[The multidirectional effects of thrombin and the possibility of their control in neurology]. / Raznonapravlennye effekty trombina na protsessy gemokoagulyatsii i vozmozhnost' ikh kontrolya v nevrologii.

The review presents the main physiological functions of thrombin. The procoagulant and anticoagulant activities of the key serine protease are discussed in both physiological and pathological conditions of hemostasis. The involvement of thrombin in atherogenesis, as well as its role as a mediator of vascular dysfunction and inflammation in both the peripheral and central nervous system, is highlighted. A pronounced imbalance between the pro- and anticoagulant systems leads to an increase in thrombin formation and creates conditions for the development of thrombosis. Tests that allow direct or indirect assessment of thrombin's functional activity are presented. The potential applications of direct thrombin inhibitors and direct blockers of thrombin PAR receptors in vascular neurology are also considered.

[Endothelial dysfunction in COVID- 19 and cognitive impairment]. / Endotelial'naya disfunktsiya pri COVID-19 i kognitivnye narusheniya.

Endothelial dysfunction is an important mechanism underlying multiple organ and systems failure in COVID-19. The development of endothelial dysfunction in COVID-19 can disrupt organ perfusion and cause a procoagulant state, leading to both macro- and microvascular thrombotic events. Cognitive impairment is a common complication of COVID-19 that develop in acute and delayed periods and is not directly related to the severity of the underlying disease. Treatment of endothelial dysfunction in patients with COVID-19 should take into account the leading pathogenetic factors of its development and with the development of neurological, including cognitive, disorders should include neuroprotective drugs. One of these drugs is actovegin, which has been shown to be effective in improving endothelial function, microcirculation and cognition.

[Prognostic value of endothelial dysfunction and von Willebrand factor in acute and chronic hemispheric intracerebral hemorrhage]. / Prognosticheskoe znachenie disfunktsii éndoteliia i faktora fon Villebranda v ostrom i otdalennom periodakh gemorragicheskogo insul'ta polusharnoi lokalizatsii.

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.

[Dynamic of cerebrovascular disorders in patients with carotid stenosis]. / Techenie tserebrovaskuliarnoi patologii u bol'nykh so stenoziruiushchim porazheniem sonnykh arterii.

AIM: To study the state of cerebral hemodynamics and platelet hemostasis in patients with carotid stenosis (CS). MATERIAL AND METHODS: The prospective study included 123 patients with atherosclerotic CS. The 1st group included 53 patients (mean age 52±12.5 yrs) who underwent carotid endarterectomy (CEA); the 2nd group - 70 patients who were treated conservatively (mean age 58.5±15.9 yrs). The state of blood flow through the main arteries of the head (Doppler flowmetry), platelet aggregation induced by adrenaline, the frequency of acute cardiovascular events that occurred during 12 months were evaluated. RESULTS AND CONCLUSION: The severity of neurological deficits and cognitive impairment increased with increasing of the degree of CS. CEA leads to an improvement of cerebral hemodynamics and stabilization of cognitive functions. The adverse course of the disease occurred in 23.6% of patients (stroke/heart attack during the year in 5.7%, progression of cerebral ischemia in 20%, restenosis within 5 years after CEA in 15%). Hyperaggregation of platelets induced by ADP and epinephrine and decreased aggregation of platelets induced by collagen in patients receiving ASA were identified in 53% of the operated and in 60% of non-operated patients. The use of combined antiplatelet therapy normalize the platelet hemostasis and reduce the frequency of acute cardiovascular events.

[Thrombolytic therapy of ischemic stroke]. / Tromboliticheskaia terapiia ishemicheskogo insul'ta.

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.