Drugs that enhance fibrinolysis (fibrinolytics). Mechanism of action and comparative characteristics of individual groups of fibrinolytics. Indications for use. Side effects. Fibrinolytics: drugs, indications for use See what "Fibrinolytics" is

The human body is a very complex system in which even one failure can lead to serious consequences.

Fortunately, medicine and science do not stand still; every year humanity learns new secrets of anatomy and ways to influence internal processes.

One of the most common ways to influence intrasystemic failures in the body are medications.

Nowadays there are a myriad of all kinds of drugs, and upon hearing their names, a person does not always understand their purpose.

These include fibrinolytics, the very name of which is surprising.

So, let's take a closer look at fibrinolytic drugs, what they are and why they are prescribed.

What kind of means are these?

Fibrinolytic agents are any medication that can stimulate the dissolution of a blood clot. They are also called thrombolytic drugs. The action of fibrinolytics is aimed at activating fibrinolysis - the process of dissolving blood clots.

Thus, the fibrinolytic activity of blood is property of the body aimed at liquefying clots.

This property distinguishes them from anticoagulants, which prevent the formation of blood clots by inhibiting the synthesis or function of various blood clotting factors.

The fibrinolytic system of the blood, which exists in the human body, is also involved in the lysis or dissolution of clots during the wound healing process. This system inhibits fibrin, which inhibits the enzyme thrombin.

The active enzyme involved in the fibrinolytic process is plasmin, which is formed under the influence of an activating factor released from endothelial cells.

Classification of drugs

There are two main classes of fibrinolytic agents: direct and indirect. The former include fibrinolysis activators, and the latter include streptokinase and urokinase. Let's consider this classification of fibrinolytics in more detail:

Fibrinolysis activator. This family of thrombolytic drugs is used for acute myocardial infarction, cerebrovascular thrombotic stroke, and pulmonary embolism. In acute myocardial infarction, tissue activators are usually preferred over streptokinase.
Streptokinase. Streptokinase and anistroplase are used for acute myocardial infarction, arterial and venous thrombosis and pulmonary embolism. These compounds are antigenic because they are derived from streptococcal bacteria.
Urokinase. Urokinase is sometimes called urinary plasminogen activator because it is produced by the kidneys and is found in urine. It has limited clinical use because, like streptokinase, it causes significant fibrinogenolysis; used to treat pulmonary embolism.

When to use

Fibrinolytic therapy is approved for the emergency treatment of stroke and heart attack.

The most commonly used drug for thrombolytic therapy is a fibrinolysis activator, but other drugs in this group can also perform this function.

Ideally, the patient should receive these medications within the first 30 minutes of arriving at the hospital. A rapid fibrinolytic effect is what these drugs are prescribed for in these cases.

Heart attacks

A blood clot can block arteries in the heart. This can cause a heart attack when part of the heart muscle dies due to lack of oxygen. Thus, thrombolytics quickly dissolve a large clot.

This helps restore blood flow to the heart and prevent damage to the heart muscle. Best results can be achieved if the medicine is administered within 12 hours of the onset of the heart attack.

The drug restores blood flow to the heart in most people. However, in some patients, blood flow may not be completely normal, and as a result, damage to the heart muscles may occur.

Stroke

Most strokes are caused when blood clots lodge in a blood vessel in the brain and block blood flow to that area.

In such cases also fibrinolytics can be used to quickly dissolve the clot.

Administering medications within 3 hours of the first symptoms of a stroke may help prevent brain damage and disability.

These drugs are also used to reduce the fibrinolytic activity of the blood.

In such cases, the body is not able to prevent the formation of blood clots on its own, so it needs medical attention.

Even if thrombolysis is successful, fibrinolytics are not able to restore tissues that have already been damaged by impaired blood circulation.

Therefore, the patient may require further treatment to address the underlying causes of blood clots and repair damaged tissues and organs.

Contraindications and side effects

Bleeding is the most common risk associated with drug use. It can also threaten the patient's life.

Minor bleeding from the gums or nose may occur in approximately 25% of patients taking the drug.

Bleeding in the brain occurs in approximately 1% of cases.

This is the same risk for both stroke and heart attack patients.

Bleeding is often noted at the catheterization site, although gastrointestinal and cerebral hemorrhages are possible.

Therefore, fibrinolytics are not usually prescribed to patients who have suffered trauma or have a history of cerebral hemorrhage.

In addition to the serious risk of internal bleeding, there are other possible side effects, For example:

bruises on the skin;
damage to blood vessels;
migration of a blood clot to another part of the vascular system;
kidney damage in patients with diabetes or other kidney disease.

Although fibrinolytics can safely and effectively improve blood flow and relieve symptoms in many patients without the need for invasive surgery, they are not recommended for everyone.

Such drugs are prohibited for patients who are taking blood thinners or for people with an increased risk of bleeding. These conditions include:

high pressure;
bleeding or severe blood loss;
hemorrhagic stroke from bleeding in the brain;
severe kidney disease;
recent surgery.

List of drugs

Speaking about fibrinolytic drugs, the list can be quite extensive; we will just name a few of them.

The most common brands of fibrinolytics include the following:

Actylase;
We perform thrombosis;
Fortelysin;
Metalise;
Thromboflux and others.

Almost all of these drugs are available by prescription, as they have a wide range of contraindications and side effects, and therefore can cause potential harm to the body.

Conclusion

If you suspect symptoms of a heart attack or stroke, you should contact an ambulance as quickly as possible, but you should never self-medicate.

Source: http://varikoznik.com/varikoz/lekarstva/fibrinoliticheskie-sredstva.html

What are Fibrinolytic drugs?

drugs that promote the dissolution of intravascular blood clots and are used for arterial and venous thrombosis, as well as for thromboembolism of the pulmonary arteries.

Among F. s. distinguish: drugs with a direct fibrinolytic effect (fibrinolysin, oraza, tricholysin, etc.

); drugs that dissolve blood clots by activating plasminogen (streptokinase, urokinase, tissue plasminogen activator, prourokinase, acylated plasminogen-areptokinase complex - plasminogen activator, streptodecase); drugs that stimulate the formation of fibrinolytic system proteins (anabolic steroids, nicotinic acid, etc.).

From F. s. direct action in domestic medical practice, mainly fibrinolysin obtained from human blood plasma is used. However, fibrinolysin is inferior in effectiveness to plasminogen-activating enzymes, and therefore, in modern conditions, streptokinase and urokinase preparations are most widely used. Streptokinase is an enzyme produced by some strains of β-hemolytic streptococci.

