This article addresses current aspects of the management of patients with ischemic and hemorrhagic stroke (IS and HS). The roles of genetic predisposition and lifestyle, air pollution with fine particles, temperature factors, anatomical features of cerebral vessel structure, stress, depression, and sleep disorders in the development of IS and HS are discussed. The role of anticoagulant drugs (AC) as a new risk factor for HS is discussed. The pathophysiology of IS and HS is considered, in particular, the mismatch of blood flow and metabolism and the stability of the penumbra in IS, as well as changes in perfusion and cerebral blood flow in HS and autoimmune mechanisms of brain damage. The issues of expanding the therapeutic window, using new-generation thrombolytic drugs, and telethrombolysis and thrombolysis (TLT) in mobile stroke units are discussed. The tactics of prescribing factor IIa and Xa blockers to patients taking AC during TLT are discussed. We address the emergency correction of hemostasis in the development of HS while taking AC, as well as subsequent resumption of AC. Neuroprotection, including the combination of neuroprotection and thrombolytic therapy, and the translation of experimental studies into clinical practice are discussed, as is immunomodulatory therapy.

Aim. To study changes in blood pressure (BP) in patients with acute hemispheric ischemic stroke (AIS), to correlate BP in patients with AIS with BP in patients with chronic brain ischemia, and to study the association of various BP indices with stroke severity and recovery.Material and methods. We included 235 patients with hemispheric AIS (age 64±11 years; women, 41,3%). BP was assessed 6 times as follows: by patient’s self-measurement during the month before the stroke onset, in the ambulance, in the admission department, in the intensive care unit using 24-hour blood pressure monitoring (BPM), in the neurologic department (BPM), and 90 days after stroke. In patients with chronic cerebral ischemia (178 patients, age 62±13 years, 46,1% women), BP was assessed 3 times: by patient’s self-measurement during the month before hospitalization, in the admission department, and in the neurologic department (BPM).Results. Patients with AIS within the month before stroke had higher systolic and pulse pressure than patients with chronic cerebral ischemia. During the acute stroke period, patients with AIS despite reaching target systolic and diastolic BP had significantly increased variability of systolic and diastolic BP compared to patients with chronic brain ischemia. Systolic BP ≥160 mm Hg recorded consecutively in ambulance, in admission department, and in intensive care unit, as well as pulse pressure ≥60 mm Hg, and systolic BP variability ≥18 mm Hg recorded on day 1-2 and day 9-10, positively correlated with National Institute of Health Stroke Scale (NIHSS) score (r≥0,37, p≤0,0017) on day 10 and with modified Rankin Scale (mRS) score (r≥0,29, p≤0,006) on day 90.Conclusion. Patients with hemispheric AIS had significantly higher systolic BP and pulse pressure within the month before stroke. During the first 10 days of AIS persistent increase in systolic, diastolic, and pulse pressure, and BP variability was associated with more severe stroke and less favorable outcome. These results should be taken into account when administering antihypertensive treatment.

