Identification and inhibitory activity against α-thrombin of a novel anticoagulant peptide derived from oyster (Crassostrea gigas) protein

2018 ◽  
Vol 9 (12) ◽  
pp. 6391-6400 ◽  
Author(s):  
Shuzhen Cheng ◽  
Maolin Tu ◽  
Hui Chen ◽  
Zhe Xu ◽  
Ziye Wang ◽  
...  
Keyword(s):  
Crassostrea Gigas ◽  
Inhibitory Activity ◽  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Pepsin Hydrolysate

A newly discovered anticoagulant peptide was isolated, purified and identified from the pepsin hydrolysate of oyster (Crassostrea gigas) which could potently prolong the activated partial thromboplastin time and the thrombin time.

EFFECTS OF NICKEL CHLORIDE ON INDICES OF HEMOCOAGULATION AND LIPID PEROXIDATION IN RATS

2019 ◽  
pp. 83-90
Author(s):  
Э.М. Гаглоева ◽  
В.Б. Брин ◽  
С.В. Скупневский ◽  
Н.В. Боциева ◽  
Т.В. Молдован
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Nickel Chloride ◽  
Activated Partial Thromboplastin Time ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Hemostasis System

Цель исследования - изучить состояние системы гемостаза при хронической интоксикации хлоридом никеля, исследовать взаимосвязь показателей гемокоагуляции с процессами липопероксидации у крыс в эксперименте. Методика. Опыты проводили на крысах-самцах Вистар (n=50, 230-250 г). Раствор NiCl2 (5 мг/кг) вводили внутрижелудочно ежедневно в течение 2 нед, 1 и 2 мес. По завершении эксперимента исследовали состояние тромбоцитарного и коагуляционного звеньев гемостаза, антикоагулянтную и фибринолитическую активность крови, а также определяли активность процессов перекисного окисления липидов и антиоксидантных ферментов. Результаты. Установлено, что через 2 нед и 1 мес интоксикации у крыс отмечались гиперкоагуляционные изменения показателей свертывающей системы крови: повышение агрегационной активности тромбоцитов, увеличение концентрации фибриногена, снижение активированного частичного тромбопластинового времени (АЧТВ) и протромбинового времени. В этот период регистрировалось увеличение антитромбиновой и фибринолитической активности крови. Через 2 мес наблюдалось подавление активности клеточного звена гемостаза - тромбоцитопения, ослабление степени АДФ-индуцируемой агрегации тромбоцитов. Выявлялась тенденция к уменьшению концентрации фибриногена. На фоне снижения АЧТВ и тромбинового времени отмечалось увеличение протромбинового времени. В то же время регистрировалось угнетение противосвертывающего звена системы гемостаза (снижалась активность антитромбина III), наблюдалось истощение резервных возможностей фибринолитического звена (замедление фXIIа-зависимого эуглобулинового лизиса) и увеличение содержания растворимых фибрин мономерных комплексов, что свидетельствует о наличии тромбинемии. Через 2 нед, один и два месяца интоксикации у животных выявлялись корреляционные связи между основными показателями системы гемостаза и активностью процессов перекисного окисления липидов и антиоксидантных ферментов. Заключение. Полученные данные подтверждают наличие взаимосвязи активности процессов липопероксидации и системы гемостаза, в том числе при хронической никелевой интоксикации. Результаты исследования позволяют рекомендовать применение антиоксидантов для разработки способов коррекции гемостатических сдвигов при воздействии на организм тяжелых металлов. The aim. To study the state of the hemostasis system in chronic nickel intoxication and to investigate the relationship between hemocoagulation indices and lipoperoxidation processes in rats. Methods. Experiments were carried out on male Wistar rats (n=50, 230-250 g). A solution of nickel chloride (5 mg/kg) was administered daily intragastrically for two weeks, one and two months. At the end of the experiments, indices of platelet and coagulation hemostasis systems, anticoagulant and fibrinolytic activity of blood plasma, and activities of lipid peroxidation and antioxidant enzymes were studied. Results. Hypercoagulative changes in indices of the coagulation system were observed in rats after two weeks and one month of intoxication, including increased platelet aggregation and fibrinogen concentration and shortened activated partial thromboplastin time and prothrombin time. During the same period, increased antithrombin and fibrinolytic activities were observed. The depressed activity of the cellular component of hemostasis evident as thrombocytopenia and impaired ADP-induced platelet aggregation was detected after two months of intoxication. A tendency to decrease in fibrinogen concentration was observed. The shortened activated partial thromboplastin time and thrombin time were associated with prolonged prothrombin time. At the same time, inhibition of the anticoagulant component of hemostasis (decreased antithrombin III activity), exhaustion of the fibrinolysis system reserve (delayed fXIIa-dependent euglobulin lysis), and a significant increase in soluble fibrin monomeric complexes indicative of thrombinemia were observed. After two weeks, one and two months of nickel intoxication, a correlation was found between the major indices of the hemostasis system and the activities of lipid peroxidation and antioxidant enzymes. Conclusion. The study confirmed a relationship between the lipid peroxidation activity and the hemostasis system, specifically in chronic nickel intoxication. This result allows to recommend the use of antioxidants in developing methods for correction of hemostatic induced affected by heavy metals.

