As trombofilias na perda gestacional de repetição: uma revisão de prevalência e condutas / Thrombophilias in recurrent pregnancy loss: a review of prevalence and conduct

Objetivo: Discutir o papel das trombofilias na perda gestacional de repetição, com foco em prevalência/associação dessas patologias com perdas de repetição e seu tratamento, por meio de resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publi- cados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando os seguintes descritores: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome" e "treatment". Resultados: A maioria dos estudos relatou forte associação entre os anticorpos antifosfolípides específicos e a síndrome do anticorpo antifosfolípide com perda gestacional de repetição. Mulheres portadoras da mutação do fator V de Leiden, mutação do gene da protrombina e deficiência de proteína S apresentaram alto risco de perda gestacional de repetição em uma grande revisão sistemática. Estudos recentes demonstraram taxas de prevalência das trombofilias hereditárias e da síndrome do anticorpo antifosfolípide, em mulheres com perda gestacional de repetição, semelhantes às da população em geral. Os estudos atuais endossam o uso da heparina associada à aspirina em mulheres com síndrome do anticorpo antifosfolípide, com aumento da taxa de nascidos vivos, mas sem diferença em re- lação às complicações obstétricas. Conclusão: Apesar de novos estudos demons- trarem que a prevalência das trombofilias hereditárias e adquiridas em mulheres com perda gestacional de repetição é semelhante à da população em geral, reco- menda-se a pesquisa rotineira de síndrome do anticorpo antifosfolípide nessas pacientes. O uso de aspirina em baixas doses associada à heparina é a intervenção farmacológica de primeira linha para a prevenção de perda gestacional de repeti- ção em pacientes com síndrome do anticorpo antifosfolípide.

Objective: To discuss the role of thrombophilias in recurrent pregnancy loss, focu- sing on the prevalence/association of these pathologies with recurrent abortion and treatment, through results of clinical trials, systematic reviews and meta-analyses. Methods: This is a non-systematic review of articles published in electronic databa- ses PubMed, Cochrane, SciELO in the last five years, using the following descriptors: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome", and "treatment". Results: Most studies have reported a strong association between specific antiphospholipid antibodies and antiphospho- lipid antibody syndrome with recurrent pregnancy loss. Women carrying the factor V Leiden mutation, prothrombin gene mutation, and protein S deficiency were shown to be at high risk of recurrent pregnancy loss in a large systematic review. Recent studies have shown prevalence rates of hereditary thrombophilias and antiphospholipid antibody syndrome, in women with re- current pregnancy loss, similar to those of the general po- pulation. Current studies endorse the use of heparin plus aspirin in women with antiphospholipid antibody syndrome, with an increase in live birth rate, but with no difference in obstetric complications. Conclusion: Although new studies demonstrate that the prevalence of hereditary and acquired thrombophilias in women with recurrent pregnancy loss is si- milar to that of the general population, routine investigation of antiphospholipid antibody syndrome in these patients is recommended. The use of low-dose aspirin plus heparin is the first-line pharmacological intervention for the prevention of recurrent pregnancy loss in patients with antiphospholipid antibody syndrome.

Prevalence of thrombophilia-associated genetic risk factors in blood donors of a regional hospital in southern Brazil

ABSTRACT Introduction: Thromboembolic events occur due to an imbalance in the hemostasis and some factors associated with this condition can be inherited. In order to evaluate the frequency of genotypes considered to be common hereditary risk factors for thrombophilia associated with venous thrombosis (g.1691G>A and g.20210G>A) and hyperhomocysteinemia (g.677C>T and g.1298A>C), samples from voluntary healthy blood donors at the Hospital de Clínicas de Porto Alegre were tested. Methods: We examined 325 blood samples from blood donors collected from October 2017 to July 2018. Blood was collected on filter paper and the DNA was extracted for single nucleotide polymorphisms (SNPs) analysis using the qualitative real time polymerase chain reaction. Results: The calculated frequencies of each genetic variant in heterozygosity were 4% for the FV gene (g.1691G> A), 4% for the F2 gene (g.20210G> A) and 42% and 39% for methylenetetrahydrofolate reductase (MTHFR), g.677C>T and g.1298A>C, respectively. Only the genetic variants of MTHFR were found in homozygosity, with frequencies of 14% and 6% (g.677C>T and g.1298A>C), respectively. Discussion: Altogether, these results describe the frequencies of genetic variants associated with venous thrombosis and hyperhomocysteinemia in the analyzed group and are important to enhance our current knowledge about the genetic profiles of Brazilian blood donors.

