The use of thrombolysis for ischemic stroke: indications and contraindications, types. Prehospital thrombolysis for myocardial infarction An absolute contraindication for thrombolytic therapy

The general population should know that if there is a sudden distortion of the face, weakness or numbness of the limbs on one half of the body, or speech disturbances, that is, if symptoms of an ischemic stroke suddenly appear, one should immediately call an ambulance and insist on hospitalization in a specialized stroke center ( or to a hospital with a neurovascular department), where it is possible to conduct thrombolysis in a ward/intensive care unit. If less than 6 hours have passed since the onset of the disease and the patient’s condition is not critical, the arriving team, as a rule, should not carry out any treatment, trying to deliver the patient to the hospital as quickly as possible, notifying the stroke team along the way.

According to the World Health Organization (or WHO), a stroke is a rapidly developing focal or global disorder of brain function lasting more than 24 hours or leading to death, when another cause of the disease has been excluded. The concept of ischemic stroke reflects the fact of the development of a disease caused by a decrease in blood flow in a certain area of ​​the brain and characterized by the formation of cerebral infarction. Cerebral infarction is a zone of necrosis formed as a result of persistent metabolic disorders resulting from insufficient blood supply to the brain area.

Despite the variety of approaches used in the treatment of patients with ischemic stroke (IS), only five provisions have a high class (I) and level of evidence (A) regarding the effect on the prognosis of the disease: [ 1 ] emergency hospitalization of patients with suspected stroke in hospitals with departments for the treatment of patients with acute cerebrovascular accidents (ACVA); [ 2 ] prescribing acetylsalicylic acid drugs in the first 48 hours from the moment the first symptoms of the disease appear; [ 3 ] carrying out systemic thrombolysis with recombinant tissue plasminogen activator (rtPA) to carefully selected patients in the first 4.5 hours of IS (one of the most effective methods of drug treatment of IS); [ 4 ] performing mechanical thrombus extraction using retriever stents in the first 6 hours of stroke in patients with confirmed occlusion of the internal carotid artery (ICA) or proximal parts (M1 segment) of the middle cerebral artery (MCA); [ 5 ] decompressive hemicraniectomy for the treatment of cerebral edema due to occlusion of the main trunk of the MCA during the first 48 hours of stroke.

« The gold standard» Reperfusion therapy for IS remains systemic thrombolysis. Thus, if considering the possibility of performing endovascular reperfusion treatments (see below) in patients who meet the criteria for systemic thrombolysis, it is necessary to perform it, according to the North American recommendations for the treatment of acute stroke, updated in 2015.

The method of systemic thrombolysis was approved by the Federal Service for Surveillance in Healthcare and Social Development as a new medical technology (permission to use a new medical technology FS No. 2008/169 dated 01.08.2008). Since 2008, thrombolysis has been an integral component of providing medical care to patients with stroke in primary vascular departments and regional vascular centers, created as part of the implementation of a set of measures to reduce mortality from vascular diseases. The procedure for conducting thrombolytic therapy (TLT) is regulated by the Order of the Ministry of Health of the Russian Federation “On approval of the procedure for providing medical care to patients with acute stroke” No. 389n dated 07/06/2009 (as amended by Orders of the Ministry of Health of the Russian Federation No. 44n dated 02/02/2010 and No. 357n dated 04/27/2011), by order Ministry of Health of the Russian Federation No. 928n dated November 15, 2012 “On approval of the procedure for providing medical care to patients with acute cerebrovascular accidents.” In 2014, the All-Russian Society of Neurologists approved the domestic Clinical Guidelines for TLT for ischemic stroke.

The use of early TLT for ischemic stroke is based on the concept that rapid (within several hours) restoration of circulation in the affected basin during recanalization of an occluded intracranial artery preserves reversibly damaged brain tissue in the ischemic “penumbra” zone, since brain cells in it retain viability for another 3 to 6 hours (ischemic “penumbra” or penumbra - an area of ​​brain tissue with critically reduced blood flow around the focus of necrosis, the latter is also called the “core” of ischemic stroke).

Ischemic stroke is a dynamic process. Ischemic stroke is a pathophysiological process that begins with blockage of a vessel and ends with the formation of cerebral infarction. As soon as the blood flow in the cerebral artery basin decreases to a level of less than 40% of normal (below 20 - 25 ml per 100 g of brain matter per minute), neurons cease to function normally and focal symptoms appear. In this case, damage to brain tissue occurs: for every minute without treatment, almost 2 million neurons die, 14 billion synapses and more than 12 km of myelinated fibers are damaged. The average volume of the infarction is 54 cm3, it forms on average in 10 hours (Saver J. L., 2006). Since the 80s last century, we know that only a certain area of ​​the brain, where perfusion is below 8 - 12 ml/100 g/min (ischemic core), receives irreversible damage in the first minutes. Around there is, as a rule, a large zone (ischemic penumbra, or penumbra), where the function of neurons is impaired, but their structural integrity and ability to recover are preserved. Until recently, it was common to depict the ischemic core and penumbra as a diagram in which one area simply surrounds the other (Fig. A). However, in most patients, the areas of the brain in the ischemic zone are not homogeneous. Rice. B illustrates the concept of the development of ischemic stroke, based on positron emission tomography data, when “islands” of hypoperfusion are located around the central core, including zones with very low blood flow characteristic of the ischemic core (Lyden P. D., 2001). Blood flow in the penumbra zone is variable and depends on the level of collateral blood supply provided by pial anastomoses of the branches of large arteries. The fate of the penumbra depends on the level of blood flow and the duration of hypoperfusion. No intervention will help restore irreversibly damaged neurons. At the same time, timely (within the so-called “therapeutic window”) restoration of blood supply makes it possible to save and subsequently restore the activity of a significant part of viable cells, which means a reduction in the size of the brain infarction and the severity of neurological deficit. The only method of reperfusion that has clinical significance is the resumption of blood flow in the occluded vessel. Recanalization has a strong direct relationship with the likelihood of a good outcome in ischemic stroke.