Streptokinase preparations, similar to the source of production and properties, are produced in various countries under the names “Cliase”, “Avelizin”, “Streptase”, “Cabikinase”, etc. By combining with plasminogen in a stoichiometric ratio (1:1), streptokinase promotes the conversion of the plasminogen molecule in plasmin. In the human body, streptokinase partially binds to antibodies, and therefore only a portion of the administered dose of this drug interacts with plasminogen.

The half-life of antibody-bound streptokinase is about 20 minutes, and that of plasminogen-bound enzyme is about 80 minutes.

In the body, streptokinase is metabolized to amino acids and peptides, which are excreted by the kidneys. Peptokinase has antigenic properties and therefore causes the formation of antibodies to it, the content of which gradually increases with systematic use of the drug, which causes a decrease in the effectiveness of streptokinase due to its binding to antibodies.

Usually, by the 6th day from the start of treatment, the level of antibodies becomes so high that the administered drug almost completely binds to them. For this reason, further use of streptokinase becomes inappropriate due to the loss of its effectiveness. The height of the titer of antibodies to streptokinase is significantly influenced by a previous streptococcal infection, which contributes to an increase in their production.

Urokinase is a specific proteolytic enzyme obtained from human urine and human embryonic kidney cell culture. Urokinase converts plasminogen into plasmin by cleaving the arginyl-valine bonds in its molecule. Like streptokinase, urokinase reacts both with plasminogen adsorbed on fibrin and with plasminogen circulating in the blood.

The drug acts for a short time (half-life when administered intravenously 9-16 minutes). Urokinase reduces the content of plasma plasminogen and fibrinogen, as well as the level of α2-antiplasmin, increases the content of fibrin and fibrinogen breakdown products, and lengthens thrombin time. When urokinase is administered, practically no allergic reactions are observed, and no antibodies to it are formed.

Tissue plasminogen activator and prourokinase have a more selective fibrinolytic effect and have very little effect on plasma fibrinogen levels.

Tissue plasminogen activator is produced by vascular endothelial cells. Being a serine protease of the trypsin type, it affects plasminogen only in the presence of fibrin.

Plasmin formed on fibrin is practically not inhibited by α2-antiplasmin.

Clinical studies of tissue plasminogen activator have shown that it is the most active thrombolytic agent, the action of which is not limited by antigenic properties and is practically not accompanied by an increase in the content of plasmin and fibrinogen. For medical purposes, the drug is obtained from a culture of human melanoma cells or using genetic technology.

Prourokinase has fibrinolytic properties similar to tissue plasminogen activator. It differs from urokinase in its resistance to inhibitors of this enzyme circulating in the blood, and also in that it is converted into the active form only upon adsorption on fibrin.

Acylated plasminogen-streptokinase complex - plasminogen activator (AP-SAC; synonym for eminase) is a drug created on the basis of the principle of acylation of enzymes by introducing an acyl group into the active site of plasminogen, which prevents the interaction of this enzyme with streptokinase contained in the complex.

Gradually freed from the acyl group, the complex acquires proteolytic activity and dissolves blood clots. In terms of efficiency and selectivity of action, it is similar to tissue plasminogen activator.

For venous thrombosis F. s. have a pronounced effect in cases where they are used within 10 days from the onset of clinical manifestations of thrombosis. The highest efficiency (lysis of blood clots in 70% of cases) when prescribing F. s. in the first 2 days. According to some authors, the most optimal is the introduction of F. y: within 12 hours.

At the same time, the highest percentage of thrombolysis and the lowest frequency of bleeding and pyrogenic reactions are noted. For thrombosis of intracerebral veins F. s. used only under the control of computed tomography. For thromboembolism of the pulmonary arteries, fibrinolytic agents are effective in cases of massive occlusions and subject to rapid administration of drugs from the onset of clinical symptoms.

For arterial thrombosis F. s. have a pronounced effect in cases where therapy begins within 12 hours from the onset of clinical symptoms. In the presence of chronic arterial stenosis, the effectiveness of F. s. is significantly reduced. Positive results of using F. s. described for thrombosis of the renal and mesenteric arteries, thrombosis of the retinal arteries, and also intracardiac thrombus. In case of myocardial infarction, the use of streptokinase can reduce mortality by 50%.

Drugs that stimulate the formation of proteins of the fibrinolytic system (anabolic steroids, etc.) are usually not able to dissolve an already formed thrombus, therefore they are used only for the purpose of preventing thrombosis in people with a tendency to form them. Streptokinase and urokinase are administered intravenously by drip or stream (slowly) into for 15 minutes, eminase - intravenously for 2-4 minutes, fibrinolysin - intravenously drip for 3-4 hours at a rate of 100-160 units per 1 minute. Doses F. s. vary depending on the location of the blood clots.

Thus, for deep vein thrombosis, an initial rapid administration of 250,000 units of streptokinase or 300,000 units of urokinase is recommended, followed by the administration of drugs for 2-3 days. The daily dose of streptokinase is 2,400,000 units, urokinase - 7,200,000 units. For pulmonary embolism, 250,000 units of streptokinase or 300,000 units of urokinase are initially administered, then every hour, 100,000 units of streptokinase or 250,000 units of urokinase for 12-24 hours.

In case of occlusion of peripheral arteries, local intra-arterial or systemic (intravenous) administration is used. The initial dose for intravenous administration is 250,000 units of streptokinase or 300,000 units of urokinase. Over the next 2-3 days, F. s. used in the same doses as for pulmonary embolism. Locally, streptokinase is prescribed in a daily dose of 240,000 units, and urokinase - 1,000,000 units. Administration is continued for 3 days.

For myocardial infarction, the following doses are recommended for intravenous administration: streptokinase - 1,500,000 units. urokinase - 2,500,000 units (over 60 minutes), tissue plasminogen activator - 80 mg over 180 minutes, eminase - 30 units over 2-4 minutes. Intracoronary urokinase is administered at a dose of 500,000 units over 60 minutes, tissue plasminogen activator - 20 mg over 60 minutes, eminase - 10 units over 15 minutes.

When using streptokinase, a rapid administration of 20,000 units is recommended, followed by 150,000 units over 60 minutes. It is not recommended to use acetylsalicylic acid concomitantly with plasminogen activators. It is usually prescribed 2 hours after the end of fibrinolytic administration.

