RU2791373C1 - Method for treatment and prevention of recurrent venous thrombosis after the novel coronavirus infection - Google Patents

Abstract

FIELD: medicine; therapy.

SUBSTANCE: invention is intended for treatment and prevention of venous thrombosis after the novel coronavirus infection COVID-19. The method consists in four stages of the treatment, in which such drugs as Clexane, Vasoket, Voltaren, Actovegin, Thrombovazim, Xarelto or Eliquis, Thrombo ACC, Wessel Due F are used.

EFFECT: acceleration of the processes of recanalization of veins affected by the thrombotic process, reduction of the treatment time with no need for surgical intervention and laboratory control.

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Description

A method for the treatment and prevention of venous thrombosis after a novel coronavirus infection COVID-19 refers to medicine, namely to surgery, in particular, to non-surgical methods of treatment, and can be used in the treatment of patients with acute venous thrombosis of various localization, as well as for prevention recurrence of thrombosis and reduction of symptoms, acceleration of recanalization, prevention of complications.

Standard therapy for acute venous thrombosis includes the administration of injectable anticoagulants of low molecular weight heparins (Russian clinical guidelines for the diagnosis, treatment and prevention of venous thromboembolic complications. Phlebology. 2015), flavonoid drugs, class II elastic compression, antiplatelet agents, systemic anti-inflammatory drugs. Taking into account the risk of complications of acute venous thrombosis, as well as the high probability of recurrence, it is advisable in clinical practice to strive to accelerate the lytic process of thrombotic masses.

The traditional method of treating venous thrombosis is the use of anticoagulant therapy in parenteral or enteral form in combination with elastic compression and phlebotonics. (Russian clinical guidelines for the diagnosis, treatment and prevention of venous thromboembolic complications. Phlebology. 2015).

The disadvantages of this method are: the duration of therapy, the lack of etiopathogenetic methods of treatment aimed at restoring the damaged vascular wall, as well as the absence of drugs that promote the lysis of thrombotic masses.

A known method for the treatment of acute ascending varicothrombophlebitis of the veins of the lower extremities by using a direct oral thrombolytic in combination with direct oral anticoagulants (RF patent No. 2759653, A61F 13/08, 11/16/2021).

The disadvantage of this method is the consistent, rather than simultaneous use of drugs aimed at all parts of the pathogenesis of the disease. In addition, the method is applied only in thrombosis of the saphenous veins and does not take into account the use in thrombosis of other veins of the human body.

A known method for the treatment of deep vein thrombosis by administering to patients with deep vein thrombosis a medicinal mixture containing a glucocorticosteroid drug, heparin and novocaine, by means of a syringe, previously using ultrasound, the places of the most pronounced inflammation of the venous wall and paravasal tissue under ultrasound control are determined (RF patent No. 2719407 , A61K 31/245, 04/17/2020).

The disadvantage of this method is the invasiveness of the procedure, the complexity of its implementation and the need to use specialized ultrasound equipment and a specially trained specialist in a manipulation room or operating room, the inapplicability of this method on the veins of the neck and subclavian veins due to the anatomical features of these localizations, as well as due to with a high risk of complications.

Known drug for the prevention and treatment of venous thrombosis 3-methyl-8-(piperazin-1-yl)-7-(thietan-3-yl)-1-ethyl-1H-purine-2,6(3H,7H)-dione hydrochloride used as an agent for the treatment and prevention of thrombosis by blocking the platelet receptor GP IIb-IIIa (RF patent No. 2662308, A61K 31/522, 07/25/2018).

However, this drug is not freely available and for sale and is currently under investigation and cannot be used for the treatment and prevention of thrombosis in humans in everyday practice.

A known method for the treatment of deep vein thrombosis by using the drug Thrombovasim orally at a dose of 1600 IU to 4800 IU per day for 10-15 days for thrombus lysis and acceleration of recanalization (RF patent No. 2613155, A61K 38/43, 03/15/2017).

