• Title/Summary/Keyword: Antithrombin III

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Inhibitory Mechanism of Blood Coagulation by the Anticoagulant Polysaccharide from Coriolus versicolor (구름버섯 기원 항응고성 다당류의 혈액응고 저해기작)

  • Lee, Hyun-Sun;Kweon, Mee-Hyang;Lim, Wang-Jin;Sung, Ha-Chin;Yang, Han-Chul
    • Korean Journal of Food Science and Technology
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    • v.29 no.4
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    • pp.817-822
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    • 1997
  • Inhibitory mechanism of the anticoagulant polysaccharide purified from the fruit body of Coriolus versicolor was investigated in this paper. The anticoagulant polysaccharide (CV-40-Va-1) was proposed to have functions of the inhibition of intrinsic pathway in the blood coagulation pathway together with the interuption of a human platelet aggregation induced by von Willebrand factor (vWF). CV-40-Va-I inhibited other factors of the coagulation cascade such as factor VIII, IX, and as well as thrombin. Especially, CV-40-Va-I inhibited the fibrin formation mediated by thromin, however the polysaccharide did not affect the fibrin formation directly but affected the anticoagulant activity through the activation of antithrombin III. The sulfation of the anticoagulant polysaccharide increased the anticoagulant activity, showing that the sulfate concentration of anticoagulant polysaccharide was important factor in the blood coagulation cascade. Low molecular weight subfraction (MW 1,000) obtained by partial hydrolysis of the CV-40-Va-1 generated potent antiplatelet activity, but showed decreased anticoagulant activity.

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Change of hemostatic markers according to the clinical state in Kawasaki disease (가와사끼병의 임상경과에 따른 지혈성 표지의 변화와 임상적 의의)

  • Kim, Yong Beom;Yoon, You Sook;Lee, Sang Yun;Kil, Hong Ryang
    • Clinical and Experimental Pediatrics
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    • v.50 no.12
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    • pp.1247-1251
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    • 2007
  • Purpose : Pathologically, Kawasaki disease (KD) is associated with widespread vascular endothelial damage in the acute phase. The vasculitis induced endothelial injury leads to coagulation abnormalities. Abnormalities of endothelial function, platelet activation, and fibrinolysis are present during acute phase and long after the onset of KD. The aim of study is to evaluate the change of hemostatic markers in the clinical stages of KD and to assess the hemostatic markers to be a useful indicator of the development of coronary artery lesion (CAL). Methods : Seventy four KD patients diagnosed in Chungnam National University Hospital from November 2004 to June 2007. Eleven febrile control and eleven healthy children were selected for healthy control. All blood samples were collected before and after Intravenous gammaglobulin (IVGG), $2^{nd}$ week, and $4^{th}-8^{th}$ week of illness of KD. Results : Initial D-dimer level of Kawasaki disease showed meaningful difference compared to control group (P<0.05). D-dimer and fibrinogen degradation products (FDP) before IVGG increased compared with normal control group and decreased after IVGG administration. It is normalized until 2 weeks later, and continue to decreasing. D-dimer and FDP were significantly different according to the CAL before IVGG. Conclusion : The hemostatic markers may change to the clinical stage of KD, which may suggest the degree of endothelial injury. Increased some hemostatic markers may be the predictors for development of CAL.

Thrombolytic Therapy for Repeated Prosthetic Valvular Thrombosis That's Associated with Pregnancy under Heparin Anticoagulation (임신과 연관된 헤파린 항응고요법 중 반복적으로 발생한 인공판막 혈전증의 혈전용해치료)

  • Choe, Ju-Won;Kim, Yong-In L.
    • Journal of Chest Surgery
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    • v.41 no.4
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    • pp.484-488
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    • 2008
  • During long-term anticoagulation treatment with using heparin in a pregnant patient with a mechanical mitral prosthesis, we observed several anticoagulation-related complications, including repeated prosthetic valve thrombosis. This was found to be caused by heparin resistance due to an anti-thrombin III deficiency. Thrombolytic therapy using urokinase or tissue plasminogen activator (tPA) was successful and safe for her as well as her baby.