read also [1 ] article: “Methods of visualization of the penumbra in ischemic stroke” M.Yu. Maksimova, Doctor of Medical Sciences, Professor, Chief Researcher cerebrovascular accident departments with intensive care units; D.Z. Korobkova, neurologist, graduate student; M.V. Krotenkova, Doctor of Medical Sciences, Head of the Department of Radiation Diagnostics of the Federal State Budgetary Institution "Scientific Center of Neurology" of the Russian Academy of Medical Sciences (journal "Bulletin of Radiology and Radiology" No. 6, 2013) [read] and [ 2 ] dissertation for the academic degree of Ph.D. “Clinical and tomographic markers that determine the course of the acute period of cerebral infarctions in the arterial basin of the carotid system” D.Z. Korobkova, Federal State Budgetary Institution “Scientific Center of Neurology” of the Russian Academy of Medical Sciences; Moscow, 2014 (pp. 22 - 28) [read]

Background information:

more details in the article “Results of implementing standardization of the process of hospitalization of patients with acute cerebrovascular accident in the regional vascular center” by P.G. Shnyakin, E.E. Korchagin, N.M. Nikolaeva, I.S. Usatova, S.V. Dranishnikov (magazine “Nervous Diseases” No. 1, 2017) [read]

TLT should only be performed if the diagnosis is made by a physician who specializes in the management of stroke patients, that is, and has experience in interpreting neuroimaging results, since in patients within the 6-hour “therapeutic window”, indications for thrombolysis are clarified using magnetic resonance imaging. - resonance imaging (MRI) in diffusion and perfusion mode, or, alternatively, using computed tomography (CT). It should be especially emphasized that modern neuroimaging methods (CT and MR angiography, CT and MRI perfusion) with minimal risk for the patient make it possible to objectify both the occlusion of the artery, which led to the development of ischemic stroke, and the recanalization achieved during the process of thrombolysis.

CT and MRI in the diagnosis of cerebral infarction[read ]

read also article“Sequence-Specific MRI Features to Help Date Ischemic Stroke” Laura M. Allen, MD; Anton N. Hasso, MD; Jason Handwerker, MD; Hamed Farid, MD; Radio Graphics 2012; 32:1285–1297; doi: 10.1148/rg.325115760 [read]

read also the post: Perfusion computed tomography(to the site)

CT remains the modality of choice when evaluating candidates for thrombolysis. The advantages of the method include the minimum duration of the study, accessibility, the ability to visualize cerebral infarction in the first minutes and hours when using contrast techniques, quickly differentiate ischemic stroke from hemorrhagic stroke, reliably diagnose intracranial hemorrhage, exclude other diseases that mimic ischemic stroke (for example, tumors, encephalitis, arteriovenous malformations). Direct signs of cerebral infarction appear on non-contrast CT scans by the end of the first day from the onset of stroke symptoms. Early CT signs of ischemic stroke include: a symptom of a hyperdense artery (increased density), loss of the insular line, blurring of the boundaries and loss of the normal outlines of the nucleus lentiformis, compression (smoothing of the subarachnoid spaces), loss of differentiation into gray and white matter in the ischemic zone.

In addition to the presence of a 4.5-hour “therapeutic window” (for systemic TLT) and neuroimaging data for thrombolysis, it is necessary to assess the severity of neurological symptoms in the acute period of ischemic stroke using the NIHSS (National Institutes of Health Stroke Scale), which allows an objective approach to the condition a patient with a stroke (the value of the assessment increases if the assessment is carried out over time: one hour after thrombolysis, then every 8 hours during the first days). The total score on the scale allows you to roughly determine the prognosis of the disease, which is of fundamental importance for planning TLT and monitoring its effectiveness. Thus, the indication for thrombolysis is the presence of a neurological deficit (according to various sources, more than 3 - 5 points on the NIHSS scale), suggesting the development of disability. Severe neurological deficit (according to various sources, more than 24 - 25 points on the NIHSS scale) is a contraindication to thrombolysis and does not have a significant effect on the outcome of the disease [see. NIHSS scale ].

about that How to correctly fill out the US National Institutes of Stroke Severity Scale (NIHSS) You can read in the elective course “Introduction to Angioneurology”, lesson 16 “Neurological and rehabilitation scales in angioneurology: US National Institutes of Health Stroke Scale, Rankin Scale, Rivermead Scale and Barthel Index, Glasgow Coma Scale”; Shmonin A.A.; First St. Petersburg State Medical University named after. acad. I.P. Pavlova, Department of Neurology and Neurosurgery with a clinic; St. Petersburg, 2014 - 2015 [read];

more detailed instructions for filling out the NIHSS scale you can obtain from the book “Clinical recommendations for the management of patients with ischemic stroke and transient ischemic attacks” (Library of a practitioner, series “Neurology”) edited by prof. L.V. Stakhovskoy, Moscow, 2017

Candidates for [systemic] thrombolysis are patients aged 18 - 80 years in whom the time of onset of stroke symptoms is clearly recorded (in cases where the stroke develops during night sleep or in the absence of an eyewitness, the time of onset should be considered the moment when the patient last observed asymptomatic), with an initial NIHSS score of ≥5 points. Prerequisites: no signs of intracranial hemorrhage on CT or MRI [see. contraindications for thrombolysis], the presence of a “therapeutic window” (the time from the onset of the first symptoms of the disease to the start of treatment does not exceed 4.5 hours), obtaining the informed consent of the patient or relatives to perform the manipulation.

