Medicinal reference book geotar. Modern aspects of anticoagulant therapy in the acute period of ischemic stroke Risk of hemorrhagic complications during heparin therapy

Complications of antithrombotic therapy for acute coronary syndrome.

Honored Doctor of the Russian Federation, anesthesiologist-resuscitator of the ICU State Budgetary Healthcare Institution "Bryansk Regional Cardiological Dispensary"

The basis of treatment for ACS (acute coronary syndrome) without ST segment elevations is active antithrombotic therapy, which consists of the use of antiplatelet agents aspirin and clopidogrel in combination with an anticoagulant - heparin (unfractionated or low molecular weight) or a synthetic factor Xa inhibitor (fondaparinux). The most important component of antithrombotic therapy in the treatment of ST-segment elevation ACS is thrombolytic therapy. Complications of antithrombotic therapy will be presented next.

The main complications of thrombolysis:

1. Bleeding(including the most dangerous - intracranial) - develop due to inhibition of blood coagulation processes and lysis of blood clots. The incidence of serious bleeding is no more than 3%. Risk of stroke with systemic thrombolysis accounts for 0.5-1.5% of cases, stroke usually develops on the first day after thrombolysis. The patient is over 65 years of age, has a body weight of less than 70 kg, arterial hypertension history, as well as the use of tPA (tissue plasminogen activator) as a thrombolytic can be considered as risk factors for hemorrhagic stroke. Undoubtedly important issue To prevent hemorrhagic complications, concomitant anticoagulant and antiplatelet therapy seems to be adequate. This is especially true for the prescription of heparin, since a prolongation of APTT (activated partial thromboplastin time) of more than 90 s correlates with an increased risk of cerebral hemorrhages. To stop minor bleeding(from the puncture site, from the mouth, nose) pressing the bleeding area is enough.
For more significant bleeding (gastrointestinal, intracranial), an intravenous infusion of aminocaproic acid is necessary - 100 ml of a 5% solution is administered over 30 minutes and then 1 g/hour until the bleeding stops, or tranexamic acid 1-1.5 g 3-4 once a day intravenously, in addition, transfusion is effective fresh frozen plasma. It should be remembered that when using antifibrinolytic drugs, the risk of coronary artery reocclusion and reinfarction increases, so they should be used only for life-threatening bleeding.

2. Arrhythmias, occurring after restoration of coronary circulation (reperfusion) are “potentially benign” and do not require intensive care.
This applies to a slow nodal or ventricular rhythm (with a heart rate less than 120 per minute and stable hemodynamics); supraventricular and ventricular extrasystole (including allorhythmic); atrioventricular block I and II (Mobitz type I) degree.
Emergency treatment is required: - ventricular fibrillation (defibrillation and a set of standard resuscitation measures are required); - bidirectional fusiform ventricular tachycardia of the “pirouette” type (defibrillation, intravenous bolus administration of magnesium sulfate are indicated); - other varieties ventricular tachycardia(use lidocaine injection or perform cardioversion); - persistent supraventricular tachycardia (stopped by intravenous jet administration of verapamil or novocainamide); - atrioventricular block II (type Mobitz II) and III degree, sinoatrial blockade (atropine is injected intravenously in a dose of up to 2.5 mg, if necessary, emergency cardiac pacing is performed).

3. Allergic reactions.
Frequency of development anaphylactic shock when using tPA less than 0.1%. Rash, itching, periorbital edema occur in 4.4% of cases, severe reactions (Quincke's edema, anaphylactic shock) - in 1.7% of cases. If an anaphylactoid reaction is suspected, the streptokinase infusion should be immediately stopped and a bolus of 150 mg prednisolone administered intravenously. In case of severe hemodynamic depression and signs of anaphylactic shock, 0.5 - 1 ml of a 1% solution of adrenaline is administered intravenously, continuing the administration of steroid hormones intravenously. For fever, aspirin or paracetamol is prescribed.

4. Recurrence pain syndrome after thrombolysis relieved by intravenous fractional administration narcotic analgesics. If ischemic changes on the ECG increase, intravenous drip administration of nitroglycerin is indicated, or if the infusion has already been established, an increase in the rate of its administration.

5. For arterial hypotension in most cases, it is sufficient to temporarily stop the thrombolytic infusion and elevate the patient's legs; if necessary, the blood pressure level is adjusted by administering fluids, vasopressors (dopamine or norepinephrine intravenously until systolic blood pressure stabilizes at 90-100 mm Hg).

Thrombolytic drugs are not used for ACS without ST segment elevations on the ECG. Data from large studies and meta-analyses did not reveal the benefits of thrombolysis in patients with unstable angina and non-Q wave MI; on the contrary, the administration of thrombolytic drugs was associated with an increased risk of death and myocardial infarction.

Complications of heparin therapy:

bleeding, including hemorrhagic stroke, especially in the elderly (from 0.5 to 2.8%); hemorrhages at injection sites; thrombocytopenia; allergic reactions; osteoporosis (rare, only with long-term use).

If complications develop, it is necessary to administer a heparin antidote - protamine sulfate, which neutralizes the anti-IIa activity of unfractionated heparin at a dose of 1 mg of the drug per 100 units of heparin. At the same time, discontinuation of heparin and use of protamine sulfate increase the risk of thrombosis. The development of complications when using heparin is largely associated with the characteristics of its pharmacokinetics. Heparin is eliminated from the body in two phases: a rapid elimination phase, as a result of the drug binding to membrane receptors of blood cells, endothelium and macrophages, and a slow elimination phase, mainly through the kidneys. The unpredictability of receptor uptake activity, and therefore the binding of heparin to proteins and the rate of its depolymerization, determines the second “side of the coin” - the impossibility of predicting therapeutic (antithrombotic) and side (hemorrhagic) effects. Therefore, if it is not possible to control the APTT, talk about required dose drug, and therefore the usefulness and safety of heparin therapy cannot be discussed. Even if the aPTT is determined, the dose of heparin can be controlled only when intravenous administration, since with subcutaneous administration there is too much variability in the bioavailability of the drug.

In addition, it should be noted that bleeding caused by the administration of heparin is associated not only with the effect of the drug on the blood coagulation system, but also on platelets. Thrombocytopenia is a fairly common complication of heparin administration. The drug should be discontinued immediately if the patient detects red blood cells in the urine, petechial rashes on the skin, unusual bleeding of the gums, nasal, intestinal or other bleeding, as well as when the number of platelets in the hemogram drops by half compared to the initial value. After 5-7 days from the start of heparin therapy, the activity of aminotransferases (especially alanine) sharply increases in a number of patients, which is most often mistakenly interpreted as a sign of current hepatitis. Using heparin for more than 10-15 days increases the risk possible development osteoporosis. Low molecular weight heparin derivatives cause thrombocytopenia much less frequently. Longer inhibition of thrombin activity and higher, compared with heparin, bioavailability of these anticoagulants allow them to be prescribed in low doses and it is easier to control the therapeutic effect.

Combination of clopidogrel with aspirin, complications.

