Lithium-Modified Sorbent: Effects on Hemostatic Responses In Vitro.

The effects of a lithium-modified sorbent based on aluminum oxide and polydimethylsiloxane (Al2O3@PDMS/Li) and a lithium-free sorbent (Al2O3@PDMS) on some indicators characterizing blood clotting under hemosorption conditions were compared in vitro. Sorbent Al2O3@PDMS/Li had significantly lower reactogenic effect on the blood passed through the column than the sorbent without lithium. This was seen from the degree of platelet reduction (66×109 vs 19×109/liter) as well as a less pronounced hypercoagulation shift in chronometric indicators. In contrast to lithium-free sorbent, Al2O3@PDMS/Li demonstrated the ability to reduce the concentration of fibrinogen. However, this had no impact on the density characteristics of the blood clot assessed by thromboelastometry such as maximum clot firmness, angle and fibrin clot formation time, amplitudes at 10 and 15 min after clotting time, which are known to depend on the quantity of platelets and the concentration of functionally active fibrinogen.

Pregnancy complications in G20210A mutation carriers associated with high prothrombin activity.

OBJECTIVE: To study the association between high activity of Factor II (prothrombin) in blood plasma with G20210A mutation and the development of great obstetrical syndromes. MATERIAL AND METHODS: A prospective clinical cohort study was conducted on 290 pregnant women (average age 31.7 ± 4.7 years old). The main group was made up of 140 G20210A patients, while the control group comprised 150 women with the wild G20210G type. The aim was to evaluate the activity of Factor II in the venous blood plasma during the stages of pregnancy with regard to trophoblast invasion waves. As per results, association analysis of Factor II activity value and gestational complications was carried out. RESULTS: In the control group, the median (Me) of Factor II activity ranged from 108% (preconception period) to 144% (pregnancy) [95% CI 130-150]. In patients with the GA type, the value was significantly higher in related periods, ranging from 149 to 181% [95% CI 142-195], p < 0.0001. With Factor II activity ranging from 148.5 to 180.6%, pregnancies in the main group had no complications. Higher levels of Factor II activity were associated with the development of early and/or severe preeclampsia (PE) and fetal growth retardation (FGR). CONCLUSION: The data obtained regarding Factor II activity in blood plasma, juxtaposed with the development of great obstetrical syndromes, allow to assume that manifestation of G20210A in early and/or severe PE and FGR is associated with this coagulation factor's level of activity. Threshold value of the Factor II activity with G20210A mutation, allowing to predict the development of PE, comprised 171.0% at the preconception stage (AUC - 0.86; p < 0.0001) and within 7-8 weeks of gestation it was 181.3% (AUC - 0.84; p < 0.0001).

[Pathogenesis, diagnosis, prevention and treatment of disseminated intravascular coagulation syndrome in COVID-19 infection].

