Morphologic and molecular study on the lens anterior capsule in systemic sclerosis / Relato sobre estudo morfológico e molecular da cápsula anterior do cristalino na esclerose sistêmica

ABSTRACT This study aimed to analyze the anterior lens capsule specimens from both eyes of a patient with systemic sclerosis and compare them to the eyes of a control patient. No significant differences between systemic sclerosis and control eyes were observed in the results from the hematoxylin-eosin and picrosirius staining. In the samples obtained from both systemic sclerosis and control eyes, there were expressions of caspase, a molecule expressed in cell death by apoptosis. Heparanase was overexpressed in the systemic sclerosis sample compared to the control sample. Therefore, the anterior lens capsule of the patient with systemic sclerosis is probably affected by the disease since it showed marked expression of heparanase 1.(AU)

RESUMO Analisamos as amostras das cápsulas anteriores do cristalino de uma paciente com esclerose sistêmica e comparamos com as de um paciente controle. Não foram observadas diferenças significativas entre esclerose sistêmica e controle nos resultados da coloração com hematoxilina-eosina e picrosirius. Nas amostras obtidas da esclerose sistêmica e do controle, obtivemos expressão de caspase, uma molécula expressa na morte celular por apoptose. A heparinase foi expressa de forma mais marcante na amostra de esclerose sistêmica quando comparada ao controle. Portanto, a cápsula anterior do cristalino da paciente com esclerose sistêmica provavelmente foi afetada pela doença, uma vez que mostrou expressão aumentada de heparinase 1.(AU)

Is the expression of the components of the carotid matrix of rats influenced by estrogen, progestin and tibolone? / A expressão dos componentes da matriz carotídea de ratos é influenciada pelo estrogênio, progestagênio e tibolona?

Abstract Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by realtime polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.

Resumo Objetivo Analisar os efeitos do estrogênio isolado ou em combinação com progestogênios e tibolona (TIB) na expressão das metaloproteinases 2 e 9 da matriz extracelular (MMP-2 e MMP-9), da perlecan e da heparanase (HPSE) das paredes vasculares das artérias carótidas. Métodos Trinta ratas Wistar ovariectomizadas com 250 dias de idade foram tratadas oralmente por 5 semanas com: a) 1 mg/kg de benzoato de estradiol (EB); b) EB + 0,2 mg/kg de acetato de medroxiprogesterona (MPA); c) EB + 0,2mg/kg de acetato de noretisterona (NETA); d) EB + 2 mg/kg de didrogesterona (DI); e) 1 mg/kg de TIB; f) placebo (CTR). Após o tratamento, a expressão de mRNA para MMP-2, MMP- 9, e HPSE foi analisada por reação em cadeia da polimerase (RCP) em tempo real, e a expressão de MMP-2, MMP-9, inibidor tecidual de metaloproteinase 2 (TIMP-2), e de perlecan foi quantificado por imunohistoquímica em artérias carótidas. Resultados Os grupos apresentaram diferenças significativas na expressão do mRNA HPSE (p = 0,048), sendo maiores nos grupos EB, EB + MPA e TIB. Não houve diferença estatisticamente significativa nas expressões de mRNA MMP-2 ou MMP-9. A expressão imunohistoquímica de MMP-2, TIMP-2, MMP-9, HPSE e perlecan não mostrou diferenças entre os grupos. Conclusão O estradiol isolado ou associado ao tratamento com MPA e TIB pode aumentar a expressão de mRNA HSPE nas paredes das artérias carótidas em ratas ovariectomizadas.

Research progress of heparinase in the field of medicine / 生物工程学报

Heparinases can produce biologically active oligosaccharides by specifically cleaving the α-(1,4) glycosidic linkages of heparin and heparan sulphate. Heparinases are divided into heparinase and heparanase. Because heparinase is an effective biocatalyst, more and more researchers pay attention to the application of heparinase in medical field in the recent years. Combined with the related research work in our group, the application value of heparinase in the medical field was summarized, such as the determination of the structure of heparin, the preparation of low-molecular-weight heparin and ultra-low-molecular-weight heparin, tumor therapy and as a heparin antagonist. In addition, we summarized the definition, source of heparinase and its application in the medicine field. Heparinases have a great application prospect in the field of medicine.