Based on the data from the CURE study, the combination of clopidogrel with aspirin is recommended for all patients with ACS without ST segment elevations on the ECG, both in the case of CBA (coronary balloon angioplasty) and without planned intervention on coronary arteries. The dose of aspirin when combined with clopidogrel should not exceed 100 mg/day. The recommended duration of administration of clopidogrel in patients who have undergone ACS is up to 9 months if the drug is well tolerated and there is no risk of bleeding. In the case of coronary artery bypass surgery, clopidogrel is discontinued 5–7 days before surgery.

Combination therapy was accompanied by an increase in the number of serious hemorrhagic complications: 3.7% versus 2.7%, p = 0.001, but there was no statistical difference in life-threatening No bleeding was detected (2.2 and 1.8%). A relationship was noted between the increase in bleeding and the dose of aspirin when combined with clopidogrel. The risk of bleeding was almost 2 times higher when taking aspirin >200 mg/day than when taking<100 мг/сут.

Platelet receptor IIb/IIIa inhibitors, complications.

Inhibitors of IIb/IIIa platelet receptors are essentially universal antiplatelet drugs that block the final stage of platelet aggregation, namely the interaction between activated receptors and adhesive proteins (fibrinogen, von Willebrand factor, fibronectin).

The most common complications with the use of platelet receptor IIb/IIIa inhibitors are bleeding and thrombocytopenia. Thrombocytopenia is rare, and stopping the infusion of IIb/IIIa receptor inhibitors usually results in normalization of platelet counts. Less commonly, platelet transfusions may be required when using absiximab. There are reports of a reduced risk of complications when low molecular weight heparins are used in combination with platelet receptor IIb/IIIa inhibitors instead of unfractionated heparins.

Literature

2. Kirichenko angina. Tutorial. Moscow, 1998.

3. Kryzhanovsky and treatment of myocardial infarction. Kyiv: Phoenix, 2 pages.

4. Acute coronary syndrome without persistent ST segment elevation on the ECG. Recommendations of the working group of the European Society of Cardiology (ESC). Supplement to the journal "Cardiology", 2001, No. 4. -28s.

5. Federal guidance for doctors on the use of medicines (formulary system) Issue III. - M.: "ECHO", 20 p.

6. Yavelov of acute coronary syndrome without ST segment elevation. Heart: a magazine for medical practitioners. 2002, vol. 1, no. 6, pp. 269-274.

7. Yavelov aspects of thrombolytic therapy for acute myocardial infarction. Pharmateka. 2003; No. 6: 14-24

Anesthesiologist-resuscitator, ICU

Chief Physician Honored Doctor of the Russian Federation

Dosage form:  solution for intravenous and subcutaneous administration 5000 IU/ml Compound:

1 ml contains:

active substance: heparin sodium 5000 IU

Excipients: benzyl alcohol - 9 mg; sodium chloride - 3.4 mg; 0.1 M hydrochloric acid solution or 0.1 M sodium hydroxide solution to pH from 5.5 to 7.5; water for injections up to 1 ml.

Description: Transparent colorless or colorless with a yellowish tint liquid. Pharmacotherapeutic group:Direct anticoagulant ATX:  

B.01.A.B.01 Heparin

Pharmacodynamics:

Heparin sodium is a biological drug. is a heterogeneous mixture of polysaccharides with a molecular weight from 2000 to 30,000 Da (mainly 15,000-18,000 Da), characterized by heterogeneity of chemical structure (variability in linear sizes, different degrees of sulfation, different locations of pharmacologically active fragments in the polysaccharide chain).

Pharmacological action - anticoagulant.

The mechanism of action of heparin is based primarily on its binding to antithrombin III, which is a natural inhibitor of activated blood coagulation factors: IIa (thrombin), IXa, Xa, XIa and XIIa. Heparin binds to antithrombin III and causes conformational changes in its molecule. As a result, the binding of antithrombia III to blood coagulation factors IIa (thrombin), IXa, Xa, XIa and XIIa is accelerated and their enzymatic activity is blocked. The binding of heparin to antithrombin III is electrostatic in nature and largely depends on the length and composition of the molecule (binding of heparin to antithrombin III requires a pentasaccharide sequence containing 3-O-sulfated). Of greatest importance is the ability of heparin in combination with antithrombin III to inhibit coagulation factors IIa () and Xa. The ratio of the activity of sodium heparin against factor Xa to its activity against factor IIa is 0.9-1.1.

Heparin reduces blood viscosity, reduces vascular permeability stimulated by bradykinin, histamine and other endogenous factors, and thus prevents the development of stasis. Heparin is able to adsorb on the surface of endothelial membranes and blood cells, increasing their negative charge, which prevents platelet adhesion and aggregation. Heparin slows down smooth muscle hyperplasia, activates lipoprotein lipase and, thus, has a hypolipidemic effect and prevents the development of atherosclerosis.

Heparin binds some components of the complement system, reducing its activity, prevents the cooperation of lymphocytes and the formation of immunoglobulins, binds histamine (i.e., has an antiallergic effect). Heparin increases renal blood flow, increases cerebral vascular resistance, reduces the activity of cerebral hyaluronidase, reduces the activity of surfactant in the lungs, suppresses excessive synthesis of aldosterone in the adrenal cortex, binds adrenaline, modulates the ovarian response to hormonal stimuli, and increases the activity of parathyroid hormone. As a result of interaction with enzymes, heparin can increase the activity of brain tyrosine hydroxylase, pepsinogen, DNA polymerase and reduce the activity of myosin ATPase, pyruvate kinase, RNA polymerase, pepsin. The clinical significance of these effects of heparin remains uncertain and poorly understood.

In acute coronary syndrome without persistent ST segment elevation on the ECG (unstable angina, myocardial infarction without ST segment elevation) in combination with acetylsalicylic acid reduces the risk of myocardial infarction and reduces mortality. In case of myocardial infarction with ST segment elevation on the ECG, it is effective with primary percutaneous coronary revascularization in combination with inhibitors of glycoprotein IIb/IIIa receptors and with thrombolytic therapy with streptokinase (increasing the frequency of revascularization).

In high doses it is effective against pulmonary embolism and venous thrombosis. In small doses, it is effective for the prevention of venous thromboembolism, incl. after surgical operations.

When administered intravenously, blood clotting slows down almost immediately. When administered subcutaneously, the effect of heparin occurs within 40-60 minutes. The duration of the anticoagulant effect of sodium heparin after intravenous and subcutaneous administration is 4-5 hours and 8 hours, respectively. A deficiency of antithrombin III in the blood plasma or at the site of thrombosis may reduce the antithrombotic effect of sodium heparin.