AIM: Clinical characteristics of disseminated intravascular coagulation (DIC) in COVID-19 infection and assessment of the effectiveness of complex therapy for this syndrome at the stages of prevention and treatment of various complications. MATERIALS AND METHODS: The study of publications was carried out through search engines on the Internet using keywords. To diagnose the infection, the COVID-19 program was used on the MeDiCase platform, which is publicly available on www.medicase.pro, which suggests a diagnosis with a sensitivity of 89.47%. The study included 85 patients with acute COVID-19 with mild to moderate disease, aged 11 to 81 years. The presence of the pathogen was confirmed immunologically in 12% of patients; in other cases, the diagnosis was based on the results of an automated survey in the MeDiCase system. All patients, according to the MGNOT recommendations, were prescribed one of the oral direct anticoagulants - Eliquis at a dose of 5 mg 2 times a day, Ksarelto at a dose of 10 mg 2 times a day or Pradax at a dose of 110 mg 2 times a day for at least 2 weeks. All other drugs with antiviral, immunomodulatory effects, antibiotics were canceled. RESULTS: The presence of DIC is substantiated by the morphological picture of changes in organs and tissues, clinical (hematoma-petechial type of bleeding in combination with thromboembolic syndrome and the presence of thrombovasculitis) and laboratory changes: an increase in the level of soluble fibrin-monomer complexes, D-dimer, hyperfibrinogenaemia, less often - thrombocytopenia, violation of fibrinolytic activity. The phenomenon of consumption of clotting factors and profuse bleeding are rare. Direct anticoagulants, fresh frozen plasma transfusions and plasmapheresis are used in the treatment of disseminated intravascular coagulation. The paper presents its own positive results of early prescription at the outpatient stage of direct oral anticoagulants in prophylactic doses (no case of disease progression), individual cases of the use of fresh frozen plasma and plasapheresis. CONCLUSION: DIC syndrome with the development of thrombovasculitis is the most important pathogenetic mechanism for the development of microthrombotic and hemorrhagic disorders in organs during infection with COVID-19, leading to dysfunction of the lungs, brain and other nerve tissues, kidneys, thromboembolic complications, etc. Many symptoms of the disease may be associated with a violation of the nervous regulation of the functions of organs and systems. Prevention of thrombovasculitis is effective already at the stage of the first manifestation of the disease with the outpatient use of direct anticoagulants (oral, low molecular weight heparins). In case of more severe manifestations (complications) of the disease, additional use of freshly frozen plasma and plasmapheresis is effective.

Clinical and laboratory manifestations of the prothrombin gene mutation in women of reproductive age.

RESEARCH OBJECTIVE: To research the association of prothrombin (factor II) activity given the prothrombin G20210A mutation carriage with its clinical manifestations as thrombotic complications. MATERIALS AND METHODS: A prospective clinical cohort study of 290 women of reproductive age was conducted. Two cohort groups were identified: the study group of 140 patients with prothrombin mutation G20210A genotype and the control group of 150 women with G20210G genotype. RESULTS: The prothrombin G20210A mutation carriage is associated with the risk of thrombotic complications compared to the wild G20210G type (RR =17.1; p<0.0001) and is characterized by thrombosis localized both in the venous (66.7%) and arterial (33.3%) vascular pools. The threshold value of prothrombin activity (174.8%) for G20210A genotype was calculated, making it possible to conclusively predict the risk of thrombotic events with the accuracy of 90.4%. CONCLUSION: The phenotypic manifestation of the prothrombin G20210A mutation in the form of venous and arterial thromboses in women of reproductive age is associated with a super-threshold increase in prothrombin (factor II) activity, which makes it possible to stratify the patients into the group of high risk of thromboses.

[The role of presepsin in the estimation of disease severity and assesment the treatment efficiency in patients purulent pyelonephritis].

AIM: to determine the importance of a presepsin plasma level for early identification of urosepsis, assessment the severity and efficiency of therapy. MATERIAL AND METHODS: From 2017 to 2018 . a prospective controlled randomized cohort study with 32 patients (6 men, 26 women) aged from 20 to 60 years was conducted. Patients with diagnosed or suspected purulent pyelonephritis were randomized into two groups depending on the treatment strategy. In Group 1, patients received drug therapy, while in Group 2 surgical treatment was performed due to ineffectiveness of drug therapy. In both groups a level of presepsin was assessed and compared with the clinical manifestation of acute pyelonephritis and the choice of adequate treatment. RESULTS: The mean presepsin level in Group 1 at the admission was 338.4 pg/ml (normal value - 97 pg/ml), while in Group 2 it was 501.125 pg/ml. The presepsin level significantly decreased in both groups on Days 6-7 (<0.005), to 120.4 pg/ml and 66.875 pg/ml, respectively. Consequently, according to clinical and laboratory data, acute purulent pyelonephritis in patients who received combined therapy was successfully managed without surgical treatment, which was confirmed by the positive changes in body temperature, pain severity, blood analysis (leucocytes, ESR) and urine (protein, leukocytes) due to timely detection of presepsin level. DISCUSSION: Our analysis showed that recovery occurred in both groups, but there are differences in the duration of the disease depending on treatment strategy. Using the presepsin level, we found: In Group 1 the level was 338.4 pg/ml (1.5 times less than in Group 2, <0.005), which indicates the possibility of systemic infection. In this group the surgical treatment was avoided without any fatal consequences. In Group 2, in patients who were undergone to surgical treatment the mean baseline presepsin level was 501.125 pg/ml, which indicates the moderate risk of systemic infection (severe sepsis) and increased risk of adverse outcomes, therefore, surgical treatment was recommended. Thus, the determination of presepsin level can influence on the choice of treatment strategy. CONCLUSION: The analysis of presepsin level is necessary for the choice of treatment strategy, since the clinical and laboratory data does not always reflect the changes in the kidneys.

