Hemostatic Factors and Its Correlation with Outcomes of COVID-19 Confirmed Patients in Ulin Regional Hospital Banjarmasin

Background: Corona Virus Disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has become a Global Pandemic and has spread to more than 200 countries including Indonesia. Previous studies show that poor prognosis has a correlation with coagulopathy conditions. Objectives: To identify coagulopathy condition and its correlation with the outcomes of COVID-19 confirmed patients at Ulin Regional Hospital Banjarmasin in the period March-August 2020. Methods: A retrospective study by extracting laboratory data from medical record of 309 patients confirmed with COVID-19 at Ulin Regional Hospital Banjarmasin in the period March-August 2020. Results: This study showed that mean values of D-Dimer level in the COVID-19 cases were increased both in survivor and non survivor cases. The mean values of PT, APTT, INR and D-Dimer were higher in non survivor cases (PT 12.31 seconds; APTT 31.78 seconds; INR 1.15; D-Dimer 4.6 mg/L) than survivor case (PT 11.63 seconds; APTT 28.43 seconds; INR 1.12; D-Dimer 2.31 mg/L) while the platelet count was the opposite (288.28 in survivor cases; 281.89 in non survivor cases). The difference was statistically significant (P <0.005) in PT, APTT and D-Dimer variables between survivor and non survivor cases. However, the relationship between hemostasis factors and outcome of patient with COVID-19 was found to be very weak on the platelets, PT, APTT and INR variables (ρ = 0-0.25; P <0.005) and weak on the D-Dimer variable (ρ = 0.26-0.50; P <0.005). Conclusions: Most COVID-19 cases cause coagulopathy conditions. However, considering the risk of poor outcomes, further studies should investigate the prognostic role of hemostatic parameters in COVID-19 patients.

Effects of IgG from the serum of ischemic stroke patients on hemostasis

Ischemic stroke is among the top diseases leading to mortality and disability in the world. The detailed investigation of the mechanisms underlying this pathology and especially mediating the tendency to relapse during the first year after stroke incident undoubtedly belongs to important tasks of modern medicine and biology. The current study aims to analyze the influence of IgG derived from the blood serum of ischemic stroke patients on some hemostasis factors. In total, 123 participants with IS, 62 with atherothrombotic ischemic stroke, 61 with cardioembolic ischemic stroke, and 57 subjects as control have been examined. The same patients have participated in the research a year after stroke. IgG from serum was isolated by affinity chromatography on protein A Sepharose column. The activity of key hemostasis factors under the influence of IgG was analyzed. Obtained results revealed that IgG of stroke patients but not healthy subjects caused the inhibition of the amidolytic activity of endogenously generated thrombin, protein C, factor Xa, and led to an increase in the degree of ADP-induced platelet aggregation. The reduction of clotting time in the test "Thrombin time" by IgG of patients at the acute phase of disease was also observed; IgG of healthy subjects mediated the opposite effect. In contrast to acute ischemic stroke IgG, IgG of patients one year after both atherothrombotic and cardioembolic ischemic stroke influenced only the activity of endogenously generated thrombin and factor Xa resulting in inhibition of their activities. It was also established that IgG of ischemic stroke patients, as well as healthy subjects, stimulated the secretion of tissue plasminogen activator by endotheliocytes.