The disadvantage of this method is the unstable and high dosage of the drug, which does not affect the clinical effect of the application, as well as the inapplicability of this method for thrombosis of the veins of the upper extremities, saphenous veins of the lower extremities, thrombosis of the veins of the neck.

The problem to be solved by this invention is to improve the efficiency of treatment of patients with acute venous thrombosis, as well as the prevention of recurrence of the disease.

The technical (therapeutic) result achieved by the invention is the lysis of thrombotic masses, the acceleration of the processes of recanalization of veins affected by the thrombotic process, the reduction of treatment time, the absence of the need for surgical intervention, the absence of the need for laboratory control.

The specified technical result is achieved by the fact that the treatment is carried out in four stages. At the first stage of treatment, lasting 10 days, low molecular weight heparins are used - Clexane at a dosage of 1 mg per kilogram of body weight twice a day, drugs - venotonics - Vasoket 600 mg 1 tablet in the morning, non-steroidal anti-inflammatory drugs - Voltaren 3.0 ml intramuscularly, constant elastic compression stocking Sigvaris of the second class, elevated position of the affected limb, microcirculation corrector and angiprotector - Actovegin 10.0 ml intravenously by drip in 200 ml of saline once a day, oral thrombolytic drug Thrombovasim at a dosage of 800 IU 2 times a day.

At the second stage of treatment, lasting 10 days, oral anticoagulants are used - Xarelto 2.5 mg or Eliquis 2.5 mg 1 tablet twice a day, a disaggregant - Thrombo ACC 100 mg 1 tablet per day, flavonoid preparations - Vasoket 600 mg 1 tablet in the morning, microcirculation corrector and angiprotector - Actovegin 5.0 ml intramuscularly twice a day, continue oral administration of the thrombolytic drug Thrombovazim at a dosage of 800 IU twice a day, angioprotector and profibrinolytic - Wessel Due F 600 LE intramuscularly once a day. Elastic compression stocking Sigvaris second class.

At the third stage of treatment, lasting 60 days, oral anticoagulants are used - Xarelto 2.5 mg or Eliquis 2.5 mg 1 tablet twice a day, a disaggregant is used - Thrombo ACC 100 mg 1 tablet per day, elastic compression is continued, stocking Sigvaris second class , use drugs - venotonics - Vasoket 600 mg, microcirculation corrector and angiprotector - Actovegin 200 mg 2 tablets three times a day; angioprotector and profibrinolytic - Wessel Due F 250 LE 1 capsule twice a day,

At the fourth stage of treatment, lasting 100 days, Xarelto 2.5 mg or Eliquis 2.5 mg 1 tablet is used twice a day, a disaggregant - Thrombo ACC 100 mg 1 tablet a day, microcirculation corrector and angiprotector - Actovegin 200 mg 2 tablets three times per day, continue elastic compression, stocking Sigvaris of the second compression class.

In practice, the method is carried out as follows.

At the first stage of treatment, namely in a hospital, in the advanced stage of the disease, the following therapy regimen is prescribed: low molecular weight heparins in a therapeutic dosage to prevent early complications in the form of pulmonary embolism (Clexane 1 mg / kg subcutaneously - twice a day - 10 days ), drugs of the flavonoid series that have a phlebotonizing effect - venotonics: Vasoket 600 mg in the morning once a day - 10 days, non-steroidal anti-inflammatory drugs: Voltaren 3.0 intramuscularly once a day - 5 days, constant elastic compression with a Sigvaris stocking of the second class, sublime limb position - to improve venous outflow from the limb, microcirculation corrector and angiprotector - Actovegin 10.0 ml intravenously drip in saline once a day, as well as oral thrombolytic drug Thrombovazim in capsules of 800 units twice a day for a period of 10 days, for the lysis of thrombotic masses in the affected veins nah.