[Cryopresipitate in comprehensive conservative therapy of patients with acute purulent pyelonephritis].

AIM: To investigate the effectiveness of cryoprecipitate in the comprehensive conservative therapy of patients with acute purulent pyelonephritis. MATERIALS AND METHODS: We conducted a retrospective analysis of medical records of patients who were diagnosed with acute non-obstructive pyelonephritis from 2007to 2015. During this period, a total of 3912 patients with acute non-obstructive pyelonephritis were treated at the Department of Urology. Patients were assigned to either receive or not receive cryoprecipitate in the comprehensive conservative therapy. The comprehensive conservative therapy of both groups included antibacterial agents, detoxification, anti-inflammatory therapy. In the study group, patients received additional treatment with cryoprecipitate. By that way we estimated the number of patients who avoided surgery in both groups. RESULTS: There were 3912 patients divided into two groups. The first group included 756 patients (19.3%) who received cryoprecipitate in the comprehensive therapy of pyelonephritis. Of them, 735 patients (97.3%) did not require surgical treatment, and only 21 patients (2.7%) underwent surgery. The second group comprised 3156 patients (80.7%) who did not receive cryoprecipitate. Of them, 2974 patients (94.2%) were treated conservatively without surgical intervention and 182 patients (5.8%) received conservative therapy concurrently with surgical treatment. Therefore, including cryoprecipitate in the comprehensive conservative therapy of acute non-obstructive pyelonephritis results in twice smaller percentage of patients (2.7% vs 5.8%) requiring surgery compared to the comprehensive conservative therapy alone.

[Antidotes to novel direct oral anticoagulants]. / Antidoty novykh priamykh oral'nykh antikoaguliantov.

During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation). The review contains the data on the existing therapeutic regimens of treating haemorrhage on the background of taking these coagulants. This is followed by analysing the present-day results of clinical trials aimed at working out pharmaceutical agents (andexanet alpha, idarucizumab, aripazine) being antidotes to direct thrombin inhibitor and the factor Xa inhibitors. Administration of these agents makes it possible to reverse coagulation and minimize the aftermaths of haemorrhage in patients taking these drugs, in emergency situations.

[Peculiarities of thrombin generation and prognosis of unfavourable outcome in patients with severe pneumonia and pneumogenic sepsis].

The study of thrombin production included 68 patients with severe pneumonia (SP) undergoing monitoring plasma thrombin potential in the thrombin generation test. Thrombin production was found to decrease in the patients who died compared with those alive on days 3-5 and 7-10 after onset of the disease. Endogenous thrombin potential decreased progressively during the first 7-10 days among the patients with the fatal outcome of SP. This trend in thrombin generation can be used to predict the unfavourable outcome of SP.

[Role of endothelial dysfunction, the interface between hemostatic and system inflammatory responses in the pathogenesis of an infectious inflammation-dependent exacerbation of chronic obstructive pulmonary disease].