Pharmacokinetics:

After subcutaneous administration, the time to reach the maximum concentration in the blood plasma is 4-5 hours. Bonding with plasma proteins is up to 95%, the volume of distribution is very small -0.06 l/kg (does not leave the vascular bed due to strong binding to plasma proteins). Does not penetrate the placenta or into breast milk. It is intensively captured by endothelial cells and cells of the mononuclear-macrophage system (cells of the reticuloendothelial system), concentrated in the liver and spleen. Metabolized in the liver with the participation of N-desulfamidase and platelet heparinase, which is involved in the metabolism of heparin at later stages. Participation in the metabolism of platelet factor IV (antiheparin factor), as well as the binding of heparin to the macrophage system explains the rapid biological inactivation and short duration of action. Desulfated molecules are converted into low molecular weight fragments by the action of kidney endoglycosidase. Half-life - 1-6 hours (average - 1.5 hours); increases with obesity, liver and/or kidney failure; decreases with pulmonary embolism, infections, and malignant tumors.

It is excreted by the kidneys, mainly in the form of inactive metabolites, and only with the administration of high doses is it possible to excrete (up to 50%) unchanged. Not excreted by hemodialysis.

Indications:

Prevention and treatment of venous thrombosis (including thrombosis of the superficial and deep veins of the lower extremities; renal vein thrombosis) and pulmonary embolism.

Prevention and treatment of thromboembolic complications associated with atrial fibrillation.

Prevention and treatment of peripheral arterial embolisms (including those associated with mitral heart defects).

Treatment of acute and chronic consumption coagulopathies (including stage I of DIC syndrome).

Acute coronary syndrome without persistent ST segment elevation on the ECG (unstable angina, myocardial infarction without ST segment elevation on the ECG).

ST-segment elevation myocardial infarction: with thrombolytic therapy, with primary percutaneous coronary revascularization (balloon angioplasty with or without stenting) and with a high risk of arterial or venous thrombosis and thromboembolism.

Prevention and therapy of microthrombosis and microcirculation disorders, incl. with hemolytic-uremic syndrome; glomerulonephritis (including lupus nephritis) and with forced diuresis.

Prevention of blood clotting during blood transfusion, in extracorporeal circulation systems (extracorporeal circulation during heart surgery, hemosorption, cytapheresis) and during hemodialysis.

Processing of peripheral venous catheters.

Contraindications:

Hypersensitivity to sodium heparin or animal products.

Heparin - induced thrombocytopenia (with or without thrombosis) in history or currently.

Bleeding (unless the benefits of sodium heparin outweigh the potential risks).

It should not be prescribed at a therapeutic dose if it is not possible to ensure regular laboratory monitoring of blood clotting.

Pregnancy and breastfeeding period.

Newborns, especially those born prematurely or with low birth weight.

Carefully:

Should be used with caution in pathological conditions associated with an increased risk of bleeding, such as:

Diseases of the cardiovascular system: acute and subacute infective endocarditis, severe uncontrolled arterial hypertension, aortic dissection, cerebral aneurysm.

Diseases of the digestive system: erosive and ulcerative lesions of the gastrointestinal tract (including stress-induced), varicose veins of the esophagus with cirrhosis of the liver and other diseases, long-term use of gastric and small intestinal drainage, ulcerative colitis, hemorrhoids.

Diseases of the hematopoietic organs of the blood and lymphatic system: leukemia, hemophilia, thrombocytopenia, hemorrhagic diathesis.

Diseases of the central nervous system: hemorrhagic stroke, traumatic brain injury.

Malignant neoplasms.

Congenital deficiency of antithrombin III and replacement therapy with antithrombin III drugs (to reduce the risk of bleeding, lower doses of heparin must be used).

Other physiological and pathological conditions: period of menstruation, threat of miscarriage, early postpartum period, severe liver disease with impaired protein-synthetic function, chronic renal failure, recent surgery on the eyes, brain or spinal cord, recent spinal (lumbar) puncture or epidural anesthesia, proliferative diabetic retinopathy, vasculitis, old age (especially in women).

The use of sodium heparin is possible in cases where the expected benefits of therapy outweigh the potential risks.

Pregnancy and lactation:

Controlled clinical studies of the use of sodium heparin in pregnant women have not been conducted. According to published data, the use of heparin during pregnancy does not have any adverse effects on the fetus. Studies in humans and animals have shown that it does not cross the placenta. not excreted into breast milk.

The use of sodium heparin during pregnancy or breastfeeding is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus or child. Sodium heparin preparations containing benzyl alcohol should not be used.

Directions for use and dosage:

Heparin sodium is administered intravenously (as a continuous infusion or repeated boluses) or subcutaneously. cannot be administered intramuscularly due to the risk of developing intramuscular hematomas.

Subcutaneous injections are preferably performed in the anterior abdominal wall. As an exception, other injection sites can be used (outer thigh, shoulder) if subcutaneous adipose tissue is sufficiently developed. It is not recommended to re-inject into previous injection sites.

Continuous intravenous infusion	Initial dose	5000-10000 M.E.i/v jet
	Continuous infusion	20000-40000 IU/day (administration rate is about 1000 IU/hour)
Bolus intravenous introduction	Initial dose:	10000 M.E.
	Maintenance doses	5000-10000 M.E.every 4-6 hours
Subcutaneous introduction	Initial dose:	333 IU/kg (with body weight less than 75 kg - 20,000ME,with a body weight of 75-90 kg 25,000 units, with a body weight of 90-105 kg - 30,000ME,with body weight over 105 kg - 35,000ME)
	Maintenance doses	250 IU/kg (15000-25000ME)every 12 hours.

Laboratory monitoring of the effectiveness and safety of sodium heparin therapy

The dose of heparin sodium should be adjusted based on laboratory blood clotting parameters. When using heparin sodium, it is necessary to monitor the activated partial thromboplastin time (aPTT) or blood clotting time (BCT). The administered dose of heparin sodium is considered adequate if the aPTT is 1.5-2.0 times higher than normal values ​​or if the patient's ICT is 2.5-3.0 times higher than control values.

With continuous intravenous infusion sodium heparin, it is recommended to determine the initial aPTT, then determine the aPTT every 4 hours, followed by increasing or decreasing the rate of sodium heparin infusion until the target aPTT level is reached (1.5-2 times higher than normal), then determine the aPTT every 6 hours.

With bolus intravenous administration heparin sodium, it is recommended to determine the initial aPTT, then determine the aPTT before each bolus injection, followed by an increase or decrease in the administered dose of heparin sodium.

When administered subcutaneously sodium heparin, it is recommended to monitor the aPTT 4-6 hours after injection with a subsequent increase or decrease in the administered dose of sodium heparin.

When using sodium heparin in low doses to prevent thromboembolic complications, it is not necessary to monitor the aPTT.

Use of heparin sodium in special clinical situations

Primary percutaneous coronary angioplasty for acute non-ST segment elevation coronary syndrome and ST-segment elevation myocardial infarction: administered intravenously as a bolus at a dose of 70-100 U/kg (if the use of glycoprotein IIb/IIIa receptor inhibitors is not planned) or at a dose of 50-60 U/kg (when used together with glycoprotein IIb/IIIa receptor inhibitors).

Thrombolytic therapy for ST-segment elevation myocardial infarction: administered intravenously as a bolus at a dose of 60 U/kg (maximum dose 4000 U), followed by intravenous infusion at a dose of 12 U/kg (no more than 1000 U/hour) for 24-48 hours. The target APTT level is 50-70 sec or 1.5-2.0 times higher than normal; APTT monitoring 3.6, 12 and 24 hours after the start of therapy.