The drug Thrombovasim has thrombolytic, anti-inflammatory and cardioprotective effects. The mechanism of thrombolytic action is associated with the direct destruction of fibrin filaments that form the main framework of a thrombus. The mechanism of anti-inflammatory action is associated with the effect on the oxidative function of blood neutrophils and tissue macrophages. The mechanism of cardioprotective action is associated with an improvement in myocardial blood supply. Thrombovasim is a low-toxic drug, it does not reduce the level of platelets and does not affect the clotting time and duration of bleeding. Thrombovasim in vitro has a direct fibrinolytic effect due to self-hydrolysis of the thrombus. The drug Thrombovasim is obtained as a result of immobilization of subtilisin-like proteinases, subtilisin, on polyethylene oxide.

The drug Wessel DUE F (Sulodexide) has an angioprotective and antithrombotic effect, reduces the thickness of the basement membrane and the production of the extracellular matrix by reducing the proliferation of mesangial cells, and also restores the density of the negative electric charge of the pores of the basement membrane of the vessels.

The clinical efficacy of Actovegin is due to a pronounced endothelioprotective effect precisely at the level of the microvascular bed. Actovegin is a deproteinized hemoderivative obtained by dialysis and homogenate ultrafiltration, which ensure the presence in the preparation of only compounds with a molecular weight of less than 5000 daltons. The drug contains more than 200 active ingredients, including peptides, amino acids, nucleosides, lipids, oligosaccharides, as well as inorganic electrolytes and trace elements. The active fraction of Actovegin has an insulin-like effect: it increases the entry of glucose into cells, activates the processes of aerobic and anaerobic oxidation of glucose, and increases the metabolism of high-energy phosphates

At the second stage of treatment, also in a hospital, from day 11 of therapy to day 20, low molecular weight heparins in injectable form are replaced with direct oral anticoagulants - Xarelto 2.5 mg or Eliquis 2.5 mg 1 tablet twice a day , use a disaggregant - Thrombo ACC 100 mg 1 tablet per day, Wessel Due F 600 LE intramuscularly once a day. Continues parenteral administration of the drug Actovegin, at a dosage of 5.0 ml intramuscularly once a day. Continue taking flavonoid preparations - Vasoket 600 mg in the morning. At this stage, Trombovazim continues to be taken in capsules of 800 IU twice a day for a period of 10 days. Thus, the total duration of taking a direct oral thrombolytic is 20 days. Petersburg Venous Forum (Christmas Meetings), St. Petersburg, 2019, pp. 75-76). In addition, the elastic compression of the bangs of the second class (Sigvaris) is continued.

At the third stage of treatment, from the 21st day of therapy until the 80th day, continue taking a direct oral anticoagulant - Xarelto 2.5 mg or Eliquis 5 mg 1 tablet twice a day, use a disaggregant - Thrombo ACC 100 mg 1 tablet per day, Wessel Due F 250 LE 1 capsule twice a day, continue elastic compression, stocking (Sigvaris) second class. Continue taking venotonic - Vasoket 600 mg in the morning. Continue taking the microcirculation corrector and angiprotector - Actovegin, in tablet form - 200 mg 2 tablets three times a day.

At the fourth stage of treatment, from the 81st day to the 180th day, Xarelto 2.5 mg or Eliquis 2.5 mg 1 tablet twice a day, continue taking the antiplatelet agent - Thrombo ACC 100 mg 1 tablet per day, apply a microcirculation corrector and angiprotector - Actovegin 200 mg 2 tablets three times a day, continue elastic compression, stocking Sigvaris second class.

The proposed method can be used in clinical practice for the treatment of patients with acute venous thrombosis of various localization inpatient and outpatient treatment.

A study was conducted to establish the effectiveness of treatment in therapy with a combination of microcirculation corrector, angioprotector, oral anticoagulant and direct oral thrombolytic.

Purpose of work: to improve the results of treatment of patients with venous thrombosis against the background of a new coronavirus infection COVID 19 by optimizing treatment tactics.