Please note! A significant achievement of the last 10 years is the expansion of the window of therapeutic opportunity from 3 to 4.5 hours. At the same time, TLT is symptomatic, since the target of its action is only a thrombus or embolus that caused blockage of one or another intra- or extracerebral artery, and not the source of thrombus formation (thrombus in the left atrial appendage, “unstable” atherosclerotic plaque, etc.). This is due to the high percentage (20 - 34) of early reocclusion and rethrombosis even after successfully performed thrombolysis (source: article “Stroke: assessment of the problem (15 years later)” by M. Yu. Maksimova et al., Federal State Budgetary Institution “Scientific Center of Neurology” of the Russian Academy of Medical Sciences, Moscow; Journal of Neurology and Psychiatry named after S.S. Korsakov.

There are the following types of thrombolysis: systemic (syn.: intravenous), selective (syn.: intra-arterial, regional catheter), thrombolysis using mechanical devices for recanalization (aspiration catheter, Penumbra, Catch, Merci Retrieval System devices, ultrasonic destruction of thrombus and etc.), combined (intravenous + intraarterial; intraarterial + mechanical). In systemic (intravenous) thrombolysis, recombinant tissue fibrinogen activator (rt-PA) [alteplase, Actilyse] is used as a thrombolytic at a dose of 0.9 mg/kg of the patient’s body weight, 10% of the drug is administered intravenously as a bolus, the remaining dose is administered intravenously by drip over 60 minutes as early as possible. An overall analysis of the data regarding the use of rtPA within a 6-hour window suggests that thrombolysis is effective for at least 4.5 hours and potentially up to 6 hours after the onset of ischemic stroke.

Scheme of fibrinolysis and the effect of some fibrinolytic drugs
Clinical protocol for the diagnosis and treatment of thrombolysis for ischemic stroke (2014) [read]; Recommendations for thrombolytic therapy in patients with ischemic stroke (2014) [read]; a guide for doctors “Antithrombotic therapy for ischemic stroke” edited by Academician of the Russian Academy of Medical Sciences Shevchenko Yu.L. (library of the National Medical and Surgical Center named after N.I. Pirogov of the Ministry of Health of the Russian Federation) [read]

Selective thrombolysis is a minimally invasive method of delivering a thrombolytic drug under X-ray control directly into the thrombus using an endovascular catheter, used to completely or partially restore the patency of the thrombosed area of ​​the vessel. Selective thrombolysis is indicated for patients with occlusion of the proximal segments of intracerebral arteries. The use of intra-arterial thrombolysis requires the patient to remain in a high-level stroke center with 24-hour access to cerebral angiography. Intra-arterial thrombolysis is the method of choice in patients with severe ischemic stroke lasting up to 6 hours, and for stroke in the vertebrobasilar region up to 12 hours. Intra-arterial thrombolysis involves a local long-term infusion of thrombolytics (rt-PA or urokinase) for a maximum of 2 hours under angiographic guidance.

The method of selective thrombolysis has a number of significant advantages over systemic thrombolysis: firstly, it helps to clarify the localization of occlusion, its nature, and to clarify the individual characteristics of cerebral circulation; secondly, it significantly reduces the dose of the fibrinolytic drug and thereby reduces the risk of hemorrhagic complications; thirdly, it provides the opportunity for additional mechanical impact on the thrombus using a microcatheter or conductor; fourthly, it can be carried out outside the 3-hour time window, and finally, the presence of a catheter in the affected artery allows using fractional angiography to monitor the process of thrombus lysis and restoration of circulation.

Clinical protocol for surgical and diagnostic intervention: regional catheter (selective) thrombolysis (2015) [read]

Currently, mechanical recanalization of the affected area of ​​the artery using special instruments – thromboembolectomy – is more effective than intra-arterial thrombolysis. This surgical intervention is performed in a cath lab. The advantages of thromboembolectomy include minimizing the risk of systemic hemorrhagic complications and the possibility of targeting a thrombus or embolus after unsuccessful intravenous thrombolysis. To date, studies have been published with devices such as Merci, Penumbra and Catch.