AIM: To analyze the systemic manifestations of vascular endothelial damage, the activation of hemostatic and inflammatory responses in patients with an infectious inflammation-dependent exacerbation of chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: The paper provides the data of examinations of 111 patients with the clinical signs of an infectious inflammation-dependent exacerbation of COPD who had 2 or 3 positive criteria elaborated by N. Anthonisen et al. (1987). The patients were divided into 2 phenotypically different subgroups: 1) 92 (82.9%) COPD patients without clinical manifestations of bronchoectasis; 2) 19 (17.1%) patients with COPD concurrent with documented bronchiectasis. The patient subgroups were matched for smoking status and the characteristics of COPD and respiratory failure. The investigators assessed the time course of changes in the serum level of endothelin-1 (ET-1), the aggregation function of platelets, and the plasma concentrations of D-dimers and homocysteine in patients with COPD compared to healthy, never smokers (n = 35) and smokers (n = 27). RESULTS: An increase in the levels of the endothelial dysfunction markers ET-1 and homocysteine was found in patients with COPD, which was comparable with the changes in these indicators in the group of smokers. In both subgroups, the rise in plasma D-dimer levels was more pronounced in the patients with a COPD exacerbation than in the smokers. Its therapy with systemic and inhaled glucocorticosteroids reduced C-reactive protein and ET-1 levels in both patient subgroups and in D-dimers in subgroup 1. Elevated D-dimer levels remained when achieving remission, which points to the risk of thrombogenic and thromboembolic events in the patients with an infectious inflammation-dependent exacerbation of COPD and concomitant circulatory system diseases. CONCLUSION: The patients with an infectious inflammation-dependent exacerbation of COPD are observed to have elevated peripheral blood markers of endothelial dysfunction and thrombinemia. These changes are pathogenetically caused by smoking or neutrophilic inflammation and associated with a higher risk of thrombogenic events.

[The monitoring of application of dabigatran as a remedy of prevention of thromboembolic complications after hip joint arthroplasty].

The analysis was applied to the indicators of hemostasis system under application of new anticoagulant, dabigatran etexilat, after hip joint arthroplasty. It is established that among the coagulation methods analysis the most specific to the effect of dabigatran is the testing of thrombin and echitox time of coagulation. Considering low sensitivity of the echitox to anticoagulation effect of D-dimer the echitox test is optimal for laboratory monitoring of application of dabigatran after orthopedic intervention.

[The preanalytical stage of studying the hemostatic system].

The efficiency of applying precision devices and multiple laboratory methods devised to reveal the causes of bleeding and thromboses significantly depends on whether a wide range of rules of the preanalytical stage of the study is observed. The paper gives detailed information on conditions for taking blood samples, their transport, and preparation for examination of the hemostatic system. The given information is based on the worldwide recommendations and many years' experience gained by the authors at the laboratory of hemostasis.

[Effect of fibrin monomer on spontaneous platelet aggregation].

Fibrin monomer (FM) was shown to cause a considerable increase in artificial shear-induced platelet aggregation. The aggregatory effect of FM was found to be tangibly higher than that in fibrinogen. The mechanism of action of FM on platelet aggregation is hypothesized.

[Effect of anesthesia and anticoagulant prophylaxis on the occurrence of postoperative thromboembolic complications in orthopedic patients].

Different prevention regimens of venous thromboembolism, by using the low molecular-weight heparin Fraxiparin, were studied in 152 patients who had undergone major orthopedic leg surgery under spinal and general anesthesia. The regimens differed in the time of Fraxiparin administration (before or after surgery). Fraxiparin and spinal anesthesia were found to promote the lower incidence of venous thromboembolism. The preoperative preventive treatment of venous thromboembolism, by using a low molecular-weight heparin in patients undergoing spinal anesthesia is unnecessary because of a high risk of epidural hematomas. If the risk for venous thromboembolism is higher before surgery and remains the same after it, thromboprophylaxis should be prolonged for at least one month.