Prevention of thromboembolic complications after surgery using low doses of sodium heparin: s/c, deep into the fold of the skin of the abdomen. The initial dose is 5000 IU 2 hours before surgery. In the postoperative period: 5000 IU every 8-12 hours for 7 days or until the patient’s mobility is completely restored (whichever comes first). When using sodium heparin in low doses to prevent thromboembolic complications, it is not necessary to monitor the aPTT.

Application in cardiovascular surgery during operations using extracorporeal circulation systems: the initial dose of sodium heparin is not less than 150 IU/kg body weight. Next, it is administered by continuous intravenous infusion at a rate of 15-25 drops/min, 30,000 IU per 1 liter of infusion solution. The total dose of sodium heparin is usually 300 IU/kg body weight (if the expected duration of the operation is less than 60 minutes) or 400 IU/kg body weight (if the expected duration of the operation is 60 minutes or more).

Use in hemodialysis: Initial dose of heparin sodium: 25-30 IU/kg (or 10,000 IU) intravenous bolus, then continuous infusion of heparin sodium 20,000 IU/100 mg sodium chloride solution at a rate of 1500-2000 IU/hour (unless otherwise indicated in the instructions for use of the systems for hemodialysis).

Use of heparin sodium in pediatrics: Adequate controlled studies of the use of heparin sodium in children have not been conducted. The recommendations presented are based on clinical experience.

Initial dose: 75-100 units/kg IV bolus over 10 minutes

Maintenance dose: children aged 1-3 months - 25-30 Units/kg/hour (800 Units/kg/day), children aged 4-12 months - 25-30 Units/kg/hour (700 Units/kg/day day), children over 1 year old - 18-20 units/kg/hour (500 units/kg/day) intravenously.

The dose of heparin sodium should be adjusted based on blood coagulation parameters (target aPTT 60-85 seconds).

Side effects:

World Health Organization (WHO) classification of adverse drug reactions by frequency: very common (>1/10 prescriptions); often (>1/100 and<1/10 назначений); нечасто (>1/1000 and<1/100 назначений); редко (>1/10000 and<1/1000 назначений); очень редко (<1/10000), включая отдельные сообщения.

Hemorrhagic complications: They develop very often. The most typical are bleeding from the gastrointestinal tract, urinary tract, from the injection sites of sodium heparin, from postoperative wounds, as well as hemorrhages in areas exposed to pressure. Hemorrhages may also develop in other internal organs, incl. into the adrenal glands (with the development of acute adrenal insufficiency), retroperitoneal space, ovaries. A more frequent occurrence of bleeding is observed in patients over 60 years of age (especially women).

Allergic reactions: uncommon - skin hyperemia, rash, itching and burning sensation in the soles, pain in the extremities, hyperthermia, urticaria, rhinitis, conjunctivitis, shortness of breath, bronchospasm, angioedema; very rarely - anaphylactic shock.

Reactions at the injection site: often - irritation, soreness, tissue hyperemia, minor hematoma and ulceration at the injection site, infrequently - histamine-like reactions (including skin necrosis at the injection site), very rarely - soft tissue calcification at the injection site (mainly in patients with severe chronic renal failure).

Heparin-induced thrombocytopenia (HIT): a severe immune reaction caused by the formation of antibodies and leading to irreversible platelet aggregation. It can develop both during heparin therapy (rarely) and within several weeks after its cessation (very rarely). Clinical manifestations: venous and arterial thrombosis (including deep vein thrombosis of the legs, pulmonary embolism, cerebral vein thrombosis, stroke, myocardial infarction, thrombosis of the mesenteric and renal arteries, thrombosis of the arteries of the extremities with the development of gangrene).

Laboratory diagnostics: The platelet count should be determined before prescribing sodium heparin, on the first day of treatment, and then every 2-3 days throughout the entire treatment period (especially from days 6 to 14 of therapy). If the platelet count decreases below 100*10 9 /l and/or with the development of recurrent thrombosis, it should be immediately discontinued. If necessary, alternative antithrombotic therapy should be prescribed.

Therapy and prevention: If HIT occurs, it should be discontinued immediately. The patient should be warned that in the future he should not be prescribed unfractionated heparin (including during hemodialysis) and low molecular weight heparins. If the patient requires antithrombotic therapy, then other drugs should be used.

Other adverse events:

From the central nervous system and sensory organs: uncommon - dizziness, headache.

From the cardiovascular system: infrequently - decreased blood pressure.

From the digestive system: infrequently - loss of appetite, nausea, vomiting, diarrhea, often - increased levels of “liver” transaminases (AST and ALT) in the blood plasma.

From the hematopoietic organs: often - moderate thrombocytopenia (platelet content 150-100 * 10 9 / l) not associated with the production of antibodies and not accompanied by thrombosis (can be observed in 6-30% of patients receiving heparin); rarely - reversible eosinophilia.

From the musculoskeletal system: rarely - osteoporosis (with long-term use of sodium heparin), spontaneous bone fractures.

From the endocrine system: rarely - hypoaldosteronism (due to inhibition of aldosterone synthesis).

From the side of water-electrolyte metabolism: rarely - reversible potassium retention, metabolic acidosis.

Others: infrequently - transient alopecia, very rarely - priapism.

Laboratory indicators: often - a reversible increase in the content of “liver” transaminases (AST and ALT); infrequently - an increase in free fatty acids after discontinuation of heparin, an increase in plasma thyroxine, a false decrease in cholesterol, a false increase in glucose and incorrect results of the bromsulfalein test.

If any side effects indicated in the instructions for use worsen, or if other adverse events not listed in the instructions occur, you should immediately notify your doctor.

Overdose:

Symptoms: bleeding of varying severity.

Treatment: for minor bleeding caused by an overdose of sodium heparin, it is enough to stop using the drug.

In case of major bleeding, excess heparin sodium is neutralized with protamine sulfate. 1 mg of protamine sulfate neutralizes 100 IU of sodium heparin. A 1% solution of protamine sulfate is administered intravenously very slowly. Do not administer more than 50 mg (5 ml) of protamine sulfate every 10 minutes. Given the rapid metabolism of heparin, the required dose of protamine decreases over time. To calculate the required dose of protamine sodium, we can assume that the half-life of heparin is 30 minutes. When using sodium protamine, severe anaphylactic reactions with fatal outcomes have been observed, and therefore the drug should be administered only in a department equipped to provide emergency medical care for anaphylactic shock. Heparin is not eliminated by hemodialysis.