Estandarización del índice internacional normalizado en pacientes pre-quirúrgicos del Hospital San Juan de Dios de Cuenca / Standarization of the Internacional Normalized Index in pre-surgical patients at Hospital San Juan de Dios of Cuenca / Padronização do Índice Normalizado Internacional em pacientes pré-cirúrgicos do Hospital San Juan de Dios em Cuenca

El índice internacional normalizado (INR, por sus siglas en inglés), es un tipo de cálculo matemático que se basa en las pruebas de tiempo de protrombina. La seguridad y eficacia de la terapia dependen del efecto anticoagulante que reciban dentro del margen terapéutico fijado por el médico en base al estudio de sus tiempos de coagulación, específicamente expresado como el intervalo de INR. Establecer los rangos de referencia del INR aplicado en resultados obtenidos en pacientes del sexo masculino y femenino en edades entre los 18 hasta 60 años de edad en el Hospital San Juan de Dios de Cuenca, durante los meses de enero a junio del año 2021. Los datos fueron recopilados de 699 pacientes que acudieron a consulta externa del Hospital San Juan de Dios de Cuenca del área de hematología, que incluyen valores de tiempo de tromboplastina y su referente INR en base al ISI establecido en el reactivo emitido por el fabricante. Se establecieron los valores normales de INR los cuales varían en referencia al sexo del paciente. Para el sexo masculino valores con límite inferior 0,82 y límite superior 1,16; para el sexo femenino con límite inferior de 0,51 y el límite superior de 1,51. Los valores de INR tienen variaciones de acuerdo al sexo siendo los valores de hombres mas altos en relación al de las mujeres en el rango inferiores, Evidentemente los factores influyentes van en relación del sexo, edad, dieta y sobretodo la genética del paciente.

The International Normalized Ratio (INR) is a type of mathematical calculation based on prothrombin time testing. The safety and efficacy of therapy depend on the anticoagulant effect they receive within the therapeutic range set by the physician based on the study of their clotting times, specifically expressed as the INR range. To establish the reference ranges of the INR applied in results obtained in male and female patients between 18 and 60 years of age at the San Juan de Dios Hospital in Cuenca, during the months of January to June 2021. The data were collected from 699 patients who attended the outpatient clinic of the Hospital San Juan de Dios de Cuenca in the hematology area, including thromboplastin time values and their INR referent based on the ISI established in the reagent issued by the manufacturer. Normal INR values were established, which vary according to the patient's sex. For the male sex values with a lower limit of 0.82 and an upper limit of 1.16; for the female sex with a lower limit of 0.51 and an upper limit of 1.51. The INR values vary according to sex, with the values for men being higher in relation to those for women in the lower range. Evidently, the influencing factors are related to sex, age, diet and above all the patient's genetics.

A Relação Internacional Normalizada (INR) é um tipo de cálculo matemático baseado em testes de tempo de protrombina. A segurança e eficácia da terapia depende do efeito anticoagulante que recebem dentro da faixa terapêutica estabelecida pelo médico com base no estudo de seus tempos de coagulação, expressa especificamente como a faixa INR. Estabelecer as faixas de referência do INR aplicadas em resultados obtidos em pacientes do sexo masculino e feminino com idade entre 18 e 60 anos no Hospital San Juan de Dios em Cuenca, durante os meses de janeiro a junho de 2021. Os dados foram coletados de 699 pacientes que compareceram ao ambulatório do Hospital San Juan de Dios de Cuenca na área de hematologia, incluindo os valores de tempo de tromboplastina e sua referência INR baseada no ISI estabelecido no reagente emitido pelo fabricante. Foram estabelecidos valores normais de INR, que variam de acordo com o sexo do paciente. Para o sexo masculino, com um limite inferior de 0,82 e um limite superior de 1,16; para o sexo feminino, com um limite inferior de 0,51 e um limite superior de 1,51. Os valores de INR variam de acordo com o sexo, sendo os valores para os homens maiores em relação àqueles para as mulheres na faixa inferior. Evidentemente, os fatores de influência estão relacionados ao sexo, idade, dieta e, acima de tudo, à genética do paciente.

Recurrent epistaxis with coagulation disorders in a boy aged 2 years / 中国当代儿科杂志

A boy, aged 2 years and 5 months, had recurrent epistaxis, and the coagulation function examination showed that activated partial thromboplastin time (APTT) was significantly prolonged. Further laboratory examinations showed that the prolonged APTT was not immediately corrected in the APTT correction test, with positive lupus anticoagulant and low prothrombin activity. The boy was diagnosed with hypoprothrombinemia-lupus anticoagulant syndrome. The condition was improved after treatment with glucocorticoid, immunoglobulin, and vitamin K1. The boy has been followed up for 6 months, and no epistaxis was observed. Prothrombin activity returned to normal, and lupus anticoagulant remained positive. This is a relatively rare disease, and for patients with bleeding symptoms and coagulation disorders, it is recommended to perform the tests such as APTT correction test, lupus anticoagulant testing, and coagulation factor dilution test, which can improve the detection rate of this disease, so as to achieve early diagnosis, provide rational treatment in the early stage, and improve the prognosis.

Effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors / 中华肝脏病杂志

Objective: To investigate the effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors. Methods: 127 cases with liver cirrhosis accompanied with esophageal and gastric varices without bleeding history were included in the endoscopic and non-endoscopic treatment group, respectively. Informed consent was obtained from both groups. Gastric varices (Lgf) and esophageal varices (Leg) were diagnosed according to LDRf classification criteria, and the corresponding treatment scheme was selected according to the recommended principle of this method.The incidence rate of bleeding from ruptured esophageal varices were observed at 3, 6 months, and 1, and 2 years in the treated and the untreated group, and the patients with different Child-Pugh scores were followed-up for 2 years. Gender, age, etiology, varicose degree, Child-Pugh grade, platelet count, prothrombin activity, portal vein thrombosis, collateral circulation, portal vein width and other factors affecting the bleeding rate were assessed. Measurement data were described as mean ± standard deviation (x¯±s), and qualitative data of categorical variables were expressed as percentage (%), and χ2 test was used. Results: 127 cases were followed up for 2 years. There were 55 cases in the endoscopic treatment group (18 cases underwent band ligation, 2 cases underwent band ligation combined with tissue adhesive embolization, 28 cases underwent sclerotherapy, and 7 cases underwent sclerotherapy combined with tissue adhesive embolization). Recurrent bleeding and hemorrhage was occurred in 5 (9.1%) and 28 cases (38.9%), respectively (P<0.05). In addition, there were 72 cases in the untreated group (P<0.05). Severe varicose veins proportions in treated and untreated group were 91.1% and 85.1%, respectively (P>0.05). There was no statistically significant difference in liver cirrhosis-related medication and β-blocker therapy between the treated and untreated group (P>0.05). There was no statistically significant difference in the bleeding rate between the different treated groups (P>0.05). The bleeding rates at 3, 6 months, 1, and 2 years in endoscopic treated and untreated group were 2.00% vs. 2.59% (P>0.05), 2.30% vs. 5.88% (P>0.05), 3.10% vs. 7.55% (P>0.05) and 4.00% vs. 21.62% (P<0.05), respectively. All patients with Child-Pugh grade A, B and C in the treated and the untreated group were followed-up for 2 years, and the bleeding rates were 1.8% vs. 8.1% (P<0.05), 1.1% vs. 9.4% (P<0.05) and 9.1% vs. 10.1% (P>0.05), respectively. There were statistically significant differences in the rupture and bleeding of esophageal and gastric varices, varices degree, Child-Pugh grade and presence or absence of thrombosis formation in portal vein (P<0.05); however, no statistically significant differences in gender, age, etiology, platelet count, prothrombin activity, collateral circulation and portal vein width (P>0.05). There was no intraoperative bleeding and postoperative related serious complications in the treated group. Conclusion: The risk of initial episodes of bleeding from esophageal and gastric varices is significantly correlated with the varices degree, Child-Pugh grade, and portal vein thrombosis. Primary preventive treatment under endoscope is safe and effective for reducing the long-term variceal bleeding risk from esophageal and gastric varices.

Prevalencia de mutaciones metilentetrahidrofolato reductasa (MTHFR), protrombina (II G20210G/G20210A) y factor V Leyden en pacientes sometidos a estudio por perfil trombofílico en el Hospital San Vicente de Paúl, Costa Rica, 2017-2018 / Prevalence of mutations Methylentetrahydrofolate reductase (MTHFR), Prothrombin (II G20210G/G20210A) and Leyden V factor in patients undergoing studies by thrombophilic profile. Hospital San Vicente de Paul. Costa Rica, 2017 to 2018

Resumen Introducción: en los últimos años se han descrito alteraciones genéticas asociadas con un mayor o menor riesgo de padecer una enfermedad trombótica. El objetivo del presente estudio es conocer la prevalencia de las mutaciones para la metilentetrahidrofolato reductasa (MTHFR), la protrombina (II G20210G/G20210A) y el factor V Leyden en las muestras de pacientes sometidas a estudio por perfil trombofílico en el Hospital San Vicente de Paúl. Metodología: con la base de datos de muestras referidas del Hospital San Vicente de Paúl, se estudiaron los marcadores de riesgo para trombofilia: MTHFR, Ac Lúpico, mutación del Factor II y Factor V Leyden correspondientes al periodo comprendido entre abril de 2017 a abril de 2018. Resultados: se observó que la frecuencia de la solicitud de estudio por trombofilia era mayor para el sexo femenino, con un 83,7 % del total de análisis, mientras que, para el sexo masculino fue de un 16,3 %. La mutación más prevalente fue la MTHFR, seguida del factor V Leyden, además, ambas se presentaron superiormente en las mujeres. Conclusión: se ha demostrado en varios estudios la asociación de las alteraciones genéticas estudiadas con los eventos trombóticos, por lo tanto, conocer su prevalencia en determinada población es de gran importancia para ayudar al clínico a llegar a un diagnóstico adecuado.

Abstract Introduction: Genetic alterations associated with a higher or lower risk of thrombotic disease have been reported in recent years, the objective of this study is to understand the prevalence of mutations for methylentetrahydrofolate reductase (MTHFR), Mutation for prothrombin (II G20210G/G20210A) and Mutation for factor V Leyden, in the samples of patients undergoing studies by thrombophilic profile, at the Hospital San Vicente de Paul. Methodology: To carry out this study, we use the database of reference samples of the Hospital San Vicente de Paúl for the study of risk markers for thrombophilia: MTHFR, Ac Lúpico, Mutation of Factor II, Factor V Leyden in the period from April 2017 to April 2018. Results: From the analyses requested for thrombophilia study, the frequency in the thrombophilia study request was observed to be higher for female sex, with a frequency of 83.7% of total testing and 16.3% for the male sex. The most prevalent mutation is MTHFR, followed by the Mutation for factor V Leyden, and both mutations occur in greater numbers in women. Conclusion: The association of genetic alterations studied with thrombotic events has been shown in several studies so knowing their prevalence in a given population is of great importance to help the clinic arrive at an appropriate diagnosis.