EPIGENETIC REGULATION OF ADAPTOGENESIS BY PATHOLOGY AND AGING

В обзоре с точки зрения эпигенетики рассмотрены адаптационные возможности организма при патологии и старении. Апаптация организма к внутренним и внешним факторам осуществляется единой гуморальной защитной системой организма, включающей гипоталамо-гипофизарно-эпифизарную и гипоталамогипофизарно-тимусную оси. Короткие пептиды AEDG, AEDP, EDR, KED, EW, KE являются эпигенетическими регуляторами экспрессии генов и синтеза белков, которые могут быть вовлечены в адаптацию при стрессе и активацию гипоталамо-гипофизарно-эпифизарной и гипоталамогипофизарно-тимусной осей. Указанные короткие пептиды регулируют синтез белков теплового шока, стресспротекторных белков, цитокинов, факторов фибринолиза и гемостаза. Эти пептиды могут участвовать в первичной и отсроченной эпигенетической регуляции адаптивного ответа при стрессе, патологии и старении. Ранняя функциональная диагностика нарушения сопряжения звеньев единой гуморальной защитной системы организма при возраст-ассоциированных заболеваниях позволит выявить недостаточную синхронность эпигенетических механизмов, при которой наступает истощение и снижение резервных возможностей организма. Применение пептидов может нивелировать проявления адаптационного синдрома при стрессе и возрастной патологии. The organism adaptive possibilities by pathology and aging are discussed in account of the epigenetic. The organism adaptation to inner and external factors is carried out by organism unite humoral protective system, inclusive hypothalamus-hypophysis-pineal and hypothalamus-hypophysis-thymus axises. AEDG, AEDP, EDR, KED, EW, KE short peptides are the epigenetic regulators of gene expression and protein synthesis, which can be involve to the adaptation by stress and in the activation of hypothalamus-hypophysispineal and hypothalamus-hypophysis-thymus axises. These short peptides regulate the synthesis of proteins of heat shock, stress-protective proteins, cytocines, fibrinolysis and hemostasis factors and can participate in primary and tardive epigenetic regulation of adaptive response by stress, pathology and aging. The early functional diagnostic of element disturbances of organism unite humoral protective system by age-associative pathology can be usefull for the detection of deficient synchronization of epigenetic mechanisms, by wich the depletion and decrease of organism reserve possibilities occurs. The use of peptide can grade the adaptive syndrome manifestation by the stress and age pathology.

The activity of hemostatic and oxidative-reduction systems according to different classes of ulcer bleeding

Haemostatic therapy of ulcer bleeding (UB) is based on activation of the coagulation system and depression of the fibrinolytic one. Though not so much attention is paid to the oxidation-reduction system. Aim of the study — To elaborate the recommendations on optimization of hemostatic therapy. Were examined 25 patients with UB. 4 patients were evaluated by Forrest classification, type ІВ, 5 – type ІІА, 6 — type ІІВ, and 10 — type ІІІС. Patients with type ІВ had endoscopic haemostasis procedures. All patients got a standard haemostatic complex. Two patients who were evaluated by Forrest classification type ІІА had bleeding recurrence. The following data was determined in blood plasma: fibrinolytic and proteolytic activity, fibrinase, antithrombin ІІІ, prothrombin index, isolated double bonds, diene conjugates, cetodienes and conjugated trienes, oxidation of neutral and alkaline proteins, malonic aldehyde, renew glutathione, catalase. Patients who were evaluated by Forrest classification type ІІА had both a disorder of redox system and hemostasis system balance, caused by a violation of synthesis of its factors. This contributes to the occurrence of bleeding recurrence. The results of redox system together with the criteria for hemostasis condition can be used to predict the recurrence of ulcer bleeding. Medicinal measures need to be adjusted, and antioxidants together with hepatoprotectors to be prescribed. So, patients with UB recurrence have an excessive activation of lipoperoxidation, low level of basic proteins, decrease in functional capacity of antioxidant mechanisms and hemostasis system imbalance, caused by a violation of synthesis of its factors, it is essential to take into account while predicting UB recurrence, and in case of UB one should add to the medication management those means that inhibit the activity of lipid oxidation and contribute to the restoration of synthesis processes of hemostasis factors. The prospect of further development is the assessment of the effectiveness of an optimized treatment complex.