Interaction:

Pharmaceutical interactions: Sodium heparin solution is diluted only with saline solution. Heparin sodium solution is incompatible with the following substances: amikacin sulfate, sodium, sodium, danorubicin, doxorubicin hydrochloride, gentamicin sulfate, haloperidol lactate, hydrocortisone sodium succinate, glucose, fat emulsions, kanamycin sulfate, methicillin sodium, netilmicin sulfate, opioids, oxytetracycline hydro chloride, polymyxin B sulfate, promazine hydrochloride, promethazine hydrochloride, streptomycin sulfate, sulfafurazole diethanolamine, tetracycline hydrochloride, tobramycin sulfate, cephalothin sodium, cephaloridin, vancomycin hydrochloride, vinblastine sulfate, labetalol hydrochloride, nicardipine hydrochloride.

Pharmacokinetic interaction: Sodium heparin displaces heparin and benzodiazepine derivatives from the sites of their binding to plasma proteins, which can lead to an increase in the pharmacological effect of these drugs. dipyridamole

The anticoagulant effect of sodium heparin is reduced when used simultaneously with ACTH, antihistamines, ascorbic acid, ergot alkaloids, nicotine, nitroglycerin, cardiac glycosides, thyroxine, tetracycline and quinine.

Heparin sodium may reduce the pharmacological effects of ACTH, glucocorticoids and insulin.

Special instructions:

Switching to warfarin therapy: To ensure sustained anticoagulant effect, full dose heparin sodium therapy should be continued until a stable target INR level is achieved. After this, the administration of sodium heparin must be stopped.

Switching to dabigatran therapy Continuous intravenous heparin sodium should be discontinued immediately after the first dose of dabigatran. With fractional intravenous administration, the patient should take the first dose of dabigatran orally 1-2 hours before the scheduled administration of the next dose of sodium heparin.

Before elective surgical interventions, to reduce blood loss during surgery and in the postoperative period, it is usually recommended to discontinue oral anticoagulants () and antiplatelet drugs (,) 7 days before surgery. As antithrombotic therapy, it is possible to prescribe sodium heparin in therapeutic doses. Administration of sodium heparin is stopped 6 hours before surgery and resumed 6 hours after surgery.

Intramuscular administration of sodium heparin should be avoided (due to the possible occurrence of hematomas).

The use of drugs containing benzyl alcohol as a preservative in newborns (especially premature infants and low birth weight infants) can lead to serious adverse events (central nervous system depression, metabolic acidosis, gasping breathing) and death. Therefore, in newborns and children under 1 year of age, sodium heparin preparations that do not contain preservatives should be used.

Resistance to sodium heparin is often observed with fever, thrombosis, thrombophlebitis, infectious diseases, myocardial infarction, malignant neoplasms, as well as after surgical interventions and with antithrombin III deficiency. In such situations, more careful laboratory monitoring (aPTT monitoring), including the determination of antithrombin III, is required.

In persons over 60 years of age (especially women), the risk of bleeding is increased, and therefore the dose of heparin sodium in this category of patients should be reduced.

During therapy with heparin sodium, it is necessary to constantly monitor clinical symptoms indicating possible bleeding (bleeding of the mucous membranes, hematuria, etc.).

When using sodium heparin in patients with arterial hypertension, blood pressure should be regularly monitored and adequate antihypertensive therapy should be provided.

Impact on the ability to drive vehicles. Wed and fur.:in most cases, it does not have a significant effect on concentration and speed of psychomotor reactions. In case of adverse reactions from the central nervous system (dizziness, headache), patients are advised to refrain from driving vehicles and other mechanisms, and also to exercise caution when engaging in activities that require increased concentration and speed of psychomotor reactions. Release form/dosage:Solution for intravenous and subcutaneous administration 5000 IU/ml. Package:

5 ml in neutral colorless glass bottles, sealed with a rubber stopper and crimped with an aluminum cap with a protective plastic cap. A label is attached to each bottle or an inscription is applied with quick-fixing paint.

5 bottles are placed in a PVC tray. 1 or 2 pallets along with instructions for use are placed in a cardboard pack.

Storage conditions:Store in a place protected from light at a temperature not exceeding 25 °C. Do not freeze! Keep out of the reach of children. Best before date: 3 years. Do not use after expiration date. Conditions for dispensing from pharmacies: On prescription Registration number: LP-002434 Close Instructions June 1, 2011

Bleeding and hemorrhages in various organs are a common complication during treatment with anticoagulants. In therapeutic departments, bleeding is observed in 5-10% of cases, and in surgical and gynecological departments - much less often (E. Perlik, 1965). Various localizations of hemorrhagic reactions in treatment with anticoagulants: fatal hemorrhages in the pericardial area (M. I. Teodori et al., 1953), intramural, pulmonary hemorrhages, intracranial hematomas, gastrointestinal bleeding (G. A. Raevskaya, 1958), etc. V. P. Romashov (1970 ) out of 400 patients with myocardial infarction, angina pectoris, hypertension, thrombotic cerebral stroke, embolism of pulmonary and peripheral vessels, treated with heparin, pelentan, syncumar, neodicoumarin, phenylin and fibrinolysin, microhemorrhages were observed in 53 people, manifested by microhematuria, the presence of hidden blood in the stool, red blood cells and streaks of blood in the sputum, hemorrhages in the sclera, short-term nosebleeds. More severe complications were found in 14 patients: bleeding from the lungs, kidneys, gastrointestinal tract, hemorrhages in the skin and muscles.

These complications are based on hypocoagulation and increased capillary fragility. Concomitant diseases that are detected in patients during the period of anticoagulant use are of great importance. For example, with arterial hypertension, capillary resistance is reduced and their fragility is increased. In addition, depending on the level of blood pressure, the concentrations of blood coagulation factors and, accordingly, tolerance to anticoagulants change. This requires careful adjustment of the doses of drugs used. Tumors and ulcers of the gastrointestinal tract, strangulated hernias and other diseases contribute to the occurrence of intraperitoneal bleeding. According to E. Perlik (1965), during chronic inflammatory and allergic processes, tolerance to endogenous heparin sharply decreases, but during acute inflammation and recurrent thromboembolism, it does not increase. Liver diseases accompanied by impaired synthesis of coagulation factors also lead to changes in the coagulation status of the blood. The danger of using anticoagulants against the background of hemorrhagic diathesis is completely proven.

Hemorrhagic complications can also occur as a result of the additional administration of other medications that have a synergistic or antagonistic effect on blood clotting and change capillary permeability and resistance. The anticoagulant effect of anticoagulants can be enhanced by the action of salicylates, some broad-spectrum antibiotics and phenothiazine derivatives. since they exhibit synergism with respect to coumarins and indanediones.

Still, the main cause of hemorrhagic complications during treatment with anticoagulants is their overdose and insufficient control over the coagulation status of the blood.

Clinically, hemorrhagic complications often manifest as renal syndrome - hematuria accompanied by renal colic due to blockage of the ureters by blood clots. Women often experience uterine bleeding. In the presence of an ulcerative process in the gastrointestinal tract, bleeding of appropriate localization with bloody vomiting and tarry stools may occur. Subserous bleeding and hemorrhage sometimes simulate an acute abdomen and lead to unnecessary surgical interventions. Consequently, depending on the location and severity of hemorrhages or bleeding, hemorrhagic complications of anticoagulant therapy can manifest themselves in various clinical syndromes.

