ABSTRACT Objective: Prolong platelet survival and functionality up to 28 days. Methods: A sample of apheresis platelets was evaluated, distributed in 3 groups according to the cryopreservative solution used: DMS05%+2%albumin; DMSO5%+NaC10,9% and DMS05%+Dextrose2%. They were then frozen at -80 °C and thawed at 7, 14 and 28 days. The in vitro survival and viability were assessed by the post-thaw platelet count and the CD41, CD61 and CD42a staining percentages by flow cytometry. The functionality was determined with the percentage of post-stimulation aggregation with INm-thrombin using the Chromo-Log490 aggregometer. The control group (CG) consisted of fresh platelets under constant agitation at 22 °C. Results: A total of 72 platelet aliquots was analyzed. The CG presented a platelet-count of 1934 ± 0.5 × 109/L and a 100% viability. The percentages of CD41, CD61 and CD42a labeling were 99, 98.5 and 96.5%, respectively. The percentage of aggregation was 99%. On day 7 of the post-freezing, the platelet count for groups 1, 2 and 3 was 1,844 ± 102, 1,856 ± 76 and 1,752 ± 226, with the viability of 98, 96 and 95%, respectively. On day 14, the counts were 1,722 ± 238, 1,649 ± 215 and 1,578 ± 223 with the viability of 96, 95 and 94% and, on day 28, they were 1,602 ± 374, 1,438.6 ± 429 and 1,406.6 ± 436, with the viability of 96, 94 and 93%, respectively. Groupl presented a higher expression of membrane antigens. Aggregation percentages were 90, 98 and 89% at day 7, 88%, 98 and 87% at day 14 and 84%, 95 and 82% at day of the 28 post-freezing, respectively, with group2 presenting the best results. Conclusion: The results support cryopreservation as a reasonable method to prolong platelet survival up to 28 days, maintaining its functionality and viability greater than 50%. Objective days Methods evaluated used DMS05%+2%albumin DMS052albumin DMSalbumin DMS05 albumin DMS DMSO5NaC109 DMSONaC DMSO5 NaC10 9 DMSO NaC DMSO5%+NaC10,9 DMS05Dextrose2 DMSDextrose Dextrose2 Dextrose DMS05%+Dextrose2% 80 -8 C 1 postthaw post thaw CD41 CD CD6 CDa cytometry poststimulation stimulation INmthrombin INm thrombin ChromoLog490 ChromoLog Chromo Log490 Log Chromo-Log49 aggregometer (CG Results analyzed plateletcount 193 05 0 5 0. 109L L 109 100 99 985 98. 965 96.5% respectively 99% postfreezing, postfreezing freezing, freezing post-freezing 1844 844 1,84 102 1856 856 1,85 1752 752 1,75 226 95% 1722 722 1,72 238 1649 649 1,64 21 1578 578 1,57 1602 602 1,60 374 14386 438 6 1,438. 42 14066 406 1,406. 436 93 93% antigens 90 89 88 88% 87 84 84% 82 Conclusion 50 50% DMS0 DMSO5NaC10 NaC1 DMSO5%+NaC10, DMS05Dextrose DMS05%+Dextrose2 8 - CD4 ChromoLog49 Log49 Chromo-Log4 19 10 96.5 184 1,8 185 85 175 75 1,7 172 23 164 64 1,6 157 57 1,5 160 60 37 1438 43 1,438 4 1406 40 1,406 DMSO5NaC1 DMSO5%+NaC10 DMS05%+Dextrose ChromoLog4 Log4 Chromo-Log 96. 18 17 16 15 143 1,43 140 1,40 DMSO5NaC DMSO5%+NaC1 1,4 DMSO5%+NaC