Tromboprofilaxis en el paciente médico hospitalizado por medicina interna Un estudio de corte transversal / Thromboprophylaxis in the hospitalized medical patient by internal medicine A cross-sectional study

Introducción: el tromboembolismo venoso es una de las principales causas de morbimortalidad prevenible seguida de una hospitalización. Las heparinas han demostrado ser eficaces para su prevención, sin embargo se ha documentado la subutilización de estos fármacos, por lo que implementar medidas que garanticen la formulación adecuada es fundamental. En nuestra institución se han instaurado estrategias para mejorar la formulación de estos fármacos con resultados iniciales favorables, pero se desconoce el efecto a más largo plazo. Métodos: estudio descriptivo, retrospectivo de corte transversal. Se evaluaron pacientes mayores de 18 años, hospitalizados por medicina interna entre junio y noviembre de 2012. Se estimó una muestra representativa de 102 pacientes. Se identificó la formulación de la tromboprofilaxis al segundo día de hospitalización, se determinó si fue adecuada según las guías institucionales y los errores en la prescripción de la misma. Se compararon los resultados con dos mediciones previas realizadas en la institución. Resultados: de los 102 pacientes evaluados, la tromboprofilaxis fue adecuada en 63 (61,8%) e inadecuada en 39 (38.2%). Las causas más frecuentes de error fueron: formulación en pacientes de bajo riesgo 18 (46.1%) y error por omisión en 12 (30.7%) pacientes. La formulación en pacientes con indicación y sin contraindicación disminuyó de 92-82% y en pacientes sin indicación aumentó de 50-56.2%, con relación a una medida previa realizada después de la difusión de guías institucionales. Conclusiones: la tromboprofilaxis en pacientes hospitalizados por medicina interna en nuestra institución se ordena en un alto porcentaje, sin embargo debe ser mejorada. El principal error es la formulación en pacientes con riesgo bajo. La implementación de estrategias para mejorar la tromboprofilaxis logró una mejoría inicial, pero tiende a disminuir con el tiempo. Se requiere un trabajo continuado de múltiples medidas que garanticen su impacto favorable a largo plazo. (Acta Med Colomb 2015; 40: 227-233).

Introduction: venous thromboembolism is one of the major causes of preventable morbidity and mortality following a hospitalization. Heparins have proven effective for prevention; however, under utilization of these drugs has been documented, so that the implementation of measures to ensure the proper formulation is essential. Strategies to improve the formulation of these drugs have been established in our institution with favorable initial results, but the longer-term effect is unknown. Methods: descriptive, retrospective cross-sectional study. Patients over 18 years hospitalized for internal medicine between June and November 2012 were evaluated. A representative sample of 102 patients was estimated. Thromboprophylaxis formulation was identified on the second day of hospitalization and it was determined if its prescription was appropriate in accordance with the institutional guidelines as well as errors in its prescription. The results were compared with two previous measurements realized in the institution. Results: Of the 102 patients evaluated, thromboprophylaxis was adequate in 63 (61.8%) and inadequate in 39 (38.2%). The most frequent causes of error were: prescription in low-risk patients 18 (46.1%) and error of omission in 12 (30.7%) patients. The formulation in patients with an indication and without contraindication decreased from 92% to 82% and in patients with no indication increased from 50% to 56.2%, compared to a previous measurement made after the dissemination of institutional guidelines. Conclusions: thromboprophylaxis in hospitalized patients in internal medicine at our institution is organized in a high percentage, but must be improved. The main error is the formulation in patients with low risk. The implementation of strategies to improve thromboprophylaxis achieved initial improvement, but tends to decrease over time. Continued work of multiple measures to ensure their favorable long-term impact is required. (Acta Med Colomb 2015; 40: 227-233).