Non-allergic complications of pharmacotherapy caused by the actual side effects of drugs.

The actual side effects of medicinal substances, not related to their pharmacological (therapeutic) effect, can be observed immediately (from several minutes to several hours) after the first administration of the drug into the body - immediate manifestations, and after a long time (weeks, months, years) after repeated administrations medications - long-term manifestations.

The first group includes acute intoxication, pathological reflex reactions (cardiac arrest, respiratory arrest), irritating effect of drugs at the site of their administration, etc. Long-term manifestations of the actual side effects of drugs are expressed in chronic intoxication, teratogenicity, tumor growth, most complications of hormone therapy, the occurrence of thromboembolism during treatment with anticoagulants, aspirin ulcers (although in rare cases they can develop as an immediate complication), lesions of the VIII pair of cranial nerves with certain antibiotics, etc.

The clinical picture, diagnosis and treatment of acute drug poisoning are described in detail in clinical toxicology manuals and individual manuals; the immediate adverse reactions of many drugs are listed in pharmacological reference books and drug annotations, so we do not dwell on them. Long-term manifestations of the actual side effects of the main groups of drugs used in the clinic deserve more detailed consideration.

On the same topic

2011-06-01

Medicine is a separate and very important field of human activity, which is aimed at studying various processes in the human body, treating and preventing various diseases. Medicine studies both old and new diseases, develops new treatment methods, medicines and procedures.

It has always occupied the highest place in human life, since ancient times. The only difference is that ancient doctors were based either on small personal knowledge or on their own intuition when treating diseases, and modern doctors are based on achievements and new inventions.

Although over the centuries-old history of medicine many discoveries have already been made, methods of treating diseases that were previously considered incurable have been found, everything is developing - new methods of treatment are being found, diseases are progressing and so on ad infinitum. No matter how many new drugs humanity discovers, no matter how many ways they come up with to treat the same disease, no one can guarantee that in a few years we will not see the same disease, but in a completely different, new form. Therefore, humanity will always have something to strive for and activities that can be increasingly improved.

Medicine helps people recover from everyday illnesses, helps in the prevention of various infections, but it also cannot be omnipotent. There are still quite a few different unknown diseases, inaccurate diagnoses, and incorrect approaches to curing the disease. Medicine cannot provide 100% reliable protection and assistance to people. But it’s not just a matter of insufficiently known diseases. Recently, many alternative methods of healing have appeared; the terms correction of chakras and restoration of energy balance are no longer surprising. Such a human ability as clairvoyance can also be used for diagnosis, predicting the course of development of certain diseases and complications.

Treatment of hemorrhagic vasculitis in children is a complex therapeutic problem. Treatment should be comprehensive, active, early, in compliance with the general principles of therapy for this disease.
The basic principles include: bed rest, hypoallergenic diet, antibacterial therapy (as indicated), anticoagulant therapy, suppression of immune complex inflammation, infusion therapy, disaggregant therapy, enterosorption, “alternative” therapy.

Bed rest(strict) is prescribed for the entire period of hemorrhagic syndrome. A week after the last rash, bed rest becomes less strict (usually it lasts 3-4 weeks). If motor activity is impaired, there may be repeated rashes - “orthostatic purpura”.

Diet therapy for hemorrhagic vasculitis should be hypoallergenic. Excluded: fried and extracted foods, chocolate, citrus fruits, muffins, coffee, strawberries, chips, eggs, apples, cocoa, canned foods, products containing dyes, flavors, and products that cause allergies in the patient.

It is undesirable to consume products that enhance peristalsis. Fermented milk products and drinking plenty of fluids (decoctions of black currants, rose hips, vegetable juices) are indicated.

At renal form Diet No. 7 is prescribed, which is aimed at reducing swelling and... This is a predominantly plant-based diet with the exception of meat and table salt. If there is no swelling, the amount of fluid is not limited. In case of edema, the volume of fluid administered depends on the amount of urine excreted over the previous day.

Products containing oxalic acid, essential and extractive substances are excluded. After achieving remission, salt can be added to the diet. After 2 weeks from the start of remission, 0.5 g of salt per day is allowed, after 1.5-2 weeks from the start of remission - 3-4 g of salt per day. After 1 month from the start of remission, boiled meat is included in the diet, after 3 months, meat broth.

At abdominal form, if pain is present, diet No. 1a is prescribed. It is aimed at sparing the gastrointestinal tract (mechanical, chemical, thermal). Products that irritate the mucous membrane of the gastrointestinal tract and stimulate gastric secretion are excluded: raw fruits and vegetables, meat broths, bread, refractory fats, seasonings, spicy foods, dry foods, baked goods. Food should be pureed, boiled in water or steam. Cold and hot dishes are also excluded.

In the absence of abdominal pain, the patient is transferred to diet No. 1. Food is given boiled, but not pureed. You can give crackers. Fruits and vegetables, spicy and fatty foods are still excluded. When remission is achieved, the patient is transferred to a hypoallergenic diet (for a year).

Etiotropic therapy consists of eliminating the allergen, fighting infection, and sanitizing existing foci of infection.
It has been proven that viral and bacterial infections occupy a leading place among the factors preceding the development of hemorrhagic vasculitis. Often, treatment of concomitant infectious manifestations affects the positive outcome of the disease. As a result, treatment of chronic diseases of the nasopharynx, treatment of helminthiasis, herpes infection, intestinal dysbiosis, viral hepatitis, etc. is carried out.

Since in childhood the leading place is occupied by the pathology of the respiratory system, we have to resort to.
Antibacterial therapy is also prescribed for the development of nephritis, persistent wave-like course of the disease, and the presence of chronic foci of infection.

Preference is given to penicillin antibiotics (penicillin, ampicillin, ampiox), macrolides (clarithromycin, azithromycin, roxithromycin), cephalosporins.
In the presence of helminthic infestation, deworming is carried out. Deworming is also indicated for persistent recurrence of skin syndrome.

Pathogenetic therapy

Taking into account the pathogenesis of the disease, therapy is carried out in the following areas:

• Blockade of the formation of immune complexes (glucocorticoids, cytostatics);
• Removal of immune complexes (infusion therapy, plasmapheresis);
• Correction of hemostasis (antiplatelet agents, anticoagulants, fibrinolysis activators);
• Suppression of immune complex inflammation (non-steroidal anti-inflammatory drugs, glucocorticoids, cytostatics).

Treatment of hemorrhagic vasculitis should be individualized, depending on the clinical manifestations of the disease. But the use of antiplatelet agents or anticoagulants is mandatory.

Anticoagulant therapy

Anticoagulant therapy is indicated for moderate to severe hemorrhagic vasculitis. For mild cases, antiplatelet agents can be used as monotherapy. But still, in most cases it is necessary to resort to heparin therapy. Heparin therapy is the basic method of treating hemorrhagic vasculitis. To carry it out, sodium heparin or low molecular weight heparins are used.

The anticoagulant activity of sodium heparin is associated with the effect on (activated by antithrombin III), activation of the 1st complement component, effect on thrombin and activation of prothrombin Xa.