ABSTRACT Objective The use of acetylsalicylic acid, even in low doses, may be associated with the onset of upper gastrointestinal bleeding as an idiosyncratic response. Considering the role of the genetic background in inter-individual responses to pharmacotherapy, we aimed to investigate the role of seven variants in the TNF-α, IL-β, and IL-1RN genes in association with the risk of upper gastrointestinal bleeding in users of low-dose acetylsalicylic acid for the prevention of cardiovascular events. Methods A case-control study was conducted in a Brazilian hospital complex. The Case Group comprised patients diagnosed with upper gastrointestinal bleeding who were administered a low dose of acetylsalicylic acid (n=50). Two Control Groups were recruited: 1) low-dose acetylsalicylic acid users without gastrointestinal complaints and under the supervision of a cardiologist (n=50) and 2) healthy controls (n=189). Sociodemographic, clinical, pharmacotherapeutic, and lifestyle data were recorded through face-to-face interviews. Genomic DNA from all participants was genotyped for rs16944 and rs1143634 (IL-β gene), rs4251961 (IL-1RN gene), and rs1799964, rs1799724, rs361525, and rs1800629 (TNF-α gene). Results No significant difference was noted in the genotypic frequencies of TNF-α, IL-β, and IL-1RN variants between the Case and Control Groups of low-dose acetylsalicylic acid users (p>0.05). The frequency of rs1800629 genotypes (TNF-α gene) differed significantly between the Case Group and healthy controls (p=0.003). None of the evaluated variants were associated with a risk of upper gastrointestinal bleeding. Conclusion This study aimed to explore pharmacogenomics biomarkers in low-dose acetylsalicylic acid users. Our data suggest that the presence of IL-1β, IL-1RN, and TNF-α variants was not associated with an increased risk of upper gastrointestinal bleeding. doses response interindividual inter individual pharmacotherapy TNFα, TNFα TNF α, α ILβ, ILβ IL β, β IL-β IL1RN ILRN 1RN RN lowdose events casecontrol case control complex n=50. n50 n n=50 . 50 recruited 1 (n=50 2 n=189. n189 n=189 189 (n=189) Sociodemographic clinical pharmacotherapeutic facetoface face interviews rs rs1694 rs114363 gene, gene , rs425196 rs1799964 rs1799724 rs361525 rs180062 gene. p>0.05. p005 p p>0.05 0 05 (p>0.05) p=0.003. p0003 p=0.003 003 (p=0.003) IL1β, IL1β 1β, 1β IL-1β IL1RN, 1RN, n5 n=5 5 (n=5 n18 n=18 18 (n=189 rs169 rs11436 rs42519 rs179996 rs179972 rs36152 rs18006 p00 p>0.0 (p>0.05 p000 p=0.00 00 (p=0.003 n= (n= n1 n=1 (n=18 rs16 rs1143 rs4251 rs17999 rs17997 rs3615 rs1800 p0 p>0. (p>0.0 p=0.0 (p=0.00 (n (n=1 rs1 rs114 rs425 rs1799 rs361 rs180 p>0 (p>0. p=0. (p=0.0 rs11 rs42 rs179 rs36 rs18 p> (p>0 p=0 (p=0. rs4 rs17 rs3 (p> p= (p=0 (p (p=

Resumen: La migraña es una enfermedad que se ha visto asociada a defectos septales auriculares y a su cierre percutáneo, estipulándose en la literatura que sería una rara complicación, pero la evidencia al respecto es escasa. Se realizó una revisión narrativa sobre definiciones, epidemiología, fisiopatología y tratamiento de la migraña y de la entidad migraña poscierre percutáneo de defectos del septum auricular, incluyendo trabajos observacionales (retrospectivos, prospectivos), estudios randomizados, reportes de casos, artículos de revisión y metaanálisis existentes en PubMed y Cochrane, para aportar al conocimiento de esta entidad.

Abstract: Migraine is a disease that has been associated with atrial septal defects and its percutaneous closure, stipulating in the literature that it would be a rare complication, but evidence is scarce. A narrative review was conducted on definitions, epidemiology, pathophysiology and treatment of migraine and the migraine entity after percutaneous closure of atrial septum defects, including observational studies (retrospective, prospective), randomized studies, case reports, review articles and meta-analyses existing in PubMed and Cochrane, to contribute to the knowledge of this entity.

