• 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.

• BMB Reports
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• v.29 no.6
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• pp.500-506
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• 1996

We have isolated a water-extracted novel regulator for blood coagulation from an earthworm, Lumbricus rubellus. As a folk remedy, the earthworm has been known to facilitate blood circulation. After complete heat inactivation of endogenous proteases in the earthworm, an anticoagulant(s) was purified through ammonium sulfate fractionation and three consecutive gel permeation chromatography of Sephacryl S-300, Sephadex G-75, and G-150 by measuring activated partial thromboplastin time (APTT) The anticoagulant was further purified to 2,800 fold with a C4 reversed-phase HPLC This activity was stable under heat ($100^{\circ}C$ for 30 min) and acidic conditions (0.4 N HCl). The effects of this partially purified anticoagulant on thrombin were observed with various substrates such as N${\alpha}$-benzoyl-DL-arginine-p-nitroanilide (BApNA), H-D-phenylalanyl-L-pipecoyl-L-arginine-p-nitroanilide (S-2238), N${\alpha}$-p-tosyl-L-arginine methyl ester (TAME), and fibrinogen as a natural substrate. Only TAME hydrolysis, due to an esterase activity of the enzyme, was inhibited among the chromogenic substrates. In addition, the anticoagulant not only inhibited the conversion of fibrinogen to fibrin but also prolonged the fibrin clot formation monitored with the in vitro coagulation test. Based on these observations, we suggest the significance of measuring the ability of antithrombotic drugs to inhibit the esterase activity of thrombin. In this report, it was also shown that the earthworm indeed contained a water-extractable, heat- and acid-stable anticoagulant which could be used as a novel antithrombotic agent.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.53-61
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• 2019

Background: Antiphospholipid antibody syndrome (APS), an important cause of acquired thrombophilia, is diagnosed when vascular thrombosis or pregnancy morbidity occurs with persistently positive antiphospholipid antibodies (aPL). APS is a risk factor for unprovoked recurrence of pulmonary embolism (PE). Performing laboratory testing for aPL after a first unprovoked acute PE is controversial. We investigated if a specific phenotype existed in patients with unprovoked with acute PE, suggesting the need to evaluate them for APS. Methods: We retrospectively reviewed patients with PE and APS (n=24) and those with unprovoked PE with aPL negative (n=44), evaluated 2006-2016 at the Asan Medical Center. We compared patient demographics, clinical manifestations, laboratory findings, and radiological findings between the groups. Results: On multivariate logistic regression analysis, two models of independent risk factors for APS-PE were suggested. Model I included hemoptysis (odds ratio [OR], 12.897; 95% confidence interval [CI], 1.025-162.343), low PE severity index (OR, 0.948; 95% CI, 0.917-0.979), and activated partial thromboplastin time (aPTT; OR, 1.166; 95% CI, 1.040-1.307). Model II included age (OR, 0.930; 95% CI, 0.893-0.969) and aPTT (OR, 1.104; 95% CI, 1.000-1.217). Conclusion: We conclude that patients with first unprovoked PE with hemoptysis and are age <40; have a low pulmonary embolism severity index, especially in risk class I-II; and/or prolonged aPTT (above 75th percentile of the reference interval), should be suspected of having APS, and undergo laboratory testing for aPL.

• Journal of Chest Surgery
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• v.39 no.5 s.262
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• pp.366-375
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• 2006

Background: Hypomagnesemia is a common complication after cardiac surgery with cardiopulmonary bypass. The purpose of this study was to assess the clinical beneficial effect of administration of magnesium sulfate in cardiac surgery. Material and Method: Thirty five patients scheduled for elective cardiac surgery were randomly assigned to magnesium group (n=20) which received magnesium sulfate in priming solution (1 g) and cardioplegic solution (1 g) or control group (n=15) which did not receive it. Arterial blood samples were drawn for measuring $Mg^{++}$ and electrolytes contents, blood gas analysis, CBC, total protein, albumin, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, tumor necrosis factor-${\alpha}$ $(TNF-{\alpha})$, interleukin-6 (IL-6), interleukin-10 (IL-10), creatine phosphokinase (CpK), creatine kinase-MB (CK-MB), lactate dehydrogenase(LDH), troponin-1 (TNI), prothrombin time (PT) and activated pratial thromboplastin time level (aPTT). Venous blood samples were drawn before and after the operation for measuring activated clotting time level (ACT). Result: $Mg^{++}$ levels in magensium group were higher than those of control group at intraoperative and post-operative periods (p<0.05). dysrhythmias were lower in magnesium group (8 cases out of 17 patients, 46.4%) than in control group (10 cases out of 10, 100%, p=0.050). Conclusion: These results showed that administration of low dose magnesium sulfate during cardiac surgery prevented hypomagnesemia and lowered incidence of dysrhythmia.