Antihemostatic Effect of Hsien-Ho-T'sao (Agrimonia pilosa)

1984 ◽  
Vol 12 (01n04) ◽  
pp. 116-123 ◽  
Author(s):  
Jih-Pyang Wang ◽  
Mei-Feng Hsu ◽  
Che-Ming Teng
Keyword(s):  
Prothrombin Time ◽  
Blood Coagulation ◽  
Partial Thromboplastin Time ◽  
Bleeding Time ◽  
Fibrinogen Level ◽  
Platelet Rich Plasma ◽  
Water Extract ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time

Bleeding time in rats was markedly prolonged after the adminstration of the water extract of Hsien-Ho-T'sao. This antihemostatic effect was more marked in the group of i.p. injection of the drug than in the group of p.o. administration for 2 to 7 consecutive days. Blood coagulation studies showed that plasma prothrombin time, activated partial thromboplastin time and stypven time were prolonged, while thrombin time adnd fibrinogen level were not changed. The thromboelastographic recording showed that reation time was prolonged and maximal elasticity of clot was decreased. In addition, ADP- and collagen- induced aggregations of platelet-rich plasma was suppressed. In conclusion, the prolongation of the bleeding time might be due to both anticoagulant and antiplatelet action of the drug.

scholarly journals ASSESSMENT OF COAGULATION PROFILE IN PATIENTS WITH LIVER CIRRHOSIS AND ATRIAL FIBRILLATION

2021 ◽  
Vol 121 (1) ◽  
pp. 22-31
Author(s):  
Alіna Baylo ◽  
Vadym Shypulіn ◽  
Volodymyr Chernyavskyi ◽  
Luiza Parunyan
Keyword(s):  
Atrial Fibrillation ◽  
Liver Cirrhosis ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
International Normalized Ratio ◽  
Activated Partial Thromboplastin Time ◽  
Fibrinolytic System ◽  
Thrombin Time ◽  
Group I ◽  
D Dimer

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.

Responsiveness of the activated partial thromboplastin time and dilute thrombin time to argatroban: Results of an in vitro study

2020 ◽  
Vol 42 (3) ◽  
Author(s):  
Erica Scalambrino ◽  
Lidia Padovan ◽  
Veena Chantarangkul ◽  
Marigrazia Clerici ◽  
Andrea Artoni ◽  
...  
Keyword(s):  
Partial Thromboplastin Time ◽  
In Vitro Study ◽  
Activated Partial Thromboplastin Time ◽  
Vitro Study ◽  
Thrombin Time

Impact of Apixaban On a Large Panel of Routine or More Specific Coagulation Assays.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2275-2275
Author(s):  
Jonathan Douxfils ◽  
François Mullier ◽  
Christian Chatelain ◽  
Bernard Chatelain ◽  
Dogné Jean-Michel
Keyword(s):  
Atrial Fibrillation ◽  
Drug Concentration ◽  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Activated Partial Thromboplastin Time ◽  
Plasma Drug Concentration ◽  
Thrombin Time ◽  
Plasma Drug ◽  
Clotting Time

