. Ipsilateral lysis occurred for reocclusion up to one month. Ipsilateral lysis occurred in 10/12, 13/13, and 0/13 of the UK, t-PA, and saline groups, respectively, with no significant difference detected between the UK and t-PA groups. Contralateral clot lysis occurred in both the UK and t-PA groups. No significant differences in the fibrinogen levels was detected among the three groups. Reocclusion occurred only in the UK group.     

Treatment of acute ischemic brain infarction with the assistance of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator

Background: Cerebral infarction is usually due to arterial occlusion. Prompt treatment with thrombolytic drugs can restore blood flow and improve recovery from an infarct.

Purpose: To evaluate the clinical efficacy and safety of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator (rtPA) in patients with acute middle cerebral artery (MCA) infarctions within 6 hours of the onset of symptoms.

Material and Methods: Sixteen patients (10 females and six males) aged from 42 to 61 years, with acute MCA territory infarcts were selected for treatment with local i.a. rtPA up to 6 hours after the onset of symptoms. Patient selection was based on clinical examination, computed tomography (CT), and digital subtraction angiography (DSA). A clinical evaluation was performed before treatment, at the time of discharge, and 90 days post-procedure on the basis of modified Rankin and NIHSS scores. Controls (n = 16, nine females and seven males) aged from 51 to 70 years were treated only with intravenous anticoagulation using i.v. heparin infusion. The control group was evaluated with multidetector CT (MDCT) angiography performed on entry to the study and at 2-4 hours afterwards.

Results: Eight patients (50%) achieved a modified Rankin score of 2 or less as the primary outcome after 90 days follow-up. The secondary clinical outcome at 90-day follow-up was as follows: NIHSS score ≤1, three (19%) of the patients; NIHSS score ≥50% decrease, nine (56%) of the patients. A recanalization rate of 75% was achieved in 12 of the 16 treated patients, but only 12.5% in two of the 16 patients in the control group. Intracerebral hemorrhage occurred in two (12.5%) of the patients in the treatment group, but in only one patient (6%) in the control group. There were no deaths in the treated group after thrombolysis up to the time of discharge; however, during the 90-day follow-up, two patients died compared to three patients in the control group (19% vs. 12.5% mortality rate).

Conclusion: Patients with cerebral infarction who were treated within 6 hours of onset using intraarterial rtPA thrombolysis had a significantly improved clinical outcome 90 days after the procedure compared to patients treated only with intravenous anticoagulation.     

Comparison of tissue plasminogen activator and urokinase in the local infiltration thrombolysis of peripheral arterial occlusions

Recanalization of the vascular lumen by means of local fibrinolysis is of major importance in the treatment of peripheral arterial occlusive disease. While urokinase and streptokinase have been extensively used for local fibrinolysis, there have been few studies of infiltration thrombolysis with genetically engineered tissue plasminogen activator (rt-PA). The aim of the investigation reported here was to establish whether there is any difference between urokinase and rt-PA in the short- and long-term outcome of local fibrinolytic therapy. One- hundred twenty patients (70 men, 50 women) with acute or subacute femoral (n = 21), femoropopliteal (n = 33), popliteal (n = 13) or popliteocrural (n = 53) thrombotic occlusions were randomized to local lysis using urokinase or rt-PA, and 6 months later follow-up investigations took place. Recanalization of thrombotically occluded vessels, particularly in the lower leg, was found more frequently, and after treatment of shorter duration, with rt-PA. Large local haematomas occurred in 8% of cases in the urokinase group and 15% in the rt-PA group. No serious haemorrhages were encountered in either group. Six months after treatment, the rt-PA group showed lower rates of Fontaine stage III and IV disease and amputation than the urokinase group, with a higher number of patients in Fontaine stage IIb. This study shows that local lysis with rt-PA yields better results than urokinase, not only in the short term but also 6 months later.     

Direct graft puncture with use of a crossed catheter technique for thrombolysis of peripheral bypass grafts

PURPOSE: To determine the efficacy and safety of direct graft puncture of peripheral arterial bypass grafts with placement of retrograde and antegrade catheters within the graft for thrombolytic therapy. This study also evaluated potential clinical benefit to patients. MATERIALS AND METHODS: A retrospective study was performed on 19 patients with 24 peripheral bypass grafts and lower extremity ischemia of less than 1 month duration. Thrombolysis was performed with a continuous high-dose infusion of urokinase. Successful lysis was defined as greater than 95% clot dissolution with antegrade flow within the graft. RESULTS: Technical success was achieved in 17 of 19 patients (89%). The complexity of operative intervention was diminished in 12 of 19 patients (63%). The major complication rate (16%) was significantly higher and, therefore, this technique has a role for patients in whom traditional access is not optimal, such as in those in whom access cannot be achieved or in those with long bypass grafts. CONCLUSION: Direct graft puncture with placement of catheters across the proximal and distal anastomoses of bypass grafts is a safe method of access, with a major complication rate similar to conventional access techniques. This mode of graft access demonstrates efficacious thrombolysis and acts as a conduit for ancillary procedures.     