Clinical protocol for surgical and diagnostic intervention: endovascular treatment of ischemic stroke in the acute period (2015) [read]

Currently, TLT for ischemic stroke can be used for damage to the arteries of both the carotid and vertebrobasilar areas. Nevertheless, all currently existing guidelines for thrombolsis are focused primarily on vascular catastrophe in the carotid region, primarily the middle cerebral artery; this is primarily due to the presence in such patients of obvious neurological deficits in the form of severe paresis and sensory disturbances. A typical functional deficit in a patient with an infarction in the posterior cerebral artery (PCA) in the acute period is not always regarded by the doctor as disabling. The assessment of neurological deficit according to the National Institutes of Health Stroke Scale (NIHSS), which is one of the criteria for selecting patients for TLT, usually is not able to fully reflect the severity of the condition of a patient with a vertebrobasilar infarction. In relation to an isolated visual field defect in acute infarction in the PCA territory, there are no recommendations at all. Therefore, TLT in patients with infarctions in the PCA territory is not widely used. However, given that hemiparesis in some cases is a significant clinical component of infarctions in the PCA territory, such patients, in the absence of contraindications, are justifiably treated with systemic and/or intra-arterial (selective) thrombolysis. When comparing the efficacy and safety profiles of intravenous thrombolysis administered within the first three hours from the onset of symptoms in patients with carotid infarctions and PCA infarctions, no significant difference in safety and treatment outcome was found. At the same time, according to a number of authors, when performing intravenous TLT for ischemic lesions in the vertebrobasilar system, and in particular the PCA, it is possible to expand the therapeutic window to 6.5 - 7 hours and even more compared to 4.5 hours for infarctions in the carotid system . Intra-arterial thrombolysis for occlusion of the middle cerebral artery is recommended within 6 hours from the onset of symptoms, and for occlusion of the basilar artery - no later than 12 hours. However, today there are no clear recommendations on the time limits for intra-arterial thrombolysis in patients with PCA lesions ( source: article “Ischemic stroke in the posterior cerebral arteries: problems of diagnosis, treatment” by I.A. Khasanov (doctor of the neurological department for patients with acute cerebrovascular accidents), E.I. Bogdanov; Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, Kazan; Kazan State Medical University (2013) [read] or [read]).

During thrombolysis and after its completion, intensive monitoring should be carried out (monitoring blood pressure, pulse, respiratory rate, body temperature and neurological status: pupil size, photoreaction, muscle strength and range of active movements in the limbs) in accordance with the provisions of international and domestic protocols [in thrombolysis time - every 15 minutes; after thrombolytic administration: the first 6 hours - every 30 minutes; up to 24 hours - every 60 minutes]. A day after thrombolysis, repeated neuroimaging (MRI/CT) is required.

Because thrombolysis (i.e., the use of thrombolytic drugs) is associated with the risk of major bleeding, the potential benefits and possible risks of thrombolysis should be discussed with the patient and family before treatment whenever possible.

The following types of bleeding associated with TLT are distinguished: minor bleeding (usually due to puncture or damage to blood vessels from the gums), major bleeding (in the central nervous system, in the gastrointestinal or urogenital tract, in the retroperitoneal space, or bleeding from parenchymal organs) . Before the thrombolysis procedure and for 24 hours after it, in order to prevent bleeding, intramuscular injections should not be performed. If it is necessary to install a urinary catheter or nasogastric tube, it is advisable to perform these manipulations before thrombolysis, since otherwise there is a risk of bleeding from injured mucous membranes. Catheterization of central non-compressible veins (subclavian, jugular) is prohibited within 24 hours after thrombolysis. It is not recommended to feed patients after thrombolysis for 24 hours. Antithrombotic therapy as part of secondary prevention can only be started 24 hours after intravenous TLT.

If during (or after) thrombolysis the patient develops severe headaches, an acute rise in blood pressure, nausea and vomiting, psychomotor agitation, vegetative symptoms (facial and scleral hyperemia, hyperhidrosis), a significant increase in focal neurological symptoms, which may indicate about the development, the thromboitic infusion is stopped (if it is still ongoing) and an emergency CT scan is performed. If signs of hemorrhagic transformation of the cerebral infarction zone are verified, fresh frozen plasma is administered. If local hemorrhages occur (from injection sites or gums [the “vampire smile” symptom]), cessation of the thrombolysis procedure is not required; bleeding can be stopped by pressing.

Hemorrhagic transformation of a brain lesion is symptomatic if its development leads to an increase in the total score on the NIHSS stroke scale by 4 points or more. In most cases of intracerebral hemorrhages after thrombolysis, the formation of asymptomatic hemorrhagic transformation is recorded, detected by CT/MRI, which often accompanies clinical improvement and is evidence of reperfusion.

In a patient who has suffered an ischemic stroke, the main criteria for the effectiveness of thrombolysis are: complete stabilization of vital functions (respiration, central hemodynamics, oxygenation, water-electrolyte balance, carbohydrate metabolism), absence of neurological complications (cerebral edema, convulsive syndrome, acute occlusive hydrocephalus, hemorrhage to the infarction zone, dislocation), minimization of neurological deficit (ideally, restoration of daily independence and, if possible, ability to work), restoration of blood flow of a stenotic [occluded] vessel (confirmed by the results of angiographic and ultrasound studies), absence of somatic complications (pneumonia, pulmonary embolism, deep vein thromboembolism lower extremities, bedsores, peptic ulcers, urinary tract infections, etc.), normalization of blood pressure levels, etc.

Ischemic stroke belongs to the category of the most common vascular diseases of the brain and is a cerebral infarction. It has been clinically proven that in the first minutes after a cerebral stroke, only a small part of the brain, called the ischemic core, is subject to irreversible damage.

The remaining parts of the brain retain their viability and minimal functioning for some time.

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That is why it is very important to make all possible attempts to restore normal blood circulation in the damaged brain tissue as soon as possible.