Expressions and correlation of HPA, CK2beta and HIF-1alpha in nasopharyngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expression of HPA, CK2beta and HIF-1alpha gene in nasopharyngeal carcinoma (NPC) tissues, and the correlation between their expression with the clinical characteristics of NPC and the relativity of HPA, CK2beta and HIF-1alpha gene in NPC tissues.@*METHOD@#HPA, CK2beta and HIF-1alpha were detected with Super-Vision immunohistochemical method using antibody in 49 NPC specimens and 30 specimens with chronic nasopharyngitis tissue (CNT).@*RESULT@#The expression of HPA, CK2beta and HIF-1alpha in NPC tissue were significantly higher than those in CNT tissue (P0.05). The expression of HIF-1alpha was significantly related to the age of NPC patient (P<0.05), while HPA, CK2beta were not. The expression of HPA, CK2beta and HIF-1alpha in NPC tissue was positively correlated with each other (P<0.05, separately).@*CONCLUSION@#HPA, CK2beta and HIF-1alpha play synergetic role in development of NPC, which plays an important role in invasiveness,recurrence and metastasis of NPC. There could be a positive cooperation among HPA, CK2beta and HIF-1alpha in the carcinogenesis and development of NPC.

Rivaroxaban frente a heparinas de bajo peso molecular para la prevención de la tromboembolia venosa posterior al reemplazo total de cadera o rodilla: revisión sistemática de la literatura y metaanálisisis / Rivaroxaban versus low weight heparins for venous thromboembolism prophylaxis after major hip and knee arthroplasty: systematic review and metaanalysis

Objetivo: evaluar la eficacia y seguridad de la tromboprofilaxis con rivaroxaban comparada con las heparinas de bajo peso molecular en cirugía mayor de cadera o rodilla. Métodos: revisión sistemática en Central Cochrane Database, MEDLINE, EMBASE, LILACS, CINAHL y artículos referenciados. Solo se consideraron ensayos clínicos controlados. La búsqueda se realizó hasta octubre 31 de 2011.Dos revisores evaluaron de forma independiente la calidad metodológica de los artículos y extrajeron los datos. Resultados: se estudiaron 15.638 pacientes (nueve estudios) programados para reemplazo total de cadera o rodilla. Comparada con la enoxaparina, la tromboprofilaxis con rivaroxaban se asoció a menor incidencia de trombosis venosa profunda, tromboembolia pulmonar y muerte por cualquier causa posterior a cirugía ortopédica mayor tanto de cadera (5.475, riesgo relativo [RR]: 0,37; intervalo de confianza del 95% [IC 95%]: 0,29-0,48]) como de rodilla (2.878, RR: 0,65; IC 95%: 0,50-0,84) sin diferencias en los eventos hemorrágicos (sangrado mayor en cirugía de cadera: 7.684, RR: 1,79; IC 95%: 0,78-4,11; y de rodilla: 5.700, RR: 1,59; IC 95%: 0,77-3,27). Conclusión: el rivaroxaban usado para tromboprofilaxis de pacientes sometidos a cirugía ortopédica mayor es más eficaz que la enoxaparina y al menos tan seguro como ella.

Objective: To assess the efficacy and safety of rivaroxaban thromboprophylaxis versus low weight heparins in major hip and knee arthroplasty. Methods: Systematic review in Central Cochrane Database, MEDLINE, EMBASE, LILACS, CINAHL, and referenced articles. Only randomized clinical trials were considered. The search was made until October 31, 2011. Two independent reviewers assessed the quality of articles and extracted the information. Results: 15.638 patients who underwent major orthopedic surgery were studied (nine trials). Compared with enoxaparin, thromboprophylaxis with rivaroxaban was associated with lower incidence of deep vein thrombosis, pulmonary embolism and death from any cause after major hip surgery (5.351, relative risk [RR]: 0.37; confidence interval 95% [IC 95%]: 0.29-0.48) and knee surgery (2.878, RR: 0.65; IC 95%: 0.50-0.84) without differences in bleeding events (major bleeding events in hip surgery: 7.684, RR: 1.79; IC 95%: 0.78-4.11) and knee surgery: 5.700, RR: 1.59; IC 95%: 0.77-3.27). Conclusion: Rivaroxaban thromboprophylaxis in major hip and knee arthroplasty is more effective than enoxaparin and as safe as the latter.