• Journal of Chest Surgery
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• v.32 no.2
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• pp.97-107
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• 1999

Background: This study was designed to develop a Korean version of the heparin-coated vascular bypass shunt by using a physical dispersing technique. The safety and effectiveness of the thrombo-resistant shunt were tested in experimental animals. Material and Method: A bypass shunt model was constructed on the descending thoracic aorta of 21 adult mongrel dogs(17.5-25 kg). The animals were divided into groups of no-treatment(CONTROL group; n=3), no-treatment with systemic heparinization(HEPARIN group; n=6), Gott heparin shunt (GOTT group; n=6), or Korean heparin shunt(KIST group; n=6). Parameters observed were complete blood cell counts, coagulation profiles, kidney and liver function(BUN/Cr and AST/ ALT), and surface scanning electron microscope(SSEM) findings. Blood was sampled from the aortic blood distal to the shunt and was compared before the bypass and at 2 hours after the bypass. Result: There were no differences between the groups before the bypass. At bypass 2 hours, platelet level increased in the HEPARIN and GOTT groups(p<0.05), but there were no differences between the groups. Changes in other blood cell counts were insignificant between the groups. Activated clotting time, activated partial thromboplastin time, and thrombin time were prolonged in the HEPARIN group(p<0.05) and differences between the groups were significant(p<0.005). Prothrombin time increased in the GOTT group(p<0.05) without having any differences between the groups. Changes in fibrinogen level were insignificant between the groups. Antithrombin III levels were increased in the HEPARIN and KIST groups(p<0.05), and the inter-group differences were also significant(p<0.05). Protein C level decreased in the HEPARIN group(p<0.05) without having any differences between the groups. BUN levels increased in all groups, especially in the HEPARIN and KIST groups(p<0.05), but there were no differences between the groups. Changes of Cr, AST, and ALT levels were insignificant between the groups. SSEM findings revealed severe aggregation of platelets and other cellular elements in the CONTROL group, and the HEPARIN group showed more adherence of the cellular elements than the GOTT or KIST group. Conclusion: Above results show that the heparin-coated bypass shunts(either GOTT or KIST) can suppress thrombus formation on the surface without inducing bleeding tendencies, while systemic heparinization(HEPARIN) may not be able to block activation of the coagulation system on the surface in contact with foreign materials but increases the bleeding tendencies. We also conclude that the thrombo-resistant effects of the Korean version of heparin shunt(KIST) are similar to those of the commercialized heparin shunt(GOTT).

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4529-4532
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• 2013

Background: Acute normovolemic hemodilution (ANH) has been widely used to prevent the massive blood loss during hepatic carcinoma. The influences of ANH on coagulation function are still controversy, especially in elderly patients. The study observed ANH effects on coagulation function and fibrinolysis in elderly patients undergoing the disease. Materials and Methods: Thirty elderly patients (aged 60-70 yr) with liver cancer (ASA I or II) taken hepatic carcinectomy from February 2007 to February 2008 were randomly divided into ANH group (n=15) and control group (n=15). After tracheal intubation, patients in ANH group and control group were infused with 6% hydroxyethyl starch (130/0.4) and Ringer's solution, respectively. Blood samples were drawn from patients in both groups at five different time points: before anesthesia induction (T1), 30 min after ANH (T2), 1 h after start of operation (T3), immediately after operation (T4), and 24 h after operation (T5). Then coagulation function, soluble fibrin monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (CD62P and activated GP IIb/GP IIIa) were measured. Results: The perioperative blood loss and allogeneic blood transfusion were recorded during the surgery. The perioperative blood loss was not significantly different between two groups (p>0.05), but the volume of allogeneic blood transfusion in ANH group was significantly less than in control group ($350.0{\pm}70.7$) mL vs. ($457.0{\pm}181.3$) mL (p<0.01). Compared with the data of T1, the prothrombin time (PT) and activated partial thromboplastin time (APTT) measured after T3 were significantly longer (p<0.05) in both groups, but within normal range. There were no significant changes of thrombin time (TT) and D-dimer between two groups at different time points (p>0.05). SFMC and F1+2 increased in both groups, but were not statistically significant. PAC-1-positive cells and CD62P expressions in patients of ANH group were significantly lower than those at T1 (p<0.05) and T2-T5 (p>0.05). Conclusions: ANH has no obvious impact on fibrinolysis and coagulation function in elderly patients undergoing resection of liver cancer. The study suggested that ANH is safe to use in elderly patients and it could reduce allogeneic blood transfusion.