One of the most effective and efficient methods is considered to be thrombolytic therapy, the main idea of ​​which is to restore normal blood circulation and dissolve the blood clot or atherosclerotic plaque that caused the blockage of the vessel.

The use of thrombolysis for ischemic stroke requires strict implementation of a number of organizational measures:

• Hospitalization of post-stroke patients as quickly as possible.
• In the first 2-3 hours after development, it is necessary to carry out all the necessary diagnostic studies, since thrombolysis is carried out only after a complete diagnosis of the patient’s condition. As a rule, the VMP protocol is most often used for this purpose - this is a kind of referral to highly qualified medical care.
• For post-stroke patients, special intensive care wards with all the necessary equipment are required.

The essence of this type of therapy is that a special drug is delivered into the vessel through a dropper, which promotes the effective dissolution of a blood clot or atherosclerotic plaque.

Timely thrombolytic therapy is an opportunity not only to save the life of a person in a post-stroke state, but also to restore hope for complete rehabilitation and a return to normal life.

Basics of therapy

As mentioned above, thrombolytic therapy should be carried out no less than 3 and no more than 6 hours after the onset of an ischemic stroke. Timely thrombolysis helps to quickly dissolve the blood clot in the affected vascular area and return blood flow to normal.

Rapid injection of a special thrombolytic into the pool of a blocked vessel leads to regression of neurological factors, which can include speech disorders, as well as numbness of certain parts of the body.

The essence of this procedure is that the thrombolytic activates the finrinolytic abilities of the blood, which becomes possible due to the degeneration of ordinary plasminogen into its active form, which is called plasmin.

Species

For quite a long period of time in medicine, there was one possible type of thrombolytic therapy, the essence of which was the intravenous administration of a special drug to a patient in a post-stroke state. The administration of the thrombolytic drug was carried out through a dropper.

Today, several modern types of thrombolysis can be distinguished:

In addition to the fact that in medicine, thrombolysis is classified into types, it is also possible to differentiate the procedure depending on the method of its implementation.

Today, thrombolytic therapy is performed by two main methods:

Local method

The essence of this method is the local administration of the drug directly into the area where the blood clot is located, clogging the blood vessel. This method is also called the catheter method, as it is performed by administering a thrombolytic medication through a catheter.

System method

This method is used in cases where it was not possible to reliably determine in which blood vessel the thrombus is located. The drug is injected into a vein and spreads throughout the circulatory system, removing and dissolving all blood clots and atherosclerotic plaques in the vessels. The dosage of the drug used during the systemic method of thrommolysis increases markedly, which can lead to the most unpleasant consequences for the general condition of the patient in the post-stroke state.

Drugs

To dissolve blood clots and atherosclerotic plaques that block blood vessels, certain medications called thrombolytics are used.

The main and most commonly used drugs for thrombolysis in stroke can be identified:

Preparation	Features of use
Streptokinase, Urokinase	These drugs can cause a strong allergic reaction in the patient’s body, so today they are used quite rarely.
Anistreplase, Metalyse, Tenecteplase	These drugs belong to the category of III generation drugs. Can be administered using the jet method.
Alteplase, Actilyse	With timely thrombolysis with these drugs, relief of the patient's condition occurs in the shortest possible time.
Prourokinase	It also refers to effective and fast-acting drugs that increase the likelihood of patient survival several times. But using this drug carries a risk of brain hemorrhage.

Indications for thrombolysis in stroke

As with each treatment method, thrombolytic therapy has its own indications.

Such indications include:

• The main indication for thrombolysis is a confirmed diagnosis of ischemic cerebral stroke.
• This type of therapy is prescribed to patients aged at least 18 and not older than 80 years.
• An extremely important indication is the fact that no more than 3-6 hours have passed since the onset of the ischemic stroke. It is in such cases that thrombolysis may be the most effective treatment for this disease.
• Before prescribing thrombolytic therapy, a computed tomography scan of the head is required. The procedure is prescribed exclusively in cases where there is no hemorrhage in the brain area.

Contraindications

Just like the indications, thrombolysis for ischemic stroke also has a number of significant contraindications that must be taken into account:

• One of the most important contraindications when performing thrombolysis for the treatment of stroke is the presence of cerebral hemorrhage, which can be determined by the results of a computed tomography scan of the head.
• Rapidly regressing neurological deficit.
• Clinical improvement of the patient’s condition immediately within 3-6 hours after an ischemic stroke.
• Behavior of severe surgical treatment during 3-4 months before stroke.
• Pregnancy, lactation period.
• Chronic liver diseases, a history of arterial aneurysm.
• Risk of aortic dissection as a result of thrombolysis.

Stroke has a significant impact on public health and is the third leading cause of death in the world.

Ischemic stroke is one of the main causes of severe post-stroke disability in the adult population.

Thrombolysis for ischemic stroke is intended to reduce the negative symptoms of stroke and reduce the likelihood of patient disability.

Ischemic stroke usually occurs due to an intravascular thrombus obstructing cerebral blood flow.

After the onset of stroke, neurons surrounding the ischemic core may remain viable for a certain period of time.

The destruction of brain cells after ischemia occurs gradually, and restoration of blood flow through early correction can save damaged neurons.

Blood clots blocking cerebral blood flow can be lysed (dissolved). Thrombolysis (thrombolytic therapy) is carried out by dissolving blood clots (thrombi) blocking a blood vessel using thrombolytic drugs.

