• Journal of Gastric Cancer
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• v.22 no.1
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• pp.47-55
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• 2022

Purpose: The use of direct oral Xa inhibitors (DXaIs) to prevent venothrombotic events is increasing. However, gastrointestinal bleeding, including that related to endoscopic resection, is a concern. In this study, we evaluated bleeding and coagulation times during the perioperative period of gastric endoscopic submucosal dissection (ESD). Materials and Methods: Patients who consecutively underwent gastric ESD from August 2016 to December 2018 were analyzed. Bleeding rates were compared among the 3 groups (antiplatelet, DXaIs, and control). DXaI administration was discontinued on the day of the procedure. Prothrombin time (PT), activated partial thromboplastin time, and the ratio of inhibited thrombin generation (RITG), which was based on dilute PT, were determined before and after ESD. Results: During the study period, 265 gastric ESDs were performed in 239 patients, where 23 and 50 patients received DXaIs and antiplatelets, respectively. Delayed bleeding occurred in 17 patients (7.4%) and 21 lesions (7.1%). The bleeding rate in the DXaI group was significantly higher than that in the other groups (30.4%, P<0.01), and the adjusted odds ratio of bleeding was 5.7 (95% confidence interval, 1.4-23.7; P=0.016). In patients using DXaIs, there was a significant (P=0.046) difference in the median RITG between bleeding cases (18.6%) and non-bleeding cases (3.8%). Conclusions: A one-day cessation of DXaIs was related to a high incidence of bleeding after gastric ESD, and monitoring of residual coagulation activity at trough levels might enable the predicted risk of delayed bleeding in patients using DXaIs.

• Natural Product Sciences
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• v.29 no.1
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• pp.42-49
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• 2023

This study investigated the effect of ethanol extracts of horsetail, alfalfa, ortie, chêne and aleppo oak on blood coagulation in vitro. Extraction was performed by the maceration method. Extracts were mixed with platelet and plasma, then prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet aggregation tests were conducted. Alfalfa extract had a dose-dependent effect on the PT. Ortie, and horsetail, reduced the PT significantly compared to control group. Alfalfa, horsetail, and ortie reduced the APTT, but their effect was insignificant compared to the control group. The pooled extract showed the highest effect compared to the single extracts in a dose-dependent manner. Horsetail and alfalfa induced platelet aggregation in response to arachidonic acid but not in response to collagen. In the case of ortie, no aggregation occurred regarding the arachidonic acid, and incomplete was observed in response to collagen. Interestingly, blood clotting occurred immediately after adding the chêne, aleppo oak and the pooled extract, and therefore platelet poor plasma (PPP) and platelet rich plasma (PRP) became jelly. Generally, chêne and aleppo oak, as well as pooled extract, were more effective in inducing both primary and secondary coagulation pathways via shortening the PT and APTT, and induction of platelet aggregation.

• Journal of Trauma and Injury
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• v.36 no.3
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• pp.210-216
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• 2023

Purpose: This preliminary retrospective cohort study analyzed the relationship between the parameters provided by sonorheometry device Quantra and the coagulation values obtained from standard venous blood samples in patients admitted in intensive care unit (ICU). Methods: We reviewed medical charts of 13 ICU adult patients in whom at least one coagulation study with Quantra was performed. The relationship between Quantra and laboratory data was analyzed with the Spearman rank correlation coefficient (rho). The 95% confidence interval (CI) was computed. A P-value <0.05 was considered statistically significant. Results: We collected 28 data pairs. Statistically significant moderate correlations were found for the following parameters: clot time (CT) and activated partial thromboplastin time (rho=0.516; 95% CI, 0.123-0.904; P=0.009; clot stiffness (CS) and the international normalized ratio (INR; rho=0.418; 95% CI, 0.042-0.787; P=0.039); INR and platelet contribution to CS (rho=0.459; 95% CI, 0.077-0.836; P=0.022); platelet count and platelet contribution to CS (PCS; rho=0.498; 95% CI, 0.166-0.825; P=0.008); and fibrinogen and fibrinogen contribution to CS (FCS; rho=0.620; 95% CI, 0.081-0.881; P=0.001). Conclusions: Quantra can provide useful information regarding coagulation status, showing modest correlations with the parameters obtained from laboratory tests. During diffuse bleeding, CT and FCS values can guide the proper administration of clotting factors and fibrinogens. However, the correlation of INR with CS and PCS can cause misinterpretation. Further studies are needed to clarify the relationship between Quantra parameters and laboratory tests in the critical care setting and the role of sonorheometry in guiding targeted therapies and improving outcomes.