During therapy F. s. hemorrhagic complications occur most often. In addition, allergic reactions may occur in the form of itching, urticaria, facial flushing, headache, as well as chills and increased body temperature. These complications rarely require discontinuation of treatment. However, if allergic and pyrogenic reactions occur, it is necessary to stop the administration of F. s. and the administration of glucocorticoids, antihistamines, or antipyretics.

In cases of minor bleeding, especially from injection sites and superficial wounds, treatment is usually not stopped, but local hemostatic agents are prescribed. Stop the administration of F. s. only in case of life-threatening bleeding, as well as in cases of urgent surgical intervention.

Hemostasis is normalized by administering fibrinogen, factor VIII, whole blood or cryoprecipitate. To quickly neutralize the effect of F. s. sometimes they resort to prescribing aminocaproic acid or other fibrinolysis inhibitors (see Antifibrinolytic agents).

F. s. are contraindicated. with hemorrhagic diathesis, gastric and duodenal ulcers in the acute stage, cavernous pulmonary tuberculosis in the acute stage, bleeding, open wounds, acute radiation sickness in the stage of a full-blown clinical picture, increased systolic blood pressure above 200 mm Hg. Art. and diastolic blood pressure above 110 mm Hg. Art., as well as in the first days after operations and childbirth.

Medicines that help dissolve a fibrin clot and are used to treat diseases accompanied by thrombosis (for example, fibrinolysin, streptase).

Source: https://dic.academic.ru/dic.nsf/enc_medicine/32811/%D0%A4%D0%B8%D0%B1%D1%80%D0%B8%D0%BD%D0%BE%D0 %BB%D0%B8%D1%82%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B8%D0%B5

Mechanism of action of thrombolytics, indications, side effects

In this article you will learn: how they work thrombolytics, to whom and for what they are prescribed. Types of drugs. Side effects, interactions with other medications, contraindications.

Thrombolytics (fibrinolytics) are drugs whose action is aimed at destroying blood clots.

Unlike antiplatelet agents and anticoagulants, which reduce blood viscosity and prevent thrombus formation, thrombolytics are able to dissolve already formed blood clots.

Therefore, antiplatelet agents and anticoagulants are the prevention of blood clots, and thrombolytics are their treatment.

This group of drugs is administered only by an experienced resuscitator or cardiologist in a hospital setting.

Mechanism of action

A special protein, fibrin, is responsible for the “viscosity” of blood. When there is not enough of it in the blood, a tendency to bleeding appears and the coagulation process slows down when tissue is damaged. But when its level is elevated, blood clots form from it.

A special enzyme, plasmin, breaks down excessive amounts of fibrin. The breakdown process is called fibrinolysis. In the blood, this enzyme is present in large quantities in an inactive form - in the form of plasminogen. And only when necessary does it turn into plasmin.

The mechanism of physiological fibrinolysis

In healthy people, the amount of fibrin and plasmin in the blood is balanced, but with a tendency to thrombosis, the level of plasmin is reduced.

Thrombolytic drugs (another name is fibrinolytics) activate the resorption of blood clots, converting plasminogen into plasmin, which is capable of breaking down fibrin, a protein that forms blood clots.

Indications

Fibrinolytics are prescribed for the following pathologies:

Myocardial infarction caused by a thrombus.
Ischemic stroke.
Pulmonary embolism.
Thrombosis of any large arteries or veins.
Intracardiac thrombi.

Drug treatment of thrombosis is advisable no later than within 3 days from the moment of thrombus formation. And it is most effective in the first 6 hours.

Types of thrombolytics

Based on novelty and effectiveness, drugs in this group are divided into 3 generations.

Despite the effectiveness of the drug, it very often causes allergic reactions. The first drug that has thrombolytic activity was Streptokinase. This enzyme is produced by bacteria - beta-hemolytic streptococci. The fibrinolytic effect of this substance was first described back in 1940.

Moreover, both Streptokinase and Urokinase provoke the breakdown of not only the dangerous fibrin that formed the blood clot, but also fibrinogen, prothrombin, clotting factor 5 and clotting factor 8. This is very fraught with bleeding.

These shortcomings of the first thrombolytics prompted scientists to develop new fibrinolytic agents that are safer for the body.

Thrombolytics 2nd and 3rd generations are more selective. They have a more targeted effect on the blood clot and do not thin the blood so much.

This minimizes bleeding as a side effect of thrombolytic therapy.

However, the risk of bleeding still remains, especially if there are predisposing factors (if they exist, the use of drugs is contraindicated).

In modern medical practice, 2nd generation thrombolytics are mainly used, since they are safer than 1st generation drugs.

Contraindications

Thrombolytic therapy is not performed in the following cases:

Heavy internal bleeding in the last six months.
History of spinal cord or brain surgery.
Hemorrhagic diathesis.
Inflammatory vascular diseases.
Suspicion of hemorrhagic stroke
Severe arterial hypertension that cannot be controlled with medication (systolic blood pressure above 185 mm Hg or diastolic blood pressure above 110 mm Hg).
Recent traumatic brain injury.
Severe injury or surgery suffered 10 days or later.
Childbirth (10 days ago and later).
Puncture of the subclavian or jugular vein and other vessels that cannot be pressed was performed less than 10 days ago.
Cardiopulmonary resuscitation that lasted more than 2 minutes, as well as one that caused injury.
Liver failure, severe liver diseases (cirrhosis, hepatitis, etc.).
Varicose veins of the esophagus.
Hemorrhagic retinopathy (tendency to hemorrhages in the retina, often found in diabetes).
Exacerbation of peptic ulcer disease in the last 3 months.
Pancreatitis in acute form.
Endocarditis of bacterial nature.
Aneurysms and other anomalies of large arteries or veins.
Tumors with an increased risk of bleeding, especially in the gastrointestinal tract, lungs, and brain.
History of hemorrhagic stroke.
History of intracranial hemorrhage.
Severe ischemic stroke, with seizures among the symptoms.
Tuberculosis with hemoptysis.
Individual intolerance to the drug.

Hemorrhagic stroke

There are also contraindications regarding the current state of the blood. Thrombolytics are contraindicated if a blood test shows the following abnormalities:

Sugar levels are greater than 400 milligrams per deciliter or less than 50 mg/dL.
Platelet count less than 100,000 per mm3.

If the drug is used for stroke, there are age restrictions. Fibrinolytics are not usually administered to patients under 18 or over 80 years of age for stroke.