Avaliação comparativa da atividade biológica de heparinas não fracionadas pelas metodologias de inibição da coagulação do plasma ovino (ICPO) e de tempo de tromboplastina parcial ativada (TTPA) / Comparative study on the biological activity of non-fractionated heparin by using sheep plasma coagulation inhibition assay (SPCIA) and activated partial thromboplastin time (APTT) methodologies

O objetivo deste trabalho foi realizar o estudo comparativo entre os métodos ICPO e TTPA, para avaliar a eficácia da implantação do TTPA como método para a avaliação da segurança e eficácia de heparinas não fracionadas em produtos farmacêuticos. Foram avaliados, comparativamente, cinco lotes de diferentes fabricantes de heparinas não fracionadas (polissacarídeo sulfatado usado como droga anticoagulante), de origem suína ou bovina, testadas com base no 5º Padrão Internacional de Heparina. Esses produtos foram provenientes de coletas efetuadas pelas autoridades sanitárias para análise no Instituto Nacional de Controle de Qualidade em Saúde (INCQS). As amostras foram analisadas quanto à pureza e potência anticoagulante, por meio de duas metodologias: inibição da coagulação do plasma ovino (ICPO) e tempo de trombo plastina parcial ativada (TTPA). Houve boa concordância entre as duas metodologias, sendo que a técnica TTPA apresentou ser mais simples, rápida e objetiva, quando da utilização do coagulômetro para a medição do tempo de formação de coágulos, em detrimento da leitura subjetiva dos graus de coagulação no ensaio de ICPO. A implantação e a execução do TTPA em paralelo à utilização do ICPO garantirão o aumento de sensibilidade técnica na avaliação da segurança e eficácia de heparinas não fracionadas.

Análisis y caracterización de la farmacoterapéutica de las heparinas de bajo peso molecular prescritas en pacientes hospitalizados en el Hospital Clínica Bíblica, Costa Rica, durante el periodo de marzo a agosto del 2010 / Analysis and characterization of the pharmacotherapy of low molecular weight heparins prescribed in hospitalized patients at the Hospital Clinica Biblica, Costa Rica, from March to August 2010

Justificación y objetivo: Analizar la farmacoterapéutica empleada con las heparinas de bajo peso molecular, HBPM, prescritas en pacientes hospitalizados en el Hospital Clínica Bíblica, hospital privado en Costa Rica, con base en los lineamientos establecidos por el Colegio Americano de Cirujanos Torácicos, 2008. Material y métodos: En el presente estudio se incluyeron pacientes internados en el período marzo-agosto 2010 que fueron tratados con HBPM. De esta población se analizaron 250 pacientes elegidos de forma aleatoria según la metodología recomendada. Se recopilaron todos los documentos e información necesaria de cada paciente para el correspondiente análisis. Resultados: Un 43 por ciento del total de pacientes hospitalizados utilizaron HBPM, 707 pacientes. En un 91 por ciento de los casos, las HBPM fueron utilizadas con un fin profiláctico. Solamente un 2 por ciento de los pacientes que utilizaron HBPM de manera profiláctica no necesitaban de la misma. En un 90 por ciento de los casos, la dosis utilizada fue correcta. En un 18 por ciento de los casos se requería un ajuste de dosis. Un 80 por ciento de los casos presentó algún tipo de interacción farmacológica de relevancia clínica. Un 4 por ciento de los pacientes presentaron algún tipo de hemorragia, en donde un 2 por ciento de los casos este efecto estaba ligado al uso de HBPM. El 9 por ciento de los casos en los que se utilizaron las HBPM como tratamiento, fueron abordados según los lineamientos. Conclusión: En el Hospital Clínica Bíblica, el uso las HBPM se apegó a las recomendaciones establecidas por la normativa de la ACCP, a pesar de la no existencia en ese momento de un protocolo en el hospital. El análisis farmacoterapéutico por parte del farmacéutico clínico, puede suministrar información importante al médico para que se tomen las medidas correctivas y/o preventivas asociadas a la correcta utilización de estos medicamentos. Realizar una correcta estratificación de riesgo e individualización del tratamiento facilita la implementación adecuada de la farmacoterapia con HBPM en este hospital, donde existe una alta proporción de pacientes que pueden desarrollar eventos tromboembólicos.