• Journal of Life Science
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• v.19 no.2
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• pp.289-298
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• 2009

Effects of Nattokinase fibrinol (NKF), defined as a fibrinolytic product, on fibrinolytic and atherogenetic markers were studied for healthy adults (20-31 years old), who is smoking more than 20 cigarettes per day. Subjects were divided into 29 for NKF group and 10 for placebo group in a short term study. They were given 2 tablets of NKF (4,000 unit) or placebo tablet and thereafter blood samples were collected at 0, 2, 4 hr prerid. For a 4-week long term study, 15 subjects for NFK group and 10 subjects for placebo group were supplemented one tablet of each NKF (2,000 unit) and placebo per day, respectively. Blood samples were collected at 0, 1, 2, 4 weeks later. The short-term experimental trial showed that NKF remarkably increased fibrinolytic activity at 2hr after consumption, which was maintained up to 4 hr, relative to that of placebo, while NKF reduced the euglobulin clot lysis time (ECLT) and retarded the activated partial thromboplastin time (aPTT), as compared to placebo group. NKF supplementation for 4 weeks elevated fibrinolytic activity, shortened ECLT and retarded aPTT. Furthermore, NKF supplementation increased anti-atherogenic index by decreasing triglyceride (TG) and elevating high-density lipiprotein (HDL)-cholesterol. These results indicate that NKF supplementation for short term or long term might have beneficial effects on preventing and treating cardiovascular disease by increasing fibrinolytic activity and improving atherogenic markers such as hyperlipidemia.

• Microbiology and Biotechnology Letters
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• v.44 no.4
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• pp.452-460
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• 2016

This study was designed to develop a functional pharma-food using Salicornia europaea (SE). Tiny seeds from the mature SE were collected, and their biological activities were evaluated. The extraction yield of the seed in hot water was found to be 29.6% and the hot water extract (HWE) contained 25.7 mg/g total polyphenol (TP) and 11.5 mg/g total flavonoid (TF), which are similar to those contained in leaf and stem of SE. Among the subsequent organic solvent fractions, the ethylacetate (EA) fraction exhibited the highest content of TP (158.3 mg/g), TF (136.2 mg/g), and total sugar (228.3 mg/g). The EA fraction exhibited broad-range antibacterial activities against gram-positive bacteria, and the butanol fraction exhibited growth inhibitory effect against only Staphylococcus epidermidis. An antioxidation activity assay of the HWE and its fractions showed the EA fraction to have the highest radical scavenging activity with $RC_{50}$ values of 57.0, 29.0, and $28.9{\mu}g/ml$ against DPPH anion, ABTS cation, and nitrite, respectively. The $RC_{50}$ values of vitamin C against DPPH anion, ABTS cation, and nitrite were 10.7, 4.0, and $18.0{\mu}g/ml$, respectively, indicating that the EA fraction of SE has potent antioxidant compounds. In an anticoagulation assay, the EA fraction exhibited a 15-fold extended thrombin time at 5 mg/ml and activated partial thromboplastin time at 7 mg/ml, which are comparable to the activities of aspirin. The HWE and its fractions had no hemolysis activities against human RBCs at up to 1 mg/ml. These results suggest that the EA fraction from SE has a great potential as a new antibacterial and anticoagulation agent.

• The Korean Journal of Food And Nutrition
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• v.24 no.3
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• pp.442-450
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• 2011

Numerous studies have suggested that dietary flavonoids contribute to prevent cardiovascular disease. Onion contains many functional phytochemicals such as quercetin. The aim of this study was to examine whether onion peel extracts supplementation affect blood lipid profiles and blood coagulation in animal model. Total 48 Sprague-Dawley male rats at 5 weeks old were divided into 6 groups with different diets(C: control, HF: high fat diet, HFOE 0.01%: high fat+onion peel extract 0.01% diet, HFOE 0.02%, HFOE 0.05%, HFOE 0.1%) for 8 weeks. Onion peel extract supplementation significantly decreased serum levels of LDL-cholesterol and increased HDL-cholesterol, while total cholesterol and triglyceride levels were not affected. Hematological parameters(hematocrit, white blood cell, red blood cell, and platelet count) and blood coagulation parameters(prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen) were not significantly different among 6 groups. However, activated partial thromboplastin time of HFOE 0.05% group was significantly longer than that of HF group. These results indicate that onion peel extract supplementation displays hypocholestrolemic effects but does not seem to have anti-coagulation effects in high fat fed SD rats.

