Trombolisis sistémica complicada en embolia cerebral múltiple por trombo intraventricular / Systemic thrombolysis following multiple embolic cerebral lesions in a patient with myocardial infarction and intraventricular thrombus

RESUMEN Se presenta un caso de trombólisis sistémica complicada con transformación hemorrágica en paciente con evento isquémico cerebral sintomático por embolia múltiple a partir de trombo intraventricular en contexto de infarto agudo de miocardio por oclusión total de arteria descendente anterior con deterioro severo de función sistólica de ventrículo izquierdo.

ABSTRACT: We describe a case of complicated systemic thrombolysis with hemorrhagic transformation in a patient with a cerebral ischemic event due to multiple embolisms from intraventricular thrombus in the context of acute myocardial infarction due to total occlusion of the anterior descending artery and severe deterioration of left ventricular systolic function.

Riesgo de sangrado en pacientes anticoagulados con antagonistas de la vitamina K que reciben antibióticos / Risk of bleeding in anticoagulated patients with vitamin K antagonists who receive antibiotics

Lograr un adecuado nivel de anticoagulación con antagonistas orales de la vitamina K suele ser un desafío frecuente en la práctica clínica, dado que su estrecho rango terapéutico suele verse afectado por diversas interacciones farmacológicas,alimentos y condiciones clínicas. A partir de un caso de un paciente anticoagulado que presenta una hemorragia gastro-intestinal posterior a realizar un tratamiento antibiótico, la autora de este artículo revisó la evidencia sobre el riesgo desangrado secundario a la interacción entre este tipo de anticoagulantes y antibióticos orales. Su conclusión tras realizar una búsqueda bibliográfica y seleccionar la mejor evidencia disponible, es que existe un aumento del riesgo relativo desangrado en pacientes anticoagulados que reciben antibióticos, por lo que deberían evitarse aquellos antibióticos con conocido potencial de interacción. Si ello no fuera posible, se recomienda monitorizar el estado de anticoagulación con dosaje de la razón internacional normatizada (RIN) posterior a la introducción del antibiótico. (AU)

Achieving an adequate level of anticoagulation with oral vitamin K antagonists is often a frequent challenge in clinical practice, given that their narrow therapeutic range is often affected by various drug interactions, food, and clinical conditions. Based on a case of an anticoagulated patient who presented gastrointestinal bleeding after antibiotic treatment, the authorof this article reviewed the evidence on the risk of secondary bleeding due to the interaction between this type of anticoagulants and oral antibiotics. Their conclusion, after performing a literature search and selecting the best available evidence, is that there is an increased relative risk of bleeding in anticoagulated patients receiving antibiotics, so antibiotics with known potential for interaction should be avoided. If it weren't possible, it is recommended to monitor the anticoagulation status with International Normalized Ratio (INR) dosing after the introduction of the antibiotic. (AU)

Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design / 中国中药杂志

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

Study on anticoagulant material basis and mechanism of Trichosanthis Semen and its shell and kernel based on spectrum-effect relationship integrated molecular docking / 中国中药杂志