Effect of low-molecular-weight heparin combined with paclitaxel on the invasiveness and migration of nasopharyngeal carcinoma cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of low-molecular-weight heparin (LMWH) combined with paclitaxel (PTX) on the invasiveness and migration of nasopharyngeal carcinoma cells and explore the molecular mechanisms.</p><p><b>METHODS</b>MTT assay was used to detect the growth inhibition induced by LMWH and PTX in CNE1 and CNE2 cells. Wound healing assay and Transwell migration assay were employed to assess the effects of the drugs on the cell migration, and Transwell invasion assay was used to evaluate the cell invasiveness. The cellular expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were analyzed by Western blotting. ELISA was used to determine the expression of heparanase (HPA) in the culture medium of the cells.</p><p><b>RESULTS</b>MTT assay showed an obvious suppression of CNE1 and CNE2 cell proliferation in response to LMWH and PTX treatments. Treatment with 200 U·ml LMWH combined with 0.1 µmol·L PTX for 24 h resulted in the inhibition rates of migration of 66.70% and 70.53% in CNE1 and CNE2 cells, respectively significantly higher than the rates in cells with PTX treatment alone. The combined treatment with LMWH and PTX for 24 h also caused a significantly higher inhibition rate of cell invasion than LMWH and PTX alone. LMWH enhanced the down-regulation of MMP-9 and HPA induced by PTX.</p><p><b>CONCLUSION</b>LMWH can enhance the inhibitory effect of PTX on the migration and invasion of nasopharyngeal carcinoma cells, the mechanism of which may involve the down-regulation of MMP-9 and HPA expressions.</p>

Purification and properties of recombinant GST-heparinase III and optimization of cultivation conditions / 生物工程学报

Heparinase III is an enzyme that specifically cleaves certain sequences of heparan sulfate. Previous reports showed that this enzyme expressed in Escherichia coli was highly prone to aggregation in inclusion bodies and lacks detectable biological activity. In this paper, we fused a glutathione-S-transferase (GST) tag to the N-terminus of heparinase III gene and expressed the fusion protein in Escherichia coli to develop an expression system of soluble heparinase III. As a result, approximately 80% of the fusion protein was soluble. The protein was then purified to near homogeneity via one-step affinity chromatography. A 199.4-fold purification was achieved and the purified enzyme had a specific activity of 101.7 IU/mg protein. This represented 32.3% recovery of the total activity of recombinant GST-heparinase III. The maximum enzyme production was achieved when bacteria were induced with 0.5 mmol/L isopropyl-beta-D-thiogalactoside at 15 degrees C for 12 h. The enzyme showed maximum activity at 30 degrees C and pH 7.5. And the enzyme activity was stimulated by 1 mmol/L Ca2+ and 150 mmol/L NaCl.