OBJECTIVE To evaluate the efficacy and safety of samPEG-IFN-β1a 180 μg and 240 μg administered once every 2 weeks for the treatment of relapsing remitting multiple sclerosis (RRMS) compared to placebo and low dose interferon beta-1a (LIB) 30 μg administered once weekly. The primary endpoint after 52 weeks of therapy was the time to first relapse, the hypotheses of non-inferiority and superiority to LIB were tested. MATERIAL AND METHODS This international, multicenter, double blind, comparative, placebo-controlled clinical study enrolled 399 patients with the diagnosis of RRMS, randomized in 4 groups: samPEG-IFN-β1a180 μg (n=114), samPEG-IFN-β1a 240 μg (n=114), LIB (n=114) and placebo (n=57). Placebo group patients participated in the study for 20 weeks. After 52 weeks of therapy and 4 weeks of follow-up, LIB group patients completed their participation in the study, patients from PEG-IFN-β1a groups continued to receive therapy until week 100 inclusive. The article presents the results of an analysis conducted after the end of 52 weeks of a double-blind, comparative, randomized, placebo-controlled clinical trial. RESULTS Final analysis of the efficacy and safety was performed after 52 weeks of study. Main statistical hypothesis testing proved that both doses of samPEG-IFN-β1a were equally effective when compared to LIB by the primary endpoint - «Time to first relapse». Due to detection of statistically significant differences in the primary endpoint between the study drug and the reference drug, indicating a greater efficacy of the study drug, an additional testing was carried out and the hypothesis of superiority of samPEG-IFN-β1a at a dose of 240 μg over the reference LIB was proved. Evaluation of the dynamics of certain key parameters of magnetic resonance imaging (MRI) of the brain and clinical outcomes demonstrated a positive effect of samPEG-IFN-β1a therapy in the form of decreased activity of the demyelinating process in the brain and reduce the number of relapses. The proportion of patients without new T2 lesions after 52 weeks was 87.6% and 90.4% in 180 μg and 240 μg samPEG-IFN-β1a groups, versus 72.6% in the LIB group (p=0.0199 and p=0.0033). No progression of multiple sclerosis was shown based on EDSS scale evaluation. During the study, the most common adverse reactions were flu-like symptoms and injection site reactions. CONCLUSION The new drug samPEG-IFN-β1a is an effective and safe agent for relapsing remitting multiple sclerosis treatment, while having an advantage over other low-dose interferons in the form of reduced frequency of intramuscular injections.

AIM OF THE STUDY:To investigate the efficacy and safety of non-immunogenic staphylokinase (NS) compared with alteplase (A) in patients with acute ischemic stroke (AIS) within 4.5 h after symptom onset.MATERIAL AND METHODS:336 patients with IS within 4.5 h after symptom onset were included in a randomized, open-label, multicenter, parallel-group, non-inferiority comparative trial of NS vs A (168 patients in each group). NS was administered as an intravenous bolus in a dose of 10 mg, regardless of body weight, over 10 s, A was administered as a bolus infusion in a dose of 0.9 mg/kg, maximum 90 mg over 1 hour. The primary efficacy endpoint was a favorable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. Safety endpoints included all-cause mortality on day 90, symptomatic intracranial haemorrhage, and other serious adverse events (SAEs).RESULTS:At day 90, 84 (50%) patients reached the primary endpoint (mRS 0-1) in the NS group, 68 (41%) patients - in the A group (p=0.10, OR=1.47, 95% CI=0.93-2.32). The difference between groups NS and A was 9.5% (95% CI= -1.7-20.7) and the lower limit of the 95% CI did not cross the margin of non-inferiority (pnon-inferiority<0.0001). There were no significant differences in the frequency of deaths between the groups: on day 90, 17 (10%) patients in the NS group and 24 (14%) in the A group had died (p=0.32). There was a trend towards significant differences in the frequency of symptomatic intracranial haemorrhage: NS group - 5 (3%) patients, A group - 13 (8%) patients (p=0.087, OR=0.37, 95% CI=0.1-1.13). There were significant differences in the number of patients with SAEs: in the NS group - 22 (13%) patients, in the A group - 37 (22%) patients (p=0.044, OR=0.53, 95% CI=0.28-0.98).CONCLUSION:The presented results of the FRIDA trial are the first in the world to use a drug based on NS in patients with IS. It has been shown that a single bolus (within 10 s) administration of NS at a standard dose of 10 mg, regardless of body weight, allows to conduct fast, effective and safe thrombolytic therapy in patients with IS within 4.5 h after symptom onset. In further clinical tials of NS, it is planned to expand the therapeutic window beyond 4.5 h after symptom onset in patients with IS.