Efecto de las diferentes drogas anticoagulantes sobre el ensayo de fibrinógeno derivado del tiempo de protrombina / Effect of different anticoagulant drugs on the prothrombin time-derived fibrinogen assay

Resumen El objetivo de este trabajo fue comparar los niveles de fibrinógeno (FBG) obtenidos por el método de Clauss con los obtenidos por el método de fibrinógeno derivado del tiempo de protrombina (FBG PT-d), con dos tromboplastinas, en pacientes anticoagulados con distintas drogas. Se estudiaron pacientes anticoagulados consecutivos: 105 con antagonistas de la vitamina K (AVK), 55 con heparina no fraccionada (HNF), 58 con heparina de bajo peso molecular (HBPM), 60 con rivaroxabán, 45 con apixabán, 60 con dabigatrán y 100 controles normales (CN). El FBG se determinó por el método de Clauss y FBG PT-d utilizando tromboplastina de cerebro de conejo o recombinante humana; los niveles de heparina, rivaroxabán y apixabán por método cromogénico anti Xa; el dabigatrán con el ensayo de tiempo de trombina diluido. Existió un sesgo positivo (p<0,001) al comparar el FBG PT-d vs. FBG por Clauss: CN: 13,7%, AVK: 31,8%, rivaroxabán: 34,8% y apixabán: 20,0% cuando se utilizó tromboplastina de conejo. En el caso de las muestras que contenían HBPM se observó este desvío con ambas tromboplastinas. El sesgo porcentual en presencia de dabigatrán y heparina no fraccionada no fue estadísticamente distinto del obtenido en el grupo control. El ensayo de FBG PT-d no debe utilizarse en pacientes anticoagulados con rivaroxabán, apixabán, HBPM o AVK, ya que sobreestima los niveles de FBG. El porcentaje de sesgo depende del tipo de tromboplastina utilizado y fue mayor con la de cerebro de conejo en el sistema de detección utilizado.

Abstract The aim of this study was to compare fibrinogen (FBG) results obtained by Clauss method (FBG-C) and by the prothrombin time-derived fibrinogen assay (FBG PT-d) with two thromboplastins in patients under anticoagulation. Consecutive anticoagulated patients were studied: 105 vitamin-K antagonist (VKA), 55 unfractioned heparin, 58 LMWH, 60 rivaroxaban, 45 apixaban and 60 dabigatran, and 100 healthy controls (NC). FBG-C was performed by Clauss and FIB PT-d with rabbit brain and human recombinant thromboplastins, respectively. Heparins, rivaroxaban and apixaban levels were measured by antiXa; dabigatran by thrombin diluted assay. A positive bias of FBG PT-d vs. FBG-C with both thromboplastins were seen in NC (13.7 and 19.0 % for HS and RP, respectively), but bias with HS in rivaroxaban, apixaban and VKA patients were significantly higher compared to NC: 34.8%, 20.0 % and 31.8 %, respectively. LMWH presented higher BIAS compared to NC with both thromboplastins. Samples with unfraction heparin and dabigatran presented similar bias to NC. FBG PT-d should not be used in patients under anticoagulant treatment because of an important overestimation of FBG could be obtained in these patients. The percentage of bias depends on the type of thromboplastin used; it was higher with rabbit brain thromboplastin in the detection system used.

Resumo O objetivo deste trabalho foi comparar os níveis de fibrinogênio (FBG) obtidos pelo método de Clauss com aqueles obtidos pelo método do fibrinogênio derivado do tempo de protrombina (FBG PT-d), com duas tromboplastinas, em pacientes anticoagulados com diferentes drogas. Pacientes anticoagulados consecutivos foram estudados: 105 com antagonista da vitamina K (AVK); 55 com heparina não fracionada (UFH); 58 com heparina de baixo peso molecular (HBPM), 60 com rivaroxabana, 45 com apixabana, 60 com dabigatrana e 100 controles normais (CN). FBG foi determinado pelo método de Clauss e FBG PT-d usando tromboplastina de cérebro de coelho ou tromboplastina humana recombinante; níveis de heparina, rivaroxabana e apixabana pelo método cromogênico anti-Xa; dabigatrana com ensaio de tempo de trombina diluída. Há um viés positivo (p<0,001) ao comparar o FBG PT-d vs FBG de Clauss: CN: 13,7%; AVK: 31,8%, rivaroxabana: 34,8% e apixabana 20,0% quando foi utilizada tromboplastina de coelho. No caso das amostras contendo HBPM, esse desvio foi observado com ambas as tromboplastinas. O viés percentual na presença de dabigatrana e heparina não fracionada não foi estatisticamente diferente daquela obtida no grupo controle. O ensaio de FBG PT-d não deve ser usado em pacientes anticoagulados com rivaroxabana, apixabana, LMWH ou VKA, pois superestima os níveis de FBG. A porcentagem de viés depende do tipo de tromboplastina utilizado e foi maior com a de cérebro de coelho, no sistema de detecção utilizado.

Non-criteria Antiphospholipid Antibodies: a narrative review

SUMMARY The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these "criteria" of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the β2 glycoprotein antibodies.