Study of expression of CD138 and heparinase in hepatocellular carcinoma by tissue microarray / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of CD138 and heparinase in hepatocellular carcinoma (HCC) and its relationship with tumor development, progression, metastasis and recurrence.</p><p><b>METHODS</b>Tissue microarray and immunohistochemical study (EnVision method) for CD138 and heparinase was performed on tissue microarray which consisted of 197 cases of HCC, including adjacent non-neoplastic liver tissues, and 66 cases of HCC metastases.</p><p><b>RESULTS</b>The rates of CD138 expression in HCC and adjacent non-neoplastic liver tissues were 48.7% (96/197) and 65.0% (128/197, P < 0.05) respectively. In early-stage and late-stage tumors, the expression rates were 61.7% (29/47) and 44.7% (67/150, P < 0.05) respectively. The rate in patients with metastasis was 33.3% (22/66), as compared with 53.6% (45/84, P < 0.05) in patients without metastasis. In patients with tumor recurrence occurring within or after 1 post-operative year, the expression rates were 23.3% (7/30) and 61.1% (11/18, P < 0.05) respectively. On the other hand, the rates of expression of heparinase in HCC and adjacent non-neoplastic liver tissues were 35.5% (70/197) and 12.7% (25/197, P < 0.05) respectively. In early-stage and late-stage tumors, the expression rates were 29.8% (14/47) and 37.3% (56/150, P > 0.05) respectively. The rate in patients with metastasis was 48.5% (32/66), as compared with 28.6% (24/84, P < 0.05) in patients without metastasis. In patients with tumor recurrence occurring within or after 1 post-operative year, the expression rates were 50.0% (15/30) and 44.4% (8/18, P > 0.05) respectively. In the 66 cases of metastatic HCC studied, the expression rate of CD138 was lower in the heparinase-positive subgroup (P < 0.05).</p><p><b>CONCLUSIONS</b>Loss of CD138 expression is related to HCC development, progression, metastasis and recurrence. Overexpression of heparinase, when coupled with loss of CD138 expression, may take part in tumor metastasis of HCC.</p>

Evaluation of the Relationship between the Patient's Severity and the Presence of Heparin Effects with the Use of Heparinase-Guided TEG in Liver Transplantation / 대한마취과학회지

BACKGROUND: Endogenous heparinoid substances have been mentioned as one of the causes of coagulopathy during liver transplantation. Some reported that heparin effects after reperfusion increase with decreasing liver function, as assessed by the Child-Pugh classification. Comparisons of native and heparinase TEG can assess the quantity of heparin effects and distinguish the cause of coagulopathy. We investigated the heparin effects before reperfusion by heparinase-guided TEG and the correlation between heparin effects and the UNOS and Child-Pugh score. METHODS: 67 liver transplanted patients were studied and divided two groups. Two groups were control group that exist heparin effect and experimental group that does not exist heparin effect during preanhepatic period. Native and heparinase TEG are performed simultaneously after anesthetic induction. Present heparin effects were defined as coagulation time (gamma + kappa) differs more than 20% between native and heparinase TEG showing the native TEG's index is out of the normal range. RESULTS: Heparin effects were present before reperfusion in 29.8% of liver transplantation cases and these were related more with the Child-Pugh classification than UNOS (gamma = 0.31, P = 0.012). There were many transfusions of packed red cells and a large infusion amount through RIS in the group with heparin effects but there was no statistical significance. CONCLUSIONS: We could confirm that heparin effects appear already before reperfusion in 29.8% of the cases using heparinase-guided TEG and this correlates with the Child-Pugh classification

Clinical Observation of Postreperfusion Heparine Effects with a Heparinase Guided Thromboelastogram in a Liver Transplanted Patient / 대한마취과학회지

Orthotopic liver transplantation is frequently associated with severe bleeding, especially after reperfusion of the grafted liver. Heparin or heparinoids are released from the grafted liver and cause additional blood coagulation disorders. Recently many investigators have used a heparinase guided thromboelastogram (TEG) to control and confirm heparin effects not only on liver transplantation but also cardiac surgery. We reported a clinical case using a heparinase guided TEG to observe the duration of postreperfusion heparin effects.

