• Proceedings of the PSK Conference
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• 2003.04a
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• pp.216.2-216.2
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• 2003

We previously reported that acharan sulfate from the African giant snail Achatina futica showed the anticoagulant activity in vitro, but it was much less than that of heparin. In present study, the anticoagulant activity of acharan sulfate was investigated in vivo. Intravenous administration of acharan sulfate prolonged the clotting time (APTT) in mice and rats in a dose-dependent manner. (omitted)

• Archives of Pharmacal Research
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• v.24 no.2
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• pp.109-113
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• 2001

Curdlan is a natural $\beta$-1,3-glucan produced by Agrobacterium biovar 1. In this study, the anticoagulant activity of sulfoalkyl derivatives of curdlan was investigated by carrying out activated partial thromboplastin time (APTT) assay and compared with that of o-sulfonated curdlan. Approximately 100-fold higher concentration of o-sulfonated curdlan than heparin was required to obtain the same level of the clotting time. Anticoagulant activity of curdlan derivatives was dependent on the degree of sulfation in prolonging the clotting time. However, the chain length of the substituent did not play a role in prolonging the clotting time. The curdlan derivatives enhanced thrombin inhibition by mediating through antithrombin III. The inhibition of thrombin by o-sulfonated curdlan was found to be approximately 10-fold weaker than that by heparin.

• Archives of Pharmacal Research
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• v.26 no.6
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• pp.441-445
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• 2003

New sulfonated amino ribofuranans were synthesized to elucidate the relationship between structure and specific biological activities such as anti-HIV and blood anticoagulant activities. The synthesis was performed by sulfonation of copolymers having various proportion of (1$\rightarrow5)-\alpha$-D-ribofuranosidic unit. The sulfonation with piperidine N-sulfonic acid produced the sulfonated amino ribofuranans in high yield. The anti-HIV activity of sulfonated 3-amino-3-deoxy-(1$\rightarrow5)-\alpha$-D-ribofuranan showed more potent by increasing the degree of sulfonation and the average molecular weights. This activity was almost equal to the activities of sulfonated ribofuranans and ribopyranans reported before in spite of low molecular weight. The blood anticoagulant activities was observed at 36-48 mg/units, more potent than standard dextran sulfonate, 22.7 mg/units. In addition, the blood anticoagulant activities of sulfamide-copolysaccharide consisting various proportion of (1$\rightarrow5)-\alpha$-D-ribofuranan units were potentiated by increasing sulfonated amino-ribofuranan units from 13 to 21 mg/units.

• Food Science and Biotechnology
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• v.17 no.4
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• pp.870-872
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• 2008

Barley $\beta$-glucan was subjected to chemical modification and the anticoagulant activity of the derivative was investigated. The barley $\beta$-glucan was successfully sulfated, showing the degree of substitution calculated by elemental analysis of 0.40. In addition, the Fourier transform infrared (FT-IR) spectra of the derivative confirmed the sulfation, which generated two new absorption bands at 1,250/cm (S=O) and 810/cm (C-O-S) compared to the native. Specially, the anticoagulant activity of barley $\beta$-glucan was created by sulfation, which increased in a concentration-dependent manner. This result demonstrated that the incorporation of sulfate groups into the $\beta$-glucan structure added a blood clotting prevention effect.

• Journal of Korean Neurosurgical Society
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• v.55 no.2
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• pp.69-72
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• 2014

Objective : There was no abundance of data on the use of anticoagulant in patients with previous high risk of thromboembolic conditions under a newly developed intracranial hemorrhage in Korean society. The purpose of this study was to evaluate the safety of discontinuance and suggest the proper time period for discontinuance of anticoagulant among these patients. Methods : We reviewed the medical records of 19 patients who took anticoagulant because of thromboembolic problems and were admitted to our department with newly developed anticoagulation associated intracranial hemorrhage (AAICH), and stopped taking medicine due to concern of rebleeding from January 2008 to December 2012. Analysis of the incidence of thromboembolic complications and proper withdrawal time of anticoagulant was performed using the Kaplan-Meier method. Results : Our patients showed high risk for thromboembolic complication. The $CHA_2DS_2$-VASc score ranged from two to five. Thromboembolic complication occurred in eight (42.1%) out of 19 patients without restarting anticoagulant since the initial hemorrhage. Among them, three patients (37.5%) died from direct thromboembolic complications. Mean time to outbreak of thromboembolic complication was $21.38{\pm}14.89$ days (range, 8-56 days). The probability of thromboembolic complications at 7, 14, and 30 days since cessation of anticoagulation was 0.00, 10.53, and 38.49%, respectively. Conclusion : Short term discontinuance of anticoagulant within seven days in patients with AAICH who are at high embolic risk ($CHA_2DS_2$-VASc score >2) appears to be relatively safe in Korean people. However, prolonged cessation (more than seven days) may result in increased incidence of catastrophic thromboembolic complications.

