• Journal of Yeungnam Medical Science
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• v.37 no.4
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• pp.321-328
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• 2020

Background: This study aimed to investigate the incidences of and risk factors for perioperative events following anticoagulant discontinuation in patients with non-valvular atrial fibrillation (NVAF) undergoing non-cardiac surgery. Methods: A total of 216 consecutive patients who underwent cardiac consultation for suspending perioperative anticoagulants were enrolled. A perioperative event was defined as a composite of thromboembolism and major bleeding. Results: The mean anticoagulant discontinuation duration was 5.7 (±4.2) days and was significantly longer in the warfarin group (p<0.001). Four perioperative thromboembolic (1.9%; three strokes and one systemic embolization) and three major bleeding events (1.4%) were observed. The high CHA₂DS₂-VASc and HAS-BLED scores and a prolonged preoperative anticoagulant discontinuation duration (4.4±2.1 vs. 2.9±1.8 days; p=0.028) were associated with perioperative events, whereas the anticoagulant type (non-vitamin K antagonist oral anticoagulants or warfarin) was not. The best cut-off levels of the HAS-BLED and CHA₂DS₂-VASc scores were 3.5 and 2.5, respectively, and the preoperative anticoagulant discontinuation duration for predicting perioperative events was 2.5 days. Significant differences in the perioperative event rates were observed among the four risk groups categorized according to the sum of these values: risk 0, 0%; risk 1, 0%; risk 2, 5.9%; and risk 3, 50.0% (p<0.001). Multivariate logistic regression analysis showed that the HAS-BLED score was an independent predictor for perioperative events. Conclusion: Thromboembolic events and major bleeding are not uncommon during perioperative anticoagulant discontinuation in patients with NVAF, and interrupted anticoagulation strategies are needed to minimize these.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.4
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• pp.712-718
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• 2000

The alkali extraction of anticoagulant from a clove revealed 3-to 6-fold more effective than hot-water extraction. The highest anticoagulant activity was found with 0.1 N NaOH at 7$0^{\circ}C$. The anticoagulant fractions from a clove, EC-2B and EC-2C were separated by alkali extraction, ethanol precipitation, cetavlon treatment, and ultrafiltration. The anticoagulant activities of these two fractions were, respectively, 6.57 and 8.63 times higher than those extracted with hot-water. As of the sensory evaluation, boiled pork added with EC-2B fraction revealed similar sensory acceptability to raw clove material, while EC-2C fraction had low sensory acceptability due to a mild chemical odor. Antibacterial characteristics against pathogenic microorganism of both fractions were confirmed in the control strain. The inhibitory effect of growth by EC-2B was noticed above 0.016% in S. aureus. Also, EC-2C showed the inhibitory effect at 0.004% in both E. cole and S. aureus control strains.

• Applied Biological Chemistry
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• v.42 no.2
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• pp.140-146
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• 1999

We have isolated two anticoagulant polysaccharides from an acidic extract of Codium fragile. The purification was conducted using three consecutive chromatographies of DEAE-Toyopearl 650C, Sephadex G-100 (G-75), and Sepharose CL-6B by measuring activated partial thromboplastin time (APTT). The two purified anticoagulant polysaccharides, CF-1-VIa-1 and CF-1-VIIa-1, were found to be nearly homogenous on HPLC using a gel permeation column and appeared to have molecular weights of about 80,000 Da and 40,000 Da, respectively. The polysaccharides consisted mainly of arabinose and galactose in a molar ratio of about 2 : 1, and also comprised 12-13% of sulfates at their constituent sugars. CF-1-VIa-1 and CF-1-VIIa-1 inhibited blood coagulation via both the intrinsic and the extrinsic pathways. The polysaccharides unlike heparin showed an inhibitory activity on thrombin when a pure fibrinogen without antithrombin III was used as a substrate. Structural modifications using sulfation and desulfation affected the anticoagulant activities directly, suggesting that the content of sulfate plays an important role in the blood coagulation cascade. The polysaccharides may inhibit some proteases involved in the blood coagulation cascade, judging from the independence of calcium concentrations in their anticoagulant activity.

