Дозирование низкомолекулярных гепаринов и анти-фактор Xa активность у пациентов с новой коронавирусной инфекцией COVID-19:

Summary. Background. Low molecular weight heparins (LMWH) are guided for all in-hospital patients with COVID-19. However LMWH effective dose is still unknown. Escalating the LMWH dose seems appropriate for the treatment of COVID-19-associated coagulopathy. Objectives: to explore the LMWHs doses effects in the treatment of COVID-19-associated coagulopathy, and to find indicators signaling the need to adjust the LMWH dose. Patients/Methods. From April to June 2020, 49 patients with COVID-19 were examined. LMWH were given to 43 patients: 25 of them received enoxaparin sodium, 18 — dalteparin sodium. Lab testing included C-reactive protein, platelet count, activated partial thromboplastin time, thrombin time, fibrinogen, antithrombin III, prothrombin time, D-dimer, and anti-factor Xa activity (anti-Xa activity). The data were presented as median (Me), lower (LQ) and upper (UQ) quartiles. Statistical analysis included the check of the distribution normality by Shapiro–Wilk test, comparing independent groups with Mann-Whitney test for p 0.6 IU/ml. That does mean that part of the administered LMWH was already “spent” for anti-inflammatory purposes, and the remaining part was enough to develop an antithrombotic effect. Other result was that ROC-analysis did not confirm the fibrinogen value for the forecast of LMWH antithrombotic effectiveness. Cluster analysis divided significantly the initial sample at the point with anti-Xa activity=0.6 IU/ml. Of the 43 patients received LMWH, the selected LMWH dose provided anti-Xa activity>0.6 IU/ml in 15 (34.9%) only, while in other patients the anti-Xa activity was lower despite a wide variation in the LMWH doses: AUC = 0.482 (95% CI = 0.298–0.665; p = 0.848). Discriminant analysis showed, and then ROC-analysis confirmed, that to an antithrombotic effect, LMWH dose adjustment is required taking into account the patient’s body weight, and the target value of anti-Xa activity is 0.65 IU/ml. Conclusions. The antithrombotic effect as the desired result of the LMWH use is achievable only under dosing with the patient’s body weight regardless of whether it is reduced, normal or increased. The LMWH antithrombotic effect should be detected and then its stability confirmed by testing the anti-Xa activity which should be at least 0.65 IU/ml. Lower anti-Xa activity may indicate the need for LMWH dose adjustment in patients with COVID-19-associated coagulopathy. References Connors J.M., Levy J.H. Thromboinflammation and the hypercoagulability of COVID‐19. J Thromb Haemost. 2020;18(7):1559–61. DOI: 10.1111/jth.14849. Connors J.M., Levy J.H. COVID‐19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033–40. 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