This study explored the anticoagulant material basis and mechanism of Trichosanthis Semen and its shell and kernel based on spectrum-effect relationship-integrated molecular docking. High performance liquid chromatography(HPLC) fingerprints of Trichosanthis Semen and its shell and kernel were established. Prothrombin time(PT) and activated partial thromboplastin time(APTT) in mice in the low-and high-dose(5, 30 g·kg~(-1), respectively) Trichosanthis Semen, the shell, and kernel groups were determined as the coagulation markers. The spectrum-effect relationship and anticoagulant material basis of Trichosanthis Semen and its shell and kernel were analyzed with mean value calculation method of Deng's correlation degree(MATLAB) and the common effective component cluster was obtained. Then the common targets of the component cluster and coagulation were retrieved from TCMSP, Swiss-TargetPrediction, GenCLiP3, GeneCards, and DAVID, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The main anticoagulant molecular mechanism of the component cluster was verified by SYBYL-X 2.1.1. The spectrum-effect relationship of Trichosanthis Semen and its shell and kernel was in positive correlation with the dosage. The contribution of each component to anticoagulation was not the same, suggesting that the material basis for anticoagulation was different, but they have common effective components(i.e. common material basis), such as adenine(peak 3), uracil(peak 4), hypoxanthine(peak 6), xanthine(peak 9), and adenosine(peak 11). Network pharmacology showed that these components can act on multiple target proteins such as NOS3, KDR, and PTGS2, and exert anticoagulant effect through multiple pathways such as VEGF signaling pathway. They involved the biological functions such as proteolysis, cell component such as cytosol, and molecular functions. The results of molecular docking showed that the binding free energy of these components with NOS3(PDB ID: 1 D0 C), KDR(PDB ID: 5 AMN), and PTGS2(PDB ID: 4 COX) was ≤-5 kJ·mol~(-1), and the docking conformations were stable. Spectrum-effect relationship-integrated molecular docking can be used for the optimization, virtual screening, and verification of complex chemical and biological information of Chinese medicine. Trichosanthis Semen and its shell and kernel have the common material basis for anticoagulation and they exert the anticoagulant through multiple targets and pathways.

Effect of heavy metal lead on anticoagulant activity of leech based on label-free quantitative proteomics / 中国中药杂志

Whitmania pigra is the most widely distributed species of leeches in the market. In this study, the effect of heavy metal lead pollution on the anticoagulant activity of Wh. pigra was studied and the potential mechanism was explored. Pb(NO_3)_2 was used to contaminate the breeding soil which was then used to rear Wh. pigra for 50 days(lead-contaminated group, LC group), and meanwhile the blank control group(CG group) was set. Proteins were extracted from the obtained leech samples, and the differentially expressed proteins between LC and CG groups were analyzed by label-free proteomics technology. In this study, a total of 152 differentially expressed proteins were screened out, of which 93 proteins were up-regulated and 59 proteins were down-regulated in LC group. Bioinformatics analysis showed that the biological processes enriched with the differentially expressed proteins were mainly vesicle-mediated transport and transport positive regulation; the enriched cell components were mainly endocytosis vesicles and apical plasma membrane; the enriched molecular functions mainly included carbohydrate binding. The differentially expressed proteins were enriched in 76 KEGG pathways, which mainly involved metabolic pathways, biosynthesis of secondary metabolites, and bacterial invasion of epithelial cells. In this study, two differentially expressed proteins with Antistasin domain were presumed, which provides reference for further exploring the regulatory mechanism and signal transduction underlying the effect of lead pollution on the anticoagulant activity of leech.

Does Enoxaparin treatment have any effects on the placenta in women with unexplained histories of habitual abortion? A case control study

ABSTRACT BACKGROUND: It is very common to offer low molecular weight heparin (LMWH) medications to women with unexplained habitual abortion, to increase the livebirth rate. Although no benefit from LMWH has been clearly demonstrated, examination of the effects of enoxaparin on placental structure is lacking. OBJECTIVE: To assess placental structural changes in pregnancies treated with enoxaparin, compared with controls. DESIGN AND SETTING: Case-control study in an obstetrics and gynecology unit of a tertiary-level university hospital in Turkey. METHODS: Forty patients who had had term pregnancies and live births but also histories of habitual abortion were recruited for this study. Placentas were sampled using a systematic random sampling method. Tissue samples were obtained, embedded and sectioned for routine histological analyses. Hematoxylin and eosin staining was used. Surface area and length estimates from placental components were evaluated by using Image J. Cell proliferation and apoptosis were also assessed via immunohistochemistry. RESULTS: There were no significant differences between the groups regarding maternal age, abortion rate, birth weight or gestational age. Comparison of the enoxaparin and control groups showed that there were no significant differences in terms of surface area and ratios of placental components. We found that Bcl-2 was generally expressed at high levels in the enoxaparin group, while there was no difference in terms of Ki-67 between the groups. CONCLUSIONS: This study demonstrates that enoxaparin did not show any significant effect on the placental structure of cases that had histories of habitual abortion.