• Journal of Chest Surgery
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• v.54 no.1
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• pp.25-30
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• 2021

Background: Life-long anticoagulant therapy is mandatory for patients who undergo heart valve replacement with implantation of a mechanical prosthesis. The aim of this study was to investigate the effects of a nurse-led patient educational program concerning oral anticoagulant therapy intake after heart valve replacement surgery on patients' knowledge of important parameters of anticoagulant administration. Methods: In this single-center study, 200 patients who underwent surgical implantation of a mechanical prosthesis were divided into 2 groups. The control group received the basic education concerning oral anticoagulants, while the intervention group received a personalized educational program. Results: Personalized education was correlated with a better regulation of therapeutic international normalized ratio (INR) levels and adequate knowledge among patients. Therapeutic levels of INR were achieved in 45% of the patients during the first month, 71% in the third month, and 89% in the sixth month after discharge in the intervention group, compared to 25%, 47%, and 76% in the control group, respectively. Patients' satisfaction with the information was higher in the intervention group than in the control group. The percentage of satisfaction reached 80% for the intervention group versus 37% for the patients of the control group. Conclusion: The implementation of the nurse-led educational programs was associated with improved clinical results and increased adherence to oral anticoagulant treatment.

• BMB Reports
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• v.28 no.2
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• pp.138-142
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• 1995

An anticoagulant/fibrinolytic protease was purified to homogeneity from the earthworm Lumbricus rubellus. The protein was a single chain glycoprotein of 32 kDa that exhibited strong proteolytic activity on human thrombin and fibrin clots. Proteolytic degradation of these plasma proteins by the purified enzyme occurred at a neutral pH range. Among several human plasma proteins tested as possible substrates for the protease reaction, the 32 kDa enzyme specifically hydrolyzed both thrombin and fibrin polymers without affecting other proteins, such as serum albumin, immunoglobulin, and hemoglobin. Treatment of the purified enzyme at neutral pH with either phenylmethylsulfonylfluoride or soybean trypsin inhibitor resulted in a loss of catalytic activity. The enzyme hydrolyzed the chromogenic substrate H-D-Phe-L-Pipecolyl-L-Arg-p-nitroanilide with a $K_m$ value of 1.1 ${\mu}M$ at a neutral pH. These results suggest that the anticoagulant/fibrinolytic enzyme from Lumbricus rubellus is a member of the serine protease family having a trypsin-like active site, and one of the potential clevage sites for the enzyme is the carbonyl side of arginine residues in polypeptide chains.

• Archives of Pharmacal Research
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• v.28 no.6
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• pp.667-674
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• 2005

The leaves of Persimmon (Diospyros kaki L.) has long been used for tea in Korea since it was thought to be effective against hypertension. An anticoagulant fraction was purified through gel filtration G-100, hydrophobic, gel filtration G-150, and FPLC, Phenyl superpose column chromatographies. The purified fraction was homogenous and its Mr was estimated 10,000 Da by gel filtration and SDS-PAGE. The purified fraction was sensitive to treatment of subtilisin B, but not to heat and its activity was not changed after periodate oxidation, indicating that the activity was not due to carbohydrates. It delayed thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) using human plasma. TT was more sensitive than APTT and PT, suggesting that the anticoagulant activity may be caused by a degradation or a defect of fibrin or thrombin. It did not cause the hydrolysis of fibrin after incubation. However, it inhibited thrombin-catalyzed fibrin formation with a competitive inhibition pattern. These results indicate that it may be an antithrombotic agent and that it is bound to fibrinogen binding sites of thrombin.

• BMB Reports
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• v.46 no.10
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• pp.484-489
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• 2013

Piperlonguminine (PL), an important component of Piper longum fruits, is known to exhibit anti-hyperlipidemic, antiplatelet and anti-melanogenic activities. Here, the anticoagulant activities of PL were examined by monitoring activated-partial-thromboplastin-time (aPTT), prothrombin-time (PT), and the activities of thrombin and activated factor X (FXa). The effects of PL on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) activated HUVECs. The results showed that PL prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. PL inhibited the generation of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, PL prolonged in vivo bleeding time and inhibited TNF-${\alpha}$ induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by PL. Collectively, our results suggest that PL possesses antithrombotic activities and that the current study could provide bases for the development of new anticoagulant agents.

• Archives of Pharmacal Research
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• v.28 no.9
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• pp.1037-1041
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• 2005

Geranium (Pelargonium inquinans Ait) leaves were extracted with $80\%$ MeOH, and partitioned into n-hexane, ethyl acetate, BuOH and $H_2O$ to isolate the anticoagulant principles. The EtOAc fraction was found to be the most active, and was further purified using silica and octadecylisilane column chromatography employing a bioassay-guided fractionation method. The active compound was isolated and identified as $1,2,3,4,6-pentagalloyl-\beta-D-glucopyranose$(PGG) (compound I). The isolated anticoagulant significantly prolonged the activated partial thrombin time (APTT) and thrombin time (TT) using normal human plasma. One microgram of $1,2,3,4,6-pentagalloyl-\beta-D-glucopyranose$ showed 0.063 heparin units in the APTT and 2.73 heparin units in the TT for anti-thrombosis. This is the first report of the isolation of PGG from geranium plants.