Abstract Abstract 2275 Introduction: Apixaban is direct factor-Xa inhibitor that reached the market for the prevention of venous thromboembolism in patients undergoing major orthopaedic surgery. It is also being evaluated in the reduction of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome and in the prevention of stroke in patients with non-valvular atrial fibrillation. Thanks to its predictable pharmacokinetic profile, biological monitoring is not required. Nevertheless, evaluation of plasma drug concentration may be valuable in specific situations such as recurrent thrombosis, bleedings, before urgent surgery, in case of bridging and in case of at least two risk factors among the following ones: drug interactions with caution, moderate renal impairment and moderate hepatic impairment; Monitoring may also be useful in infants, pregnant women or in extreme body weights, although no relevant data on drug levels associated with approximate therapeutic and harmful ranges are currently available. Material and Methods: Apixaban was spiked at increasing concentrations (0, 5, 10, 20, 50, 100, 200 and 500 ng/mL) in pooled citrated normal human platelet poor plasma (PPP) to measure Prothrombin Time (PT) and dilute PT with different thromboplastin, Thrombin Generation Assay (TGA) with different inducers and activity on different anti-Xa chromogenic assays. Activated Partial Thromboplastin Time with different reagents, Thrombin Time (TT), Ecarin Clotting Time (ECT) and Reptilase Time (RT), measurement of fibrinogen (Clauss method and PT-derived method) and antithrombin (anti-IIa and anti-Xa based chromogenic assays) were also tested. We also evaluated the impact of apixaban on assays used for the determination of lupus anticoagulant such as the DRVV-T.. (Screen and Confirm) as well as the PTT-LA.. and the Staclot-LA.. . Results and Discussion: As mentioned in previous studies, PT showed a weak sensitivity towards apixaban in comparison with the plasma range obtained in short pharmacokinetic studies. Indeed, the concentration needed to double the clotting time was 154 ng/mL with the most sensitive reagent while the mean Cmax obtained in a short PK study after one oral intake of 5 mg apixaban (dose given in atrial fibrillation) was 96 ng/mL. Therefore, the sensitivity of PT is not strong enough to allow accurate quantitative measurement of the plasma drug concentration (Table 1). Activated Partial Thromboplastin Time presented a better sensitivity but showed a plateau after 100 ng/mL reflecting the uselessness of this test for the quantification of apixaban. Thrombin Time, ECT and RT were logically not affected while DRVV-T.. showed a sensitivity of 205 ng/mL (Screen), which is once again not enough sensitive. On the opposite, chromogenic anti-Xa assays seemed to be very sensitive (Figure 2 and Table 1). Nevertheless, the relation was not always linear and some methodologies needed to be adapted to ensure a broader range of application. TGA (Figure 1) may be useful to assess the pharmacodynamics effects of apixaban on the coagulation process. Nevertheless, the turn around time and the lack of standardisation are currently limitations that restrict the use of this method. In the case of the exploration of an haemorrhagic event, specific tests such as RT, fibrinogen (Clauss and PT-derived method (dFib)), TT and clotting factor activity may be used. Apixaban did not interfere with these tests. Antithrombin determination if also of importance and chromogenic anti-IIa based assays should be used in face of patients treated with apixaban to avoid misdiagnosis since an overvaluation of 12% by 100 ng/mL was shown using one chromogenic anti-Xa based assay. Conclusion: PT may not be used as screening test to assess the risk of bleedings. A more specific and sensitive assay such as chromogenic anti-Xa assays using calibrators should be used to correctly assess the concentration of apixaban. Determination of lupus anticoagulant using DRVV-T.. and PTT-LA.. or Staclot LA.. as well as the determination of antithrombin using factor-Xa based chromogenic assays, were influenced by apixaban. Finally, standardization of the time between the last intake of apixaban and the sampling is mandatory. Figures: Disclosures: No relevant conflicts of interest to declare.

scholarly journals Anti-thrombotic effect of Zingiber officinale (ginger) in sprague dawley rats

2019 ◽  
Vol 7 (9) ◽  
pp. 3239
Author(s):  
Kipyegon Shadrack ◽  
Alkizim Faraj ◽  
Muriithi K. Alex ◽  
Ngure Kenneth
Keyword(s):  
Platelet Count ◽  
Partial Thromboplastin Time ◽  
Bleeding Time ◽  
Methanolic Extract ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Thrombotic Diseases