Safety and efficacy of regional citrate anticoagulation in continuous blood purification treatment of patients with multiple organ dysfunction syndrome

The aim of this study was to discuss the safety and efficacy of regional citrate anticoagulation (RCA) on continuous blood purification (CBP) during the treatment of multiple organ dysfunction syndrome (MODS). Thirty-five patients with MODS were divided into two groups: the local citrate anticoagulation (RCA) group, and the heparin-free blood purification (hfBP) group. The MODS severity was assessed according to Marshall's MODS score criteria. Blood coagulation indicators, blood pressure, filter lifespan, filter replacement frequency, anticoagulation indicators, and main metabolic and electrolyte indicators were analyzed and compared between RCA and hfBP groups. RCA resulted in lower blood pressure than hfBP. The filter efficacy in RCA treatment was longer than in the hfBP group. The blood clearance of creatine, blood urea nitrogen and uric acid was better in the RCA group. RCA also led to higher pH than hfBP. Neither treatment resulted in severe bleeding events. In addition, MODS score was positively correlated with prothrombin time and activated partial thromboplastin time but negatively correlated with platelet concentration. RCA is a safer and more effective method in CBP treatment; however, it could also lead to low blood pressure and blood alkalosis.

Uso de varfarina em pediatria: características clínicas e farmacológicas / Use of warfarin in pediatrics: clinical and pharmacological characteristics

RESUMO Objetivo: Descrever como as crianças respondem à anticoagulação oral com varfarina, verificando a influência da idade, da condição clínica, da via de administração da varfarina e do uso de Nutrição Parenteral Total (NPT), e apresentar a presença de fatores de risco para eventos tromboembólicos (TE). Métodos: Estudo transversal retrospectivo com pacientes ≤18 anos que iniciaram o uso da varfarina em um hospital universitário. Os pacientes foram divididos conforme condição clínica, idade, forma de administração do medicamento e uso de NPT. Foram utilizados os dados dos prontuários dos pacientes, considerando os fatores de risco para TE já descritos na literatura, o tempo e a dose necessária para atingir a primeira Razão Normalizada Internacional (INR) no alvo e eventos adversos nesse período. No período posterior ao alcance de INR, foi verificada a manutenção da anticoagulação, por meio da dose prescrita e dos exames de INR. Resultados: Vinte e nove pacientes foram incluídos no estudo. O principal fator de risco para TE foi o uso de cateter venoso central, em 89,6% dos pacientes. Os pacientes com síndrome do intestino curto e em uso de NPT necessitaram de doses significativamente maiores (p≤0,05) para atingir e manter a INR no alvo. Os pacientes com ≤1 ano levaram mais tempo e necessitaram de uma dose maior para anticoagular e para manter o INR no alvo que os pacientes mais velhos. A mediana de exames de INR abaixo do alvo foi de 48,2% nos grupos estudados. Conclusões: A complexidade da terapia anticoagulante reforça a necessidade da elaboração de protocolos que orientem a prática clínica.

ABSTRACT Objective: To describe how children respond to oral anticoagulation with warfarin, verifying the influence of age, clinical condition, route of administration of warfarin and use of total parenteral nutrition (TPN), as well as to describe risk factors for the occurrence of thrombotic events (TE) in childhood. Methods: A retrospective descriptive study including all patients ≤18 years old for whom warfarin was prescribed in a university hospital. Patients were divided according to clinical condition, age, route of medication administration and use of TPN. Data was collected from the patients' medical records and the analysis considered the risk factors for TE already described in the literature, the time and the dose required in order to reach the first International Normalized Ratio (INR) in the target and the adverse events in this period. After reaching the INR, the maintenance of anticoagulation was verified by the prescribed dose and INR tests. Results: Twenty-nine patients were included in the study. The major risk factor for TE was the use of a central venous catheter in 89.6% of the patients. Patients with short bowel syndrome and total parenteral nutrition required significantly higher doses (p≤0.05) to achieve and maintain the INR in the target. Patients ≤1 year old needed longer periods and required an increased dose of anticoagulation and maintenance than older patients. The mean number of INR examinations below the target was 48.2% in the groups studied. Conclusions: The observed complexity of anticoagulant therapy reinforces the need to develop protocols that guide clinical practice.