[A new method for determination of antithrombin III and its diagnostic significance]. / Novyi metod opredeleniia antitrombina III i ego diagnosticheskoe znachenie.

A new assay based on using an original chromogenic substrate (z-Ala-Ala-Arg-pNa) and designed for the determination of antithrombin III is described in the paper. It was used in examinations of patients with malignancy after surgery. The content of antithrombin III was detected to be lower in 12% of cases in 2 days after surgery. Additionally, patients with DIC, as complications after surgery, were examined to find out that the antithrombin III content was decreasing in them.

[Structure, function and the role of factor XIII in human pathology]. / Struktura, funktsii i rol' faktora XIII v patologii cheloveka.

Modern views on the functioning of coagulation system are constantly replenished with the facts obtained using the newest methods of molecular biology and medicine. The purpose of many components of this system is non-uniform and covers the whole spectrum of biochemical reactions responsible for homeostasis. Current data on one of such components--the factor XIII (fibrin stabilizing factor) are stated. Except for the description of the enzyme structure and functions, information is presented about the methods of its detection, which development has resulted in accumulation of knowledge on the role of fibrin stabilizing factor in bleedings and thrombosis genesis. Data are given on hereditary and acquired deficiency of the factor XIII, as well as on conditions accompanied with the increase of its activity.

[Immunostimulating and anticoagulating activity of fucoidan from brown algae Fucus evanescens of Okhotskoe sea]. / Immunostimuliruiushchaia i antikoaguliantnaia aktivnost' fukoidana iz buroi vodorosli Okhotskogo moria Fucus evanescens.

Fucoidan--nontoxic sulfated polysaccharide was isolated from brown algae Fucus evanescens in Okhotskoe Sea. Chemical analysis of the compound was performed, it was shown that fucoidan is freely soluble in water and acid solutions. Immunotropic and anticoagulating properties of the compound were evaluated in comparison with heparin. It was demonstrated that fucoidan in wide range of doses stimulated phagocytic and bactericidic activity at leucocytes of mice peritoneal exudate. Heparin on the contrary demonstrated depressive effect on these functions at high dose. It was shown that fucoidan has dose-dependent anticoagulating activity in vitro and in vivo comparable with heparin activity. The results of investigation demonstrated possibility of fucoidan application as immunomodulating and anticoagulating agent of plant origin.

Anticoagulant activity of fucoidan from brown algae Fucus evanescens of the Okhotsk Sea.

In vitro and in vivo experiments showed that anticoagulant activity of sulfated polysaccharide from Fucus evanescens (brown algae of the Okhotsk Sea) was similar to that of heparin. Anticoagulant properties of fucoidan are determined by thrombin inhibition mediated via plasma antithrombin III.

[A method for determining plasminogen with a Russian chromogenic substrate and its diagnostic significance]. / Metod opredeleniia plazminogena s otechestvennym khromogennym substratom i ego diagnosticheskoe znachenie.

Measurement of plasminogen, the key component of fibrinolysis system, is one of the basic methods for estimation of fibrinolysis. Methods based on the use of chromogenic substrates are often used in diagnosis. Plasminogen measurements are important for laboratory diagnosis of thrombophilia caused by deficiency or abnormalities of this fiber, for detection and evaluation of the DIC syndrome, and for monitoring the treatment by fibrinolytic preparations (streptokinase, t-PA, urokinase, etc.). An original chromogenic substrate having no foreign analogs has been created at Institute of Genetics and Selection of Industrial Microorganisms and Research Center of Hematology (Moscow). Unlike previously described plasmin substrates, pNa has been obtained by microbiological methods with Russian commercial enzymes subtilisine 72 and megaterine. This paper presents the results of plasminogen measurements in patients with DIC with the use of the original chromogenic substrate. The results were compared with those of tests with Berihrom-Plasminogen diagnostic kit (Behringwerke AG).