The work is based on the results of diagnosis, treatment and follow-up of 44 patients with acute venous thrombosis after a new coronavirus infection, who were in the vascular surgery department of the Ulyanovsk Regional Clinical Hospital in the period from 2020 to 2021. Men were 40.9% (18), women - 59.1% (26). The age of the patients ranged from 28 to 65 years, averaging 43.1±4.8 years. According to the localization of the thrombotic process, the patients were divided as follows: deep vein thrombosis of the lower extremities was detected in 45.45% (20) patients, subcutaneous and deep vein thrombosis of the lower extremities in 22.72% (10) of patients, vein thrombosis of the upper extremities was 18.18% (8) of people, and thrombosis of the central veins (subclavian or jugular) - in 13.63% (6) of patients. The diagnosis was established on the basis of the clinical manifestations of the disease and the results of Doppler ultrasound and duplex scanning. When examining patients, attention was paid to the history and timing of the disease, the prevalence of the thrombotic process, the age of the patients, as well as the severity of the new coronavirus infection. To assess the state of blood flow through the veins, determine the level of the thrombotic process, the nature of the thrombus, as well as the presence of thrombus head flotation, all patients underwent duplex angioscanning, which was performed using a stationary device "Acussion S2000" by "Siemens" (Germany), with linear and convex sensors. During the examination, the nature of the venous thrombus was established: parietal, occlusive and floating thrombi (Krivoshchekov E.P. Acute venous thrombosis: diagnosis, treatment and prevention Krivoshchekov E.P., Korymasov E.A., Lysov N.A., Katorkin S. E., Textbook Moscow, 2020 242 pp.; Kirienko A.I., Matyushenko A.A., Andriyashkin V.V. Acute thrombophlebitis. M.: Litterra, 2006; 108 p.). All patients were prescribed systemic basic therapy: venotonic Vasoket 600, analgesics (for pain), antihistamines, parenteral anticoagulants, elastic bandaging (in case of localization of a thrombus in the limb). The patients were divided into two similar groups. The groups were comparable to the level of spread of blood clots, age, gender and concomitant somatic pathology. In the first group (n=20), basic therapy was combined with the transfer of patients to direct oral anticoagulants from the 10th day of treatment for a period of 6 months, regardless of the localization of the thrombotic process, its spread. In the second group (n=24), in addition to the basic treatment, patients were transferred to direct oral anticoagulants and the direct oral fibrinolytic Thrombovazim, the angioprotector Wessel Due F, and the microcirculation corrector Actovegin were added to the treatment. Thrombovazim was administered at 800 IU twice a day, orally 30-40 minutes before meals, for a course of 20 days (Krivoshchekov E.P. Acute venous thrombosis: diagnosis, treatment and prevention Krivoshchekov E.P., Korymasov E.A., Lysov N.A., Katorkin S.E., Textbook Moscow, 2020 242 pp. Romanov V.E., Madonov P.G., Ershov K.I., Shilova M.A. Pharmacological properties and clinical use of thrombovazim. Phlebology, 2014; 8; 2: 90-91). Angioprotector Wessel Due F was prescribed 600 LE intramuscularly for a period of 10 days. (Krivoshchekov E.P., Katorkin S.E., Elshin E.B., Romanov V.E. The use of sulodexide at the post-hospital stage of treatment of patients with a new coronavirus infection COVID-19. Preventive medicine. 2022. V. 25. No. 1 pp. 91-97, DOI 10.17116/profmed20222501191). Microcirculation corrector Actovegin was prescribed as follows: 10 ml twice a day intravenously by drip for a period of 10 days, from 11 to 20 days inclusive, the drug was administered intramuscularly at a dosage of 5.0 ml twice a day, subsequently, patients were transferred to the tablet form of the drug 200 mg 2 tablets three times a day for a period of at least 140 days. (Kovalchuk V.V. The role of a new coronavirus infection (COVID-19) in the progression and development of cerebrovascular diseases.