Thrombolysis is a type of pharmacological therapy aimed at restoring blood flow in a vessel by dissolving a blood clot under the influence of various agents inside the vascular bed.

Thrombolysis for acute ischemic stroke is a key intervention that can reduce disability.

Thrombolytic therapy is carried out by injecting alteplase (g-TPA), a substance belonging to the group of thrombolytic agents, into the patient’s veins.

Alteplase works by converting inactive plasminogen to the active form plasmin, which promotes thrombolysis of fibrin by breaking it down.

The lysis procedure is performed by introducing into the patient's bloodstream 0.9 mg of alteplase (g-TP) per 1 kilogram of the patient's weight over 60 minutes (but not more than 90 mg), with 10% given as a bolus.

Thrombolysis can destroy the clot and reduce cerebral ischemia.

Species

There are two types of thrombolysis aimed at freeing a blocked vessel from a blood clot.

Thrombolysis using thrombolytic agents

The most commonly used thrombolytic drugs include:

• Eminase (Anistreplase);
• Retavaz (Reteplase);
• Streptase (Streptokinase, Cabikinase);
• tPA (a class of drugs that includes Activase);
• Tenecteplase;
• Abbokinase, Kinlitik (Urokinase).

Depending on the pattern of stroke development, the doctor may choose one of the listed drug treatment options.

The drug is usually given through a long catheter that is threaded into the blood vessel directly to the site of the clot to deliver the drugs directly to the site of the blockage.

During thrombolysis, the doctor uses X-ray tomography to see the result of the dissolution of the blood clot. If the clot is relatively small, the lysis process may take several hours. A severe blockage may take several days to heal.

Mechanical thromboembolism

Doctors may also choose another type of thrombolysis called mechanical thromboembolism.

During this procedure, a long catheter that has a tip with a small cuff and a rotating device is inserted into the blood vessel.

A high-speed jet of liquid or ultrasonic radiation is used to physically destroy a blood clot.

Modern stroke management includes, among other things, rapid assessment of the admitted patient, management protocols, early management in the stroke unit, early use of aspirin and appropriate physiological monitoring.

Indications and contraindications

Thrombolytic therapy aimed at restoring cerebral blood flow has proven benefit for some patients with acute cerebral ischemia and may lead to resolution or improvement of acute neurological deficits.

Acute neurological deficit in stroke includes insufficient mobility of the patient's limbs and body and changes in his intellectual, sensitive and emotional spheres.

There are two points of view on thrombolytic therapy, based on statistical data:

1. Thrombolysis has a beneficial effect on cerebral symptoms.
2. The increased risk of intracranial hemorrhage during thrombolytic therapy leaves mortality at the same level.

Studies of stroke patients treated with thrombolytic therapy indicate that:

1. Intravenous fibrinolytic therapy within the first 3 hours after the onset of ischemic stroke offers significant benefit in virtually all patients with potentially disabling deficiency.
2. Intravenous fibrinolytic therapy within 3 to 4.5 hours of stroke onset offers modest benefit when administered to all patients with potentially disabling deficiency.
3. Intra-arterial fibrinolytic therapy over a period of 3 to 6 hours offers modest benefit when used in all patients with potentially disabling deficiency and thrombotic occlusion of a great cerebral artery.
4. Timely MRI of the extent of the patient's cerebral infarction core (irreversibly damaged tissue) and penumbra (tissue at risk that can still be salvaged) can improve the therapeutic yield of lytic therapy, especially during the 3- to 9-hour window.

Major barriers to thrombolysis include:

1. Lack of public awareness and inaccessibility of emergency medical services.
2. About 80% of emergency patients fall outside the “window period” of the effectiveness of this therapy, that is, they arrive at the department 4.5 hours after the first signs of stroke appear.
3. After an MRI imaging procedure, approximately 70% of patients are excluded as candidates for therapy. Of these, about 60% have intracranial hemorrhage, 14% had a transient ischemic attack and an improvement in neurological symptoms, relatives of approximately 6% of patients refuse to consent to thrombolysis, 5.7% of patients were diagnosed with a metabolic disorder (hypoglycemia, hyperglycemia, hyponatremia ).
4. Other reasons for exclusion from therapy are the patient's post-ictal status, recent thrombolysis, recent surgery, delay in contact with the radiologist, and often lack of time to make the necessary decision agreed with the patient's relatives. Another difficult issue of thrombolytic therapy is economic. The cost of drugs and measures taken is quite high.

Thrombolysis is indicated for a sick patient in the following cases:

1. No more than 3 - 4.5 hours have passed since the onset of stroke symptoms.
2. The hemorrhagic nature of the stroke is excluded and vascular hemorrhage is guaranteed to be excluded.
3. The patient has a significant neurological deficit associated with a cerebral stroke.

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Thrombolysis at the prehospital stage

In an analysis of various clinical trials involving more than 6000 patients who received prehospital or inpatient thrombolysis, a significant reduction in early mortality rates (17%) was found with prehospital thrombolysis. A meta-analysis of 22 clinical trials found a greater reduction in mortality in those patients who received thrombolysis within 2 hours of the onset of clinical manifestations compared with later periods. These data support the need for thrombolytic therapy in the prehospital setting when a reperfusion strategy is indicated. More recent post hoc analyzes of several clinical trials and registry data have confirmed the effectiveness of prehospital thrombolysis.