RESUMO A classificação de Sapporo revisada para a síndrome antifosfolipídica definida de 2006 incluiu como critérios laboratoriais aqueles testes para anticorpos antifosfolípides cuja acurácia era considerada satisfatória de acordo com a evidência então disponível. Porém, na prática, a sensibilidade e especificidade desses anticorpos antifosfolípides "critério" são por vezes insuficientes para identificar ou descartar a síndrome antifosfolípide. Tem-se estudado se a acurácia do diagnóstico laboratorial da síndrome poderia ser melhorada por meio da testagem de anticorpos antifosfolípides não critério. Neste trabalho revisamos a evidência a respeito das associações clínicas e valor diagnóstico dos anticorpos não critério mais estudados, nomeadamente: anticorpos antifosfatidiletanolamina, antianexina A5, antiprotrombina, anticomplexo fosfatidilserina/protrombina, IgA anticardiolipina e IgG antidomínio I da anti-β2 glicoproteína I.

Trombolisis endovenosa post reversión de acenocumarol con complejo de protrombina: caso clínico / Intravenous thrombolysis after reversion of acenocoumarol anticoagulation: report of one case

We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.

Exploratory Factor Analysis of the Adolescent Version of the General Behavior Inventory in Korean Youth

OBJECTIVES: We examined the factor structure of the Adolescent version of the General Behavior Inventory (A-GBI) for Koreans. METHODS: We retrospectively reviewed the medical records of 220 adolescents (age, 12–18 years) who completed the A-GBI through the Department of Psychiatry at Asan Medical Center, Seoul, Korea, from October 2011 to December 2018. Caregivers of the study participants completed the Parent version of the GBI (P-GBI) 10-item Mania Scale. The adolescents were evaluated based on the A-GBI, Children's Depression Inventory (CDI), and Revised-Children's Manifest Anxiety Scale (RCMAS). Subsequently, an exploratory factor analysis (EFA) using the maximum likelihood method with direct oblimin rotation and correlation analyses with other scales were performed. RESULTS: The EFA identified a two-factor structure as having the best fit: factor I included depressive symptoms and factor II included hypomanic/biphasic symptoms. Factor I was very strongly correlated with the A-GBI depressive subscale (r=0.990, p<0.001) and strongly correlated with CDI (r=0.764, p<0.001) and RCMAS (r=0.666, p<0.001). Factor II was also very strongly correlated with the A-GBI hypomanic/biphasic subscale (r=0.877, p<0.001) and weakly correlated with CDI (r=0.274, p<0.001) and RCMAS (r=0.332, p<0.001). CONCLUSION: The above findings support a two-dimensional model of mood symptoms in Korean youth.

Performance of HemosIL ReadiPlasTin, a Liquid Reagent for Prothrombin Time Measurement / 임상검사와정도관리

BACKGROUND: Prothrombin time (PT) measurement is an important test for screening blood coagulation disorders and monitoring anticoagulant therapy. In this study, we evaluated the analytical performance of HemosIL ReadiPlasTin (Instrumentation Laboratory, USA), a liquid reagent for PT measurement. METHODS: The precision of HemosIL ReadiPlasTin was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) EP5-A3 guidelines. Further, comparison with HemosIL RecombiPlasTin 2G (Instrumentation Laboratory, USA) was made according to the CLSI EP9-A3 guidelines. The reference intervals were established according to the CLSI C28-A3 guidelines. RESULTS: The coefficient of variation values for repeatability and total imprecision at two levels of control materials were lower than 1.1% and 3.4%, respectively. The performance of HemosIL ReadiPlasTin was comparable to that of HemosIL RecombiPlasTin 2G, with a high correlation (r=0.996). The reference interval for normal subjects was 10.4–13.3 seconds. CONCLUSIONS: HemosIL ReadiPlasTin showed an acceptable degree of imprecision and its performance showed high correlation with that of a conventional reagent. Therefore, it is expected to be useful for PT measurement in clinical laboratories.

Genetic correlation between Prothrombin G20210A polymorphism and retinal vein occlusion risk

The aim of this study was to perform an updated meta-analysis to quantitatively investigate the association between G20210A polymorphism of Prothrombin gene and the risk of retinal vein occlusion (RVO), based on the available publications with inconsistent results. We utilized the Stata software to perform the heterogeneity test, association test, Begg's and Egger's tests, and sensitivity analysis. We searched three on-line databases (PubMed, Embase, and WOS) and obtained a total of 422 articles. Based on our selection criteria, 24 case-control studies were finally enrolled in this overall meta-analysis; a subgroup analysis by the factors ethnicity, control source, and RVO type was done. Through the association test of overall meta-analysis, we did not observe a significant difference between RVO cases and controls under the A vs G (allele) (z=1.49, P=0.137), A vs G (carrier) (z=1.42, P =0.155), GA vs GG (z=1.50, P=0.135), and GA+AA vs GG (z=1.50, P=0.135). Furthermore, we observed similar negative results in the association test of subgroup analysis (all P>0.05). Heterogeneity, Begg's, and Egger's tests excluded the presence of high heterogeneity and publication bias. Statistically stable results were observed in the sensitivity analyses. Based on integrated analysis of the current evidence, Prothrombin gene G20210A polymorphism is likely unrelated to the risk of RVO.