Background: The prevalence of thrombotic diseases is rising globally. Presently, stroke and ischemic heart disease account for 25% of all deaths. Use of anti-thrombotic drugs have proven effective in prevention of these ailments but might not be affordable especially in developing countries. They are also associated with undesirable side effects. This study sought to determine the anti-thrombotic effect of ginger since it is affordable, accessible and is widely used as a food enhancer and a medicinal herb.Methods: The current study employed an in-vivo experimental study design. Three groups Sprague dawley rats (N=5) were given different doses of methanolic extract of ginger for 30 days. Two other groups (N=5) which served as controls received 5% dimethyl sulfoxide and aspirin for the same duration. Measurement of bleeding time, platelet count, prothrombin time, activated partial thromboplastin time and thrombin time was done to assess the anti-thrombotic property.Results: There was a statistically significant difference in bleeding time (P=0.03) across the groups investigated. There was however no significant difference across the groups in platelet count, prothrombin time, activated partial thromboplastin time and thrombin time (P=˃0.05).Conclusion: This study demonstrates that methanolic extract of ginger possesses an anti-thrombotic property probably through inhibition of platelet function. Regular consumption of ginger may therefore confer protection against thrombotic diseases.

Effect of Fondaparinux on Coagulation Assays: Results of College of American Pathologists Proficiency Testing

2006 ◽  
Vol 130 (11) ◽  
pp. 1605-1611 ◽  
Author(s):  
Agata Smogorzewska ◽  
John T. Brandt ◽  
Wayne L. Chandler ◽  
Mark T. Cunningham ◽  
Timothy E. Hayes ◽  
...  
Keyword(s):  
Factor Viii ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Cost Effective ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Standard Curve ◽  
Relevant Effect ◽  
Clinically Significant

Abstract Context.—Fondaparinux, a factor Xa inhibitor, is approved for thromboprophylaxis after orthopedic surgery and for treatment of venous thromboembolism. It may also be efficacious, safe, and cost-effective for other patients; thus, more widespread use of fondaparinux is likely. The effect of fondaparinux on coagulation testing needs to be thoroughly examined. Objective.—To report the effects of fondaparinux on coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, factor VIII, thrombin time, anti–factor Xa) across diverse methodologies. Design.—Samples with different concentrations of fondaparinux (0, 0.4, 0.8, and 2.0 μg/mL) were sent to laboratories participating in the College of American Pathologists Comprehensive Coagulation proficiency survey (N = 898). Laboratory-specific methods were used to assay coagulation parameters. Results.—Prophylactic or therapeutic fondaparinux prolonged the prothrombin time by approximately 1 second and the activated partial thromboplastin time by 4 to 5 seconds, and reduced factor VIII from 119% to 107% and 102%, respectively. Supratherapeutic fondaparinux reduced factor VIII to 85%. The activated partial thromboplastin time was prolonged in 19%, 29%, and 52% of laboratories with prophylactic, therapeutic, and supratherapeutic fondaparinux levels, respectively. Fibrinogen, antithrombin, and thrombin time assays did not show clinically significant changes. When measuring fondaparinux concentration using an anti–factor Xa assay, the most accurate results were obtained when fondaparinux was used as the calibrator. Conclusions.—Fondaparinux, even in prophylactic doses, slightly prolongs the prothrombin time and activated partial thromboplastin time and can interfere with factor VIII assays, but it has no clinically relevant effect on fibrinogen, antithrombin, or thrombin time. A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti–factor Xa assay.

Thromboelastography - Viscoelastic Haemostatic Assay (VHA) Versus Routine Plasma Based Coagulation Parameters in Trauma Patients to Detect Coagulopathy within 24 Hrs After Injury

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5248-5248
Author(s):  
Bhaumik Arvindkumar Shah ◽  
Arulselvi Subramanium ◽  
Subhadra Sharma ◽  
Deepak Agrawal ◽  
Gaurav Chhabra ◽  
...  
Keyword(s):  
Head Injury ◽  
Prothrombin Time ◽  
Whole Blood ◽  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Trauma Patients ◽  
Thrombin Time ◽  
Coagulation Parameters ◽  
Conventional Methods ◽  
D Dimer

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.

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