STUDY OF THE PLASMA COMPONENT OF THE BLOOD AGGREGATION REGULATORY SYSTEM IN SUBJECTS IN THE EXPERIIMENT WITH 120-DAY ISOLATION INSIDE PRESSURIZED MODULE SIRIUS-19

2021 ◽  
Vol 55 (1) ◽  
pp. 59-62
Author(s):  
D.S. Kuzichkin ◽  
◽  
А.А. Markin ◽  
О.А. Zhuravleva ◽  
Z.А. Krivitsina ◽  
...  

Citrate plasma samples gathered 31 days prior to, on days 37, 63, 120 in and on days 7 and 14 after isolation (project Sirius-19) were analyzed for blood aggregation parameters including fibrinogen (FBG), D-dimer (DD), plasminogen (PG), antithrombin III (АТ3), protein C (PC) and α2-antiplasmin (AP), thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT). DD was lowered in all samples gathered during isolation. The complex of isolation factors combined with physical exercise reduced levels of fibrin formation and fibrinolysis. However, after isolation the procoagulent activity showed an increase manifested by elevated DD and reduced APTT. Appears that in the absence of insertion and reentry effects (redistribution of body fluids in microgravity) and high psychophysiological stresses it is the appropriate use of physical countermeasures that ensures plasma efficiency within the blood aggregation control system, and good body tolerance of the spaceflight factors.

1979 ◽  
Author(s):  
H. Bounameaux ◽  
G.A. Marbet ◽  
H. Airenne ◽  
E. Grossmann ◽  
B. Stanojevic ◽  
...  

In 63 plasma samples from patients under heparin we determined the heparin concentration using the chromogenic substrats S-2222 (COATEST Heparin). Thrombin time (TT), activated partial thromboplastin time (APTT), antithrombin III activity (ATIIIact) and concentration (ATIIIimm) were also measured. A good correlation was found between heparin concentration and TT (r= .850, p< .001), heparin concentration and APTT (r =669, p < .001) while the correlation coefficient r between TT and APLT was .896 (p< .001).We found a statilttically significant reduction of ATIIIact with increasing APTT (p < .05. The ATIIIact and ATIIIimm values were also lower (p < .001) in the overanticoaculated group (n=ll) than in the group with insufficient heparinisation (0.18). The mean (±SO) heparin concentration in 12 plasmas with both TT and APTT in the therapeutic range was .54 (±.15) USP-U/al, very similar to that of 13 plasma (.68 ± .46 U/al) insufficiently heparinised accordirig to the APTT. However, the TT recognised then as correctly anticoagulated. Regarding these findings and our good experience without complication by monitoring heparin therapy with TT we assume that TT is more accurate than APTT for this aim.


1987 ◽  
Author(s):  
J Takamatsu ◽  
H Saito ◽  
T Kamiya ◽  
Y Muranaka ◽  
Y F Minami ◽  
...  

A new mucopolysaccharide(FGAG) has been isolated from the cell wall of Stichopus japonicua. The molecular weight of FGAG is about 50,000. The component sugar of the FGAG are identified as galactosamine, glucuronic acid, fucose and sulfate with the molar ratioof 1:0.94:0.84:3.60,respectively. The anticoagulant effects of FGAG were studied. At low concentration(lμg/ml), FGAG completely inhibited the rabbit plateletaggregation induced by thrombin and prolonged thrombin time of not only human plasma but purified fibrinogen solution to a similar extent, suggesting that action of FGAG is not depend on plasma component(antithrombin III and/or Heparin c.ofactor II).After intravenous injection into rabbits(lmg/kg),significant prolongation of activated partial thromboplastin time(APTT) was observed. Although the in vivo antithrombin activity of the FGAG was weaker than that of heparin.it lasted longer than that of heparin and was not inhibited by platelet factor 4.These results suggested that FGAG is a new and unique mucopolysaccharide with antithrombin activity and may come into use for the treatment ofDiseminated Intravascular Coagulation.