The new coronavirus SARS-CoV-2 and the disease it causes COVID-19 involves not only respiratory system damage, but can also lead to disorders of the central and peripheral nervous system, as well as the muscular system. This article presents published data and our own observations on the course of neurological disorders in COVID-19 patients. There is a relationship between the severity of COVID-19 and the severity and frequency of neurological manifestations. Severe neurological disorders are mostly seen in severe cases of COVID-19 and include acute cerebrovascular accidents (aCVA), acute necrotizing encephalopathy, and Guillain–Barré syndrome. Factors potentially complicating the course of COVID-19 and increasing the development of neurological complications include arterial hypertension, diabetes mellitus, and chronic cardiac and respiratory system diseases. Questions of the possible effects of human coronaviruses on the course of chronic progressive neurological diseases are addressed using multiple sclerosis (MS) as an example. We discuss the management of patients with aCVA and MS depending on the risk of developing coronavirus infection.

Results of epidemiologic reseach of environmental risс factors for multiple sclerosis among Moscow population are given. It was shown, that provoking factors for development or exacerbation this pathology are infections and stress situations. Diet habits, chronic bacterial infections of respiratory tract are significant too. The obtained results can be used in development of a certain diet and preventive measures.

Objectives. To identify changes in the biochemical composition of the plasma in a group of patients at risk of developing Parkinson’s disease (PD) at the prodromal stage in comparison with age-matched controls. Materials and methods. Subjects in the risk group were selected on the basis of the having impairments to sleep, olfaction, and peristalsis. The risk group consisted of 12 people and the control group of eight people. Results. The results showed that of seven catecholamines and their metabolites, the only blood change was in the L-dihydroxyphenylalanine (L-DOPA) level, which decreased in the risk group from the level in controls. A decreased L-DOPA concentration is regarded as a marker for selective degeneration of central and peripheral catecholaminergic neurons in PD. In contrast to L-DOPA, the blood concentrations of seven of 12 sphingomyelins increased. Given that changes in sphingomyelin metabolism are linked with apoptosis, autophagy, and synucleinopathies, increases in their concentrations in the risk group are regarded as indicators of systemic degeneration of central and peripheral neurons. Furthermore, the risk group showed a tendency to decreased urate concentrations, which are endogenous neuroprotectors. Conclusions. The results obtained here suggest that changes in blood L-DOPA, sphingomyelin, and urate levels can serve as diagnostic markers for the development of PD at the prodromal stage.

Respiratory failure syndrome often develops due to the development of acute stroke but is not always diagnosed and treated. A new method of treating this syndrome improves the clinical course and prognosis of acute stroke.

The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility» analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.

OBJECTIVE:To study kinematic gait parameters during early rehabilitation period in patients with supra- or subtentorial ischemic stroke (IS).MATERIAL AND METHODS:We examined 24 patients (11 women, 13 men, age 61.3±8.2) 4-6 weeks after stroke onset. 15 patients had supratentorial IS (middle cerebral artery location), 9 patients had subtentorial IS (brainstem and cerebellum). NIHSS score was 6.4±0.6/6.1±0.8, modified Ashwort scale score - 0.5±0.6/0.4±0.7, hand paresis - 3.4±0.9/3.7±0.7, leg paresis - 4.1±0.7/4.0±0.8 points. Kinematic gait parameters were recorded on video analysis system Physiomed Smart (Physiomed, Germany, Davis protocol).RESULTS:Gait kinematic parameters in paretic and in unaffected leg were changed in both groups. Patients with supratentorial lesion had on paretic side exaggerated pelvic obliquity, an excessive internal rotation and amplitude of movements in the paretic hip joint, and an insufficient plantar extension on both sides. Patients with subtentorial stroke had exaggerated pelvic tilt forward, excessive flexion and insufficient extension of the hip joint, insufficient extension of the knee joint, excessive plantar flexion, and insufficient plantar extension on both sides.CONCLUSION:Patients with supra- or subtentorial IS with muscle weakness less than 3-4 points and slightly changed or normal muscle tone differed in kinematic parameters in pelvic motions and in joints of paretic and unaffected lower extremity. These results highlight the importance of differentiating rehabilitation techniques according to supra- or subtentorial focus location and cerebellar involvement.