Thrombolytic therapy with recombinant human tissue-type plasminogen activator: a comparison of two doses

The efficacy and safety of two doses of recombinant human tissue-type plasminogen activator (rt-PA) were compared. Forty patients with peripheral arterial occlusions were treated with intraarterial rt-PA. Group A (n = 21) received 0.1 mg/kg/h, and group B (n = 19) received 0.05 mg/kg/h. Infusion durations varied from 4 to 8 hours. Complete thrombolysis occurred in 20 of 21 patients (95%) in group A and in all 19 patients (100%) in group B. In group A, fibrinogen levels were greater than 75% of baseline in ten of 21 patients (48%) at infusion termination. In group B, fibrinogen levels were greater than 75% of baseline in 12 of 19 patients (63%) at infusion termination. Three of 40 patients (7%) had significant complications resulting from rt-PA infusion. The results demonstrate that over similar infusion times, a dose of 0.05 mg/kg/h is as efficacious and results in less systemic fibrinogenolysis than a dose of 0.1 mg/kg/h.     

Complications associated with the use of urokinase and recombinant tissue plasminogen activator for catheter-directed peripheral arterial and venous thrombolysis

PURPOSE: Catheter-directed thrombolytic dissolution of peripheral arterial and venous thrombus is in widespread use, yet the frequency and nature of associated complications remain ill defined. In an effort to better characterize the complications associated with urokinase (UK) and recombinant tissue plasminogen activator (rt-PA), the clinical course of patients treated for lower extremity vascular occlusions at a single institution was reviewed. MATERIALS AND METHODS: Over a 9-year period, 653 consecutive patients were treated for lower extremity arterial (527 patients) or venous (126 patients) occlusions with catheter-directed UK (483 patients), rt-PA (144 patients), or both (26 patients). Decisions regarding the choice of thrombolytic agent were made by the clinician. In-hospital complications were subcategorized into hemorrhagic and nonhemorrhagic events and the rate of intracranial hemorrhage was specifically tabulated. RESULTS: There were no significant differences in the demographics or clinical presentation of patients treated with either UK or rt-PA. Bleeding complications occurred less often in the patients treated with UK (insertion site hematoma 21.9% vs. 43.8%, P<.0001, any bleeding necessitating transfusion 12.4% vs. 22.2%, P = .004, and intracranial hemorrhage 0.6% vs. 2.8%, P = .031). Cardiopulmonary complications necessitating transfer to the intensive care unit occurred more frequently in the patients treated with rt-PA (4.9% vs. 1.5%, P = .015). The risk of mortality was not statistically different between the UK and rt-PA treated patients (2.7% vs. 6.2%, P = .221). CONCLUSIONS: Thrombolysis appears safer with UK than with rt-PA, with a lower incidence of hemorrhagic complications. It is possible that this finding is related to differential dosing regimens or intrinsic pharmacologic differences between the agents. The observations of this retrospective analysis require confirmation with a prospective, randomized evaluation.     

Intra-arterial thrombolysis: tissue plasminogen activator and other thrombolytic agents

Recanalization rates with the administration of intravenous tissue plasminogen activator in acute ischemic stroke are low. Adjuvant endovascular techniques that achieve recanalization by direct intra-arterial (IA) delivery of thrombolytics, mechanical clot retrieval, clot aspiration, and stenting may complement intravenous pharmacotherapy. IA thrombolytics can be administered within 6 hours of symptom onset in anterior circulation strokes and within 24 hours in posterior circulation strokes. This review describes the indications, patient selection, and technique for IA administration of thrombolytics.     

Studies on mRNA expression of tissue-type plasminogen activator in bruises for wound age estimation

We investigated mRNA expression of tissue-type plasminogen activator (tPA) and inflammatory cell dynamics for wound age estimation of bruises in mice. Neutrophils were detected from 1 h post-injury. Up to 8 h, they accumulated in subcutaneous tissue and the lower part of the dermis, and thereafter they extended to all the layers. Macrophages became detectable 3 h post-injury, and moderate infiltration of lymphocytes was seen from 144 h. In addition, epidermal thickening was also seen from 72 h. tPA mRNA expression peaked at 1 h, and increased slightly at 72 h post-injury. tPA mRNA was detected in epidermal cells, fibroblasts, and endothelial cells before and after injury, from 3 h in neutrophils and from 72 h in macrophages, respectively. This study presents the time-dependent expression of tPA mRNA in bruises in relation to temporal histologic characteristics during wound healing, which was considered to be useful for wound age estimation. Furthermore, it is suggested that tPA plays an important role in the first step of tissue remodeling.     