• Journal of Chest Surgery
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• v.48 no.6
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• pp.432-434
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• 2015

Anticoagulation therapy is essential after cardiac valve surgery. However, spontaneous bleeding remains a major concern during anticoagulation therapy. Spontaneous gallbladder (GB) hemorrhage (hemobilia) is a rare occurrence during standard anticoagulation therapy. This report presents a case of GB hemorrhage that occurred shortly after initiating oral anticoagulant therapy in a patient who had undergone mitral valve replacement surgery.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.277-281
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• 1995

An anticoagulant, 4-hydroxy-3-[1, 2, 3, 4-tetrahydro-3-[4-(4-trifluoromethylbenzyloxy)phenyll-1 -naphthyl]coumarin (Flocoumafen) was synthesized in 8 steps starting from phenylacetyl shloride and anisole. The key step in the synthesis involves the reaction of 3-(4-methoxyphenyl)-1-teralol with 4-hydroxycoumarin to give 4-hydroxy-3 [1, 2, 3, 4-tetrahydro-3-[4-emthoxyphenyl]-1-naphthyl]coumarin.

• BMB Reports
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• v.40 no.5
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• pp.832-838
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• 2007

A novel inhibitory protein against blood coagulation factor Va (FVa) was purified from muscle protein of granulated ark (Tegillarca granosa, order Arcoida, marine bivalvia) by consecutive FPLC method using anion exchange and gel permeation chromatography. In the results of ESI-QTOF tandem mass analysis and database research, it was revealed that the purified T. granosa anticoagulant protein (TGAP) has 7.7 kDa of molecular mass and its partial sequence, HTHLQRAPHPNALGYHGK, has a high identity (64%) with serine/threonine kinase derived from Rhodopirellula baltica (order Planctomycetales, marine bacteria). TGAP could potently prolong thrombin time (TT), corresponding to inhibition of thrombin (FIIa) formation. Specific factor inhibitory assay showed that TGAP inhibits FVa among the major components of prothrombinase complex. In vitro assay for direct-binding affinity using surface plasmon resonance (SPR) spectrometer indicated that TGAP could be directly bound with FVa. In addition, the binding affinity of FVa to FII was decreased by addition of TGAP in dose-dependant manner ($IC_{50}$ value = 77.9 nM). These results illustrated that TGAP might interact with a heavy chain of FVa ($FVa_H$) bound to FII in prothrombin complex. The present study elucidated that non-cytotoxic T. granosa anticoagulant protein (TGAP) bound to FVa can prolong blood coagulation time by inhibiting conversion of FII to FIIa in blood coagulation cascade. In addition, TGAP did not significantly (P < 0.05) show fibrinolytic activity and cytotoxicity on venous endothelial cell line (ECV 304).

• ALGAE
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• v.22 no.3
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• pp.247-252
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• 2007

Crude fucoidan was extracted from the sporophyll of Korean Undaria pinnatifida collected at a coastal area ofWando, Korea, mainly by dilute acid extraction, ethanol precipitation, CaCU Precipitation, with an yield of approxi-mately 3.9% in mass. It was further purified by DEAE-cellulose column chromatography and its chemical composi-don and in vitro anticoagulant activity was determined. The average molecular mass of the purified fucoidan wasestimated about 2.1 x 103 kDa by size-fractionation HPLC and it consisted of neutral sugar (52.34% in mass), uronicacid (26.2%), and sulfate esters (7.4%). From the HPAEC-PAD analysis, the monosaccharide composition of thepurified fucoidan was shown to be fucose, galactose, xylose, and mannose, with a molar ratio of 1, 0.2, 0.02, 0.15,respectively, demonstrating that major monosacd-iande was fucose (72.3% in mol percentage) and other sugars,xylose (1.5%), galactose (14.6%), and mannose (10.9%) were present as minor component. The results suggested thatthis fucoidan is a sulfated, U-type fucoidan. The activated partial thrombloplastin time (APTT) assay of the purifiedfucoidan showed that the purified fucoidan elicited anticoagulant activity in a dose-dependent manner. Five jUg ofsporophyll fucoidan delayed the blood clotting time up to 5 times than untreated control and also up to 1.5 timesthan the same amount of the commercial fucoidan, respectively. Although it is preliminary, these results suggestthat the fucoidan of Korean Undaria vinnatifida sporophyll would be promising candidates for the development ofan anticoaeulant.