Most of these studies found similar findings to PTA, provided early angiography was performed and PTA was performed in patients who required the procedure. However, studies comparing the clinical consequences of prehospital thrombolysis and early PTA in patients have not been conducted.

Provided that thrombolytic therapy is the most preferred strategy for myocardial reperfusion, prehospital thrombolysis should be considered as a priority treatment method, provided that all the conditions for its implementation are met: medical and emergency personnel trained in this technique and the ability to interpret on site or transmit an ECG to the hospital for decoding. In this case, the goal is to initiate thrombolysis therapy within 30 minutes of first contact with the patient.

Complications of thrombolysis

Thrombolysis therapy leads to a slight increase in the incidence of stroke compared with all complications that appear during the first days after treatment. Early strokes are caused by bleeding in the brain, while later strokes are caused by thrombosis or embolism. Old age, low body weight, female gender, a history of cerebral vascular pathology, systolic or diastolic hypertension at admission are the main risks of intracranial hemorrhage.

In recent studies, intracranial bleeding occurred in the range of 0.9 to 1.0% among the study population. Massive non-cerebral bleeding (bleeding that requires transfusion of blood components or the blood itself, which are life-threatening conditions) occurs in 4-13% of the total number of patients who received thrombolytic therapy.

Contraindications to thrombolytic therapy

Absolute and relative contraindications to thrombolytic therapy are listed in Table. 1. Diabetes mellitus (in particular, diabetic retinopathy) and successful resuscitation are not contraindications to thrombolytic therapy. Thrombolytic therapy should not be performed in the setting of unsuccessful resuscitation measures.

Table 1

Absolute and relative contraindications to fibrinolytic therapy

Absolute contraindications . Hemorrhagic stroke or stroke of unknown origin at any time Ischemic stroke in the previous 6 months Damage to the central nervous system or neoplasm Recent major trauma/surgery/head injury (within previous 3 weeks) Gastrointestinal bleeding within the past month Known Bleeding Aortic dissection Punctures in areas that cannot be compressed (eg, liver biopsy, lumbar puncture)

Relative contraindications Transient ischemic attack in the previous 6 months Taking anticoagulants orally State of pregnancy or within 1 week after birth Refractory arterial hypertension (systolic blood pressure greater than 180 mmHg and/or diastolic blood pressure greater than 110 mmHg) Advanced liver disease Infective endocarditis Exacerbation of peptic ulcer Ineffective resuscitation measures

Angiography after thrombolysis

Provided that thrombolysis has been successfully performed (reduction of ST segment displacement by more than 50% within 60-90 minutes, occurrence of typical reperfusion arrhythmias, disappearance of chest pain), angiography is indicated. This is supported by data obtained from the CARESS (Combined Abciximab Reteplase Stent Study) and TRANSFER-MI studies, where patients referred for angiography after failed thrombolysis had worse long-term outcomes than angiography. all patients followed by (if appropriate indications) PTA.

To avoid early PTA during the prothrombotic period after thrombolysis, on the one hand, and to minimize the risk of reocclusion, on the other hand, the required period of time after successful thrombolysis should be 3-24 hours.

Christian W. Hamm, Helge Möllmann, Jean-Pierre Bassand and Frans van de Werf

Acute coronary syndrome

Thrombosis is one of the most common pathological phenomena in the human body, the fight against which must be timely. This process leads to many adverse consequences, including the death of a person. To get rid of it, doctors may prescribe thrombolysis.

General information about thrombolysis

The natural process of thrombolysis occurs in the body of every person. It is carried out with the help of special enzymes found in the blood. But these substances are not able to fully cope with large blood clots. They are effective only in the presence of small blood clots.

As a result, large clots that form block the lumen of the vessel completely or partially. Because of this, blood circulation fails, which leads to starvation of body cells and even their death. This phenomenon disrupts the functioning of internal organs.

Therefore, the question arises: how to dissolve a blood clot? To solve this problem, artificial thrombolysis is used. The essence of the technique is that the doctor injects medications into the veins that are intended to dissolve blood clots.

Thrombolytic treatment is carried out in two ways:

1. Systemic. Its peculiarity is that it does not matter where exactly the blood clot is located. The medicine spreads throughout the body along with the blood and eventually collides with the blood clot, dissolving it. But this method of thrombolysis has one drawback - the need to use a large dosage of medication, which negatively affects the circulatory system.
2. Local. This method differs in that the medicine is injected directly into the area where the blood clot is located. The drug is delivered to the vessel using a catheter. This method is quite complicated; the implementation is controlled by an X-ray machine.

Which method to give preference to during thrombolytic treatment is decided by the attending physician individually for each patient.

Where is thrombolytic therapy performed? Treatment can be carried out both at home and after hospitalization. Emergency thrombolytic treatment is the most effective, as it has an advantage in terms of timing. After all, the sooner the procedure is performed, the greater the chances of saving a person.

In this regard, hospital thrombolysis has a significant disadvantage. It is prescribed only after the patient has been fully examined. Therefore, the speed of therapy is lower, but it is possible to check the presence of contraindications to the use of thrombolytics, which allows one to avoid many adverse complications.

The use of thrombolysis for stroke and heart attack

Brain stroke is a dangerous pathology that often leads to death. Even if a person survives, recovery is very difficult for him. After all, when the disease occurs, the blood supply to brain cells is blocked, which leads to acute cerebrovascular accident (ACVA) and tissue death.

