Thrombolytic (Fibrinolytic) Drugs
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If this procedure is unsuccessful, a thrombolytic agent may be used after the effects of prior anticoagulation have been allowed to diminish. Some treat other conditions that can lead to stroke.
Although the benefit of aspirin administered with alteplase or anistreplase has not been studied, it is widely held that the combination of aspirin and any thrombolytic agent is likely to have benefit similar to that of aspirin and streptokinase. Because they burst like small microexplosions, they help to mechanically degrade the clot.
Tissue-type plasminogen activator complex - May be more clot-selective than anistreplase, streptokinase, or urokinase. Stability: The reconstituted solution is to be administered within 30 minutes after reconstitution.
In , 2017 Fibrinolytic Therapy Tissue plasminogen activators have been administered to horses in an attempt to increase activity of plasmin and hence the rate of lysis of fibrin in the pleural cavity. Earlier attempts at fibrinolytic therapy used streptokinase or urokinase and were not beneficial. Use of modified compounds, such as alteplase and tenecteplase, is effective in hastening fibrinolysis, enhancing resolution of accumulated pleural fluid, and improving survival. The procedure in one case involved intrapleural infusion of 12 mg of tenecteplase in 500 ml of isotonic saline after drainage of excessive pleural fluid. Pharmacokinetics of alteplase in horses are described. Aronson, in , 2005 Nervous system When alteplase and strep-tokinase are used in the treatment of myocardial infarction the most feared adverse effect is intracranial hemorrhage. Hemorrhagic stroke was more common with alteplase 0. If GUSTO-1, in which alteplase was given in an accelerated fashion, was excluded, the hemorrhagic stroke rates were 0. There was no difference in 35-day mortality between the drugs. Harald Sontheimer, in , 2015 6. Not surprisingly, there are a number of candidates at various stages of clinical testing. Some have an improved half-life; others promise to offer faster and more complete clot-busting activity. An interesting experimental approach aimed at improving outcome is the combination of tPA with transcranial ultrasound. The ultrasound mechanically assists in the disintegration of the clot, which is chemically weakened by tPA. These bubbles adhere to the clot surface and are activated to burst through ultrasound energy. Because they burst like small microexplosions, they help to mechanically degrade the clot. Catherine Kiruthi, in , 2015 Drug Interactions Recombinant tissue plasminogen activator rt-PA is known to increase the risk of angioedema especially in those using ACEIs. ARBs are generally not thought to carry the same risk of angioedema, however, several cases have been reported. One recent case is the first known case of its kind to showcase angioedema from use of an ARB and rt-PA therapy. A 80-year-old Asian female presented with left-sided weakness and was given rt-PA with improvement in symptoms. The patient started developing difficulty breathing, throat pain, dysarthria and an odd sensation in her mouth 6 minutes after the end of infusion. Angioedema of the tongue, uvula, and lips was diagnosed and steroids started for treatment with presentation attributed to rt-PA. Olmesartan was initiated at 20 mg daily for hypertension after angioedema developed. Qureshi, in , 2007 6. It is the most familiar fibrinolytic agent in emergency departments and the most often used agent for treatment of coronary artery thrombosis, pulmonary embolism, and acute stroke. Unfortunately, this occurs at the cost of a marginal increase in stroke rate. Geraint Fuller MD FRCP, in , 2010 Specific measures Thrombolysis Intravenous recombinant tissue plasminogen activator alteplase given within 3 hours of an anterior circulation ischaemic stroke improves outcome despite the increased risk of iatrogenic intracranial haemorrhage. Thus patients who might be candidates need urgent assessment and CT scanning to exclude cerebral haemorrhage. Anticoagulants should be avoided if possible as they increase the risk of deterioration from haemorrhagic transformation. Transfer to stroke unit There is good evidence that multidisciplinary care on a stroke unit improves the outcome of patients with stroke. Assess swallow Aspiration pneumonia is a significant complication after