A competent choice of means of pathogenetic therapy is the key to the success of treatment and prevention. The view of a specialist from the "red zone". Neurology, neuropsychiatry, psychosomatics. 2021. Vol. 13. No. 1. pp. 57-66. DOI 10.14412/2074-2711-2021-1-57-66.). The comparability of the groups was analyzed according to the following criteria: age, gender, number of days from the onset of the disease, laboratory data before the start of therapy. The groups were comparable, no statistically significant differences in the analyzed characteristics between the groups were found. Statistical processing of the results was carried out at the end of clinical trials. Statistica v.6.0 software was used for statistical data processing. The safety assessment of the drug was carried out in all patients at all visits based on taking into account all possible adverse events and serious adverse events identified according to the physical examination, analysis of vital signs, clinical laboratory studies, as well as instrumental methods provided by the study design. In the first group of patients (n=20) who received basic therapy, there was no progression of the thrombotic process at the time of discharge. However, in the majority of patients in this group (87%), the thrombotic process persisted in the affected veins throughout the entire observation period (6 months), complete recanalization was not achieved. In the second group of the study (n=24), who received, in addition to basic therapy and direct oral anticoagulants, an oral fibrinolytic agent, an angioprotector and a microcirculation corrector, there was no progression of the thrombotic process at the time of discharge. According to the control ultrasound, recanalization in the early phase was noted in 18.18% (4) of patients. In the long-term follow-up period, for a period of 6 months, complete recanalization of the affected veins was achieved in 59.09% (13) of patients.

Thus, the conducted clinical studies of the combination of Wessel Due F, Actovegin and Thrombovasim in patients with acute vein thrombosis after coronavirus infection COVID 19 showed that this scheme is an effective and safe method of treating venous thrombosis, statistically significantly improving the results of therapy. The inclusion of Thrombovasim in the complex therapy of venous thrombosis significantly increases the effectiveness of therapy. The effective dosage is 1600 units per day (Romanov V.E., Madonov P.G., Ershov K.I., Shilova M.A. Pharmacological properties and clinical use of thrombovazim. Phlebology. 2014; 8; 2: 90-91) . In patients who received a combination of drugs Wessel Due F, Actovegin and Thrombovazim, based on the data of an instrumental study, there were no cases of a decrease in blood flow in the compromised veins. None of the patients treated with this regimen experienced adverse events and/or serious adverse events on physical examination, analysis of vital signs and instrumental methods.

With this four-stage method of treatment, there is no need to perform surgical intervention, laboratory control and monitoring of the patient is not required, the need for parenteral administration of fibrinolytic drugs or invasive methods of therapy is eliminated, the processes of recanalization and complete restoration of the patency of the affected veins are accelerated, thereby significantly reducing the frequency development of post-thrombotic disease.

Based on clinical experience, data from an objective study, the nature of the dynamics of the inflammatory process, the assessment of subjective symptoms in patients, it can be concluded that when using the claimed method of treating vein thrombosis, there is a faster relief of pain, a faster transition of the thrombotic process to the recanalization phase, no need for surgical intervention. Also, due to the proposed method, the formation of post-thrombotic syndrome is prevented, the risk of thrombosis recurrence is reduced, thereby reducing the likelihood of thromboembolic complications. There were no hemorrhagic complications when using this method of treatment. The described method can be used in surgical practice at the inpatient and outpatient stages of treatment of patients, including in the departments of vascular surgery.

Clinical example 1

Patient P., 48 years old, lowered his eyes to the Department of Thoracic and Vascular Surgery of the Regional Regional Clinical Hospital on March 16, 2021 with a diagnosis of 182.8 Thrombosis of the deep and saphenous veins of the right upper limb without signs of flotation; thrombosis of the right internal jugular vein. Concomitant: Arterial hypertension 2 tbsp., 2 tbsp., risk 3; convalescent for a new coronavirus infection COVID-19; transferred bilateral viral pneumonia of moderate severity. Upon admission, the patient complained of pain and swelling of the right upper limb. According to anamnestic data, the patient was treated in the infectious diseases hospital for bilateral viral pneumonia caused by the COVID-19 virus, during inpatient treatment, multiple intravenous infusions were performed into the peripheral veins of the upper extremities, and a catheter was implanted into the right internal jugular vein, which was deleted 4 days before discharge. The patient underwent further examination in the form of fibrogastroduodenoscopy, chest X-ray, ultrasound examination of the veins and arteries of the upper and lower extremities, ultrasound examination of the main arteries and veins of the head. At the same time, no significant pathology affecting the course of the underlying disease was identified. Conservative treatment was prescribed: Clexane 0.8 s / c twice a day, permanent elastic compression of the right upper limb of the second class, Voltaren 3.0 / m at night No. 5, Vasoket 600 mg in the morning, Thrombovasim at a dosage of 800 IU twice a day day, Actovegin 10.0 ml intravenously twice a day - 10 days, then 5.0 ml intramuscularly twice a day - 10 days. Elastic compression stocking Sigvaris second class. At the same time, there were no allergic reactions or side effects during the treatment.