Móleculas protrombóticas en niños con Diabetes Mellitus Tipo 1 / Study of prothrombotic molecules in type 1 diabetes mellitus children

Introducción: la hiperglucemia contribuye a cambios moleculares que alteran la hemostasia. Objetivos: determinar moléculas circulantes que indiquen la presencia de un estado protrombótico en una población infanto juvenil con diabetes mellitus tipo 1 (DM1), sin manifestación clínica de enfermedad vascular, y compararla con una población control. Pacientes y métodos: se estudiaron 35 pacientes con DM1, de 11,0±2,5 años de edad y 3,7±2,0 años de evolución de la enfermedad, sin complicaciones vasculares y 20 controles sanos de edad, sexo e IMC semejantes. Se determinaron: fibrinógeno (Fg), inhibidor del activador del plasminógeno 1 (PAI-1), antígeno del factor von Willebrand (FvW:Ag), ligando CD40 soluble (sCD40L) y pruebas globales de coagulación como recuento de plaquetas, tiempo de protrombina (TP) y tiempo de tromboplastina parcial activado (APTT). El control glucémico se evaluó mediante glucemia en ayunas y A1c, y se descartó la presencia de retinopatía y nefropatía. Los datos se analizaron con el programa SPSS 20 para Windows y se expresaron como media±DE. El coeficiente de Pearson se usó para investigar las correlaciones entre las variables estudiadas. Resultados: los pacientes con DM1 presentaron valores significativamente mayores de Fg (308±66 vs 246±18 mg/dL, p=0,0001), PAI-1 (41,6±12 vs 11,7±1,0 ng/mL, p=0,0001), FvW:Ag (284±55 vs 121±19 %, p=0,0001) y sCD40L (1608±109 vs 149±17 pg/mL, p=0,0001). Sin embargo las pruebas globales de hemostasia no mostraron diferencias entre ambos grupos. El PAI-1 y sCD40L se correlacionaron con glucemia, A1c, Fg y FvW:Ag. Conclusiones: los niveles elevados de Fg, PAI-1, FvW:Ag y sCD40L sugieren la presencia de un estado protrombótico en la población infanto juvenil con DM1

Introduction: hyperglycemia contributes to molecular changes that alter hemostasis. Objectives: to determine molecules of a prothrombotic state in a child-juvenile population with type 1 diabetes (T1D), without clinical manifestation of vascular disease, and compare it with a control population. Patients and methods: thirty-five patients with T1D (11.0±2.5 years and 3.7±2.0 years of disease duration), without vascular complications and 20 healthy controls were studied. Plasma fibrinogen (Pf), plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor antigen vWF:Ag and soluble CD40 ligand (sCD40L) and coagulation global tests such as platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) were determined. The data obtained were analized by Statistics SPSS 20 software and were expressed as the mean±standard desviation. Pearson coefficient was used to investigate correlations between variables. Results: diabetic patients presented significantly higher values of glycaemia, A1c, Fg (308± 66 vs 246±18 mg/dL, p=0.0001), PAI-1 (41.6±12 vs 11.7±1, 0 ng/mL, p=0.0001), vWF:Ag (284±55 vs 121±19%, p= 0.0001) and sCD40L (1608±109 vs 149±17 pg/mL, p=0.0001). However, overall hemostasis tests showed no differences between both groups, PAI-1 and sCD40L correlated with glycemia, A1c, Fg and vWF:Ag. Conclusions: high levels of Fg, PAI-1, vWF:Ag and sCD40L suggest the presence of a prothrombotic state in the infant population juvenil with DT1

Prevención de hemorragias en el posoperatorio temprano de cirugía bariátrica: Papel de la vitamina K / Prevention of hemorrhage in the early postoperative period of bariatric surgery: Role of vitamin K

Introducción: la cirugía bariátrica es el tratamiento más eficaz para la obesidad mórbida. La hemorragia se presenta en el 0,5-5% de las pacientes. La preparación prequirúrgica con dieta líquida y el uso de antibióticos para Helicobacter pylori podría alterar el metabolismo de la vitamina K y asociarse a hemorragia. Objetivo: describir el comportamiento de la concentración de protrombina (basal = B-PT y prequirúrgica = preQ-PT) en estos pacientes. Material y métodos: se realizó un estudio de cohorte prospectivo donde se comparó la concentración de B-PT (15-180 días previos a la cirugía) y la preQ-PT (24 horas previas a la cirugía). Resultados: se incluyeron 194 pacientes, de los cuales el 72% (n = 139) fueron mujeres, de entre 19 y 69 años, con BMI (IMC) 45 (33 a 58) y pérdida de peso prequirúrgica del 7% (-2 a 17). El promedio de B-PT fue 91,9% (DE 9,529), el promedio de la preQ-PT fue 81,1% (DE 10,760); descendió un 10,8% (p < 0,001). No hubo diferencias significativas cuando se comparó el comportamiento en la preQ-PT entre los diferentes subgrupos (uso de antibióticos para Helicobacter pylori, de acuerdo con la pérdida de peso y en relación con la suplementación de vitamina K); sin embargo, siempre se detectó descenso de la preQ-PT. No hubo ninguna complicación hemorrágica (necesidad de transfusiones o reoperación); tampoco hubo muerte por hemorragias ni eventos tromboembólicos. Conclusión: realizar dosaje de protrombina 24 horas antes de la cirugía bariátrica permite detectar alteraciones iatrogénicas de la coagulación inducidas por la dieta y el uso de antibióticos.