Author(s):  
George P Kozynets ◽  
Volodymyr P Tsyhankov ◽  
Daria S Korolova ◽  
Olga V Gornytska ◽  
Olexiy M Savchuk ◽  
...  

Abstract This work is dedicated to the detection of imbalance between the pro- and anti-coagulant branches of hemostasis at severe burn injuries by evaluating the content or activity of individual clotting factors. To select the targets for accurate diagnostics we measured the concentrations of soluble fibrin monomeric complexes and fibrinogen, levels of total prothrombin, factor X, protein C and antithrombin III, and recorded the time of clotting in activated partial thromboplastin time and prothrombin time tests. Factor X level was increased in 26 % of patients on the first day after the burn and it rose further in 62 % patients on the 14 th day of recovery. Increasing factor X level is assumed to be a risk factor of thrombotic complications. We propose to use it as a marker of predisposition to thrombosis at severe burn injury.


2021 ◽  
Vol 121 (1) ◽  
pp. 22-31
Author(s):  
Alіna Baylo ◽  
Vadym Shypulіn ◽  
Volodymyr Chernyavskyi ◽  
Luiza Parunyan

The comorbid course of liver cirrhosis and atrial fibrillation causes higher levels of hospitalizations, mortality and ischemic stroke. According to current data, hemostasis in patients with liver cirrhosis is in a rebalanced dynamic state, but there are no data on the effect of atrial fibrillation on the hemostasis in patients with liver cirrhosis. Aims of the study. To assess abnormalities in primary, secondary haemostasis and fibrinolytic system in patients with liver cirrhosis and atrial fibrillation by using standard laboratory coagulation parameters and to investigate their changes depending on the stage of liver cirrhosis A, B, C according to Child-Pugh score. Materials and methods. A cross-sectional prospective study was conducted with the inclusion of 106 patients aged 42 to 83 years: group I (n = 70) - with liver cirrhosis and atrial fibrillation, II (n = 36) - with liver cirrhosis, which were distributed depending on the Child-Pugh score stages of cirrhosis and 20 healthy individuals. The levels of platelets, activated partial thromboplastin time, international normalized ratio, prothrombin time, thrombin time, fibrinogen, D-dimer were assessed on a Steellex M200 coagulometer. Statistical analysis (IBM SPSS Statistics) was performed. Results. The level of platelets in patients of group I was reduced by 37.4% (200 ± 8.33 vs. 274.7 ± 3.4; p,000.001), an activated partial thromboplastin time was prolonged by 38.6% (44.35 ± 1.39 vs. 32.01 ± 0.63, p˂0.001), prothrombin time was prolonged by 73.5% (19.4 ± 0.87 vs. 11.18 ± 0.53, p˂0.001), thrombin time was prolonged by 2.07 (25, 7 ± 1.31 vs. 12.4 ± 0.66, p˂0.001), the international normalized ratio was increased by 24.3% (1.38 ± 0.04 vs.1.11 ± 0.01, p˂0.001) compared to control. The fibrinogen level was 20.9% higher (4.17 ± 0.17 vs. 3.45 ± 0.11, p˂0.001) than in control group and was 83.7% higher (4.17 ± 0.17 vs. 2.27 ± 0.13, p˂0.001) than in group II. The D-dimer level was 83% higher than in control (675 ± 22.3 vs. 368.8 ± 21.85, p˂0.001) and 44% higher (675 ± 22.3 vs. 469 ± 37.18, p ˂0.001) compared with group II. Conclusions. In patients with liver cirrhosis and atrial fibrillation abnormalities of primary hemostasis are detected due to decrease of platelets on the background of portal hypertension. At the secondary stage of hemostasis indicators of external and internal coagulation mechanisms are prolonged due to the reduced synthesis of coagulation factors by the liver. Increased level of fibrinogen is determined at the stage of compensated and subcompensated cirrhosis with a gradual decrease at the stage of decompensation. The high activity of the fibrinolytic system is observed due to increase in the D-dimer levels, which may indicate a prothrombotic state in these patients.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2568-2568
Author(s):  
Heiko Rühl ◽  
Janine Rossa ◽  
Christina Berens ◽  
Anna Winterhagen ◽  
Johannes Oldenburg ◽  
...  