Various degrees of pulmonary insufficiency (PI) (PaO2 ≤60 mm Hg, SaO2 ≤90%) are diagnosed in most of patients with severe acute stroke (AS). Frequency and severity of PI positively correlates with the severity of AS. PI worsens patient's condition, prolongs the hospitalization period, and increases the probability of fatal outcome. Early clinical signs of PI may be undiagnosed due to the severity of stroke and thus not treated. The initiating pathogenic mechanism of PI is stress-related activation of sympathetic nervous system (SNS) and systemic immunosuppression. In severe stroke with mass effect, the rapid and significant increase in intracranial pressure may additionally activate the SNS. Risk factors of PI include older age, previous pulmonary disease, prolonged supine position, respiratory muscle dysfunction, apnea, and concomitant somatic diseases. Decompensation of somatic diseases leads to multiple stage reactions with facilitation of functional and morphologic changes in the pulmonary system, hypoxemia and hypoxia, promotes infectious complications and multiple organ failure and worsens neurological outcome. Diagnosis and treatment of PI in AS decreases mortality and improves rehabilitation prognosis.

AIM:To evaluate possibilities of routine X-ray methods for the diagnosis of atherosclerosis of carotid arteries.MATERIAL AND METHODS:At the initial stage of the study, 468 X-ray radiograms of the cervical spine with the detailed description of soft tissues and projections of the neck vessels were studied. The next stage included evaluation of 'screening' abilities of digital fluorography of lungs (886 X-ray radiograms were analyzed). The last stage is a current pilot project aimed to introduce opportunistic screening of atherosclerosis of carotid arteries using X-ray and ultrasound examination of the thyroid gland taking into account disease history collected with help of a special questionnaire and clinical examination.RESULTS AND CONCLUSION:The study shows a high specificity of the shadows in the projections of the neck vessels as a sign of atherocalcinosis. During mass examinations these X-ray findings are useful to identify patients who need duplex scanning and other high-tech methods.

Objectives. To study the characteristics of the movement stereotype in the early recovery period of ischemic stroke in the basin of the internal carotid artery and the vertebrobasilar system. Materials and methods. Eleven patients (five men, six women, mean age 57.2 ± 5.2 years) were studied 4–6 weeks after ischemic stroke. Initial scores on the NIHSS averaged 6.2 ± 0.8, with 3.9 ± 0.7/3.7 ± 0.8 points for arm/hand paresis and 4.3 ± 0.6/4.0 ± 0.5 points for leg/foot paresis. Foci were located in the basin of the internal carotid artery in seven patients and in the vertebrobasilar system in four. Investigations were run on admission and after 2–2.5 weeks. Changes on the FIM and Ashworth spasticity scales, a hand dexterity test (nine hole peg test, NHPT), and the Timed Up and Go test (TUG) were evaluated, along with changes on the Berg balance test and the 20-point vertigo scale, the MMSE, and the Beck and Spielberger questionnaires. Video analysis of movements was carried out using a Physiomed Smart system (Physiomed, Germany) using the Davis protocol. Results. On the background of rehabilitation measures, all patients showed decreases in the severity of paresis, improvements on the FIM, Ashworth, and Berg scales and on the NHPT and TUG tests. Patients with foci in the vertebrobasilar system, in contrast to those with foci in the basin of the internal carotid artery, had impairments to balance detected on the 20-point vertigo scale. On video analysis, all patients showed changes in the movement stereotype in the form of shortening of the length and increases in the width of the gait, with decreases in speed and lengthening of the stepping cycle; these changes were more marked for foci in the vertebrobasilar system. A distinguishing feature for foci located in the vertebrobasilar system was forward tilting of the pelvis, while lateral tilting of the pelvis was seen with foci located in the basin of the internal carotid artery. Conclusions. Focus location in mild ischemic stroke can affect the features of recovery and movement stereotypy, and this should be considered in rehabilitating these patients.