Background: bariatric surgery is the most efficient treatment for morbid obesity. Bleeding occurs in 0.5-5% of patients. Pre-surgical preparation with liquid diet and the use of antibiotics for Helicobacter pylori could alter the metabolism of vitamin K and be associated with hemorrhage. Objective: to describe the behavior of the concentration of Prothrombin (basal = B-PT and pre-surgical = preQ-PT) in these patients. Material and methods: a prospective cohort study comparing B-PT concentration (15-180 days prior to surgery) and preQ-PT (24 h prior to surgery) was performed. Results: a total of 194 patients were included in the study, with 72% (n = 139) women aged 19-69 years, BMI 45 (33 to 58) and preoperative weight loss of 7% (-2 to 17). The media B-PT was 91.9% (SD 9.529), the media pre-PT was 81.1% (SD 10.760); declined 10.8% (p <0.001). There was no significant difference when comparing the behavior in the preQ-PT among different subgroups (use of antibiotics for Helicobacter pylori, according to weight loss and in relation to vitamin K supplementation), however, there was always a decrease of the preQ-PT. There were no bleeding complications (need for transfusions or re-intervetion), nor was there death for bleeding or thromboembolic events. Conclusion: prothrombin measurement 24 hours before bariatric surgery allows the detection of iatrogenic coagulation alterations induced by diet and the use of antibiotics.

Nível de informação e adesão à terapia de anticoagulação oral com varfarina em pacientes acompanhados em ambulatório de atenção primária à saúde / Knowledge and information levels and adherence to oral anticoagulant therapy with warfarin in patients attending primary health care services

A anticoagulação oral com varfarina é usada por milhões de pacientes em todo o mundo, apresentando segurança e eficácia bem estabelecidas. Ainda assim, na atenção primária à saúde, os anticoagulantes estão entre as classes de medicamentos mais associadas a erros de medicação fatais. Objetivo: Verificar o nível de informação e a adesão ao tratamento com varfarina em pacientes acompanhados em ambulatório de atenção primária à saúde. Método: Foi realizado um estudo transversal de uma coorte prospectiva com 60 pacientes em uso de varfarina no município de Ijuí, Rio Grande do Sul. Utilizou-se questionário para verificar o nível de informações dos usuários quanto à prescrição e o nível das informações prestadas pela equipe de saúde aos usuários. A Escala de Adesão Terapêutica de Morisky de Oito Itens (MMAS-8) e o coeficiente internacional normatizado ( international normalized ratio , INR) foram usados para verificar a adesão ao tratamento. Resultados: Os resultados foram expressos em valores absolutos e relativos e razão de prevalência, com seu respectivo intervalo de confiança de 95%. Verificou-se que 83,3% dos participantes tiveram nível de informação insuficiente prestada pela equipe de saúde, 50,0% não souberam informar sobre o uso correto do medicamento, 86,7% foram não aderentes ao tratamento segundo a MMAS-8, e 63,3% estavam fora do intervalo terapêutico adequado. Conclusão: Neste estudo, observou-se a necessidade de melhorar a qualidade das informações prestadas aos usuários e criar estratégias para adesão ao tratamento, visando à segurança do paciente em tratamento com varfarina na atenção primária à saúde.

Oral anticoagulation therapy with warfarin is widely used around the world and its safety and efficacy are well-established. Nevertheless, anticoagulants are among the drug classes most associated with fatal medication errors in primary health care. Objective: To investigate patient knowledge, the level of information provided, and medication adherence in patients treated with warfarin at a primary health care service. Method: A cross-sectional study of a prospective cohort of 60 patients on warfarin treatment in the town of Ijuí, Rio Grande do Sul, Brazil. A questionnaire was administered to test patients' knowledge about their prescriptions and the level of information provided by the health team. The 8-item Morisky Medication Adherence Scale (MMAS-8) and International Normalized Ratio (INR) were used to verify adherence to treatment. Results: The results were expressed in absolute and relative values and prevalence ratios were calculated, with respective 95% confidence intervals. It was found that 83.3% of the participants had been given insufficient information by the health team, 50% did not know how to use the medication correctly, 86.7% were not adherent to the treatment according to MMAS-8 and 63.3% were outside of the correct INR range. Conclusion: In this study, we observed a need to improve the quality of information provided to users and to develop strategies to improve adherence to treatment, to ensure the safety of patients treated with warfarin in primary health care services.