The patient underwent control ultrasound of the veins of the upper extremities and MAG after 10 and 20 days of treatment. The initial signs of recanalization of the thrombotic process in the affected veins were revealed, no thrombus flotation was detected. No hemorrhagic complications were observed during inpatient treatment.

From 11 to 21 days the patient was transferred to the outpatient stage of treatment. When discharged, he did not complain of pain, objectively the edema of the right upper limb remained. Enoxiparin injections were canceled, Eliquis 2.5 mg twice a day, Wessel Due F 600LE intramuscularly once a day, Thrombo ACC 100 mg in the evening were prescribed, Actovegin was prescribed, but in tablet form - 200 mg tablets 2 tablets three times a day , continued taking Vasoket 600 mg in the morning. Elastic compression stocking Sigvaris second class.

The patient was examined at the outpatient stage by a vascular surgeon monthly from the moment of discharge from the hospital. On examination, he did not complain of pain, the edema of the limb was completely stopped. Clinical and ultrasound signs of the formation of post-thrombotic disease were not observed.

He takes Eliquis 2.5 mg twice a day, continued taking Thrombo ASS at a dosage of 100 mg per day. Starting from the 22nd day, an angioprotective drug was prescribed - Wessel DUE F (sulodexide), 250 LE, twice a day, one capsule for 60 days. Continued taking Actovegin, but in tablet form - tablets of 200 mg 2 tablets three times a day, continued taking Vasoket 600 mg in the morning. Elastic compression stocking Sigvaris second class continued.

At the fourth outpatient stage, the patient from the 81st day to the 180th day, Eliquis 2.5 mg 1 tablet twice a day, continues to receive the antiplatelet agent - Thrombo ACC 100 mg 1 tablet per day. Apply a microcirculation corrector and angiprotector - Actovegin 200 mg 2 tablets three times a day, elastic compression will continue, stocking Sigvaris of the second class.

The patient was examined at the outpatient stage by a vascular surgeon. He did not complain of pain, there was no edema of the limb. Clinical and ultrasound signs of the formation of post-thrombotic disease were not observed, complete recanalization was noted. The patient began to perform his duties.

Clinical example 2

Patient D., 51 years old, was admitted to the Department of Thoracic and Vascular Surgery of the Regional Regional Clinical Hospital on July 28, 2021 with a diagnosis of 182.8 Thrombosis of the deep and saphenous veins of the left lower limb without signs of flotation, occlusion phase; thrombosis of the lateral saphenous vein of the left forearm and shoulder without flotation, occlusion phase. Varicose disease, varicose veins in the basin of the great saphenous vein of the left lower limb. Concomitant: Chronic atrophic gastritis; intramural uterine fibroids; convalescent for a new coronavirus infection COVID-19; transferred bilateral viral pneumonia of severe severity; right-sided pleurisy of small volume. Upon admission, the patient complained of pain and swelling of the left lower limb, induration along the varicose veins of the left lower extremity, pain and induration along the lateral saphenous vein of the left forearm and shoulder. According to the anamnestic data, the patient underwent inpatient treatment in the infectious diseases hospital for bilateral viral pneumonia caused by the COVID-19 virus; . basilica) on the left forearm in n / 3, which was removed two days before discharge. The patient underwent additional examinations in the form of fibrogastroduodenoscopy, chest x-ray, ultrasound examination of the veins and arteries of the upper and lower extremities, ultrasound examination of the main arteries and veins of the head, the patient was examined by related specialists: a gastroenterologist, a gynecologist. At the same time, no significant pathology affecting the course of the underlying disease was identified. Conservative treatment was prescribed: Clexane 0.6 s / c twice a day, permanent elastic compression of the right upper limb of the second class, Voltaren 3.0 / m at night No. 5, Vasoket 600 mg in the morning, Thrombovasim at a dosage of 800 IU twice a day day, Actovegin 10.0 ml intravenously twice a day - 10 days, then 5.0 ml intramuscularly twice a day - 10 days. Elastic compression stocking Sigvaris second class, elastic compression sleeve Sigvaris. At the same time, there were no allergic reactions, side effects during the treatment.

