Treating Stroke With Thrombolysis - Oren Zarif - TPA Stroke
The use of tPA has largely been approved for treating patients with acute stroke. However, European attendees to a recent stroke conference were not convinced that tPA should be standard of care within 3 hours after the onset of symptoms. Consequently, the European Medicines Agency conditionally approved tPA in 2002. Then, in 2005, another group of European experts published the results of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study registry, which showed that tPA was effective even when given after 4.5 hours.
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In addition to the effectiveness of tPA, it is associated with increased patient survival rates. The tPA group resulted in an increased rate of patients with no or minimal disability. Researchers estimate that eight and a half times as many patients with a tPA-treated stroke will experience early clinical improvement, with only three patients receiving a worse outcome after the first treatment. While this is a small difference in the number of patients who will benefit, it is still a substantial benefit for patients.
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The majority of patients who experience an acute stroke are not able to reach the hospital in time to receive thrombolytic therapy. The results of the study showed that 27% of patients who presented within three hours of their stroke were given tPA. However, a similar proportion of patients were excluded because their symptoms were too mild or were improving rapidly. Despite these positive results, tPA is not a cure for stroke.
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During the current protocol, patients eligible for tPA are delivered to the CT suite where a bolus of the clot-busting agent is administered. Patients whose angiography confirms LVO are transferred to the angio table to undergo MT. Nevertheless, this does not account for all of the delay. While tPA administration is a significant contributor to the time it takes for a patient to receive MT, many other factors may delay the patient's transfer to the angio suite.
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Achieving this goal can be accomplished by decreasing the time between the onset of a stroke and the administration of tPA. This can be done through a number of strategies, including prehospital measures to decrease the risk of thrombosis and lower DTN. Further, these measures can improve patient outcomes and lower OTT. The HASTE study found that these interventions reduced the time between the onset of the stroke and tPA administration in the CT scanner.
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A multicentre retrospective stroke study involving 58,353 patients demonstrated that tPA treatment could improve outcomes in a patient's condition. However, delayed administration of the clot-busting agent was associated with an increased risk of HT and ICH. In addition to thrombolysis, delayed tPA administration increased the risk of post-treatment complications such as reperfusion injury. In addition, tPA activates matrix metalloproteases, which further compromises the BBB and increases in-hospital mortality.
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Moreover, it may be beneficial to use neuroprotectants that interfere with the ischemic cascade. However, this therapy has not been effective enough for a number of stroke patients. This is because the drugs' delivery was not adequate in cases of decreased cerebral blood flow and occluded cerebral blood vessels. However, neuroprotectants may improve the rate of neurological recovery by inhibiting the inflammatory cascade and protecting dying neurons. These agents may also improve neurological outcomes in patients undergoing tPA.
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In addition to its neuroprotective and antioxidant effects, tPA has been shown to reduce the risk of ischemic stroke in a rat model. Epigallocatechin gallate (20 mg/kg) in tPA-treated rats reduced infart volume and edema, and regulated MMP-2 expression. Furthermore, it decreased the number of inflammatory cells and increased PAI-1 expression. All these effects could have beneficial effects on the treatment of stroke.
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In addition to the adverse effects of tPA, a patient's decision to undergo tPA should be documented. Failure to follow tPA protocols can result in a favorable verdict in stroke cases. The timeframe for thrombolytic therapy is limited, and doctors should follow the protocol in accordance with this. If the decision is not clear, the patient must be provided with alternative treatments or undergo a surgical procedure.
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The use of tPA in acute stroke is beneficial, but sustaining high rates of its administration in patients has proved difficult. Access to the drug has been hindered by late diagnosis of the condition. In the meantime, the health system factors have been implicated in the lack of access to tPA. Further, no agreed benchmark of the number of tPA-treated stroke patients is available. Nevertheless, substantial improvement is possible if these challenges are overcome.
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