Introduction: Severely ill COVID-19 patients receiving prophylactic-dose anticoagulation exhibit high rates of thrombosis and mortality. The escalation of anticoagulation also does not reduce mortality and has an uncertain impact on thrombosis rates. The reasons why escalated doses fail to outperform prophylactic doses in reducing risks of thrombosis and death in severely ill COVID-19 patients remain unclear. We hypothesized that escalated anticoagulation would not effectively prevent hypercoagulability and, consequently, would not reduce the risk of thrombosis and death in some severely ill patients. Methods: We conducted a prospective multicenter study that enrolled 3860 COVID-19 patients, including 1654 severely ill. They received different doses of low-molecular-weight or unfractionated heparin, and their blood coagulation was monitored with activated partial thromboplastin time, D-dimer, and Thrombodynamics. A primary outcome was hypercoagulability detected by Thrombodynamics. Blood samples were collected at the trough level of anticoagulation. Results: We found that escalated anticoagulation did not prevent hypercoagulability in 28.3% of severely ill patients at the trough level of the pharmacological activity. Severely ill patients with such hypercoagulability had higher levels of inflammation markers and better creatinine clearance compared to severely ill patients without it. Hypercoagulability detected by Thrombodynamics was associated with a 1.68-fold higher hazard rate for death and a 3.19-fold higher hazard rate for thrombosis. Elevated D-dimer levels were also associated with higher hazard rates for thrombosis and death, while shortened APTTs were not. The simultaneous use of Thrombodynamics and D-dimer data enhanced the accuracy for predicting thrombotic events and fatal outcomes in severely ill patients. Conclusions: Thrombodynamics reliably detects hypercoagulability in COVID-19 patients and can be used in conjunction with D-dimer to assess the risk of thrombosis and death in severely ill patients. The pharmacological effect of LMWH at the trough level might be too low to prevent thrombosis in some severely ill patients with severe inflammation and better creatinine clearance, even if escalated doses are used.

Introduction: Critically ill COVID-19 patients receiving prophylactic-dose antico-agulation exhibit high rates of thrombosis and mortality. Escalation of anticoagu-lation also does not reduce mortality and has an uncertain impact on the throm-bosis rates. The reasons why escalated doses fail to outperform prophylactic doses in reducing risks of thrombosis and death in critically ill COVID-19 patients remain unclear. We hypothesized that escalated anticoagulation would not ef-fectively prevent plasma hypercoagulability and, consequently, would not reduce the risk of thrombosis and death in some patients. Methods: We conducted a prospective multicenter study that enrolled 3860 COVID-19 patients, including 1654 critically ill. They received different doses of low-molecular-weight or unfractionated heparin, and their plasma coagulability was monitored with activated partial thromboplastin time, D-dimer, and Throm-bodynamics. A primary outcome was plasma hypercoagulability detected by Thrombodynamics. Blood samples were collected at the trough level of antico-agulation. Results: We found that escalated anticoagulation did not prevent hypercoagula-bility in 28.3% of critically ill patients at the trough level of the pharmacological activity. Critically ill patients with hypercoagulability not suppressed by anticoag-ulants had higher levels of inflammation markers and better creatinine clearance compared to critically ill patients without such hypercoagulability. Hypercoagu-lability detected by Thrombodynamics was associated with a 1.75-fold higher hazard rate for death and a 3.19-fold higher hazard rate for thrombosis. Elevated D-dimer levels were also associated with higher hazard rates for thrombosis and death, while shortened APTT were not. Simultaneous use of Thrombodynamics and D-dimer data enhanced the accuracy for predicting thrombotic events and fatal outcomes in critically ill patients. Conclusions: Thrombodynamics reliably detected hypercoagulability in COVID-19 patients and can be used in conjunction with D-dimer to assess the risk of thrombosis and death in critically ill patients. Pharmacological effect of LMWH at the trough level might be too low to prevent thrombosis in some critically ill pa-tients with severe inflammation and better creatinine clearance even if escalated doses are used.

Введение. Тяжелое течение коронавирусной инфекции COVID‑19 приводит к высокому риску развития тромботических осложнений. Данные отечественных и зарубежных исследований указывают на то, что скрининговые тесты системы гемостаза являются малочувствительными к изменениям свертывания, индуцированными COVID‑19. С другой стороны, уровень D-димера является значимым показателем для прогнозирования тяжести протекания COVID‑19 и риска летального исхода. Цель исследования: изучить нарушения системы гемостаза у больных COVID‑19 с использованием основных скрининговых коагулологических тестов и сопоставить полученные данные с клинической картиной заболевания. Материалы и методы. В проспективном нерандомизированном исследовании приняли участие 7 городских клинических больниц г. Москвы, в исследование вошли 3503 пациента. В качестве конечных точек рассматривали госпитализацию в терапевтическое отделение (ТО), либо в отделение интенсивной терапии (ОИТ) из приемного отделения и наличие/отсутствие тромботических осложнений при поступлении в стационар. Кроме того, учитывали исходы госпитализации пациентов. Результаты. Установлено, что скрининговые коагулологические тесты, такие как активированное частичное тромбопластиновое время (АЧТВ), протромбиновое время (ПВ), а также число тромбоцитов значимо не коррелируют со степенью тяжести заболевания и с наличием/отсутствием тромботических осложнений у пациентов с COVID‑19. С другой стороны, уровень D-димера значительно повышался у тяжелых больных и у пациентов с тромбозом. Значения D-димера > 1775 нг/мл (пиковые) и > 930 нг/мл (при поступлении) являются значимыми прогностическими показателями для оценки риска смертель­ного исхода. Заключение. Полученные данные на большой группе пациентов с COVID‑19 подчеркивают значение D-димера в клинической практике при оценке степени тяжести заболевания, позволяют более точно определять высокий риск возникновения тромботических осложнений и вероятность летального исхода, что может способствовать принятию своев­ременных необходимых мер для их предотвращения. Introduction. Severe COVID‑19 is associated with a high risk of thrombotic complications. Data from domestic and international studies indicate that screening coagulation tests are less sensitive to coagulation changes induced by COVID‑19. On the other hand, the level of D-dimer is a significant indicator for predicting COVID‑19 severity and the risk of fatal outcomes. Aim: to investigate hemostatic disorders in COVID‑19 patients using basic screening coagulation tests and to compare the obtained data with the clinical presentation of the disease. Materials and Methods. The prospective non-randomized study involved 7 city clinical hospitals in Moscow and included 3503 patients. The endpoints of the study were hospitalization in a therapeutic department (TD) or intensive care unit (ICU) from the emergency department, as well as the presence/absence of thrombotic complications upon admission. In addition, patient hospitalization outcomes were taken into account. Results. The study results have shown that screening coagulation tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and platelet count do not significantly correlate with disease severity or the presence/absence of thrombotic complications in patients with COVID‑19. On the other hand, D-dimer level significantly increased in severe cases and in patients with thrombosis. D-dimer levels > 1775 ng/mL (peak) and > 930 ng/mL (upon admission) were found to be significant prognostic indicators for assessing the risk of fatal outcomes. Conclusion. Obtained data from a large group of patients with COVID‑19 highlight the significance of D-dimer in clinical practice for assessing disease severity. These data allow for a more precise identification of high risk for thrombotic complications and the likelihood of unfavorable outcomes, which may aid in timely interventions to prevent such complications.