The patient underwent control ultrasound of the veins of the upper and lower extremities after 10 and 20 days of treatment. The initial signs of recanalization of the thrombotic process in the affected veins were revealed, no thrombus flotation was detected. No hemorrhagic complications were observed during inpatient treatment.

From 11 to 21 days the patient was transferred to the outpatient stage of treatment. When discharged, she did not complain of pain, objectively the edema of the left lower extremity persisted. Enoxiparin injections were canceled, Eliquis 2.5 mg twice a day, Wessel Due F 600LE intramuscularly once a day, Thrombo ACC 100 mg in the evening were prescribed, Actovegin was prescribed, but in tablet form - 200 mg tablets 2 tablets three times a day , continued taking Vasoket 600 mg in the morning. Elastic compression with Sigvaris stocking and second class Sigvaris sleeve.

The patient was examined at the outpatient stage by a vascular surgeon monthly from the moment of discharge from the hospital. On examination, she did not complain of pain, the edema of the limb was completely stopped. Clinical and ultrasound signs of the formation of post-thrombotic disease were not observed.

He takes Eliquis 2.5 mg twice a day, continued taking Thrombo ASS at a dosage of 100 mg per day. Starting from the 22nd day, an angioprotective drug was prescribed - Wessel DUE F (sulodexide), 250 LE, twice a day, one capsule for 60 days. Continued taking Actovegin, but in tablet form - tablets of 200 mg 2 tablets three times a day, continued taking Vasoket 600 mg in the morning. Elastic compression stocking Sigvaris second class continued.

At the fourth outpatient stage, the patient from the 81st day to the 180th day, Eliquis 2.5 mg 1 tablet twice a day, continues to take the antiplatelet agent - Thrombo ACC 100 mg 1 tablet per day. A microcirculation corrector and angiprotector are used - Actovegin 200 mg 2 tablets three times a day, elastic compression with a Sigvaris stocking and a Sigvaris sleeve of the second class will continue.

The patient was examined at the outpatient stage by a vascular surgeon. She did not complain of pain, there was no edema of the lower and upper extremities. Clinical and ultrasound signs of the formation of post-thrombotic disease were not observed, complete recanalization of deep and saphenous veins of the left lower limb, as well as saphenous veins of the left upper limb was noted. The patient began to work.

Information sources:

1. Russian clinical guidelines for the diagnosis, treatment and prevention of venous thromboembolic complications. Phlebology. 2015;

2. Patent No. 2759653 C1 Russian Federation. Application number: 2021101866 Registration date: 01/27/2021 Publication date: 11/16/2021 "A method for the treatment of patients with acute thrombophlebitis of the superficial veins of the lower extremities";

3. Patent No. 2719407 C1 Russian Federation. Application number: 2018142468 Registration date: 11/30/2018 Publication date: 04/17/2020 "Method of administering a drug mixture in patients with deep vein thrombosis";

4. Patent No. 2662308 C1 Russian Federation. Application number: 017145727 Registration date: 12/25/2017 Publication date: 07/25/2018 "Means for the treatment and prevention of thrombosis";