• Journal of Chest Surgery
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• v.27 no.3
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• pp.177-186
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• 1994

Pentastarch is a hydroxyethyl starch similar to hetastarch, but lower average molecular weight and fewer hydroxyethyl groups which result in enhanced enzymatic hydrolysis and faster renal elimination.This report was performed to compare the clinical efficacy and safety of 10 % pentastarch[Pentaspan , group I] for plasma volume expansion after open heart surgery with that of 5% albumin[Plasmanate, group II]. There were no statistically significant differences between the group I [n=18] and group II [n:19] in the preoperative parameters [age, sex, body weight] and operative parameters[bypass time, aorta cross clamping time]. During the first 24 hours after arrival of the patient in the surgical intensive care unit, colloid solution [500--1000 ml] was infused to maintain left atrial pressure of more than 8 mmHg, or cardiac index of 2.0 L/min/M2 of more. In results, there were 3 complications of hypotension immediately after infusion of 5 % albumin solution and 2 among the 3 patients were excluded for the study. However there was no complication after infusion of 10 % pentastarch solution. Hemodynamic responses to infusion was similar for both groups, although in group I a greater increase in both left atrial pressure[mean 1.8 versus 0.7 mmHg, p< 0.05] and right atrial pressure [mean 2.2 versus 1.7 mmHg, p < 0.05] was observed during infusion of the first 500 ml. There were no significant differences in any of the measured respiratory parameters[PaO2, intrapulmonary shunt, and effective lung compliance]. Homodilution with colloid significantly reduced hemoglobin [mean 1.2 versus 0.8 gm/dl], and serum protein and albumin level[total protein;4.8$\pm$ 0.5 versus 5.2 $\pm$0.5 gm/dl, p < 0.05: albumin: 3.2 $\pm$0.4 versus 3.6 $\pm$0.6 gm/dl, p < 0.05] by 6:00 AM on 1 day postoperatively, however there were no significant differences on 7 day postoperatively. The mean serum colloid osmotic pressure and osmolarity was similar in both group.There were no abnormal findings of liver function and kidney function in all the patients. There were no significant between-group differences in bleeding time, platelets, prothrombin time, activated partial thromboplastin time and amount of chest tube output measured on 1st and 7th postoperative day. These findings demonstrated that 10% pentastarch is more effective and safe for plasma volume expension than 5 % albumin solution with no adverse effects on coagulation. Also 10 % pentastarch is less expensive than 5 % albumin and it would appeare to be a reasonable first choice for plasma volume expansion.

• Journal of Life Science
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• v.28 no.9
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• pp.1068-1075
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• 2018

Kaempferia parviflora, an herbaceous plant in the family Zingiberaceae, is popular in many tropical regions. It is called as black ginger or krachaidum in Thailand and Laos, and its raw or dried root have been used as spices and teas. The rhizomes also have been traditionally used to treat gastrointestinal disorders, ulcers, gout, dysentery, allergies and to improve physical work capacity. Recently, its anti-obesity, anti-oxidant, anti-inflammatory and blood clot-lysis activities were reported. In this study, the anti-thrombosis activity of black ginger was investigated, since improvement in blood fluidity leads to the prevention of various lifestyle-related diseases. The hot water and ethanol extract and their subsequent solvent fractions (hexane, ethylacetate, butanol fractions and water residue) were prepared, and their anti-coagulation and platelet aggregation inhibitory activities were determined, respectively. Among the black ginger extracts and their fractions, the ethylacetate fraction (EAF) of ethanol extract only showed significant extensions of blood coagulation time determined by thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (aPTT). At 5 mg/ml concentration, TT, PT and aPTT were extended to 1.22, 1.49 and >15-folds compared to non-treatment. The EAFs of ethanol and hot water extract showed strong inhibitions against collagen-induced platelet aggregations, which are comparable to inhibitions of aspirin. Also the EAFs from black ginger did not show any hemolysis activity against human RBC up to 0.5 mg/ml. Our results suggest that the EAF of black ginger has a potential as novel anti-coagulation and ant-platelet aggregation agent. This report provides the first evidence of anti-coagulation activity of black ginger.

