Changes in Coagulation and Fibrinolysis Markers in Acute Ischemic Stroke Treated With Recombinant Tissue Plasminogen Activator

Background and Purpose-Patients with high-grade basilar artery stenosis secondary to thromboembolism are at high risk of developing subsequent vessel occlusion. Optimal medical management of this condition is unclear. Summary of Case-We present a patient with a small subacute brain stem infarction and filiform distal basilar residual lumen attributable to arterioarterial or cardiogenic embolism. Beginning 3 days after symptom onset, low-dose intravenous thrombolysis with 0.125 mg/kg recombinant tissue plasminogen activator was continuously infused for 48 hours. Follow-up magnetic resonance angiography revealed complete resolution of the embolus. No further cerebral ischemic episodes occurred during 3-month follow-up, and the basilar artery remained patent. Conclusion-Our observation suggests a potential for prolonged low-dose intravenous thrombolysis in basilar artery embolism, but further data are needed to judge the effectiveness and risk of this intervention. (Stroke. 2006;37:e9-e11.)

Section: Discussionmentioning

confidence: 99%

Prolonged Low-Dose Intravenous Thrombolysis in a Stroke Patient With Distal Basilar Thrombus

Veltkamp

Jacobi

Kress

et al. 2006

“…5,19 From experimental data obtained in a rat thromboembolic stroke model, simultaneous treatment with thrombolytic and GPIIb/IIIa inhibitory agents significantly attenuates neuronal damage with no increase in the incidence of cerebral hemorrhage. 9,10 Compared with full-dosage rtPA, an enhancement in large-and small-vessel patency contributed to smaller infarct sizes and a better neurological outcome.…”

Section: Recanalization and Lesion Size After Combined Thrombolysismentioning

confidence: 99%

“…4 As in myocardial infarction, treatment of acute ischemic stroke with thrombolytic agents such as rtPA inevitably leads to concomitant activation of the coagulatory system. 5 Thus, even in successful initial recanalization, neurological deterioration related to repeated vessel occlusions is observed in every third case after rtPA treatment. 6 Combined thrombolytic treatment with fibrinolytic and platelet glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitory agents led to improved patency rates in myocardial reperfusion therapy compared with rtPA alone.…”

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confidence: 99%

Systemic Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Acute Middle Cerebral Artery Occlusion

Straub

Junghans

Jovanovic

et al. 2004

Background and Purpose-In acute ischemic stroke, thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) is limited by a concomitant activation of the coagulatory system, leading to incomplete or delayed reperfusion, microcirculatory disturbances, or even repeated vessel occlusions. Our pilot study sought to assess the therapeutic potential of a new treatment strategy combining rtPA at reduced dosages with a platelet glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitory agent in acute middle cerebral artery occlusion. Methods-Nineteen patients suffering from acute middle cerebral artery occlusion (Thrombolysis in Myocardial Infarction[TIMI] flow grade 0 to 1) underwent combined intravenous thrombolytic treatment using rtPA at reduced dosages and the GPIIb/IIIa antagonist tirofiban. Stroke MRI (diffusion-and perfusion-weighted imaging) and MR angiography were performed at baseline and between days 1 and 2 after treatment. Clinical scores (National Institutes of Health Stroke Scale and modified Rankin Scale) were assessed at baseline and after 1 week. Results-Middle cerebral artery recanalization (TIMI flow grade 2 and 3) occurred in 13 of 19 patients (68%). The ischemic lesion on follow-up MRI was significantly smaller in patients with recanalization compared with those without recanalization (Pϭ0.001). Only patients with recanalization improved neurologically (PϽ0.001). Because no symptomatic hemorrhage was observed, the power of our study to detect a symptomatic bleeding rate of Ն8% was at least 80%. Conclusions-Combined

“…10,11 Reocclusion after tPA treatment is induced, at least in part, by the activation of the coagulation cascade by tPA. 12,13 These findings indicate that the use of antiplatelet drugs is potentially a double-edged sword in the context of tPA treatment; that is, use of antiplatelet agents is likely to be beneficial for stroke outcome despite increased risk of hemorrhagic infarction. Consistent with these findings, a randomized controlled trial in the Netherlands has shown that thrombolysis in combination with antiplatelet drugs prevented reocclusion and improved the clinical outcome.…”

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confidence: 99%

Cilostazol Reduces the Risk of Hemorrhagic Infarction After Administration of Tissue-Type Plasminogen Activator in a Murine Stroke Model

Kasahara

Nakagomi

Matsuyama

et al. 2012

Background and Purpose-Prior use of antiplatelet agents improves stroke outcome in patients undergoing thrombolytic therapy as shown by reduced arterial reocclusion, although the risk of cerebral hemorrhage can be increased. Methods-The effect of cilostazol, an antiplatelet drug that improves endothelial function through upregulation of intracellular cAMP, on cerebral hemorrhage after thrombolytic therapy was investigated using a highly reproducible transient ischemia model. Results-Treatment with cilostazol for 7 days before ischemia significantly suppressed the risk and severity of cerebral hemorrhage after injection of tissue-type plasminogen activator, although treatment with aspirin had no such protective effect compared with nontreated mice. Immunohistological analysis revealed that treatment with cilostazol suppressed disruption of the microvasculature in the ischemic area associated with reduced matrix metalloproteinase-9 activity. Conclusions-Our results suggest that patients treated with cilostazol before onset of stroke could have a lower risk of cerebral hemorrhage after thrombolytic therapy and might also have a longer therapeutic time window for thrombolysis. Furthermore, the risk of cerebral hemorrhage can be significantly altered by prestroke therapies, and analysis of the effects of multiple drugs on tissue-type plasminogen activator-induced cerebral hemorrhage in animal models is essential for the extending safe and effective thrombolytic therapy to a wider group of patients.