Abstract Introduction: In a recent study, we performed autologous serum infusions to evaluate the elimination kinetics of hemostasis-related biomarkers in healthy human subjects. In order to monitor a serum-induced activation of coagulation, we measured free thrombin in the infused serum and in plasma samples taken during and after infusion, but did not detect any de novo thrombin formation [PLoS One. 2015; 10(12): e0145012]. To study if the low levels of free thrombin in the infused serum induce generation of activated protein C (APC) we additionally measured APC in samples drawn after autologous serum infusion and in vitro in a purified system. Methods: Autologous serum was infused (50 mL/30 min) into 19 healthy volunteers. Four of them were simultaneously receiving infusions of the thrombin inhibitor argatroban (1 µg/kg/min), initiated 1 h before and ceased 1 h after starting the infusion of serum. Thrombin and APC were measured in serum and in plasma samples drawn before and in 15-min intervals during the infusion of serum, using a highly-sensitive oligonucleotide-based enzyme capture assay (OECA) platform. In in vitro experiments, APC formation was induced by addition of purified thrombin or serum to buffer containing protein C and thrombomodulin in excess, and CaCl2 at physiological concentrations. The formation of APC was subsequently measured by OECA. Results: In the autologous serum median (interquartile range) concentrations of thrombin and APC were 6.68 (4.63 - 8.73) ng/mL and 9.17 (7.63 - 13.91) ng/mL, thus doses of 0.12 (0.07 - 0.15) ng/mL of thrombin and 0.16 (0.14 - 0.22) ng/mL of APC were infused per mL of the subjects' plasma volume. In the plasma of probands, that did not receive argatroban, peak thrombin levels of 0.04 (0.00 - 0.08) ng/mL were measured, indicating a rapid inactivation of thrombin by endogenous inhibitors present in the plasma. However, with 1.41 (0.76 - 2.97) ng/mL peak APC levels exceeded the infused APC doses by a multiple. This was also true for the plasma samples from the probands that received argatroban, in which peak levels of APC of 0.94 (0.79 - 1.22) ng/mL were measured despite thrombin inhibition indicated by prolongation of the aPTT of 42.9 (40.1 - 44.4) s and thrombin time of 78.3 (69.3 - 87.2) s. In the in vitro experiments addition of argatroban at the concentrations achieved in the probands completely abolished APC generation up to a thrombin concentration of 5 ng/ml. Addition of human serum as a source for thrombin in the same purified system consistently induced generation of greater amounts of APC than expected on the basis of the amount of thrombin present in the serum samples. Conclusions: The data obtained provide evidence for a thrombin-independent mechanism of APC formation. Further in vitro studies with endothelial cells are required to identify the components that are involved in this alternative way of APC generation. Disclosures Rühl: CSL Behring: Research Funding; Bayer: Consultancy, Honoraria. Müller:Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.


1996 ◽  
Vol 76 (04) ◽  
pp. 502-504 ◽  
Author(s):  
A Fiumara ◽  
R Barone ◽  
P Buttitta ◽  
R Musso ◽  
L Pavone ◽  
...  

SummaryCDG syndrome (CDGS) type I is the most frequent form of a group of metabolic disorders characterised by a defect of the carbohydrate moiety of glycoproteins. A large number of plasma glycoproteins, including clotting factors and inhibitors, are decreased and stroke-like episodes have been described in about half of the reported patients. We studied blood coagulation factors, inhibitors and D-dimer plasma levels in four subjects, aged 12-23 years, with CDGS type I. Factors VIII, XI, antithrombin III activity, antigen plasma levels of antithrombin III, free protein S and protein C were decreased whereas protein C as activity was normal. In addition two patients had reduction of factors II, V, VII, IX, X reflecting the phenotypic heterogeneity associated with CDGS type I. D-dimer plasma concentrations were elevated in all subjects. The hypercoagulable state as consequence of the combined deficiencies of coagulation inhibitors could contribute to the stroke-like phenomena in CDGS type I.