Reunión multidisciplinaria sobre el uso de los anticoagulantes orales directos en la fibrilación auricular no valvular / Multidisciplinary meeting about the use of direct oral anticoagulants in nonvalvular atrial fibrillation

Resumen: Conociendo el impacto real de la fibrilación auricular en el evento vascular cerebral, la Sociedad Mexicana de Electrofisiología y Estimulación Cardiaca (SOMEEC) contempló la iniciativa de desarrollar una reunión multidisciplinaria de expertos con la finalidad de actualizar la evidencia científica disponible a partir de guías de práctica clínica, metaanálisis y ensayos clínicos controlados, y complementarla con la experiencia y los puntos de vista de un grupo de expertos. Para cumplir con este objetivo, se reunió a un grupo de especialistas en el área de cardiología, electrofisiología, neurología y hematología que, dada su experiencia en ciertas áreas, compartieron la evidencia científica disponible ante el panel de expertos para dejar abierta una discusión sobre la información que se presentaría en el presente artículo. Este documento reúne la mejor evidencia científica disponible y pretende ser una herramienta útil que agilice la toma de decisiones para uso de los nuevos anticoagulantes orales en fibrilación auricular no valvular y cardiopatía isquémica, o referente al manejo de pacientes que presentan evento vascular cerebral, o insuficiencia renal, e incluso en aquellos que serán sometidos a procedimientos invasivos y cirugía electiva. En la misma se manejan esquemas comparativos de seguimiento y tratamiento que simplifica la toma de decisión por los especialistas participantes.

Abstract: Knowing the real impact of atrial fibrillation in the stroke, the Sociedad Mexicana of Electrofisiología y Estimulación Cardiaca (SOMEEC) had the initiative to develop a multidisciplinary meeting of experts the with the purpose to update the available scientific evidence from clinical practice guidelines, meta-analyses, controlled clinical trials, and complementing with the experience and views of a group of experts. To meet this goal, SOMEEC gathered a group of specialists in the area of cardiology, electrophysiology, neurology and hematology that given their experience in certain areas, they share the scientific evidence with the panel of experts to leave open a discussion about the information presented in this article. This document brings together the best scientific evidence available and aims to be a useful tool in the decision to use of new oral anticoagulants in nonvalvular atrial fibrillation and ischemic heart disease, or relating to the management of patients with stroke or renal failure, and even those that will be submitted to elective surgery and invasive procedures. In the same, they handled comparative schemes of follow-up and treatment which simplifies the decision making by the specialists participants.

Doppler velocimetry in fetal rats exposed to enoxaparin and unfractionated heparin (UFH) during pregnancy

Abstract Purpose: To evaluate the effects of enoxaparin and unfractionated heparin (UFH) administered in prophylactic and therapeutic doses on fetal vessels in healthy pregnant Wistar rats, according to Doppler velocimetry measurements. Methods: Fifty animals were assigned to one of five groups: controls (saline), prophylactic and therapeutic enoxaparin (1 and 2 mg/kg/day, respectively), and prophylactic and therapeutic UFH (72 and 400 UI/kg/day, respectively). Uterine horns were examined by ultrasound for identification of live fetuses. A sample of these fetuses underwent Doppler velocimetry. Spectral curves, peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery, ductus venosus, and umbilical artery were investigated. Differences were considered statistically significant when p<0.05. Results: No significant differences in PSV, PI, or RI values were observed among the groups. Conclusion: Doppler velocimetry measurements revealed no significant effects of enoxaparin or unfractionated heparin on fetal vessels in pregnant Wistar rats.