Heparin has anticoagulant, antiallergic, anti-inflammatory, lipolytic, fibrinolytic effects.

Heparin therapy is effective if certain rules are followed:

• It is necessary to choose the correct dose of the drug.
  — for a simple form, heparin is prescribed at a dose of 100-150 IU/kg per day;
  — with a mixed form — 200-400 IU/kg per day;
  — for nephritis — 200-250 IU/kg/day;
  — in the abdominal form, up to 500 IU/kg/day.
  With the correct dose, the blood clotting time should increase by 2 times from the initial level. In the absence of clinical or laboratory effect, the dose of heparin is increased by 50-100 units/kg/day. You should also be aware that the lack of effect from high doses of heparin may be due to a deficiency of antithrombin III or a high content of acute phase proteins of inflammation. The duration of heparin use can range from 7 days to 2-3 months. The duration depends on the form and severity of the disease. For a moderate form, usually 25-30 days, for a severe form, 45-60 days, for nephritis - 2-3 months;
• Ensure uniform action of heparin throughout the day.
  This can be achieved by continuous intravenous administration of the drug, which is practically difficult to do. Also, intravenous administration of heparin every 4 hours does not lead to the desired hypocoagulation, since after 2.5-3 hours the effect of heparin is not recorded. Preference is given to subcutaneous administration of sodium heparin every 6 hours into the anterior abdominal wall in equal doses. This administration of the drug creates a depot and a more uniform and prolonged hypocoagulative effect (due to the peculiarities of the blood supply to this area);
• Conduct laboratory monitoring of the hypocoagulant effect of heparin
  It is necessary to check blood clotting before the next administration of heparin. If hypocoagulation is insufficient, the dose of the drug is increased. If the blood clotting time increases by more than 2 times from the initial level, the dose of heparin is reduced. A mistake is considered to be reducing the frequency of administration (number of injections). It is necessary to first reduce the single dose of the drug, and then the frequency of administration ;
• If necessary, additionally administer antithrombin III.
  For heparin to act, its plasma cofactor antithrombin III (the main thrombin inhibitor) is required. AT III is the main potential of the anticoagulant system and if it is depleted, heparin therapy is not effective.
  The main source of AT III is fresh frozen plasma. In addition to AT III, there are other antithrombotic components in the plasma (plasminogen, fibronectin, protein C, physiological antiplatelet agents), which normalize the coagulation process and antiprotease activity of the plasma.
  Fresh frozen plasma is administered 10-15 ml/kg per day in one or two doses. Along with it, heparin is administered: 500 units of heparin per 50 ml of plasma. A contraindication for plasma administration is capillary toxic Schönlein–Henoch nephritis. When AT III is administered, the effect of heparin increases, which must be taken into account for further calculation of heparin.
  Plasma administration for hemorrhagic vasculitis is currently being reconsidered. This is due to the fact that plasma also contains other protein substances, which are a source of antigenic stimulation and can aggravate the immunopathological process. Of course, it is better to administer ready-made AT III drugs, such as Cybernine, Antithrombin III human. But these drugs are not yet approved for use in children.

Heparin administration is discontinued 7 days after the last rash appears. First, the dose of the drug is reduced by 100 units/kg/day every 2-3 days, and then the frequency of administration. The criteria for heparin withdrawal are an increase in blood clotting by 2.5-3 times or the presence of hemorrhages at the injection sites.

For anticoagulant therapy, both unfractionated heparin and fractionated (fine, low molecular weight) heparin can be used.

In recent years, finely divided heparins (Fraxiparin, Fragmin, Clivarin, Clexane, Fluxum, Calciparin) have begun to be used more often.
The administration of these drugs is less traumatic (administered 1-2 times a day). Thus, fraxiparin is administered once a day subcutaneously into the anterior abdominal wall at a dose of 150-200 IU/kg (course of treatment is 5-7 days).

Low molecular weight heparins have a more pronounced antithrombotic effect and less pronounced anticoagulant activity compared to heparin. They have a rapid and long-lasting antithrombotic effect due to the inhibition of factor Xa (4 times more pronounced than heparin). They also inhibit the formation of thrombin, which provides their anticoagulant effect.

In addition, finely divided heparins are characterized by:

• rare frequency of bleeding;
• higher bioavailability when administered subcutaneously;
• less need for blood clotting control (as they have little effect on blood clotting).

Hormone therapy

The main goal of hormonal therapy is to stop the immune process.

Glucocorticoids are indicated for:

• the presence of two or more syndromes;
• wave-like course of skin rashes;
• widespread skin rashes with a pronounced thrombohemorrhagic component and necrosis;
• significant exudative component of the rash;
• abdominal syndrome (severe);
• nephritis with nephrotic syndrome or macrohematuria.

Glucocorticoids have pronounced anti-inflammatory and immunosuppressive effects. When using glucocorticoids, the circulation of immune complexes is significantly reduced and the increased level of proteases is normalized.

With early administration of glucocorticoids, the clinical symptoms of the disease are quickly relieved, the duration of therapy is reduced, and further kidney damage is prevented.
Prednisolone is prescribed at a dose of 0.5-1.0 mg/kg per day for 3-4 weeks.
With the development of nephritis, the dose of prednisolone is increased to 2 mg/kg per day for 1-2 months, then the dose is reduced by 2.5 mg once every 5-7 days until complete withdrawal.

However, one should remember the hypercoagulable effect of glucocorticoids, which inhibit the fibrinolysis system and activate the coagulation system and platelets. Therefore, they are recommended to be used in conjunction with antiplatelet agents and anticoagulants. Also, when using prednisolone, potassium supplements should be prescribed.

In severe cases of the disease, pulse therapy is used. During pulse therapy, 1000 mg of methylprednisolone (250 mg in a bottle) diluted in 200 ml of saline is simultaneously administered at a rate of 60 drops per minute. For nephrotic syndrome, pulse therapy is carried out 3 days in a row, or every other day. If necessary, it can be repeated once a month, up to 10-12 times. The use of pulse therapy has fewer side effects and gives a better effect than oral glucocorticoids in regular dosages.

Plasmaphoresis

Plasmaphoresis is used for treatment-refractory forms of hemorrhagic vasculitis. The therapeutic effect of plasmaphoresis is the elimination of immune complexes, breakdown products, inflammatory mediators, and platelet aggregation factors. As a result, cellular immunity is unblocked and the properties of the blood are restored.

Indications for plasmaphoresis:

• High content of immune complexes;
• Severe abdominal syndrome;
• Nephritis with nephrotic syndrome;
• Acute renal failure.

The course of treatment is 3-8 sessions. Initially, 3 sessions are carried out daily, then once every 3 days.
Plasmaphoresis helps improve microcirculation, increase the activity of immune cells, and increase sensitivity to drugs. However, you should know that plasmaphoresis removes only large circulating complexes from the blood.
The best effect of plasmaphoresis is observed when it is carried out in the first 3 weeks of the disease.

