The heavy current of COVID-19 caused by SARS-CoV-2 caused need of researches in the field of a pathogeny of a disease and determination of the features distinguishing it from other pneumonia. The most serious complication at COVID-19 is emergence of respiratory insufficiency, but the atypical coagulopathy which is characterized by substantial increase of the D-dimera level serves as one of reliable signs of development of a severe form of a disease. Elderly patients and patients with associated diseases presumably have higher D-dimera level that in turn demonstrates risk of development of a critical state up to a lethal outcome. In this regard it is recommended to hospitalize patients with the increased D-dimera level even in the absence of other clinical signs of a disease, considering high risk of incidence and mortality in this group.
In spite of the fact that at the patients who died of COVID-19 increase in a prothrombin time (PTV) is observed, these changes have slight character and can remain unnoticed if are expressed through its derivative — INR (the international normalized relation). On the other hand, thrombocytopenia not necessarily indicates development of a severe form of a disease. According to the recommendations of the International society of specialists in thrombosis and a hemostasis, it is necessary to measure the D-dimera level, PTV and quantity of thrombocytes (in decreasing order of importance) at all patients with COVID-19.
Now for prevention of development of thromboembolisms in the hospitalized patients, including patients with COVID-19, mainly low-molecular heparin (NMG) is used, nevertheless the possibility of use and other anticoagulants is not excluded.
In terms of normal physiology, the pulmonary alveolar space is considered as the pro-fibrinolitic environment. Disturbances of functioning of a fibrinolitic system often arise at acute injury of lungs and pleurae, including at ARDS (acute respiratory distress syndrome), characterized by fibrin deposits that leads to formation of hyaline membranes and an alveolar pneumosclerosis. Delay of process of a fibrinolysis in lungs is generally caused by increase in level of inhibitor of a plasminogen activator 1 (PAI) both in a blood plasma, and in liquid after bronchoalveolar lavage.
As it was supposed, any means accelerating process of a fibrinolysis in lungs can promote improvement of clinical indicators of patients with acute pulmonary insufficiency, including with ORDS. Restoration of process of a fibrinolysis on model of injury of lungs at animals managed to be reached by means of nebulizirovanny forms of a fabric plasminogen activator (t-PA), PAI-1 monoclones/inhibitors or by intravenous administration of t-PA, an urokinase or plasmin.
According to recently carried out metaanalysis of preclinical trials it is established that the fibrinolitic therapy applied at acute pulmonary insufficiency improves process of gas exchange in lungs, reduces quantity of neutrophils in alveoluses, the area of a fluid lungs and extent of histologic changes. But in researches viral pneumonia with ORDS was not considered. Possibilities of conduct of clinical trials on the person are limited, nevertheless results of the first phase of researches on which to patients with the last stage of ORDS entered an urokinase or Streptokinasa, showed that these drugs reduce risk of mortality and development of bleedings. Plasmin effectively splits not only fibrin, but also other groups of matrix proteins and which first of all are incorrectly curtailed or dead squirrels. The last group of proteins prevails in lungs at ORDS and COVID-19, that is in hyaline membranes there is an accumulation of dead proteins. Plasmin splits incorrectly curtailed or dead squirrels with the same kinetics, as kinetics of formation of fibrin and also with the participation of a lysine as this process is inhibited to lysine-traneksamovoy derivatives by acid.
Substantial increase of the D-dimera level in blood indicates fibrin disintegration, nevertheless there are no markers of disintegration of other substrates at patients with COVID-19. Thus, despite rather high D-dimera level, this indicator not always precisely indicates extent of activation of plasminogen at COVID-19 and the related diseases at which there is an accumulation of the dead or incorrectly curtailed proteins. It is reported about use of fibrinolitic drugs with the direct mechanism of action for treatment of patients with heavy or critical COVID-19.
At patients to whom entered plasminogen pulmonary function improved, the level of oxygen saturation of an organism was temporarily stabilized and heart rate decreased. Instead of fibrinolitic agents of direct action use of other agents, namely not less safe endogenous plasminogen activators which are developed by in situ plasmin from exogenous plasminogen deserves attention. It is supposed that the refusal of use of fibrinolitic agents of direct action (t-PA or u-PA) will reduce risk of developing of bleedings at a thrombolysis.
However there are data that at a koronavirusny infection activation of a fibrinolitic system promotes acceleration of infectious process and creates difficulties in performing anti-fibrinolitic therapy where it is necessary. Thus, the clinical paradox is that formation of plasmin or is positive, or negatively influences the current of COVID-19. Therefore, it is not possible to predict result in advance and carrying out further researches in this area is necessary.