Interaction with other drugs

Drugs for thrombolytic therapy are not administered while patients are taking anticoagulants (such as Warfarin).

When used simultaneously with drugs that affect platelet levels (cephalosporin antibiotics, non-steroidal anti-inflammatory drugs, corticosteroids), the risk of bleeding increases.

Patients taking antiplatelet drugs on a regular basis also have an increased risk of bleeding. The doctor must take this into account when calculating the dosage of thrombolytics.

If the patient took ACE inhibitors shortly before the administration of the fibrinolytic, the risk of an allergic reaction increases.

Side effects

The main side effect of all thrombolytics is bleeding:

1. External. From recently damaged vessels, for example, from which blood was taken for analysis. From the gums, nose.
2. Hemorrhages into the skin. In the form of petechiae (dots), bruises

Petechial hemorrhages

Internal. From the mucous membranes of the gastrointestinal tract, organs of the genitourinary system. Hemorrhages in the retroperitoneal space. In the brain (manifested by neurological symptoms: seizures, speech disorders, retardation). Less commonly, bleeding from parenchymal organs (liver, adrenal glands, spleen, pancreas, thyroid and other glands, lungs).

Internal bleeding in patients without contraindications is quite rare.

Arrhythmias (which will require the use of antiarrhythmic medications), decreased blood pressure, nausea, vomiting, and increased body temperature may also occur.

In case of an allergic reaction to the drug, a rash, bronchospasm, swelling, and decreased blood pressure appear. An allergy to a medication can lead to fatal anaphylactic shock. Therefore, it is important to use antiallergic drugs in a timely manner when the first symptoms appear.

Side effects are most pronounced in 1st generation products. When using fibrinolytics of 2 and 3 generations, they occur less frequently and are not so severe.

When using 1st generation thrombolytics, bleeding may be so heavy that a blood transfusion will be required.

Further treatment

The body's response to a sudden thinning of the blood is an increased production of thrombin - a substance that increases blood clot formation.

This may lead to recurrence of thrombosis.

For prophylaxis, thrombolytics of the 2nd or 3rd generation can be reintroduced (but not the 1st due to higher bleeding after their use).

Instead of repeated administration of fibrinolytic, anticoagulants (heparin) or antiplatelet agents (acetylsalicylic acid) can be used to prevent re-formation of blood clots.

Overdose

Since the drug is quickly eliminated from the body, overdose rarely occurs. However, it is very dangerous, as it provokes heavy bleeding, after which a blood transfusion is required.

To eliminate the overdose, stop administering the drug.

Antifibrinolytics (fibrinolysis inhibitors) can also be administered - drugs with a reverse effect that restore blood clotting and stop bleeding. The most common medication in this group is aminocaproic acid.

The human body is a very complex system in which even one failure can lead to serious consequences. Fortunately, medicine and science do not stand still; every year humanity learns new secrets of anatomy and ways to influence internal processes. One of the most common ways to influence intrasystemic failures in the body are medications.

Nowadays there are a myriad of all kinds of drugs, and upon hearing their names, a person does not always understand their purpose. These include fibrinolytics, the very name of which is surprising. So, let's take a closer look at fibrinolytic drugs, what they are and why they are prescribed.

Fibrinolytic agents are any medication that can stimulate the dissolution of a blood clot. They are also called. The action of fibrinolytics is aimed at activating fibrinolysis - the dissolution process.

Thus, the fibrinolytic activity of blood is property of the body aimed at liquefying clots.

This property distinguishes them from anticoagulants, which prevent the formation of blood clots by inhibiting the synthesis or function of various blood clotting factors.

The fibrinolytic system of the blood, which exists in the human body, is also involved in the lysis or dissolution of clots during the wound healing process. This system inhibits fibrin, which inhibits the enzyme thrombin.

The active enzyme involved in the fibrinolytic process is plasmin, which is formed under the influence of an activating factor released from endothelial cells.

For a better understanding of the subject, let's answer the question: fibrinolytic action - what is it and how to understand it? The action of such drugs is aimed at the rapid resorption of clots formed in the blood. Unlike coagulants, they are designed to eliminate the problem, not prevent it.

Classification of drugs

When to use

Fibrinolytic therapy is approved for the emergency treatment of stroke and heart attack.

The most commonly used drug for thrombolytic therapy is a fibrinolysis activator, but other drugs in this group can also perform this function.

Ideally, the patient should receive these medications within the first 30 minutes of arriving at the hospital. A rapid fibrinolytic effect is what these drugs are prescribed for in these cases.

Heart attacks

A blood clot can block arteries in the heart. This can cause a heart attack when part of the heart muscle dies due to lack of oxygen. Thus, thrombolytics quickly dissolve a large clot.

This helps restore blood flow to the heart and prevent damage to the heart muscle. Best results can be achieved if the medicine is administered within 12 hours of the onset of the heart attack.

The drug restores blood flow to the heart in most people. However, in some patients, blood flow may not be completely normal, and as a result, damage to the heart muscles may occur.

Stroke

Most strokes are caused when blood clots lodge in a blood vessel in the brain and block blood flow to that area.

In such cases also fibrinolytics can be used to quickly dissolve the clot.

Administering medications within 3 hours of the first symptoms of a stroke may help prevent brain damage and disability.

These drugs are also used to reduce the fibrinolytic activity of the blood.

In such cases, the body is not able to prevent the formation of blood clots on its own, so it needs medical attention.

Important! Although thrombolysis is usually successful, the treatment fails to dissolve blood clots in about 25% of patients. Another 12% of patients subsequently develop blood clots or blockages in their blood vessels again.

Even if thrombolysis is successful, fibrinolytics are not able to restore tissues that have already been damaged by impaired blood circulation. Therefore, the patient may require further treatment to address the underlying causes of blood clots and repair damaged tissues and organs.

Contraindications and side effects

Bleeding is the most common risk associated with drug use. It can also threaten the patient's life. Minor bleeding from the gums or nose may occur in approximately 25% of patients taking the drug. Bleeding in the brain occurs in approximately 1% of cases.

This is the same risk for both stroke and heart attack patients. Bleeding is often noted at the catheterization site, although gastrointestinal and cerebral hemorrhages are possible. Therefore, fibrinolytics are not usually prescribed to patients who have suffered trauma or have a history of cerebral hemorrhage.