Heparinas de bajo peso molecular en la cardiopatía isquemica metab¢lica: bases moleculares: experiencia clínica y resultados / Heparin of low weight molecular in the cardiopatic ischemic metabolic: base molecular: experience clinical and result

Las Heparinas de Bajo Peso Molecular (HBPM) se aíslan a partir de la heparina no fraccionada, siendo su mecanismo de acción el efecto inhibitorio que ejerce sobre el factor Xa por la antitrombina. Las HBPM más utilizadas a nivel mundial son la enoxaparina (Clexane), nadroparina (Fraxiparina) y la dalteparina sodica (Fragmin). Un considerable numero de ensayos clínicos ha comparado el efecto de las HBPM con la NHF en el tratamiento de la trombosis venosa profunda y del tromboembolismo pulmonar donde se confirma la eficacia de las HBPM sobre las NHF. Con base a estudios anteriores, utilizamos la dalteparina sodica a dosis de 5000 Ul/día durante 10 días; indofubeno a dosis de 400 mg/día y trimetazidina a dosis 60 mg/día durante 3 meses en pacientes con cardiopatía isquémico-metabolica. Nuestros resultados muestran una mejoría significativa en la mayoría de los pacientes observándose estabilización en la frecuencia cardíaca, desaparición del dolor precordial y desaparición de los signos de isquémia, lesión y necrosis en el electrocardiograma, por lo que sugerimos la utilización de esta terapéutica no invasiva y ambulatoria en pacientes con cardiopatía Isquémico-metabolica

Heparinase is More Reliable than Protamine for Detecting Heparin Effects on Thromboelastography on Reperfusion of Liver Transplantation / 대한마취과학회지

BACKGROUND: Heparin released from grafted liver immediately after declamping is one of causes of coagulopathy, and its presence has been diagnosed by comparing thromboelastography(TEG) of blood treated with 0.01% of protamine and untreated blood. However, protamine may affect coagulation if the amount of protamine is not optimal to heparin in the blood sample. Heparinase, an enzyme isolated from Flavobacterium Heparinum, neutralizes heparin without adversely affecting coagulation. Therefore we compared the TEGs of blood treated with heparinase and protamine to clarify the sensitivity and reliability of heparinase in reversing the heparin effect. METHODS: Differences in Reaction time(R time), Alpha angle, Maximal Amplitude(MA) between native and heparinase treated TEG on reperfusion in 8 cases of orthotopic liver transplantations were compared with those between native and protamine in 14 cases of OLT. RESULTS: On reperfusion, all of TEGs treated with heparinase showed more improved data rather than native one in R time, Alpha angle and MA. But, in protamine treated blood, R time and Alpha angle in 6 patients and MA in 3 patients were more depressed. The scattergram show that TEGs treated with heparinase on reperfusion have almost positive difference, but TEGs treated with protamine did not have positive results consistently. CONCLUSIONS: Heparinase is a more reliable reagent and activator than protamine on TEG for detecting heparin effects on reperfusion without showing in-vitro anticoagulation. Those results suggest that heparinase on TEGs can make diagnosis of coagulopathy developed immediately after reperfusion efficiently.

Heparinase is More Reliable than Protamine for Detecting Heparin Effects on Thromboelastography on Reperfusion of Liver Transplantation / 대한마취과학회지

BACKGROUND: Heparin released from grafted liver immediately after declamping is one of causes of coagulopathy, and its presence has been diagnosed by comparing thromboelastography(TEG) of blood treated with 0.01% of protamine and untreated blood. However, protamine may affect coagulation if the amount of protamine is not optimal to heparin in the blood sample. Heparinase, an enzyme isolated from Flavobacterium Heparinum, neutralizes heparin without adversely affecting coagulation. Therefore we compared the TEGs of blood treated with heparinase and protamine to clarify the sensitivity and reliability of heparinase in reversing the heparin effect. METHODS: Differences in Reaction time(R time), Alpha angle, Maximal Amplitude(MA) between native and heparinase treated TEG on reperfusion in 8 cases of orthotopic liver transplantations were compared with those between native and protamine in 14 cases of OLT. RESULTS: On reperfusion, all of TEGs treated with heparinase showed more improved data rather than native one in R time, Alpha angle and MA. But, in protamine treated blood, R time and Alpha angle in 6 patients and MA in 3 patients were more depressed. The scattergram show that TEGs treated with heparinase on reperfusion have almost positive difference, but TEGs treated with protamine did not have positive results consistently. CONCLUSIONS: Heparinase is a more reliable reagent and activator than protamine on TEG for detecting heparin effects on reperfusion without showing in-vitro anticoagulation. Those results suggest that heparinase on TEGs can make diagnosis of coagulopathy developed immediately after reperfusion efficiently.