stroke. Minimise this risk by assessing swallowing and using a nasogastric tube for fluids and food if swallowing unsafe. Early mobilisation Help patients sit up when possible and mobilise early. The currently underway Norwegian Tenecteplase Stroke Trial NOR-TEST aims to compare the efficacy and safety of tenecteplase 0. This study will compare hemorrhagic transformation, symptomatic cerebral hemorrhage, major neurological improvements, recanalization and death in a prospective, randomized, open label and blinded endpoint trial. To date tenecteplase has been studied in small highly selected groups. Cardiovascular A 37-year-old male with acute pericarditis chest pain that was misdiagnosed as an acute myocardial infarction was reported in this study. He received thrombolytic therapy resulting in hemopericardium and cardiac tamponade with lethal consequences. Nervous System A 75-year-old man with acute right hemiparesis and no contraindication for thrombolysis underwent thrombolytic therapy with 72 mg of tissue plasminogen activator tPA 120 minutes after symptom onset. He showed recovery of functional deficits before the end of the infusion and within 24 hours he was able to ambulate. On third day of treatment he developed neck pain and right hemiparesis. MRI showed an acute c3—c6 level right posterolateral epidural spinal hematoma. He underwent bilateral microsurgical evacuation of hematoma and was eventually discharged in stable condition on month after the surgery. Epidural hematomas are the most common type of spinal hematomas in post thrombolytic period. Treating physicians should have a low threshold for evaluating neck or back pain in patients who recently have received tPA. Hematologic Intracerebral hemorrhage ICH is the most feared complication of thrombolytic use in ischemic stroke patients. The Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register SITS-ISTR is an internet-based prospective, ongoing, multinational, observational monitoring register of patients with acute ischemic strokes that were managed with thrombolysis. A study based on SITS-ISTR data compared the development of remote parenchymal hemorrhage PHr and parenchymal hemorrhage PH among 43 494 patients between 2002 and 2011. It was observed that 970 patients 2. A combination of PHr and PH was observed in 438 patients 1. Risk of PHr was higher in subjects with female sex, higher age 74 vs. On the other hand risk of PH was higher among subjects with a hyperdense cerebral artery sign HCAS , high National Institutes of Health Stroke Scale NIHSS score, hyperglycemia, diabetes, and atrial fibrillation. After thrombolysis, PHr was closely associated pre-existing vascular pathology, for example, cerebral amyloid angiopathy and prior stroke. Localized PH was associated with large vessel occlusions. A retrospective study compared the risk factors associated with hemorrhagic transformation HT of ischemic stroke managed with intra-arterial thrombolysis. Regardless of the hemorrhagic conversion status, the mortality rates were similar. Patients who had high NIHSS score, elevated globulin level and prothrombin time activity PTA percentage were at higher risk of HT. Elevated globulin level is an independent risk factor for hemorrhagic transformation. An 89-year-old female developed splenic hemorrhage after receiving alteplase for acute ischemic stroke. She was transferred to tertiary care. During MRI her vitals deteriorated and bedside abdominal ultrasound examination was performed by the emergency physician. Musculoskeletal A reported case of thrombolysis-induced sternocleidomastoid hematoma after acute ischemic stroke managed with intravenous alteplase was seen in an 83-year-old female. Notably the patient had lateral cervical extrapulmonary tuberculosis and an ipsilateral TB lymphadenitis proximal to the bleeding sternocleidomastoid muscle at the time of diagnosis. Drug—Drug Interaction An 80-year-old female with acute left hemiparesis received alteplase with improvement in her neurological function while receiving alteplase. A few minutes after the completion of alteplase she developed mild swelling of her tongue, uvula and lips. The airway was patent and did not require intubation. She received steroids with minimal improvement in tongue and lip swelling. She was receiving olmesartan for hypertension prior to alteplase therapy and was continued. Persistent swelling over next few days was suggestive of medication