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Validation of the Center for Epidemiological Studies Depression Scale among Korean Adolescents

OBJECTIVE: The Center for Epidemiological Studies Depression Scale (CES-D) is designed to measure the current level of depressive symptomatology in the general population. However, no review has examined whether the scale is reliable and valid among children and adolescents in Korea. The purpose of this study was to test whether the Korean form of the CES-D is valid in adolescents. METHODS: Data were obtained from 1,884 adolescents attending grades 1–3 in Korean middle schools. Reliability was evaluated by internal consistency (Cronbach’s alpha). Concurrent validity was evaluated by a correlation analysis between the CES-D and other scales. Construct validity was evaluated by exploratory factor and confirmatory factor analyses. RESULTS: The internal consistency coefficient for the entire group was 0.88. The CES-D was positively correlated with scales that measure negative psychological constructs, such as the State Anxiety Inventory for Children, the Korean Social Anxiety Scale for Children and Adolescents, and the Reynold Suicidal Ideation Questionnaire, but it was negatively correlated with scales that measure positive psychological constructs, such as the Korean version of the Rosenberg Self-Esteem Scale and the Connor-Davidson Resilience Scale-2. The CES-D was examined by three-dimensional exploratory factor analysis, and the three-factor structure of the scale explained 53.165% of the total variance. The variance explained by factor I was 24.836%, that explained by factor II was 15.988%, and that explained by factor III was 12.341%. The construct validity of the CES-D was tested by confirmatory factor analysis, and we applied the entire group’s data using a three-factor hierarchical model. The fit index showed a level similar to those of other countries’ adolescent samples. CONCLUSION: The CES-D has high internal consistency and addresses psychological constructs similar to those addressed by other scales. The CES-D showed a three-factor structure in an exploratory factor analysis. The present findings suggest that the CES-D is a useful and reliable tool for measuring depression in Korean adolescents.

Differential protein expression in patients with urosepsis / 中华创伤杂志(英文版)

PURPOSE@#Urosepsis in adults comprises approximately 25% of all sepsis cases, and is due to complicated urinary tract infections in most cases. However, its mechanism is not fully clarified. Urosepsis is a very complicated disease with no effective strategy for early diagnosis and treatment. This study aimed to identify possible target-related proteins involved in urosepsis using proteomics and establish possible networks using bioinformatics.@*METHODS@#Fifty patients admitted to the Urology Unit of Lanzhou General PLA (Lanzhou, China), from October 2012 to October 2015, were enrolled in this study. The patients were further divided into shock and matched-pair non-shock groups. 2-DE technique, mass spectrometry and database search were used to detect differentially expressed proteins in serum from the two groups.@*RESULTS@#Six proteins were found at higher levels in the shock group compared with non-shock individuals, including serum amyloid A-1 protein (SAA1), apolipoprotein L1 (APOL1), ceruloplasmin (CP), haptoglobin (HP), antithrombin-III (SERPINC1) and prothrombin (F2), while three proteins showed lower levels, including serotransferrin (TF), transthyretin (TTR) and alpha-2-macroglobulin (A2M).@*CONCLUSION@#Nine proteins were differentially expressed between uroseptic patients (non-shock groups) and severe uroseptic patients (shock groups), compared with non-shock groups, serum SAA1, APOL1,CP, HP, SERPINC1and F2 at higher levels, while TF, TTR and A2M at lower levels in shock groups.these proteins were mainly involved in platelet activation, signaling and aggregation, acute phase protein pathway, lipid homeostasis, and iron ion transport, deserve further research as potential candidates for early diagnosis and treatment. (The conclusion seems too simple and vague, please re-write it. You may focus at what proteins have been expressed and introduce more detail about its significance.).

Association between thrombophilic genes polymorphisms and recurrent pregnancy loss susceptibility in the Iranian population: a systematic review and meta-analysis

Studies have indicated that thrombophilic genes polymorphisms are associated with recurrent pregnancy loss [RPL] in the Iranian population. We aimed to evaluate the precise association between thrombophilic genes polymorphisms [MTHFR C677T, MTHFR A1298C, Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G] and RPL risk in the Iranian population. PubMed, Web of Science, Google Scholar, and ISC were searched for eligible articles published up to April 1, 2017. In total, 37 case-control studies in 18 relevant publications were selected: 1,199, 1,194, 630, 830, and 955 RPL cases and 1,079, 1079, 594, 794, and 499 controls for MTHFR C677T, MTHFR A1298C,Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G, respectively. The results indicated a significant increased risk of RPL in all genetic models in the population. Also, Prothrombin G20210A and FVL G1691A as well as PAI-1 4G/5G polymorphisms were associated with RPL risk in the Iranian population. Hence, thrombophilic genes polymorphisms are associated with an increased RPL risk in the Iranian population

Non-Vitamin K Oral Anticoagulants Associated Bleeding and Its Antidotes / 대한뇌졸중학회지

Oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) accounts for nearly 20% of all ICH. The number of patients with an indication for oral anticoagulant therapy (OAT) increases with increasing age. OAT became less complicate with the introduction of non-vitamin K oral anticoagulants (NOAC) OAT because of easier handling, favorable risk-benefit profile, reduced rates of ICH compared to vitamin K antagonists and no need for routine coagulation testing. Consequently, despite a better safety profile of NOAC the number of patients with OAC-ICH will increase. The mortality and complication rates of OAC-ICH are high and therefore they are the most feared complication of OAT. Immediate normalization of coagulation is the main goal and therefore knowledge of pharmacodynamics and coagulation status is essential. Laboratory measurements of anticoagulant activity in NOAC patients is challenging as specific tests are not widely available. More accessible tests such as the prothrombin time and activated partial thromboplastin time have important limitations. In dabigatran-associated ICH 5 g Idarucizumab should be administered. In rivaroxaban and apixaban-associated ICHs administration of andexanet alpha should be considered. Prothrombin complex concentrate may be considered if andexanet alpha is not available or in case of an ICH associated with edoxaban.