In addition to the serious risk of internal bleeding, there are other possible side effects, For example:

bruises on the skin;
damage to blood vessels;
migration of a blood clot to another part of the vascular system;
kidney damage in patients with diabetes or other kidney disease.

Although fibrinolytics can safely and effectively improve blood flow and relieve symptoms in many patients without the need for invasive surgery, they are not recommended for everyone.

Such drugs are prohibited for patients who are taking blood thinners or for people with an increased risk of bleeding. These conditions include:

high pressure;
bleeding or severe blood loss;
hemorrhagic stroke from bleeding in the brain;
severe kidney disease;
recent surgery.

List of drugs

Speaking about fibrinolytic drugs, the list can be quite extensive; we will just name a few of them.

The most common brands of fibrinolytics include the following:

Actylase;
Fortelysin;
Metalise;
Thromboflux and others.

Almost all of these drugs are available by prescription, as they have a wide range of contraindications and side effects, and therefore can cause potential harm to the body.

Under no circumstances should you take these medications without a doctor's prescription.

Conclusion

If you suspect symptoms of a heart attack or stroke, you should contact an ambulance as quickly as possible, but you should never self-medicate. Be healthy!

ALTEPLASE

Synonyms: Actilyse.

Pharmachologic effect. Recombinant human plasminogen activator (a blood protein involved in the regulation of blood coagulation), which is part of the drug, is a glycoprotein (complex protein), which, after systemic administration, is in the plasma in an inactive form until it binds to fibrin (an insoluble protein formed in blood clotting process). Once activated, the drug activates the transition from plasminogen to plasmin and leads to the dissolution of the fibrin clot, thereby increasing fibrinolysis (dissolution of the blood clot) only in the thrombus tissue.

Indications for use. Acute arterial and venous thrombosis (formation of a blood clot in a vessel).

Method of administration and dose. Administered intravenously over 1-2 minutes at a dose of 10 mg, then dropwise over 3 hours at a dose of 90 mg (in this case, 50 mg is administered over 60 minutes, and the remaining 40 mg is administered over the 2nd and 3rd hours from speed 20 mg/h).

If bleeding occurs due to an overdose of the drug, a transfusion of fresh frozen plasma or fresh blood is indicated; In addition, fibrinolysis inhibitors (drugs that inhibit the dissolution of a blood clot) can be used.

Side effect. Nausea, vomiting, fever, allergic reactions in the form of urticaria, headaches, rarely - bleeding, reperfusion arrhythmias (heart rhythm disturbances as a result of restoration of blood flow through the arteries of the heart).

Contraindications. Hemorrhagic diathesis (increased bleeding), bleeding, previous surgery or injury less than a week old, malignant arterial hypertension (persistent rise in blood pressure, difficult to treat), bacterial endocarditis (disease of the internal cavities of the heart due to the presence of bacteria in the blood), acute pancreatitis ( inflammation of the pancreas), complicated diabetes mellitus, sickle cell anemia (a hereditary disease characterized by increased breakdown of sickle-shaped red blood cells and the presence of functionally defective hemoglobin (oxygen carrier) in them), childhood, pregnancy, breastfeeding, hypersensitivity to the drug. The drug is prescribed with caution to patients with concomitant pulmonary diseases, as well as to patients over the age of 75 years.

Release form. Dry substance for infusion of 0.02 g and 0.05 g in bottles in a package of 1 piece complete with solvent.

Storage conditions. List B. In a cool place.

STREPTODECASA FOR INJECTION (Streptodecasum pro injectionibus)

It belongs to the group of “immobilized” (fixed on a polymer carrier) enzymes and is an activator of the human fibrinolytic (blood clot-dissolving) system, modified by a water-soluble polymer matrix of a polysaccharide nature.

Pharmachologic effect. It has thrombolytic activity (dissolves a blood clot), converts blood plasminogen into plasmin and inactivates its inhibitors, and has a prolonged (long-lasting) fibrinolytic effect.

Indications for use. Acute peripheral arterial thrombosis (formation of a blood clot in an artery) or thromboembolism (blockage of a vessel with a blood clot), except in cases where emergency surgery is indicated; peripheral phlebothrombosis (blockage of a vein with a blood clot), acute thromboembolism in the pulmonary artery system or in cases of recurrent thrombosis of its small branches (periodically repeated blockage of a blood vessel with a blood clot); thrombosis of the central vein and artery of the retina; acute myocardial infarction on the 1st-2nd day of the disease or its recurrent course (reappearance of signs of the disease), with rethrombosis after thrombectomy (repeated blockage of a vessel by a blood clot after its removal).

Method of administration and dose. Intravenously. Streptodecase is administered intravenously in a bolus, usually at an initial dose of 300,000 FU (test dose), then an hour later, in the absence of side effects, an additional 2,700,000 FU (total dose of 3,000,000 FU) is administered additionally in a bolus (within 1-2 minutes) at the rate of 300 000-600,000 FU per minute.

In these doses, the drug causes a significant and long-term increase in fibrinolytic activity of the blood, an increase in the content of stasminogen activator and plasmin, and has a pronounced therapeutic effect.

Streptodecase in therapeutic doses has little effect on blood coagulation parameters.

To prevent rethrombosis (re-occlusion of a vessel by a blood clot), combination therapy with streptodecase and heparin is advisable. Starting from the end of the 1st day after the administration of a therapeutic dose of streptodecase (3,000,000 FU), heparin is administered at the rate of 40,000 units per day (10,000 units every 6 hours) for 7-10 days.

Repeated administration of streptodecase is permissible no earlier than after 3 months. after treatment according to the specified regimen and only after studying the titer of streptococcal antibodies. If necessary, repeated administration is usually carried out after 6 months.

For the treatment of retinal vein thrombosis, it is proposed to administer streptodecase retrobulbarly (behind the eyeball) at 30,000 - 50,000 FU in 0.2-0.3 ml of isotonic sodium chloride solution at intervals of 5 days. In the intervals between injections, heparin and dexamethasone are administered retrobulbarly (see pages 448, 583).

Side effect. Allergic reactions are possible (chills, fever, headache, hyperemia /redness/, urticaria, lower back pain, etc.), and when combined with heparin - hemorrhagic complications: (bleeding, formation of hematomas: limited accumulation of blood in tissues / bruise/), hematuria (blood in urine), etc.