Current indications and results of thrombolysis by intravenous recombinant tissue plasminogen activator

A number of landmark trials have proven the efficacy of thrombolysis by intravenous recombinant tissue plasminogen activator in the acute phase of the ischemic stroke. Despite the recently extended time window of 4.5 hours, the number of people who are being treated in most centers is low. Several reasons seem to account for this, including poor recognition of symptoms, delays in emergency transport, low levels of public awareness, or age limits originally imposed by drug regulatory rules. Trials are ongoing to possibly extend the indications to the treatment. A major effort is to extend the time window by bridging the treatment with neuroprotective approaches, or by identifying subgroups that may particularly benefit from recanalization and reperfusion. Procedures using ultrasounds or alternative intravenous compounds are also being investigated with promising results.     

Coagulation alterations due to local fibrinolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) in patients with peripheral arterial occlusive disease

Purpose To determine the systemic effects of local fibrinolytic therapy with low-dose recombinant tissue-type plasminogen activator (rt-PA). Methods Ten patients received intrathrombal infusion of 20 mg rt-PA and heparin for local thrombolysis and had subsequent percutaneous transluminal angioplasty (PTA). Eight controls underwent PTA and received heparin alone. We measured t-PA, D-Dimer, and fibrinogen levels before, directly after, and 20, 40, and 60 min and 24 hr after therapy. Results In the thrombolysis group the t-PA level peaked immediately after infusion and then declined within 1 hr. D-Dimer increased and remained elevated, whereas in the control group only t-PA levels increased, and only after 24 hr. Fibrinogen remained within the normal range in both groups. Eight of ten patients in the thrombolysis group and seven of eight with PTA had clinical improvement after the procedure. Conclusions The increase in D-Dimer in the rt-PA group indicates a good local fibrinolytic effect. The fact that fibrinogen levels remained unchanged indicates that there is a lack of systemic fibrinogenolysis.     

Thrombosed hemodialysis grafts: lyse and wait with tissue plasminogen activator or urokinase compared to mechanical thrombolysis with the Arrow-Trerotola Percutaneous Thrombolytic Device

PURPOSE: To determine if the lyse and wait (L&W) technique with a 4-mg dose of alteplase (tissue plasminogen activator; tPA) is a safe and effective method of declotting dialysis grafts as compared to use of the Arrow-Trerotola Percutaneous Thrombectomy Device (PTD) or the L&W technique with use of urokinase (UK). MATERIALS AND METHODS: Forty patients were randomized prospectively to undergo L&W declotting with use of 4 mg of tPA or mechanical thrombolysis with the PTD. The time interval to restored graft flow, total procedure time, hemostasis time, and anatomic success, clinical success, complications, and patency rates were analyzed. These were compared with historic results in 20 patients treated with the L&W technique with use of 250,000 U UK. RESULTS: The immediate anatomic success rate was 95% in the tPA L&W and PTD groups. The mean in-room lysis time with restored flow was 10 minutes for L&W with tPA and 19 minutes for PTD (P = .002). The mean in-room procedure time was 39 minutes for L&W and 45 minutes for PTD (P = NS). Mean hemostasis time with use of manual compression was 44 minutes for L&W with tPA and 23 minutes for PTD (P = .057). The historic group of 20 patients who underwent L&W with UK had a 95% anatomic success rate, a mean of 14 minutes of lysis time, a mean of 34 minutes of procedure time, and a mean of 26 minutes of time to hemostasis. No bleeding complications occurred in the PTD group. Seven episodes of bleeding occurred in six patients given tPA; four were delayed 60-90 minutes after the procedure, one necessitated hospitalization, and two required additional therapies. Four of the 20 patients undergoing L&W with UK had minor puncture site bleeding during the procedure. The 3-month primary patency rates were 65%, 65%, and 60% for L&W with tPA, PTD, and L&W with UK, respectively (P = NS). CONCLUSION: The 4-mg dose of tPA is effective but results in more bleeding complications and longer hemostasis times than mechanical thrombolysis with use of the PTD. Unlike in our experience with UK, bleeding complications with tPA were both major and delayed.