Endothelial dysfunction today is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and induction of apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in the pathogenesis of MS.

INTRODUCTION:At the present time, there is an increased interest in the search for biological predictors of the course and outcome of ischemic stroke (IS). Numerous studies have shown the relationship between neuroinflammation (in the brain) and systemic inflammatory response (in the blood).AIM:To study the relationship of inflammatory and autoimmune markers in blood serum of patients with acute ischemic stroke (on the 1st day) with the dynamics of the severity of neurological deficit (on the 1st and 10th day) and to assess the predictive ability of these indicators.MATERIAL AND METHODS:Twenty-two patients in the acute period of IS (mean age 60±15.5 years) were examined. The severity of neurological deficit was assessed by ESS and NIHSS. The enzymatic activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), level of autoantibodies to S-100B and MBP in serum was determined. The control group consisted of 33 healthy subjects. Blood samples were carried out on the 1st day of the post-stroke period, the clinical examination was performed on the 1st and 10th day of observation.RESULTS:Depending on the dynamics of neurological symptoms by the 10th day of observation, two subgroups of patients were identified. The1st subgroup was characterized by the normalization of neurological deficit (n=10). In the 2nd group, the negative dynamics of neurological deficit/lack of any positive changes was observed (n=12). Both subgroups demonstrated the increase in the LE and α1-PI activity as compared to the control (p=0.0019, p=0.00079; p=0.038, p=0.00041, respectively). The highest LE activity was detected in the 1st subgroup (p=0.035). The high level of autoantibodies to MBP was also observed in the 1st subgroup as compared to the control and the 2nd group (p=0.047, p=0.03, respectively). The 2nd subgroup was characterized by a higher functional activity of acute phase protein α1-PI (p=0.04). Using regression analysis, a model for predicting the course of the early post-stroke period depending on the determined immunological parameters was developed.CONCLUSION:The results suggest that the studied inflammatory and autoimmune markers may be possible predictors of the course of the early post-stroke period.

AIM:To study the changes in endothelial dysfunction and von Willebrand factor activity in acute and chronic stages of hemispheric intracerebral hemorrhage (ICH) and their influence on clinical severity and functional recovery.MATERIAL AND METHODS:Fifty patients with hemispheric ICH, aged 61.6±11.2 years, and 30 patients with AH, aged 59.6±6.2 years, (comparison group) were examined. Patients with ICH were examined on admission, 6-8th, 13-15th days, and 11.1±0.9 months after stroke onset. Patients with arterial hypertension (AH) were examined on admission. Changes in NIHSS, Glasgow coma scale, and modified Rankin scale were studied. Restocetin induced platelet aggregation (RIPA) was assessed by optical aggregometry (BIOLA LA230-2 AGGRWB) in modification by G. Born and Z. Gabbasov. von Willebrand factor (vWF) activity was examined as described by J. Olson.RESULTS:RIPA was significantly higher in acute ICH compared to chronic ICH, AH and reference values. RIPA values were negatively correlated with hematoma volume and midline shift (r≥ -0.308, p≤0.035). vWF activity was significantly higher in ICH patients than in AH and reference values. Patients with AH also had significantly higher vWF activity than reference values. In acute ICH, vWF activity steadily increased reaching maximal values by 13-15th day. In chronic ICH, vWF activity decreased compared to the acute phase, but still remained higher than in AH patients or reference values. In acute phase, 1% increment in vWF values resulted in 0.5% increase in the risk of death during the follow-up period (95% CI 1.001-1.008, p=0.007).CONCLUSION:Endothelial dysfunction assessed by vWF activity increases during the acute hemispheric ICH and remains elevated in the chronic stage. vWF activity may be used as a marker in assessing stroke outcome and prognosis.