Protocolos de actuación y tratamiento anticoagulante oral / Performance protocols and oral anticoagulant treatment

Los anticoagulantes orales son medicamentos de probada eficacia utilizados en la prevención de la morbilidad y mortalidad relacionada con la enfermedad tromboembólica. Se estima que en los países desarrollados la población que se encuentra bajo tratamiento anticoagulante oral alcanza montos de hasta 5 000 por millón de habitantes y se pronostica un aumento progresivo por encima de un 15 por ciento por año en el número de enfermos sujetos a este tratamiento....

Destaques do VII international symposium of thrombosis and anticoagulation (ISTA) / Highlights of VII international symposium of thrombosis and anticoagulation (ISTA)

O VII Simpósio Internacional de Trombose e Anticoagulação (ISTA) foi realizado em São Paulo, SP, Brasil, nos dias 24 e 25 de outubro de 2014, tendo como principais propósitos a discussão e o compartilhamento de conhecimentos sobre os avanços recentes na abordagem diagnóstica e terapêutica de pacientes com distúrbios trombóticos, nas suas diversas formas de apresentação clínica. O programa científico deste simpósio foi cuidadosamente desenvolvido por líderes de três importantes institutos de pesquisa clínica: o Instituto Brasileiro de Pesquisa Clínica(BCRI), o Duke Clinical Research Institute (DCRI), e Instituto de Pesquisa do Hospital do Coração. Composto por dois dias de apresentações acadêmicas e discussão aberta, o simpósio teve como principal objetivo educar, motivar e inspirar os clínicos, cardiologistas, hematologistas, e outros médicos através de apresentações e discussões de aspectos práticos de condutas que envolvem síndromes relacionadas à trombose e suas respectivas terapias antitrombóticas. Estas atividades possibilitaram uma interação direta entre a plateia e o corpo de palestrantes, composto por médicos de grande experiência clínica e pelos médicos pesquisadores que desenvolveram os principais estudos publicados que guiam nossas condutas em situações relacionadas ao tema "trombose e anticoagulação". Este artigo resume os anais deste simpósio.

The VII International Symposium on Thrombosis and Anticoagulation (ISTA) was held in São Paulo, Brazil, on 24 and 25 October 2014, with the main objectives to discuss and share knowledge on recent advances in the diagnosis and management of patients with thrombotic disorders. The scientific program of this symposium was carefully developed by leaders of three major clinical research institutes: the Brazilian Institute of Clinical Research (BCRI), the Duke Clinical Research Institute from Duke University, and the Research Institute from Hospital do Coração. Comprising two days of academic presentations and open discussion, the symposium aimed to educate, motivate and inspire clinicians, cardiologists, hematologists, and other doctors through presentations and discussions of practical aspects in themes related to thrombosis and anticoagulation. These activities were presented by physicians of great clinical experience and who participated in the main publications that guide our approach on situations related to the theme "thrombosis and anticoagulation". This article summarizes the proceedings of this symposium.

Novos anticoagulantes orais (NOACs) na prevenção de acidente vascular encefálico (AVE) e fenômenos tromboembólicos em pacientes com fibrilação atrial / New oral anticoagulants (NOACs) in prevention of stroke brain and thromboembolic events in patients with atrial fibrillation