Contraindications. Hemorrhagic diathesis (increased bleeding), bleeding, peptic ulcer of the stomach and duodenum, for 4 days. after surgery and childbirth, acute streptococcal infection, sepsis (blood infection by microbes from the focus of purulent inflammation), endocarditis (disease of the internal cavities of the heart), acute inflammatory diseases of the abdominal organs (pancreatitis, cholecystitis, appendicitis, etc.), pregnancy up to 18 weeks. , high arterial hypertension (high blood pressure), active tuberculosis process, malignant neoplasms, allergies to fibrinolytic drugs in the past; diabetes mellitus, bronchiectasis with a pronounced destructive process (bronchial disease associated with the expansion of their lumen, accompanied by destruction of the bronchi), cirrhosis of the liver, kidney stones in the acute stage, severe atherosclerosis.

Release form. Lyophilized (dehydrated by freezing in a vacuum) powder of 1,500,000 FU (fibrinolytic units) in 10 ml bottles in a package of 2 bottles.

Storage conditions. List B. At a temperature not higher than +10 °C.

STREPTOKINASE

Synonyms: Avelizin, Streptase, Cabikinase.

Pharmachologic effect. Activates the fibrinolytic (blood clot dissolving) enzyme system, breaks down the fibrin contained in blood clots, resulting in thrombolysis (blood clot dissolution).

Indications for use. Embolism (blockage) of the pulmonary artery and its branches; thrombosis (formation of a blood clot in a vessel) of arteries and embolism of peripheral arteries with conservative (non-surgical) treatment; thrombosis of superficial and deep veins of the extremities; acute myocardial infarction during the first 12 hours; blockage of blood vessels in the retina of the eye.

Method of administration and dose. Streptokinase is administered intravenously, and, if necessary, intra-arterially.

It is usually administered intravenously at an initial dose of 250,000 IU (IU) in 50 ml of isotonic sodium chloride solution over 30 minutes (30 drops per minute). This dose usually causes the onset of lysis (dissolution) of the clot. Then the administration of streptokinase is continued at a dose of 100,000 IU per hour. The total duration of administration is, as a rule, 16-18 hours. Subsequent treatment is carried out with heparin and indirect anticoagulants.

With extensive arterial and venous thrombosis, long-term administration of streptokinase is sometimes necessary.

Intra-arterial administration of streptokinase is used in the acute period of myocardial infarction (initial dose 20,000 IU; maintenance dose - 2000-4000 IU per minute for 30-90 minutes).

In all cases, the administration of streptokinase should be started as early as possible, since the best effect is observed with fresh blood clots.

Treatment with streptokinase is carried out under the control of thrombin time (an indicator of blood clotting) and the level of fibrinogen in the blood (one of the blood clotting factors).

Side effect. Nonspecific reactions to protein are possible; headache, nausea, slight chills; allergic reactions; hematomas (limited accumulation of blood in the tissue /bruise/) with intramuscular injections; bleeding after puncture (piercing with a needle). To prevent allergic reactions, it is recommended to administer 50 mg of prednisolone intravenously simultaneously with streptokinase."

Contraindications. Hemorrhagic diathesis (increased bleeding), recent bleeding, severe hypertension (persistent rise in blood pressure), streptococcal sepsis (blood infection by microbes / streptococci / from the focus of purulent inflammation), stomach ulcer, septic endocarditis (disease of the internal cavities of the heart due to the presence of microbes in the blood) , severe diabetes, pregnancy. The drug should be used with caution in severe liver and kidney diseases, and in active tuberculosis.

Release form. In bottles of 100,000, 250,000, 750,000 and 1,500,000 IU of streptokinase.

Storage conditions. In a cool place.

UROKINASE

Synonyms: Ukidan.

Pharmachologic effect. Fibrinolytic (blood clot dissolving) agent. Breaks down blood clots by activating plasminogen, which is an inactive precursor of plasmin (a protein that breaks down clotted blood clots).

Indications for use. Thromboembolic occlusive vascular diseases (vein thrombophlebitis /inflammation of the vein wall with blockage/, embolism /blockage of the pulmonary artery), formation of local thrombi (blood clots) in arteriovenous hemodialysis shunts (special devices worn by patients for periodic connection to the device " artificial kidney") or intravenous cannulas (devices for intravenous infusions), some forms of chronic meningitis (myelomeningocele /spina bifida/), coronary thrombosis (formation of a blood clot in the artery of the heart), bleeding in the anterior chamber of the eye and vitreous body.

Method of administration and dose. The average dose is 1000-2000 IU/kg/hour; when used within 24 hours, generalized proteolysis (enzymatic breakdown of proteins) does not occur, but fibrinolysis (dissolution of the blood clot) is ensured at the level of the blood clot; treatment continues until the blood clot is disobliterated (complete restoration of blood flow in a vessel previously blocked by a blood clot) in combination with heparin therapy. In the case of pulmonary embolism, arterial ischemia (arterial thrombosis), myocardial infarction, urokinase can be administered in situ (artery affected by a thrombus) at a dose of 1000-2000 IU/kg/hour; for severe pulmonary embolism - 15,000 IU/kg/hour in the form of a single injection lasting 10 minutes. In some cases - with thrombosis of shunts (formation of a blood clot in special devices worn by the patient for periodic connection to the artificial kidney apparatus), bleeding in the anterior chamber of the eye - local installations (instillations) of 5000-30,000 IU are used.

During pregnancy, the concentration of antiurokinase bodies gradually increases towards childbirth, making treatment

ineffective. Special observation is required if the patient has diabetes, accompanied by severe retinopathy (non-inflammatory lesions of the retina). If it is necessary to combine this drug with heparin, it should be administered sequentially at a certain time interval. If it is necessary to simultaneously administer urokinase with sodium heparinate in solution, a pH (an indicator of the acid-base state) should be created more than 5.0, and with calcium heparinate - 5.0-7.0.

Side effect. Development of shock, changes in liver tests, nausea, vomiting, loss of appetite, fever, chills, headache, lethargy, and in case of drug overdose - bleeding.

Contraindications. Hemorrhagic stroke (acute cerebrovascular accident as a result of rupture of cerebral vessels), bleeding or the risk of bleeding, recent intracranial surgery, hemostasis deficiency (impaired function of the blood coagulation system), recent biopsy (tissue sampling for morphological studies) of any organ, severe arterial hypertension (persistent rise in blood pressure), severe liver or kidney failure. Relative contraindications: recent surgery, recent arterial puncture (puncture), inaccessible to local compression (local compression), pregnancy.

