Thrombolytic infusion

After a baseline angiogram confirms the presence and location of the vascular occlusion, a microcatheter is navigated over a microwire into the occluded vessel, traversing the thrombus. Once the microcatheter is positioned immediately distal to the clot, thrombolytic infusion begins the microcatheter is then pulled back through the clot while dmg is infused. Dose adjustments and total dose calculations are made depending on the clinical circumstances, pretreatment dose of rt-PA received, degree of recanalization, and relative size and function of the territory at risk. 

Unfractionated heparin should not be used during thrombolytic therapy. Neither the aPTT nor any other anticoagulation parameter should be monitored during the thrombolytic infusion... 

Abbas AE, Brewington SD, Dixon SR, et al. Intracoronary fibrin-specific thrombolytic infusion facilitates percutaneous recanalization of chronic total occlusion. JACC 2005 46 793-798. 

There are several small studies examining this concept of thrombolytic infusion with GPIIb/llla inhibition to reduce lytic infusion time and improve efficacy as summarized below. This concept is not universally proven in these studies. A larger randomized trail is needed to examine this concept before a clinical practice recommendation can be made. 

Tepes et al. reported the first clinical experience with abcix-imab and urokinase combination therapy in the peripheral circulation (44). Schweizer et al. used abciximab and rt-PA versus rt-PA with ASA in an 84 patient trial and found a significantly shorter duration of thrombolytic infusion was required to achieve lytic success in the combination group as well as improved clinical endpoints of less re-hospitalization, re-intervention, and amputation compared to ASA and heparin (45),... 

Several authors have reported their experience with thrombolytic infusions lasting 3-12 h for the treatment of fibrin sheaths. Clinical success ranged... 

Several clinical trials have been conducted with streptokinase adrninistered either intravenously or by direct infusion into a catheterized coronary artery. The results from 33 randomized trials conducted between 1959 and 1984 have been examined (75), and show a significant decrease in mortaUty rate (15.4%) in enzyme-treated patients vs matched controls (19.2%). These results correlate well with an ItaUan study encompassing 11,806 patients (76), in which the overall reduction in mortaUty was 19% in the streptokinase-treated group, ie, 1.5 million units adrninistered intravenously, compared with placebo-treated controls. The trial also shows that a delay in the initiation of treatment over six hours after the onset of symptoms nullifies any benefit from this type of thrombolytic therapy. Conversely, patients treated within one hour from the onset of symptoms had a remarkable decrease in mortaUty (47%). The benefits of streptokinase therapy, especially in the latter group of patients, was stiU evident in a one-year foUow-up (77). In addition to reducing mortahty rate, there was an improvement in left ventricular function and a reduction in the size of infarction. Thus early treatment with streptokinase is essential. 

Anistreplase has a considerably longer a half-life than streptokinase, ie, 90 min compared to 20 min (87,88). Moreover, it does not require prolonged infusion to achieve its thrombolytic effects. Anistreplase was found to be highly effective after a single intravenous dose of 30 units over a 5-min period compared to a 60-min infusion of 1.5 million units of streptokinase (89—94). In direct comparative studies, anistreplase was as effective as intracoronary (95,96) and intravenously (96—100) adrninistered streptokinase. In a randomized, double-blind, placebo-controUed study (AIMS trial) with 1004 patients given this modified enzyme, the 30-day mortaUty rate was 12.2% for patients receiving placebo, compared to 6.4% for patients who received 30 units of anistreplase intravenously within six hours of the onset of symptoms (101). 

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

Local intra-arterial thrombolysis (lAT) has several theoretical advantages over IV thrombolysis. For instance, by using coaxial microcatheter techniques, the occluded intracranial vessel is directly accessible and the fibrinolytic agent can be infused directly into the thrombus. This permits a smaller dose of fibrinolytic agent to reach a higher local concentration than that reached by systemic infusion, and ideally it allows for more complete recanalization with lower total doses of thrombolytic. With the smaller dose, complications from systemic fibrinolytic effects, including ICH, can theoretically be reduced. 

Suarez Jl, Zaidat OO, Sunshine JL, Tarr R, Selman WR, Landis DM. Endovascular administration after intravenous infusion of thrombolytic agents for the treatment of patients with acute ischemic strokes. Neurosurgery 2002 50 251-259 [discussion 259-260]. 

Alteplase has proven effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event) are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min) results in a steady-state alteplase concentration of 3-4 mg l 1 during that period. However, the product is cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

UFH should not be used during thrombolytic therapy. The aPTT should be measured after the completion of thrombolytic therapy. If the aPTT at that time is <2.5 times control, a UFH infusion should be started and adjusted to maintain the aPTT in the therapeutic range. If the posttreatment aPTT is >2.5 times control, it should be remeasured every 2 to 4 hours and a UFH infusion started when the aPTT is <2.5 times control. 

Hegele (H23) reported an acute reduction of Lp(a) during tPA infusion. The success of this type of thrombolytic therapy for acute myocardial infarction seems to be unaffected by high Lp(a) levels (H32). 

Human recombinant tPA and streptokinase are used as thrombolytic agents e.g. they are infused into the bloodstream as soon as possible after a heart attack. 

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