Author(s):  
Д.И. Поздняков ◽  
В.М. Руковицина ◽  
А.В. Сосновская ◽  
Е.А. Олохова

Введение. «Цитокиновый шторм» представляет собой расстройство иммунной системы с выраженной гиперцитокинемией, характеризующееся развитием коагуляционных нарушений с высоким уровнем летальности. Цель исследования: оценить влияние новых аналогов халкона на изменение реакций гемостаза у крыс в условиях экспериментального «цитокинового шторма». Материалы и методы. Исследование было выполнено на 80 крысах- самцах линии Wistar, разделенных на 8 равных групп по 10 особей. «Цитокиновый шторм» моделировали путем внутрибрюшинного введения липополисахарида в дозе 10 мг/кг. Исследуемые соединения в дозе 20 мг/кг интраперитонеально и препарат сравнения — гепарин (20 ЕД/кг, подкожно) вводили через 60 мин после моделирования патологии. Через 24 ч в сыворотке крови у крыс оценивали содержание фибриногена, D-димера, растворимых фибрин-мономерных комплексов (РФМК), активность антитромбина III (АТ-III), тромбиновое время (ТВ) и степень АДФ-стимулированной агрегации тромбоцитов. Результаты. Применение аналогов халкона способствовало восстановлению гемостатических реакций, что выражалось в снижении концентраций фибриногена, D-димера, РФМК, степени агрегации тромбоцитов и повышении активности АТ-III и ТВ. При этом в ряду изучаемых веществ соединение, содержащее гидроксил во 2-м положении и метильную группу в 5-м положении, проявляло несколько больший уровень фармакологической активности, нежели остальные исследуемые соединения. Заключение. На основании полученных данных можно предположить актуальность дальнейшего изучения аналогов халкона как средств, нормализующих гемостаз при гиперцитокиновых расстройствах. Background. «Cytokine storm» is a disorder of the immune system with severe hypecytokinemia, characterized by the development of coagulation disorders with a high level of mortality. Objectives: to evaluate the effect of new chalcone analogues on changes of hemostasis reactions in rats under the conditions of an experimental «cytokine storm». Materials/Methods. The study was performed on 80 male Wistar rats divided into 8 equal groups of 10 individuals. The «cytokine storm» was modeled in animals by intraperitoneal injection of lipopolysaccharide at a dose of 10 mg/kg. The test-compounds at a dose of 20 mg/kg intraperitoneally and the reference drug — heparin (20 U/kg, subcutaneously) were administered 60 minutes after the pathology simulation. After 24 hours, the serum levels of fi brinogen, D-dimer, soluble fibrin-monomer complexes, antithrombin III activity, thrombin time, and the degree of ADP-stimulated platelet aggregation were evaluated in rats. Results. The study showed that the use of chalcone analogues contributed to the restoration of hemostasis reactions, which was expressed in a decrease in theconcentration of fibrinogen, D-dimer, soluble fibrin-monomer complexes, the degree of platelet aggregation, and an increase in antithrombin III activity and thrombin time. At the same time, among the studied substances, the compound containing hydroxyl in the 2nd position and the methyl group in the 5th position showed a slightly higher level of pharmacological activity than the other test compounds. Conclusions. Based on the obtained data, it is actuality to assume the relevance of further study of chalcone analogues as agents that normalize hemostasis in hypercytokine disorders.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5248-5248
Author(s):  
Bhaumik Arvindkumar Shah ◽  
Arulselvi Subramanium ◽  
Subhadra Sharma ◽  
Deepak Agrawal ◽  
Gaurav Chhabra ◽  
...  