Disaggregant therapy

Disaggregant therapy improves microcirculation by blocking platelet aggregation. It is indicated for all forms of the disease.
The following drugs are used for disaggregant therapy:

• Dipyridamole (chimes) - 3-8 mg/kg per day in 4 divided doses;
• Pentoxifylline (trental) - 5-10 mg/kg per day in 3 doses;
• Ticlopidine (ipatone) - 10-15 mg/kg/day 3 times a day

In severe cases of the disease, two drugs with different mechanisms of action are used. You can prescribe chimes with trental or with indomethacin, which also has a disaggregation effect.

Disaggregants should be used long-term:

• For mild cases - 2-3 months;
• For moderate severity – 4-6 months;
• In case of severe recurrent course and nephritis, up to 12 months;
• In case of chronic course - in courses for 3-6 months.

Activators of fibrinolysis.

In hemorrhagic vasculitis, depression of fibrinolysis has been identified, therefore there are indications for the administration of fibrinolysis activators. Non-enzyme activators are prescribed - nicotinic acid and xanthinol nicotinate. They are vasoactive substances and promote the release of vascular plasminogen activators into the bloodstream. But it should be remembered that their effect is short-term (no more than 20 minutes after intravenous administration). They are prescribed at a dose of 3-5 mg/kg/day, taking into account individual sensitivity. For the same purpose, you can use nikoshpan - 0.1 g 2 times a day.

Infusion therapy

Infusion therapy for hemorrhagic vasculitis is used to improve peripheral microcirculation.

Indications for infusion therapy are:

• Severe hemorrhagic rashes;
• Hypercoagulation;
• Abdominal syndrome;
• Severe thrombocytosis;
• Hematocrit above 40%.

For infusion therapy, low molecular weight plasma replacement solutions are used at a dose of 20 ml/kg/day. They improve the rheological properties of blood, prevent the aggregation of red blood cells and platelets, and absorb and remove toxins from the body.

For the abdominal form, a glucose-novocaine mixture is used (glucose 5% and novocaine 0.25% in a 3:1 ratio). The dose of the mixture is 10 ml/kg of body weight, but not more than 100 ml. In addition to the analgesic effect, novocaine improves peripheral blood circulation and blocks the action of cholinesterase, which is increased in hemorrhagic vasculitis.

Antispasmodics

Antispasmodics are prescribed for the abdominal form. Use noshpa 2% -2 ml, aminophylline 5 mg per kg per day in 200 ml saline. solution.

Antihistamines

The prescription of antihistamines is pathogenetically justified during the initial manifestations of hemorrhagic vasculitis, when there is a release of histamine and other similar substances. Tavegil, suprastin, terfenadine, cetirizine, etc. are used. In the first days of the disease, their parenteral use is possible. The course of using antihistamines is no more than 7 days.
But there is another point of view - that the use of antihistamines, as well as vascular strengthening agents, is not justified, since they aggravate hemocoagulation changes.

Enterosorption

Enterosorbents are used when food agents are the provoking factor of the disease. They bind toxins and active substances in the intestines, which prevents them from entering the bloodstream. The duration of therapy with enterosorbents in acute cases is from 2 to 4 weeks. With an undulating course, up to 1-3 months. Used: carbolene, enterosgel, smecta, litovit, enterodes, nutriclinz, polyphepan. Drugs in this group should be used with caution in the abdominal form, as increased bleeding or increased pain is possible.

Alternative therapy

This therapy is used for undulating or recurrent skin rashes. This includes the use of anti-inflammatory therapy, cytostatics, and membrane stabilizers.

Anti-inflammatory drugs are used for:

• Persistent, wave-like course of hemorrhagic purpura;
• With high leukocytosis, a significant increase in NRC;
• With hyperfibrinogenemia, increased seromucoids;
• For articular form, when glucocorticoids are not prescribed;
• When there are contraindications to the use of glucocorticoids.

The drugs used are: ibuprofen (15-20 mg/kg per day), diclofenac sodium (1-2 mg/kg per day), indomethacin (3-4 mg/kg), etc.
The action of these drugs is associated with limiting the development of various phases of inflammation. They also have a disaggregating effect, which has a beneficial effect on treatment. They are used with caution in case of kidney disease, due to the possibility of increased hematuria. Duration of treatment is from 4 to 8 weeks.

4-aminoquinoline derivatives

These drugs are prescribed when the activity of severe forms of the disease subsides while prednisolone is discontinued or its dose is reduced. The following drugs are used: Plaquenil, Delagil. They have anti-inflammatory, immunosuppressive, antiplatelet effects.
Plaquenil is prescribed at a dose of 4-6 mg/kg once at night, for a course of 4-12 months. It is used for nephrotic and mixed forms of nephritis, for gross hematuria while reducing the dose of prednisolone. The use of Plaquinil for nephritis in most cases allows one to achieve remission.

It should be noted that the effect of the use of 4-aminoquinoline derivatives develops after 6-12 weeks from the start of therapy. Be sure to monitor a general blood test (leukopenia is possible) and undergo an examination by an ophthalmologist (there may be pigment deposition on the cornea, decreased vision).

Cytostatics

Cytostatics should be used with caution, as they suppress the bone marrow, immunity and cause various complications.

Indications for their use are:

• Rapidly progressing course of nephritis;
• Ineffectiveness of glucocorticoids;
• Contraindications to treatment with glucocorticoids;
• Relapse of nephritis with gross hematuria;
• Severe skin syndrome with areas of skin necrosis.

In children, use: cyclophosphamide (2-3 mg/kg/day) and azathioprine (2 mg/kg). The course of treatment is at least 6 months. Treatment is carried out under the control of a general blood test. In case of leukopenia, cytostatics are discontinued.

Membrane stabilizers

Membrane stabilizers are natural catalysts for the synthesis of urokinase, as a result of which the inflammatory process is reduced.

Indications for their use:

• Severe skin rashes;
• Wave-like course of skin rashes;
• Presence of jade.

Therapy with these drugs reduces the permeability of the vascular wall, has an immunomodulatory effect, improves trophic processes, and enhances the effect of anti-inflammatory drugs.

Use: Essentiale Forte - 2 mg/kg/day, retinol - 1.5-2 mg/kg, lipostabil, dimephosphone - 50-75 mg/kg. The course of treatment is at least 1 month. Treatment is carried out in repeated courses.

Immunomodulators.

Immunomodulators are used for undulating skin purpura and capillary toxic nephritis.
The following are used: dibazole (1-2 mg/kg in 2 doses for 4-5 weeks), levamisole (2 mg/kg per day for 3 days with breaks between courses of 5 days), Immunal (10-20 drops 3 times a day). day for 8 weeks), tonsilgon (15 drops 3 times a day for 6 weeks). Antioxidants are also used for the purpose of immunomodulation.

In conclusion, I would like to note that the main principle of drug therapy for hemorrhagic vasculitis is to reduce the amount of medications to the required minimum and quickly discontinue the drug if an allergic reaction occurs to it.

Mikhail Lyubko

Literature: Modern approaches to the treatment of Henoch-Schönlein purpura and its prospects. O.S. Tretyakov. Simferopol.