Biological Variation of Hemostasis Variables in Thrombosis and Bleeding: Consequences for Performance Specifications

BACKGROUND Levels of hemostasis factors vary between and within individuals as a result of genetic and environmental factors and analytical variation of the assays. The current state of the art for defining analytical precision requirements for analytical testing is based on this between- and within-individual (biological) variation. However, information on biological variation in hemostasis variables is still limited. The aim of this study was to determine the biological variation of coagulation variables involved in thrombosis and bleeding to provide a recommendation for performance specifications and to assess whether hemostasis assays fulfill the recommendation. METHODS We performed a longitudinal study by repeated blood sampling (in total 13 times over a 1-year period) in 40 healthy individuals and measured prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, factor VIII, factor IX, von Willebrand factor (VWF), protein C, and protein S. We evaluated the effect of the biological variation on parameters of analytical variation and propose required performance specifications. RESULTS Biological variation was highly different for various hemostasis variables: the within-subject variation ranged from 2.6% (PT) to 25.6% [VWF collagen binding (CB) activity], the between-subject variation varied from 4.1% (PT) to 31.2% (VWF:ristocetin cofactor acitivity), and the assay variation from 1.3% (PT) to 12.9% (VWF:CB). CONCLUSIONS With the reagents and analyzers used in this study, most of the hemostasis tests variables fulfill the current quality criteria for diagnosis and monitoring of routine hemostasis assays.

Thrombogenicity and cardiovascular effects of ambient air pollution

Exposure to air pollution is associated with adverse effects on health. In particular, a strong epidemiologic association is observed between acute and chronic exposures to particulate matter and the occurrence of cardiovascular events, coronary artery disease, cerebrovascular disease and venous thromboembolism, especially among older people and people with diabetes and previous cardiovascular conditions. Multiple mechanisms have been postulated to cause the increase in atherothrombotic and thromboembolic events, including the activation by particulate matter of inflammatory pathways and hemostasis factors, production of reactive oxygen species through the oxidative stress pathway, alterations in vascular tone, and decreased heart rate variability (a marker of cardiac autonomic dysfunction and a predictor of sudden cardiac death and arrhythmias). Current knowledge on the biologic mechanisms and the clinical effect of short- and long-term exposure to particulate air pollutants is discussed, emphasizing that life expectancy improved significantly in sites where air pollutants were controlled.

Some antiphospholipid antibodies bind to various serine proteases in hemostasis and tip the balance toward hypercoagulant states

The body has an elaborate system that maintains blood circulation and rapidly stops bleeding when vessels are damaged. Abnormalities that disrupt this balance may lead to thrombosis. While β2-glycoprotein I is generally accepted as the major antigen for antiphospholipid antibodies in the antiphospholipid syndrome, our accumulated studies show that some antiphospholipid antibodies bind homologous enzymatic domains of several serine proteases involved in hemostasis and fibrinolysis. Functionally, some of the protease-reactive antiphospholipid antibodies hinder anticoagulant regulation and resolution of clots, thus tip the balance toward thrombosis. Intriguingly, several serine protease-reactive antiphospholipid antibodies also react with β2-glycoprotein I, and interactions between antiphospholipid antibodies and antigens are cross-inhibited, indicating that these antiphospholipid antibodies recognize conformational epitope(s) on β2-glycoprotein I and target serine proteases. Viewed as a whole, these results extend previous reports that antiphospholipid antibodies bind to various hemostasis factors, and provide a new perspective about some antiphospholipid antibodies in terms of their binding specificities and related functional properties in promoting thrombosis.

Reality and perspective of instrumental diagnostics hemostasis system functional state in critical medicine

In article to discuss diagnostic value of blood aggregate regulation system (BARS) and complexity of diagnostics, particularly, in critical state.Advantages and disadvantages of instrumental diagnostics technique were analyzed: thromboelastographia and lowfrequency piezoelectric hemocoagulographia of whole blood. Estimates new next-generation instrumental method of research - lowfrequency contact conductometry. This method permits to evaluate role blood plasma, cells hemostasis factors and wall of vessels in critical state BARS dysfunction.