• Journal of Chest Surgery
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• v.33 no.6
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• pp.502-506
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• 2000

Background: Anticoagulant therapy can be required during pregnancy with prosthetic heart valves. Warfarin and heparin provide real protection against thromboembolic phenomena, but they also carry serious risks for the fetus and the mother. In an attempt to identify the best treatment for pregnant women with cardiac valve prostheses who are receiving anticoagulant, we studied 19 pregnancies, the warfarin was discontinued and heparin was administered every 12 hours by subcutaneous injection in doses adjusted to keep the midinterval aPTT in the therapeutic range(at least 2-2.5 control) from the conception to the 12th week of gestation and oral antiocagulant was then administered until the middle of the third trimester in the therapeutic range(at least 2 INR), and heparin therapy was restared until delivery. Also in order to avoid an anticoagulant effect during delivery, it has been our practice to instruct women to either discontinue their heparin injections with the onset of labur or to stop heparin injections 12 hours prior to the elective induction of labour. Result: The outcome of 19 pregnancies managed with above protocol was spontaneous abortion in 3 cases, voluntary termination in 2 cases, premature delivery at 35 weeks in 1 case and delivery at full-term in 14 cases. There was no maternal morbidity and moratality and fetopathy. Conclusion: We conclude that in the second and third trimester of pregnancy, warfarin provide effective protection against thromboembolism, Oral antiocagulant therapy should be avoided in 2 weeks before delivery because of the risk of serious perinatal bleeding caused by the trauma of delivery to the anticoagulated fetus. However, the substitution of heparin at first trimester and 2 weeks before delivery reduce the incidence of complications.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.418-423
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• 2006

Tabanus anticoagulant protein (TAP) was isolated from the whole body of the tabanus, Tabanus bivittatus, using three purification steps (ammonium sulfate fractionation, gel filtration on Bio-Gel P-60, and ion exchange chromatography on DEAE Sephadex gel). The purified TAP, with a molecular weight of 65 kDa, was assessed to be homogeneous by SDS-polyacrylamide gel electrophoresis, and an isoelectric point of 7.9 was determined by isoelectric focusing. The internal amino acid sequence of the purified protein was composed of Ser-Leu-Asn-Asn-Gln-Phe-Ala-Ser-Phe-lle-Asp-Lys-Val-Arg. The protein was activated by $Cu^{2+}\;and\;Zn^{2+}$, and the optimal conditions were found to be at pH $3\sim6\;and\;40\sim70^{\circ}C$. Standard coagulation screen assays were used to determine thrombin time and activated partial thromboplastin time. Chromogenic substrate assays were performed for thrombin and factor Xa activity. TAP considerably prolonged human plasma clotting time, especially activated partial thromboplastin time in a dose-dependent manner; it showed potent and specific antithrombin activity in the chromogenic substrate assay. Specific anti-factor Xa activity in TAP was not detected. Overall, this result suggested that TAP has significant anticoagulant activity on blood coagulation system.

• Applied Biological Chemistry
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• v.39 no.2
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• pp.159-164
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• 1996

Screening of anticoagulant activity was conducted for the hot water extracts of 73 kinds of medicinal herbs, 41 kinds of Korean edible plants, and 5 kinds of sea weeds using plasma recalcification test(Tr). In the first screening several extracts of the plants, Alisma calndiculatum, Corydalis ternata Panax notoginseng, Allium sativum, Ganderma luidum, Codium fragile, showed high activities. When the plants were reextracted with various solvent conditions, acidic water extracts of Codium fragile showed the highest activity in APTT. A crude polysaccharide fraction(CF-1) was prepared by methanol reflux, ethanol precipitation, dialysis and Iyophilization of the acid extracts. CF-1 comprised 80.8% total sugar consisting of arabinose, galactose and glucose as the main monomers, 8.7% protein, and 13.3% sulfate. The anticoagulant activity of CF-1 was not changed by pronase digestion, but decreased by periodate oxidation, and this indicated that the anticoagulant activity was attributed to the polysaccharide portion.