Release form. Bottles containing 5000, 25,000, 100,000, 250,000, 500,000, 1,000,000 IU of urokinase complete with solvent bottles.

Storage conditions. In a dry, cool place.

FIBRINOLYSIN (Fibrinolysinum)

Dry protein preparation of a natural enzyme isolated from donor blood plasma.

Pharmachologic effect. A physiological component of the body's natural anticoagulant system, the basis of which is the ability to dissolve fibrin threads.

Indications for use. Thromboembolism (blockage of blood vessels with a blood clot) of the pulmonary and peripheral arteries, thromboembolism of cerebral vessels, fresh myocardial infarction, acute thrombophlebitis (inflammation of the vein wall with blockage), exacerbation of chronic thrombophlebitis.

Method of administration and dose. Intravenously (drip) in an isotonic solution of sodium chloride (100-160 units of the drug in 1 ml of solution) with the addition of heparin (up to 20,000 - 40,000 units).

Side effect. Nonspecific reactions to protein (hyperemia/redness/ of the face, pain along the vein, pain behind the sternum and in the abdomen, chills, fever, urticaria, etc.).

Contraindications. Hemorrhagic diathesis (increased bleeding), bleeding, open wounds, peptic ulcer of the stomach and duodenum, nephritis (inflammation of the kidney), fibrinogenopenia (low levels of fibrinogen in the blood - one of the blood clotting factors), tuberculosis (acute form), radiation sickness.

Release form. In bottles of 20,000 units.

Storage conditions. At temperatures from +2 to +10 °C.

CELIASE (Celyasa)

Pharmachologic effect. Celiase activates the fibrinolytic proenzyme contained in the blood (a protein involved in the dissolution of a blood clot) - plasminogen, which is converted into plasmin. Penicast penetrates the thrombus (blood clot) and causes its dissolution.

Indications for use. Systemic and local arterial and venous thrombosis (formation of a blood clot in a vessel). The drug is most effective when used in the first 7 days of the disease.

Method of administration and dose. Intravenous drip or intra-arterial. The contents of the ampoule are dissolved in 1-2 ml of solvent (complete dissolution occurs within 1-2 minutes, the presence of suspensions, turbidity, and sediment is not allowed). Reopolyglucin, isotonic sodium chloride solution, and 5% glucose solution are used as solvents. After complete dissolution, the contents of the ampoule are transferred with a syringe into a bottle with one of the solvents listed above. The solution retains specific activity for 24 hours.

Celease treatment is carried out according to a special regimen only in a hospital setting (in a hospital).

Side effect. Resorptive fever (a sharp increase in body temperature associated with the entry into the bloodstream of thrombus breakdown products). Possible reactions in the form of hyperthermia (fever), chills, headache, pain in the lumbar region, nausea,

caused by the presence of a heterogeneous (foreign) protein in the preparation.

Contraindications. Diseases and conditions predisposing to bleeding: hemorrhagic diathesis (increased bleeding), ulcerative lesions of the gastrointestinal tract, severe forms of sepsis (blood poisoning by microbes from the focus of purulent inflammation), hemorrhagic stroke (acute cerebrovascular accident resulting from rupture of cerebral vessels), tuberculosis lungs with cavernous process, active rheumatic process and other infections caused by streptococci; acute alcohol intoxication (alcohol poisoning), early (up to 3 days) postoperative, postpartum period, pregnancy. Persistent arterial hypertension (persistent rise in blood pressure). In severe forms of diabetes mellitus, the use of celiac is possible only for health reasons.

Release form. In ampoules in lyophilized form (powder dehydrated by freezing in a vacuum) 250,000 ME each, 10 pieces in a package.

Storage conditions. List B. At temperatures from +2 °C to +10 °C.

These are medications that are used to dissolve formed blood clots.

Fibrinolytic agents catalyze the formation of plasmin (fibrinolysin), a proteolytic enzyme that destroys (lyses) fibrin strands that form the basis of a blood clot, which can lead to the dissolution of existing intravascular thrombi.

Plasmin circulating in the blood is quickly inactivated by α 2 -antiplasmin and other inhibitors and therefore does not normally cause systemic fibrinolysis.

However, the risk of bleeding still exists, since the specificity of plasmin is not high and it can also cause the destruction of fibrinogen and some other factors of the blood coagulation system.

Streptokinase, urokinase, and human tissue plasminogen activator drugs are used as fibrinolytic agents.

Fibrinolytic agent.

Streptokinase (syn. Avelysin)

Fibrinolytic agent.

A waste product of β-hemolytic streptococcus.

Protein with a molecular weight of 47000 Da. It has the ability to bind to plasminogen, which causes a conformational rearrangement of its structure and the appearance of proteolytic activity, as a result of which the complex of streptokinase and plasminogen acquires the ability to convert plasminogen into plasmin. The latter breaks down fibrin, which leads to lysis of the resulting blood clot.

Used for fibrinolytic therapy for acute myocardial infarction (within the first 6 hours), thromboembolism of the pulmonary artery and its branches, thrombosis and thromboembolism of the vessels of the extremities, brain, retina and other conditions occurring with acute embolism and thrombosis in order to cause vascular recanalization and restoration of blood flow in them.

Administered intravenously, starting with a dose of 250,000 IU in 50 ml of isotonic sodium chloride solution over 30 minutes. If well tolerated, further administration is continued at a rate of 100,000 IU per hour until the desired effect is achieved, usually within 16 to 18 hours.

If necessary, streptokinase can be administered intra-arterially.

In all cases, the administration of streptokinase should be started as early as possible, since the best effect is observed with fresh blood clots.

Undesirable effects: bleeding, allergic reactions, including anaphylactic shock, fever, hypotension.

F.v.: lyophilized powder for the preparation of solution for injection in bottles of 100,000, 250,000, 750,000 and 1,500,000 IU.

Anistreplase (syn. Eminase)

A fibrinolytic agent containing a streptokinase complex with acylated lysine-plasminogen.

The presence of an acyl group prevents spontaneous activation of the complex in the blood.

It was believed that the cleavage of the acyl group and activation of the complex would occur only after the latter binds to fibrin inside the blood clot. Thus, it was hoped to limit the fibrinolytic effect of anistreplase only against blood clots and avoid systemic action.

Unfortunately, even when administered directly into the coronary vessels in recommended doses (30 units), systemic fibrinolysis is also observed.

Urokinase (syn. Abbokinase)

Obtained from a culture of human embryonic kidney cells.