• Journal of Chest Surgery
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• v.13 no.1
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• pp.13-20
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• 1980

Heparin would have been used for preventing clotting of blood during extracorporeal circulation and subsequent use of protamine sulfate and made possible the neutralization of heparin. This procedure has been adopted for eliminating one of the great causes of bleeding, especially in cardiac surgery. In this experiment, the hypocoagulability of blood induced by heparin followed by neutralization with treatment of protamine sulfate were estimated by the Lee-White clotting time [CT], partial thromboplastin time [PTT] and protamine titration test. The results were as follows: 1] Comparison of clotting time between the heparinized [2.0 mg/kg] and non-heparinized dogs was done using CT and PT`I` of the blood. In heparinized group [Group I], the CT lasted infinitively and prolongation of PTT [4 times than normal] until 60 minutes. The CT [2 times] and PTT [3 times] has been shortened after 90 minutes, however they returned to normal limit level within 180 minutes. 2] The determination of appropriate ratio of heparin and protamine In vivo were performed. The group II [heparin 2.0 mg/kg, protamine 1.0 mg/kg] revealed rapid decrease of CT and PTT, but returned to normal after 120 minutes. The group III [heparin 2.0 mg/kg, protamine 2.0 mg/kg] returned rapidly to normal within 15 minutes. The group IV [heparin 2.0 mg/kg, protamine 3.0 mg/kg] recovered its normal level after 60 minutes. The group V [heparin 2.0 mg/kg, protamine 4.0 mg/kg] recovered its normal level after 90 minutes. 3] In the combined experimental study In vivo and vitro, the protamine titration test was done using the dog which were given 2.0 mg/kg and 3.0 mg/kg of heparin, respectively and coagulation time were checked after 15, 30, 60 and 120 minutes. The complete neutralization was showed to be heparin-protamine ratio of 1:1 to 1.5. 4] In vitro study, fresh blood was drawn into known amount of heparin content [20, 40, 60 and 100/ug per 1 ml of blood] syringe, thereafter protamine titration test was done. In all cases, the complete neutralization was found in heparin-protamine ratio of 1:0.85 to 1.5. 5] It was found by the present experiment that the ideal heparin-protamine ratio was 1:1 within 60 minutes and 1:0.5 after 60 minutes for avoiding the serious side effect due to overadministration of protamine sulfate.

• Journal of The Korean Society of Clinical Toxicology
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• v.7 no.2
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• pp.90-96
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• 2009

Purpose: This study explored and evaluated the systemic complications resulting from the bite of Korean venomous snake, focussing on hematologic and neurologic features. Methods: Medical records (demographic data, clinical measurements including laboratory results, severity score, and amount of antidote administration, and hospitalization course) of consecutive patients who presented with snakebites to two university teaching hospital during a 10-year period were retrospectively reviewed. Subgroup analysis was conducted for evaluations of anti-acetylcholine esterase administration in complicated victims. Results: The 170 patients displayed occurrence rates of hematologic and neurologic complications of 12.9% and 20.6%, respectively. Among 22 patients with hematologic complications, isolated thrombocytopenia was evident in eight patients (36.4%), prothrombin time (PT) / activated partial thromboplastin time (aPTT) prolongation in 11 patients (50.0%), and both in three patients (13.6%). The mean time to recovery was $4.5{\pm}1.8$ days for isolated thrombocytopenia, and $5.1{\pm}1.8$ days for PT and aPTT prolongation. Hematologic complications could occur suddenly 1?4 days after hospitalization. Among 35 patients with neurologic complications, dizziness was evident in 16 patients (45.7%), and diplopia / blurred vision in 19 patients (54.3%). The mean time to recovery was $3.4{\pm}0.6$ days in patients receiving anti-acetylcholine esterase and $6.9{\pm}1.8$ days in those not receiving anti-acetylcholine esterase (p=0.00). Conclusion: Occurrence rates of hematologic and neurologic complications following venomous snake bite differed as compared to other studies conducted in Korea. Onset of hematologic complications can occur rapidly days after admittance. Anti-acetylcholine esterase administration may be effective in treating neurologic complications.