JUSTIFICATIVA E OBJETIVOS: Pacientes com fibrilação atrial (FA) estão mais propensos à ocorrência de eventos vasculares, como acidente vascular encefálico (AVE) e fenômenos tromboembólicos, sendo necessária anticoagulação oral. A varfarina, o anticoagulante mais utilizado, tem uma série de limitações referentes ao seu uso. Nesse contexto, foram desenvolvidos novos anticoagulantes orais (NOACs): inibidores da trombina (dabigatrana) e do fator Xa (rivaroxabana e apixabana). Essa revisão sistemática procurou elencar os principais resultados de Ensaios Clínicos Randomizados (ECRs) abordando o tema NOACs em pacientes com fibrilação atrial para a prevenção de acidente vascular encefálico e/ou fenômenos tromboembólicos. CONTEÚDO: Foram pesquisados Ensaios Clínicos Randomizados, cegos ou abertos, em indivíduos adultos, nas bases PubMed, Scopus, Web of Science, SciELO, LILACS e Cochrane CENTRAL. A avaliação da qualidade dos estudos foi feita utilizando a escala Downs & Black. Foram selecionados cinco Ensaios Clínicos Randomizados e descritos os seus resultados. A rivaroxabana se mostrou não inferior a varfarina no que diz respeito ao desfecho combinado embolismo sistêmico e acidente vascular encefálico, enquanto que a apixabana e a dabigatrana 150mg mostraram-se superiores. Todos os três medicamentos estiveram associados a menor incidência de hemorragia intracraniana quando comparado a varfarina. A apixabana mostrou perfil mais favorável em relação à ocorrência de qualquer sangramento. CONCLUSÕES: os Ensaios Clínicos Randomizados selecionados demonstraram a eficácia dos NOACs na prevenção de acidente vascular encefálicos e/ou embolismo sistêmico em pacientes com fibrilçao atrial. Contudo, são necessários mais estudos para preencher as lacunas do conhecimento quanto à eficácia e segurança desta nova classe de anticoagulantes orais.

BACKGROUND AND OBJECTIVES: Patients with atrial fibrillation (AF) are more likely to the occurrence of vascular events including stroke and thromboembolism systemic. Thus anticoagulation is necessary to prevent these events. Warfarin is the current gold standard but has a number of limitations regarding your use. In this context, new oral anticoagulants (NOACs) were developed: thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban). The aim of this systematic review was to analyze the results of the main randomized clinical trials (RCTs) envolving NOACs in patients with atrial fibrillation for the prevention of stroke and/or thromboembolic events. CONTENTS: Double blinded or open label randomized clinical trials envolving patients with FA testing these drugs were researched in PubMed, Scopus, Web of Science, SciELO, LILACS and Cochrane CENTRAL. The quality assessment of studies used the Downs & Black Scale Five randomized clinical trials were selected, envolving 57.457 patients. Dabigatran, apixaban and rivaroxaban were at least non inferior to the warfarin in the outcome of stroke and systemic embolism. Apixaban and dabigatran 150mg were also superior than warfarin in efficacy. All three drugs were associated with a lower incidence of intracranial hemorrhage. Apixaban was related to lower risk of total bleeding. CONCLUSIONS: NOACs have efficacy to prevent AVE and systemic thromboembolism in patients with FA. However further studies are needed to resolve the issues that remain open and to provide more security to the use of these drugs in clinical practice.

Scoring System for Detecting Spurious Hemolysis in Anticoagulated Blood Specimens

BACKGROUND: The identification of in vitro hemolysis (IVH) using a hematology analyzer is challenging because centrifugation of the specimens cannot be performed for cell counts. In the present study, we aimed to develop a scoring system to help identify the presence of hemolysis in anticoagulated blood specimens. METHODS: Thirty-seven potassium EDTA anticoagulated blood specimens were obtained, and each specimen was divided into 3 aliquots (A, B, and C). Aliquots B and C were mechanically hemolyzed by aspirating 2 and 5 times, respectively, using a 27-gauge needle and then tested; aliquot A was analyzed immediately without any hemolysis. After the cells were counted, aliquots B and C were centrifuged and the supernatants were tested for the hemolytic index and lactate dehydrogenase levels. RESULTS: The 4 hematologic parameters were selected and scored from 0 to 3 as follows: or =38.5 for mean cell hemoglobin concentration (MCHC, g/dL); or =0.04 for red blood cell ghosts (10(12)/L); or =1.31 for difference value (g/dL) of measured hemoglobin and calculated hemoglobin; and or =3.35 for difference value (g/dL) of MCHC and cell hemoglobin concentration mean. The hemolysis score was calculated by adding all the scores from the 4 parameters. At the cutoff hemolysis score of 3, the IVH of aliquots B and C were detected as 64.9% and 91.9%, respectively. CONCLUSIONS: The scoring system might provide effective screening for detecting spurious IVH.