• Journal of Chest Surgery
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• v.51 no.2
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• pp.114-121
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• 2018

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin $(IL)-1{\beta}$ levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.4
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• pp.133-137
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• 2011

The monitoring of heparin therapy is using almost aPTT assay. This study is compare to estimating aPTT therapeutic range using in vitro heparin-spiked sample and aPTT therapeutic range using in vivo heparin-treated sample. Normal pooled plasma was collected from 20 healthy representative individuals. 11 concentration of heparinized plasmas from 0 U/mL to 1.0 U/mL at intervals of 0.1 U/mL made by addition of heparin to normal pooled plasma were measured aPTT. The aPTT therapeutic range was performed through correlation analysis between heparin level 0.2 to 0.4 U/mL and aPTT. 30 plasmas from patients on heparin therapy were measured aPTT and anti-Xa activity. The aPTT therapeutic range was performed through correlation analysis between anti-Xa activity 0.3 to 0.7 U/mL and aPTT. The aPTT therapeutic range corresponded by heparin level-vs-aPTT value regression analysis was 60.7 to 102.4 seconds. The aPTT therapeutic range corresponded by anti-Xa activity-vs-aPTT value regression analysis was 85.3 to 147.5 seconds. The validation of heparin sensitivity using in-vitro heparin sample was not considered. The establishing aPTT therapeutic range is recommended anti-Xa activity using in-vivo sample.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.460-466
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• 2006

We wondered whether the mechanisms of antiplatelet aggregation of DJS-WE were through multiple pathways. Danggijakyak-san(DJS) consisting of 6 herbes of Paeoniae Radix, Poria Cocos, Angelicae Sinensis Radix, Cnidii Rhizoma, Atractylodis Macrocephalae Rhizoma and Alismatis Rhizoma, is a crude mixture of a commonly used Korean herbal medicine. The water extract (DJS-WE) of DJS has been known to have an anti-platelet aggregation activity. We have reported that DJS-WE inhibited ADP-induced aggregation as well as arachidonic acid-induced aggregation of human platelet. Clinical studies on the cardiovascular effects of DJS-WE have been done in Korea. The DJS has been used as a remedy for gastrointestinal disorders (abdominal pain, dysentery), headache, amenorrhea, and postpartum hemorrhage. It has also been claimed to have a remarkable central stimulant effect, a transient hypertensive effect, and positive inotropic and chronotropic effects. In this paper, we evaluated the possible mechanisms of the antiplatelet activity of DJS-WE using human platelets. On the other hand, the role of DJS-ethanol extract on the inhibition of platelet aggregation and hemolytic effect have not yet been investigated in detail. We also used the method of activated partial thromboplastin times (APTT) for the first time to study the inhibition on platelet aggregation activity of DJS-ethanol extract. The effect of DJS-WE on hemolysis was also investigated. DJS-WE showed a high hemolysis ability on human blood.

• Korean Journal of Food Science and Technology
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• v.36 no.6
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• pp.1008-1013
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• 2004

Effects of extraction conditions and molecular fractionation on anticoagulant activities of major brown seaweeds in Korea were investigated. Hot water extracts of C. costata, U. pinnatifida (Sporophyte), L. japonica, K. crassifolia, E. stolonifera, E. bicyclis, S. horneri, and E. kurome increaced activated partial thromboplastin time (APTT) over 190 seconds, which may be related to intrinsic pathway of blood coagulation. Hot water extract of E. Kurome (EKJ) was further fractionated by ethanol precipitation. EKJ-eim, ethanol-insoluble material of EKJ, showed higher anticoagulant activity than EKJ. EKJ-eim was further fractioned with ultrafiltration. EKJ-eim 1, (over 100 kDa) fraction showed higher APTT activity than EKJ-eim. A EKJ-eim 1 was sulfated polysaccharide consisting of fucose, xylose, mannose, galactose, glucose and, sulfate at molar ratio of 1 : 0.05 : 0.10 : 0.15 : 0.17 : 1.46. The anticoagulant activity increased as sulfate content and molecular weight increased.