Deoxyribonucleic Acid Was Responsible for the Anticoagulatory Effect of an Earthworm, Lumbricus rubellus

  • Paik, Seung-R.;Woo, Jeong-Im;Kim, Gyoung-Mi;Cho, Jin-Mo;Yu, Kyoung-Hee;Chang, Chung-Soon
    • BMB Reports
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    • v.30 no.1
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    • pp.37-40
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    • 1997
  • Earthworm extracts are known for anti-inflammatory, analgesic. antipyretic, and anticancer effects but can also influence blood circulation. It was previously shown that an earthworm, Lumbricus rubelius. contained a water-extractable anticoagulant which was a heat- and acid-stable molecule with hydrophilic property. In order to uncover the biochemical nature of this molecule, the anticoagulant was processed with various hydrolases such as trypsin, DNase, RNase. and lysozome. When the digested samples were analyzed with an in vitro coagulation test measuring activated partial thromboplastin time (APTT) and agarose gel electrophoresis, the anticoagulant proved to be a relatively homogeneous DNA fragment with relative molecular size around 72 base pairs. Interestingly, the activity was further stimulated with a trypsin digestion. RNA. on the other hand, did not prolong the APTT. It was also demonstrated that the DNA accelerated the antithrombin III (AT-III) inhibition of thrombin from $IC_{50}$ of 0.34 to 0.16 unit determined with S-2238 as a substrate, whereas heparin, a popular anticoagulant. shifted the value to 0.05. Therefore, it is suggested that the DNA could be considered as an alternative antithrombotic agent to heparin, which would exhibits bleeding side effects.

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설페이티드 다당류의 실험실적 효능 검색과 동물내에서의 비교

  • 김영식
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.76-76
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    • 1993
  • 헤파린은 혈액응고계에서 antithrombin III 존재하에서 thrombin과 factor Xa의 작용을 억제함으로써 항응고제로서 작용을 한다. 심정맥혈전증 등 임상에 응용성이 높지만 장기적 사용시 혈소판 감소효과, 출혈, 골다공증 등의 부작용이 나타나고 있다. 본연구는 식물성 생약으로부터 당을 분리 정제하여 화학적으로 sulfation시켜 in vitro와 ex vivo에서 항응고활성을 비교하였다. 우선적으로 aPTT를 측정하여 응고시간의 연장을 시키는 다섯종류의 식물생약을 선택하였고 이 중에서 청호(Artemisiae apiaceae)로부터 산성당을 분리하여 pyridine과 chlorosulfonic산으로 sulfation 시켰율 때 in vitro상에서 항응고활성은 sulfation전에 비해 두드러지게 증가하였다. 농도를 달리 하여 실험동물에 투여시 응고시간의 연장 역시 비슷한 양상을 보여주었다. Thrombin 억제는 발견되지 않았지만 sulfate기와 항응고 활성과는 관계가 있는 것처럼 보였다.

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Anticoagulant Activity of Sulfoakyl Derivatives of Curdlan

  • Lee, Kyung-Bok;Bae, Jong-Hwan;Kim, Jong-Seung;Yoo, Yung-Choon;Kim, Beom-Soo;Kwak, Sang-Tae;Kim, Yeong-Shik
    • 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.

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Anticoagulant Activity of Sulfated Polysaccharides Isolated from Codium fragile (청각 산추출물에서 정제한 함황다당류의 항응고활성)

  • Park, Mee-Kyung;Kweon, Mee-Hyang;Cho, Hong-Yon;Yang, Han-Chul
    • 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.