effect other than alteplase. Olmesartan was stopped promptly and swelling improved. David Chiu MD, FAHA, in , 2011 31 What is the treatment for a completed stroke? Intravenous tissue plasminogen activator tPA given within the first 3 hours of an acute ischemic stroke significantly improves the likelihood of a good neurologic outcome. Candidates for thrombolytic treatment should have a potentially disabling deficit that is not rapidly resolving. In , 2008 Primary use Systemic These tissue plasminogen activators t-PA are produced by recombinant DNA technology and are primarily indicated for the management of acute myocardial infarctions. Alteplase is also used in the management of acute ischemic stroke and pulmonary embolism. Ophthalmic Used to treat submacular hemorrhages, post vitrectomy fibrin syndrome, fibrin lysis, lysis of blood clots, intravitreal t-PA and pneumatic displacement for submacular hemorrhages, central retinal artery occlusion. Ocular side effects Systemic administration — intravenous injections Certain Fig. Fluorescein angiography of diffuse granular hyperfluorescence. Photo courtesy of Chen S-N, et al. Retinal toxicity of intravitreal tissue plasminogen activator. Ophthalmology 110: 704—708, 2003. ERG high dosage — reduce scotopic and photoic a and b waves 3. Vitreous hemorrhages Clinical significance The major toxicity of tissue plasminogen activators t-PAs is hemorrhage. This results either from lysis of fibrin at the sites of vascular injury or a systemic lytic state from the formation of systemic plasmin, which produces fibrinogenolysis and the destruction of other coagulation factors. Systemically administered t-PA for various illnesses can cause bleeding anywhere within the eye or periorbital tissues. This may occur in sites of recent ocular surgery Khawly et al 1996; Roaf et al 1997 or be associated with the presence of exudative macular degeneration or retinal vascular diseases Kaba et al 2005. Visual outcomes vary from no complications to blindness, or loss of the eye. Chorich et al 1998 emphasized that the onset of eye pain or vision loss after systemic t-PA should alert physicians to the possibility of an ocular or adnexal hemorrhage. Hyphemas Tripathi et al 1991; Lundy et al 1996; Loffler et al 1997 , subconjunctival hemorrhage Lee et al 1995 and vitreous hemorrhages Kim et al 1998 have all been reported. Rehfeldt and Hoh 1999 , in their series of 185 intracameral t-PA injections, had a 5. This included one case of Fuch's dystrophy, which had irreversible corneal endothelial decompensation. Hesse et al 1999a confirmed the temporary endothelial toxicity of t-PA. Damage to the corneal endothelium allows phosphate buffer of t-PA and calcium from the aqueous humour to distribute within the corneal stroma. The insoluble calcium phosphate may then be precipitated within the stroma. This results in irreversible corneal opacification. While this side effect is rare, it is easily produced in experimental animal models when the cornea endothelium is disturbed Hesse et al 1999b. Frequently, intravitreal t-PA is used along with pneumatic displacement, which adds a mechanical variable for possible ocular complications. Hesse et al 1999b described four patients given 100 μg intravitreal t-PA who developed exudative retinal detachment followed by hyperpigmentation of the retinal pigment epithelium in the area of the detachment. Chen et al 2003 reported a case similar to the above after two successive injections of 50 μg intravitreal t-PA, 3 days apart with a minimal recovery of visual acuity. Because of numerous reports of retinal toxicity in animals and humans Hrach et al 2000 , Chen et al 2003 advocate not using an injection over 25 μg. Hassan et al 1999 varied this by recommending 25—100 μg and Hesse et al 1999b felt higher dosages were indicated. Intravitreal t-PA can cause sudden severe vitreous hemorrhages as an immediate complication Kokame 2000.
Lancet 1992; 339: 753-70. Circulation 1987; 76: 142-64. Hematologic Intracerebral hemorrhage ICH is the most feared complication of thrombolytic use in ischemic stroke patients. Specific rtPAs include, and. The reperfusion rate is dependent on the interval between the onset of symptoms and the initiation of therapy. Half-life: Alteplase: Distribution: Less than 5 minutes. Philadelphia, PA: Elsevier Saunders; 2016:chap 407. However, the prophylactic efficacy of these medications has not been established.
