Introduction Defects of platelet functional responses in COVID-19 were reported, but their origin and pathophysiological significance are unclear. The objective of this study was to characterize the thrombocytopathy in COVID-19. Materials and methods Analysis of platelet functional responses to activation by flow cytometry and aggregometry in 46 patients with confirmed COVID-19 of different severity (non-ICU, ICU, and ECMO) over the course of hospitalization alongside with plasma coagulation, inflammatory markers (CRP, fibrinogen, NETosis assays in smears) was performed. Results and conclusions All patients had increased baseline percentage of procoagulant platelets (healthy: 0.9 ± 0.5%; COVID-19: 1.7 ± 0.6%). Patients had decreased agonist-induced platelet GPIb shedding (1.8 ± 0.7 vs 1.25 ± 0.4), P-Selectin exposure (1.51 ± 0.21 vs 1.1 ± 0.3) and aggregation. The values of these parameters among the non-ICU and ICU cohorts differed modestly, while the ECMO cohort differed significantly. Only ECMO patients had pronounced thrombocytopenia. While inflammatory markers improved over time, the observed platelet functional responses changed only moderately. SARS-CoV-2 RNA was found in 8% of blood samples and it did not correlate with platelet counts or responses. All patients had increased NETosis that moderately correlated with platelet dysfunction. High cumulative dosages of LMWH (average > 12,000 IU/day over 5 days) resulted in an improvement in platelet parameters. The observed pattern of platelet refractoriness was reproduced by in vitro pre-treatment of washed platelets with subnanomolar thrombin or perfusion of blood through a collagen-covered flow chamber. We conclude that platelet dysfunction in COVID-19 is consistent with the intravascular-coagulation-induced refractoriness rather than with an inflammation-induced mechanism or a direct activation by the virus.

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This work is devoted to the study of pricing issues for obtaining maximum profit when selling consumer goods at a constant purchase price. The said goods come in from either manufacturers or warehouses where the retail companies buy the goods in order to sell them directly to the consumers. The dependence of the selling rate per unit of time on the level of the added price in relation to the purchase price of the item is established by the means of sales price variation. The object of the research is the specific case of a linear approximation of said dependence, which is usually actualized in the event of either more elastic or less elastic demand for goods, when they are sold through Internet platforms. The proposed approach to determining prices of all the goods which are being sold for maximizing the total profit from the sales of all consumer goods or maximizing the total revenue throughout the whole period of sales time, based on the search of extremum points of the profit and revenue functions for each item of goods remains valid in the case of more complex approximations by quadratic and cubic functions of demand function. The type of the function of maximum value added revenue and the type of the function of maximum profit can be both found per unit of time depending on the variable level of the added price included into the sales price of the item. The type of maximum revenue function can be found per unit of time depending on the sales price of the item. The extremum points of the found functions are being determined. The theorems have been proved, that the extremum points which are being determined appear to be the maximum points of the researched functions for each item of goods, when the maximum profit or the maximum revenues are reached by selling goods to consumers. All common variables of said functions are found by summing up these functions among the multitude of goods on the interval of the whole sales time. The received data is used for the practical implementation of an effective sales strategy that ensures maximum profits for companies specializing in direct sales to consumers of the purchased goods. An applied methodicalэф approach to the sales of goods which ensures maximum profit from the sales in the field of elastic demand approximated by a linear function and under the condition of a constant purchase price for goods is proposed and theoretically substantiated.

Background The average frequency of thrombosis in patients with COVID-19 is still high despite low molecular weight heparin (LMWH) prophylactic. Global hemostasis assays, particularly thrombodynamics (TD), known to be sensitive to both hypercoagulation and heparin effects, could potentially be useful for individual management of anticoagulant therapy. Methods A total of 74 patients with lung involvement >50% were randomized into two groups: Group A (44 patients) received weight-based dosing of LMWH, and Group B (30 patients) received the first LMWH dose by a weight-based dosing protocol and then received an adjusted dose based on TD daily results. The endpoints of the study were thrombosis and bleeding as well as discharge or death of the patient. Results The incidence of thrombosis was 3 times lower in Group B under TD control compared to Group A without TD control: 7% versus 23 respectively ( p = .05). The relative risk of thrombosis if the average clot growth rate V in TD exceeded the threshold value of 25 μm/min was 14.3 ( p = .0005, 95% confidence interval 3.2-63.7). There were no clinically significant bleeding episodes in Group B while there were 7% in unregulated Group A. Mortality in Group B under TD control was lower than that in Group A without control: 27% versus 36%, respectively ( p = .13). Conclusions The dosing LMWH under thrombodynamics control in severe patients with COVID-19 allows for a significant reduction in thrombotic complications. Long-term hypercoagulation revealed by thrombodynamics (3 and more days) is a strong predictor of thrombosis (AUC = 0.83).