Thrombolysis for stroke helps prevent adverse consequences. It quickly resolves the blood clot and prevents necrosis of brain cells. In this case, you need to have time to administer the drug within 6 hours from the moment signs of pathology appear.

The same thing happens with a heart attack. The disease also occurs due to blockage of the artery lumen by a thrombus. This is often accompanied by thrombophlebitis. To prevent myocardial tissue from dying, thrombolytic treatment should be performed. It allows you to eliminate acute coronary syndrome (ACS), reduce the area of ​​muscle damage, preserve the function of the left ventricle, which pumps blood, and also reduce the risk of complications and ensure stable heart function.

When is thrombolytic treatment necessary?

Indications for thrombolysis are various diseases of the heart and blood vessels, which are united by the phenomenon of thrombus formation. Such diseases include:

1. Stroke.
2. Myocardial infarction.
3. PE - pulmonary thromboembolism.
4. Blockage of deep veins, peripheral arteries or artificial prostheses located in the vascular lumens by a clot.

The need for thrombolytic treatment is determined by the attending physician after examining the patient.

Who should not be prescribed therapy?

Doctors identify several factors in the presence of which thrombolytic therapy is impossible. If you prescribe treatment without paying attention to contraindications, there is a high risk of complications.

It is prohibited to perform thrombolysis for the following pathologies:

1. High blood pressure.
2. Diabetes mellitus.
3. Allergy to medications used during treatment.
4. Damage to blood vessels.
5. Malignant tumors.
6. Poor blood clotting.
7. Kidney or liver failure.
8. Diseases of the digestive organs.
9. Diseases that can cause bleeding, such as an aneurysm.

In addition to pathological conditions, thrombolytic therapy is not allowed for women who are pregnant, as well as people taking anticoagulants, who have recently undergone surgery, or who have suffered a skull injury in the last 2 weeks. Thrombolysis is also contraindicated in patients over 75 years of age.

What dissolves blood clots?

There are a huge number of thrombolytic drugs in medicine. They are constantly improving. Currently, there are the following types of medications, differing in the nature of their effects:

1. Natural enzymes. They are used only for systemic TLT. They help restore fibrinolysis and have a resolving effect on blood clots. But the drugs also affect the entire body, which can lead to bleeding and the development of allergies. Therefore, they are used to a limited extent.
2. Genetic engineering tools. Restore fibrinogen in the blood. They only affect the blood clot. They are characterized by instant dissolution in the blood, so they are used with caution.
3. Advanced group drugs. They are characterized by the fact that they act selectively and over a long period.
4. Combined medications. They include several medical products at once.

From all groups, several thrombolytics can be distinguished, which are most often used for thrombolysis. These include:

• "Streptokinase". It has the lowest cost among all thrombolytic drugs. The disadvantage of its use is that a person often becomes intolerant to it, develops allergies and other unpleasant complications.
• "Urokinase." Despite the fact that the price of this drug is higher than the previous one, its advantages are small. When using the medication, additional use of Heparin is required.
• "Tenecteplase." On sale it has a different name - “Metalise”. It is administered by injection and requires the use of Heparin and Aspirin. The drug may cause bleeding.
• "Anistreplase". It also has a high cost. The introduction of this product can be carried out in a stream. When using, it is not necessary to inject Heparin into a vein.
• "Alteplase". An expensive medicine that is highly effective. After its use, the survival rate of patients is significantly higher than with the use of other drugs. However, the drug has serious side effects.
• "Actylase". The medication acts directly on the blood clot and does not cause strong blood thinning, which prevents hemorrhage.

In addition to thrombolytics, other drugs are used for thrombus formation, for example, diuretics (Fitolysin), anticoagulants (Heparin), antiplatelet agents (Aspirin). Also, to eliminate symptoms and improve blood circulation, it is allowed to additionally use folk remedies. In extreme cases, surgical intervention is resorted to.

The doctor prescribes surgical or medicinal treatment, taking into account the patient’s condition, the degree of development of the pathology, the presence of concomitant diseases and other factors.

Possible complications

Thrombolysis can not only save the patient, but also cause adverse consequences. These include:

1. Bleeding. Occurs due to deterioration of blood clotting.
2. Allergic reaction. Manifests itself in the form of skin rashes, accompanied by itching and swelling.
3. Arrhythmia. Appears after restoration of coronary blood flow.
4. Recurrence of pain. In case of such a complication, the injection of a narcotic analgesic into a vein is prescribed.
5. Decreased blood pressure. To eliminate this side effect, it is enough to stop using thrombolytics.

Efficacy of therapy

The effectiveness of thrombolytic tablets and injections depends primarily on how timely the therapy was carried out. The greatest effect is achieved if the drug is administered no later than 5 hours after the onset of symptoms of the pathology.

Unfortunately, it is not always possible to carry out thrombolysis during this time. The problem lies in the fact that not all medical institutions have the opportunity to use the technique in question.

How effective the therapy was can be found out through an examination. To do this, magnetic resonance or computed tomography is performed in case of stroke or coronary angiography in case of heart attack. Diagnostics after thrombolysis shows expansion of the lumen of the vessel and destruction of the blood clot.

Thus, thrombolytic therapy is an effective way to eliminate blood clots. This technique gives us the answer to the question of how to dissolve in other parts of the body. It helps to quickly achieve the resorption of a blood clot and avoid consequences dangerous to human life and health.