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A Case of Thromboembolic Complication in Right Common Iliac Artery in a Child with Minimal Change Nephrotic Syndrome (미세변화형 신증후군 환아에서 발생한 우측총장골동맥 혈전증 1례)

  • Nam Hyun-Joo;Kim Ji-Hong;Kim Pyung-Kil;Chang Byung-Chul
    • Childhood Kidney Diseases
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    • v.2 no.1
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    • pp.69-72
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    • 1998
  • Thromboemolism is one of the severe complications of nephrotic syndrome. And arterial thromboembolism is rare than venous thromboembolism. Hypercoagulability is the main pathophysiologic factors of thromboembolism in nephrotic syndrome with severe hypoalbuminemia. We experienced one case of arterial thromboembolism which occured in right common iliac artery. It was seen in a 6 year-old male child that presented with generalized edema and rigth ankle joint pain. Emergency embolectomy and anticoagulant therapy (heparin and antithrombin III) was performed. He didn't have to be amputated and recovered to self ambulation. This is an uncommon case that successful recovery was possible by early diagnosis and invasive surgical management with proper anticoagulant therapy.

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Studies on the Blood Anticoagulant Polysaccharide Isolated from Hot Water Extracts of Hizikia fusiforme (톳 열수추출물로부터 분리한 혈액 항응고성 다당류에 관한 연구)

  • 양한철;김경임;서혜덕;이현순;조홍연
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.27 no.6
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    • pp.1204-1210
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    • 1998
  • This study was focused on the purification, characterization and promotion mode of an anticoagulant polysaccharide from Hizikia fusiforme. The anticoagulant crude polysaccharide(HF 0) was obtained by using hot water extraction at 100oC for 3 hrs after homogenizing desalted Hizikia fusiforme. The anticoagulant polysaccharide(HF 2 3 1a) was purified from the crude extract(HF 0) through stepwise gradient ethanol precipitation(HF 2), DEAE Toyopearl 650C(HF 2 3), Sephadex G 75(HF 2 3 1), Sepharose CL 6B(HF 2 3 1a) chromatography and HPLC to homogeneity. HF 2 3 1a was estimated at 5.3$\times$105 Da molecular weight and composed of fucose(51.92%), galactose(19.34%), mannose(13.92%), xylose (7.14%), arabinose(3.95%) and rhamnose(3.78%), and comprimised 29.7 % sulfate residue. The sulfated anticoagulant polysaccharide from HF 2 3 1a was proposed to inhibit via the intrinsic pathway and common pathway in the blood coagulation. The HF 2 3 1a exhibited the anticoagulant activity by activating an antithrombin III and the activity depended on the concentration of HF 2 3 1a. Acute toxicity of HF 2 in mice was not detected. Only 14 of 33 control mice(11.4%) that had taken saline survived for 30 min after injecting thrombin(100 NIH unit/ml).

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A Case of Streptococcus pneumoniae associated Hemolytic Uremic Syndrome with DIC

  • Kim, Seong Heon;Kim, Su Young
    • Childhood Kidney Diseases
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    • v.19 no.1
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    • pp.48-52
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    • 2015
  • Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) is one of the causes of atypical hemolytic uremic syndrome, and increasingly reported. They are more severe and leave more long-term sequelae than more prevalent, typical hemolytic uremic syndrome. But it is not so easy to diagnose SpHUS for several reasons (below), and there was no diagnostic criteria of consensus. A 18 month-old-girl with sudden onset of oliguria and generalized edema was admitted through the emergency room. She had pneumonia with pleural effusion and laboratory findings of HUS, DIC, and positive direct Coombs' test. As DIC or SpHUS was suspected, we started to treat her with broad spectrum antibiotics, transfusion of washed RBC and replacement of antithrombin III. On the $3^{rd}$ day, due to severe hyperkalemia and metabolic acidosis, continuous renal replacement therapy (CRRT) was started. She showed gradual improvement in 4 days on CRRT and discharged in 16 days of hospital care. At the follow up to one year, she has maintained normal renal function without proteinuria and hypertension. We report this case with review of articles including recently suggested diagnostic criteria of SpHUS.