Исследование нейроиммунных взаимодействий является одним из наиболее развивающихся направлений в изучении патогенеза рассеянного склероза. Механизмы этого взаимодействия до конца не ясны. Полагают, что ключевое значение в регуляции этого взаимодействия может принадлежать нейротрансмиттерам. Наибольшее внимание привлекают катехоламины, в частности, дофамин и норадреналин, рецепторы к которым экспрессируют клетки как нервной, так иммунной систем. Установлено, что модулируя функции иммунокомпетентных клеток дофамин и норадреналин способны влиять на течение как экспериментального аутоиммунного энцефаломиелита, так и рассеянного склероза. В работе представлен обзор литературы и собственных данных о значении дофамина и норадреналина в регуляции взаимодействия нервной и иммунной систем при рассеянном склерозе. Обсуждаются возможные механизмы, опосредующие влияние дофамина и норадреналина на патогенез рассеянного склероза, в частности, влияние дофамина и норадреналина на функционирование Th17-клеток, а также на опосредованный дендритными клетками Th17-зависимый иммунный ответ, играющий одну из ключевых патогенетических ролей при рассеянном склерозе. The neuroimmune interaction is one of fast developing directions in studying the pathogenesis of multiple sclerosis. The mechanism of this interaction is not sufficiently understood. The key role in regulation of this interaction is assumed to belong to neurotransmitters, among which catecholamines, specifically dopamine and norepinephrine, attract the greatest attention. Cells of both nervous and immune systems express dopaminergic and noradrenergic receptors. Dopamine and norepinephrine can influence the course of experimental autoimmune encephalomyelitis and multiple sclerosis by modulating functions of immune cells. This review presents literature and authors’ own data on the role of dopamine and norepinephrine in regulation of the nervous and immune system interaction in multiple sclerosis and focuses on possible mechanisms mediating the effect of dopamine and norepinephrine on the pathogenesis of multiple sclerosis, particularly the effect of dopamine and norepinephrine on the Th17 cell function and the dendritic cell-mediated Th17 immune response that plays a key role in the pathogenesis of multiple sclerosis.

AIM:To evaluate the efficacy of semax and timing of rehabilitation on the dynamics of plasma BDNF levels, motor performance, and Barthel index score in patients after ischemic stroke (IS).MATERIAL AND METHODS:One hundred and ten patients after IS (43 men, 67 women, mean age 58.0±9.7, Ме 63 years) were examined. All patients were divided into early (89±9 days) and late (214±22 days) rehabilitation groups. Each group was subdivided into semax+ and semax- subgroups. Standard regimen of semax included 2 courses (6000 mcg/day) for 10 days with 20 day interval. Plasma BDNF levels, motor performance on the British Medical Research Council scale and Barthel index were assessed in all groups.RESULTS:Administration of semax, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during the whole study period. In semax- subgroups high BDNF plasma levels were positively correlated with early rehabilitation. Administration of semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index. There was a positive correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance improvement. The correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation.CONCLUSION:Early rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance.

Reperfusion therapy is one of the main treatment strategies of ischemic stroke. The first studies of the efficacy of thrombolytic medications started form the use of streptokinase and fibrinolysin in patients with ischemic stroke in late 50 - early 60 of the XX century in the United States, Soviet Union, and Western Europe. After the development of recombinant tissue plasminogen activator, thrombolysis became one of the main methods of reperfusion in patients with acute ischemic stroke, acute myocardial infarction, or other acute vascular thrombotic events. Later, modified variants of tissue plasminogen activator with prolonged clearance time, high fibrin-selectivity, and bolus delivery were introduced. Another group of thrombolytic agents includes derivatives of flora and fauna - external plasminogen activators, of which streptokinase, staphylokinase, and desmoteplase are most common drugs. These medications are not a structural part of the human organism, and overcoming of immunogenicity while preserving fibrinolytic activity and fibrin specificity is one of the main tasks in applying them in clinical practice.