Comparative Study of Heparinase Treated Activated Clotting Time with Hephrinase Treated Thromboelastography for Detecting Residual Heparin Effects Following Cardiopulmonary Bypass / 대한마취과학회지

Residual heparin effects after protamine reversal is a potential bleeding disorder associated with cardiopulmonary bypass(CPB). To differentiate this from the other multiple factors causing coagulopathy should be initialized in the setting of management. The purpose of this study was to compare simple activated clotting time(ACT) and thromboelastography(TEG) with heparinase treated ACT and TEG for detecting residual heparin effects to distinguish rapidly the presence of heparin from the effects of other factors because the enzyme heparinase specifically neutralized heparin. After institution approval, 20 patients who required open heart surgery were studied. Baseline kaoline ACT, heparinase ACT, TEG and heparinase TEG(Haemoscope) were obtained before CPB on the same blood sample. The repeated tests were performed on the same blood samples 20 minutes after protamine reversal following CPB. Differences between heparinase treated tests and untreated tests were also evaluated at the same time. Wilcoxon signed ranked test was used to compare the results between before and after bypass. None of patients had significant postoperative bleeding complication. All tests before bypass were normal. Twenty minutes after protamine reversal, 3 patients showed kaoline ACT were extended above 10% of the value of heparinase ACT but all of them remained within normal range. However, nearly all patients showed heparin effects on TEG. The heparin effects on TEG were defined as significant differences in all of parameters, especially in alpha angle and R+K time between simple TEG and heparinase TEG. In Conclusion, heparinase treated ACT and native ACT are not sensitive to residual heparin effects after CPB. Their normal results did not preclude residual heparin effects on heparinase modified TEG. However, it might be further investigated to need additional protamine in the case of residual heparin effects on TEG.

Heparin Independent Coagulation Monitoring during Open Heart Surgery / 대한마취과학회지

Thromboelastography(TEG) is a useful monitor for assessing coagulation function in patients undergoing open heart surgery. However, whole blood clotting patterns on TEG are not able to obtain during the cardiopulmonary bypass(CPB) with heparin anticoagulation. When pretreating TEG sample with heparin antidote, heparinase or protamine (heparinase-modified TEG or protamine modified TEG) can make possible assessing the changes of clotting on TEG during the CPB. In this study, data from heparinase(N=50) and protamine(N=26) modified TEG were obtained before, during and after CPB in 76 open cardiac patients, which are presented to describe their usefulness concerning about prediction for coagulation after weaning of CPB. Heparin neutralized TEG revealed that all of depressed values initially after starting bypass were returning back to the values of before starting bypass on weaning CPB. These results suggested that function of the fibrinogen and platelet were relatively well maintained during the bypass. The fibrinolysis during the bypass were commonly developed in 51.2% without affecting by time course of CPB. Even though initial dose of protamine reversal after bypass, there were obviously residual heparin effects on heparinase-modified TEG as simultaneously comparing with native TEG. Regarding correlation of TEG findings in cases excluding fibrinolysis between before and after bypass, R time and MA before bypass were significantly correlate with R time and MA on heparinase-modified TEG after bypass but not on native TEG. (R time: R 0.46, MA: R=0.54). The data gathered in this study suggested heparin independent TEG assay can be useful to assess the coagulation function during the bypass and to predict the values of TEG after bypass, but residual heparin effect must be initially excluded to avoid underestimating the coagulation status after protamine reversal.