A protein consisting of two polypeptide chains, containing 411 amino acid residues, possessing proteolytic activity, and, unlike streptokinase, is a direct plasminogen activator, converting it into plasmin.

Used to dissolve fresh blood clots.

Prescribed intravenously, starting with a loading dose of 1000–4500 units/kg and subsequent infusion at a rate of 4400 units/kg per hour.

Less common than streptokinase, it causes allergic disorders. However, the specificity is not sufficient to activate only fibrin-bound plasminogen in the thrombus, and therefore, like streptokinase, it causes systemic fibrinolysis and can lead to bleeding.

F.v.: lyophilized powder for the preparation of solutions for injections in bottles of 100,000, 500,000 and 1,000,000 IU.

Prourokinase (syn. Saruplase)

Single-chain urokinase obtained recombinantly.

It is believed to have a higher selectivity of action against plasminogen associated with fibrin in the thrombus compared to double-chain urokinase.

Alteplase (syn. Actilyse)

Recombinant human tissue plasminogen activator (t-PA) drug.

A protein produced in endothelial cells. Contains 527 amino acid residues and has proteolytic activity. Catalyzes the conversion of plasminogen to plasmin.

It acts predominantly on plasminogen bound to fibrin, which occurs in the resulting blood clot.

In the blood it binds to specific inhibitors and therefore has less effect on plasminogen circulating in the blood, and also does not have a noticeable effect on other factors of the coagulation system and therefore affects systemic blood coagulation to a lesser extent compared to streptokinase and urokinase.

Used for coronary thrombolysis in acute myocardial infarction, as well as pulmonary embolism.

Prescribed intravenously, first 15 mg bolus, then over the next 30 minutes drip based on a dose of 0.75 mg/kg and then 0.5 mg/kg over the next hour to a total dose of 35 mg/kg.

Undesirable effects: hemorrhagic complications, hypotension, fever.

F.v.: lyophilized powder 50 mg in vials.

Currently, there are two generations of fibrinolytics: fibrinolytics of the first generation - fibrin-specific (causing fibrinolysis and fibrinogenolysis) and fibrinolytics of the second generation - fibrin-specific (having a high tropism for thrombus fibrin and causing only fibrinolysis).

The first generation includes streptokinase (streptase, streptoliase, streptodecase) - a waste product of beta-hemolytic streptococcus and urokinase, obtained from urine.

The second generation includes tissue plasminogen activator TPA (obtained from a culture of human melanoma cells); APSAC – acetylated plasminogen-streptokinase activated complex (1:1), which is streptokinase deposited on human plasminogen, which serves as a conductor to thrombus fibrin; prourokinase (formed in the kidneys).

The resulting effect of first generation drugs is fibrinolysis and fibrinogenolysis, leading to increased bleeding.

A feature of second generation fibrinolytics is their high thrombofibrin specificity. If all fibrinolytics are arranged in a series in descending order of thrombospecificity, this series will be as follows:

Pharmacokinetics of fibrinolytics. They are distinguished by a short T1/2, which is 23 minutes for streptokinase, 20 minutes for urokinase, 5-10 minutes for tPA, 90 minutes for APSAK, and 4 minutes for prourokinase. The duration of effect for these drugs is 4 hours, and only for APSAC - 6 hours.

Streptokinase and APSAC are inactivated by forming a complex with antithrombin III and further elimination through the reticuloendothelial system. Urokinase undergoes rapid and complete metabolism in the liver (T1/2 may increase in liver diseases). TPA is rapidly metabolized by the liver. Other pharmacokinetic parameters have not been sufficiently studied.

Indications for the use of fibrinolytics:

· myocardial infarction no more than 6 hours old, in which the effectiveness of all fibrinolytics is approximately the same. When prescribed later, second-generation fibrinolytics showed better results;

· unstable angina;

· PE of large trunks up to 5-7 days old;

· acute arterial and venous thrombosis up to 3 days old (for streptokinase and urokinase); not recommended for thrombosis of cerebral vessels.

Contraindications: hemorrhagic diathesis (due to the risk of hemorrhage); peptic ulcer (in the acute phase and 1 month after scarring); tumors localized in the stomach, lungs, brain (increased risk of bleeding); arterial hypertension with high (more than 115 mm Hg) diastolic blood pressure (due to the risk of hemorrhagic stroke); recent surgery or biopsy (at least 2 weeks); diabetes mellitus with microangiopathy and retinopathy; active pulmonary tuberculosis (with decay); phlebothrombosis (possible embolism); septic endocarditis (possible embolism); liver failure (degree of decrease in protein-synthetic function).

Fibrinolysin is an enzyme formed upon activation of plasminogen (profibrinolysin) contained in the blood. Fibrinolysin (plasmin) is a physiological component of the body's natural anticoagulant system. The action of the enzyme is based on its ability to dissolve fibrin filaments. This effect is observed in vitro and in vivo. By the nature of its action, fibrinolysin can be considered a tissue proteinase (tissue proteolytic enzyme). The most pronounced effect of fibrinolysin is on fresh fibrin clots before their retraction. In connection with these properties, fibrinolysin is used to treat diseases accompanied by intravascular loss of fibrin clots and the formation of blood clots.

Streptokinase an enzyme preparation obtained from a culture of β-hemolytic streptococcus group C. Streptokinase has fibrinolytic activity, which is due to its ability to interact with blood plasminogen. The complex of streptokinase with plasminogen has proteolytic activity and catalyzes the conversion of plasminogen to plasmin. The latter is capable of causing fibrin lysis in blood clots; inactivate fibrinogen, as well as blood clotting factors V and VII.

Streptokinase is used to restore the patency of thrombosed blood vessels; the drug causes lysis of blood clots, acting on them not only from the surface, but also penetrating inside the blood clot (especially with fresh blood clots). Indications for the use of streptokinase are embolism of the pulmonary artery and its branches, thrombosis and embolism of peripheral arteries, thrombosis of superficial and deep veins (limbs, pelvis), acute myocardial infarction (within the first 12 hours), thrombosis of the vessels of the retina and other conditions occurring with acute embolism and thrombosis and with the threat of blood clots.

When using streptokinase, nonspecific reactions to protein may develop: headache, nausea, mild chills, allergic reactions (for severe allergic reactions, the use of corticosteroids is recommended). With rapid intravenous administration, hypotension and cardiac arrhythmia may develop. The possibility of embolism (due to the mobilization of thrombus elements) should be taken into account.