5. Patent No. 2613155 C1 Russian Federation. Application number: 2016120472 Registration date: 05/25/2016 Publication date: 03/15/2017 "A method for the treatment of patients with acute thrombosis of the venous bed of the lower extremities";

6. Krivoshchekov E.P., Ways to improve recanalization of acute deep vein thrombosis of the lower extremities Krivoshchekov E.P., Katorkin S.E., Elynin E.B. Romanov V.E. Topical issues of phlebology. 12th St. Petersburg Venous Forum (Christmas meetings). St. Petersburg, 2019, p. 75-76;

7. Krivoshchekov E.P. Acute venous thrombosis: diagnosis, treatment and prevention Krivoshchekov E.P., Korymasov E.A., Lysov N.A., Katorkin S.E., Textbook Moscow, 2020 242 C;

8. Kovalchuk V.V. The role of the new coronavirus infection (COVID-19) in the progression and development of cerebrovascular diseases. A competent choice of means of pathogenetic therapy is the key to the success of treatment and prevention. The view of a specialist from the "red zone". Neurology, neuropsychiatry, psychosomatics. 2021. Vol. 13. No. 1. pp. 57-66. DOI 10.14412/2074-2711-2021-1-57-66;

9. Krivoshchekov E.P., Katorkin S.E., Elypin E.B., Romanov V.E. The use of sulodexide at the post-hospital stage of treatment of patients with a new coronavirus infection COVID-19. Preventive medicine. 2022. V. 25. No. 1. pp. 91-97. DOI 10.17116/profmed20222501191;

10. Kirienko A.I., Matyushenko A.A., Andriyashkin V.V. Acute thrombophlebitis. Moscow: Litterra, 2006; 108 p.);

11. Romanov V.E., Madonov P.G., Ershov K.I., Shilova M.A. Pharmacological properties and clinical use of thrombovazim. Phlebology. 2014; 8; 2:90-91.

Claims (1)

A method for the treatment and prevention of venous thrombosis after a new coronavirus infection, which consists in the fact that the treatment is carried out in four stages: at the first stage, lasting 10 days, low molecular weight heparins are used - Clexane at a dosage of 1 mg per kilogram of body weight twice a day, drugs - venotonics - Vasoket 600 mg 1 tablet in the morning, non-steroidal anti-inflammatory drugs - Voltaren 3.0 ml intramuscularly for the first 5 days, permanent elastic compression with Sigvaris stocking of the second class, elevated position of the affected limb, microcirculation corrector and angiprotector - Actovegin 10.0 ml intravenous drip for 200 ml of saline once a day, oral thrombolytic drug Thrombovasim at a dosage of 800 IU twice a day; at the second stage, lasting 10 days, oral anticoagulants are used - Xarelto 2.5 mg or Eliquis 2.5 mg 1 tablet twice a day, a disaggregant is used - Thrombo ACC 100 mg 1 tablet per day, flavonoid preparations - Vasoket 600 mg 1 tablet in the morning, microcirculation corrector and angiprotector - Actovegin 5.0 ml intramuscularly twice a day, continue oral administration of the thrombolytic drug Thrombovasim at a dosage of 800 IU twice a day, angioprotector and profibrinolytic - Wessel Due F 600 LE intramuscularly once a day, elastic compression stocking Sigvaris second class; at the third stage of treatment, lasting 60 days, oral anticoagulants are used - Xarelto 2.5 mg or Eliquis 2.5 mg 1 tablet twice a day; , use drugs - venotonics - Vasoket 600 mg, microcirculation corrector and angiprotector - Actovegin 200 mg 2 tablets three times a day, angioprotector and profibrinolytic - Wessel Due F 250 LE, 1 capsule twice a day; at the fourth stage of treatment, lasting 100 days, use Xarelto 2.5 mg or Eliquis 2.5 mg 1 tablet twice a day, a disaggregant - Thrombo ACC 100 mg 1 tablet a day, a microcirculation corrector and angiprotector - Actovegin 200 mg 2 tablets three times per day, continue elastic compression with Sigvaris stockings of the second class.