Abstract Abstract 5248 In India trauma related deaths occur every 1.9 minutes. Mortality in severe traumatic injury (ISS>16) is six times higher in developing country like India. Coagulopathy is observed in almost 25– 30% of trauma patients which itself is an independent risk factor for haemorrhage. Coagulopathy detected early after injury is indicative of injury severity and itself is a prognostic factor for mortality. Aim To find out the usefulness of thromboelastography (TEG) in detecting coagulopathy in contrast to conventional methods of plasma based standard coagulation parameters (PT, aPTT, TT, fibrinogen, D-dimer) Objective To detect coagulopathy early by TEG in trauma patients within 24 hrs after injury which can be useful to guide haemostatic therapies to reduce mortality. Materials and methods Patients admitted to trauma casualty were studied within 24 hrs after injury. Native whole blood was withdrawn through venepuncture appropriately in syringe using 21G needle and TEG was performed within 2 mins. Blood was also collected in citrated tube to assess standard coagulation parameters (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer) and also by means of thromboelastography. Results Patients (n=87,New ISS-24.78(mean)) admitted to J.P.N Apex trauma centre casualty from 1st April,2011 to 31st July,2011 were studied. The cases included in the study were isolated head injury (n=40, NISS-25.87(mean)), multiple trauma with head injury (n=13,NISS – 30.69 (mean)) and trauma other than head injury (n=34, NISS-21.24 (mean)).Thromboelastography was performed using whole blood (n=69) and citrated blood (n=18). Coagulation tests were performed on all 87 patients using both TEG and conventional coagulation parameters. Total 52 patients showed coagulopathy by TEG and only 14 patients showed coagulopathy by standard coagulation parameters (prothrombin time, activated partial thromboplastin time). Only in 10 cases coagulopathy was detected by both methods. 4 patients showed coagulopathy only by conventional methods while 42 patients showed coagulopathy by only Thromboelastography (TEG). To find out whether there is any stastistical significance in the observed apparently better result by TEG, McNemar Test was carried out and P value was <0.0001. Conclusion Thromboelastography could be a better technique as compared to conventional measurements of PT, aPTT, TT, Fibrinogen, D-dimer in early detection of coagulopathy in trauma patients. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jianguo Zhang ◽  
Xing Huang ◽  
Daoyin Ding ◽  
Zhimin Tao

Abstract Background One year into the coronavirus diseases 2019 (COVID-19) pandemic we analyzed the blood coagulopathy in severe and non-severe COVID-19 patients and linked to those of influenza patients for a comparative study. Methods We reported 461 COVID-19 patients and 409 seasonal influenza patients admitted at separated medical centers. With their demographic data and medical history, hematological profiles with coagulation characters were emphasized, and compared between two cohorts before and after treatment. Results For 870 patients included in this study, their median age was (64.0, 51.0–76.0), and among them 511 (58.7%) were male. Hypertension, diabetes, cardiovascular diseases, and bronchitis constituted the leading comorbidities. Upon hospital admission blood test results differentiated COVID-19 patients from influenza cases, and for COVID-19 patients, leukocytosis, neutrophilia, lymphocytopenia, and thrombocytopenia were associated with disease severity and mortality. In addition, COVID-19 cohort demonstrated a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), increased INR, shortened thrombin time and decreased fibrinogen, compared to those in influenza cohort, leaving D-dimer levels indistinguishably high between both cohorts. Platelet hyperreactivity in COVID-19 is more evident, associated with worse hyper-inflammatory response and more refractory coagulopathy. For severe COVID-19 patients administered with anticoagulants, bleeding incidence was substantially higher than others with no anticoagulant medications. Conclusions Comparison of coagulation characteristics between COVID-19 and influenza infections provides an insightful view on SARS-CoV-2 pathogenesis and its coagulopathic mechanism, proposing for therapeutic improvement.


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