Analysis of Novel Anticoagulants for Atrial Fibrillation – Pharmacokinetics and Pharmacological Considerations.

Atrial Fibrillation (AF) is the most common arrhythmia. AF is a major risk factor for stoke. Warfarin has been available for more than 60 years and until recently it was the only oral anticoagulant used for the prevention of stroke. Despite the extensive studies and proven efficacy, its utility is limited by multiple factors. Warfarin interacts with a multitude of drugs and foods, has a delayed onset of action, has a narrow therapeutic range, requires routine lab monitoring and exhibits variable responses in patients. The novel agents dabigatran, rivaroxaban and apixaban have the potential to have some of the limitations of warfarin. This article will discuss the pharmacokinetic and pharmacological considerations and different characteristics of the novel anticoagulants when used for the prevention of AF.

Personalized medicine and the clinical laboratory / Medicina personalizada e o laboratório clínico

Personalized medicine is the use of biomarkers, most of them molecular markers, for detection of specific genetic traits to guide various approaches for preventing and treating different conditions. The identification of several genes related to heredity, oncology and infectious diseases lead to the detection of genetic polymorphisms that are involved not only in different clinical progression of these diseases but also in variations in treatment response. Currently, it is possible to detect these polymorphisms using several methodologies: detection of single nucleotide polymorphisms using polymerase chain reaction methods; nucleic acid microarray detection; and nucleic acid sequencing with automatized DNA sequencers using Sanger-derived methods and new generation sequencing. Personalized medicine assays are directed towards detecting genetic variations that alter interactions of drugs with targets or the metabolic pathways of drugs (upstream and downstream) and can be utilized for the selection of drug formulations and detect different immunogenicities of the drug. Personalized medicine applications have already been described in different areas of Medicine and allow specific treatment approaches to be applied to each patient and pathology according to the results of these assays. The application of such a protocol demands an increasing interaction between the clinical laboratory and the clinical staff. For its implementation, a coordinated team composed of basic researchers and physicians highly specialized in their areas supported by a highly specialized team of clinical analysts particularly trained in molecular biology assays is necessary.

Medicina personalizada é o uso de biomarcadores, em sua maioria marcadores moleculares, para a detecção de traços genéticos específicos, a fim de orientar diversas abordagens para a prevenção e o tratamento de diferentes doenças. A identificação de vários genes relacionados a doenças hereditárias, oncológicas e infecciosas permite a detecção de polimorfismos genéticos que estão envolvidos em diferentes evoluções clínicas dessas doenças, bem como com variações na resposta ao tratamento. Atualmente, já é possível detectar esses polimorfismos utilizando diversas metodologias: a detecção de polimorfismos de nucleotídeo único pela reação de polimerização em cadeia; a detecção de microarranjos de ácidos nucleicos; e o sequenciamento de ácidos nucleicos com sequenciadores de DNA automatizados usando métodos derivados de sequenciamento Sanger ou de nova geração. Os ensaios de medicina personalizada são dirigidos para detectar variações genéticas que alteram interações de fármacos com alvos ou vias metabólicas de fármacos (anabólicas e catabólicas), podendo ser utilizados para a seleção de formulações farmacêuticas e para detectar diferentes imunogenicidades da droga. As aplicações de medicina personalizada já foram descritas em várias áreas da Medicina e permitem que abordagens de tratamento específicas sejam aplicadas para cada paciente e para cada doença, de acordo com os resultados dos ensaios utilizados. A aplicação de um protocolo desse tipo exige uma relação intensa entre o laboratório e o corpo clínico. Para sua execução, é necessária uma equipe coordenada, composta por investigadores de pesquisa básica e médicos altamente especializados em suas áreas, apoiada por um time bastante especializado de analistas clínicos treinados em testes de biologia molecular.