Resumo: A enxaqueca é uma doença que tem sido associada a defeitos do septo atrial e seu fechamento percutâneo, estipulando na literatura que seria uma complicação rara, mas as evidências são escassas. Foi realizada uma revisão narrativa sobre definições, epidemiologia, fisiopatologia e tratamento da enxaqueca e da entidade migranosa após fechamento percutâneo de defeitos do septo atrial, incluindo estudos observacionais (retrospectivos, prospectivos), estudos randomizados, relatos de caso, artigos de revisão e metanálises existentes no PubMed e Cochrane, para contribuir com o conhecimento dessa entidade.

Abstract Background Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR). Objectives To realize a systematic literature review to determine the impact of genetic variants on AR. Methods Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included. Results The genetic variants rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2), and rs5918 (ITGB3) were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance (p< 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 and rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 and rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP), and rs662 (PON1), while these differ in real interference in AR: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1), and rs20417 (PTGS2). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences. Conclusion It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR. CVD . (CVD) acid vasoconstriction Nevertheless AR (AR) MEDLINEPubMed MEDLINE PubMed MEDLINE/PubMed Cochrane Scopus LILACS screened 29 26 criteria 2 casecontrol case included rs rs112664 ITGA2, ITGA2 ITGA , (ITGA2) rs384278 PTGS1, PTGS1 PTGS (PTGS1) rs2041 PTGS2, PTGS2 (PTGS2) rs591 ITGB3 ITGB (ITGB3 studied relevance 6 p< p (p 0.05 005 0 05 95 CI [CI] article them results rs137109 P2RY1, P2RY1 PRY P RY (P2RY1) rs104564 MDR1, MDR1 MDR (MDR1) rs105193 rs775693 PLA2G7, PLA2G7 PLAG PLA G (PLA2G7) rs207174 HO1, HO1 HO (HO1) rs113188 rs452 TBXA2R, TBXA2R TBXAR TBXA R (TBXA2R) rs43447 ALOX12, ALOX12 ALOX (ALOX12) rs931504 ALOX5AP, ALOX5AP ALOXAP AP (ALOX5AP) rs66 PON1, PON1 PON (PON1) ITGB3, rs224309 GP1BA, GP1BA GPBA GP BA (GP1BA) rs133034 PTGS2. limitations differences area Therefore (CVD (AR rs11266 (ITGA2 rs38427 (PTGS1 rs204 (PTGS2 rs59 (ITGB 0.0 00 9 [CI rs13710 P2RY (P2RY1 rs10456 (MDR1 rs10519 rs77569 PLA2G (PLA2G7 rs20717 (HO1 rs11318 rs45 (TBXA2R rs4344 ALOX1 (ALOX12 rs93150 (ALOX5AP rs6 (PON1 rs22430 (GP1BA rs13303 rs1126 (ITGA rs3842 (PTGS rs20 rs5 0. rs1371 (P2RY rs1045 (MDR rs1051 rs7756 (PLA2G rs2071 (HO rs1131 rs4 rs434 (ALOX1 rs9315 (PON rs2243 rs1330 rs112 rs384 rs2 rs137 rs104 rs105 rs775 rs207 rs113 rs43 (ALOX rs931 rs224 rs133 rs11 rs38 rs13 rs10 rs77 rs93 rs22 rs1 rs3 rs7 rs9

Resumo Antecedentes A farmacogenética promete melhorar o controle de doenças como as cardiovasculares. O ácido acetilsalicílico, a aspirina, previne a formação de um agente ativador da agregação plaquetária e vasoconstrição e é usado na prevenção de tais doenças. No entanto, os pacientes podem ter falha no tratamento devido a variantes genéticas que modificam o metabolismo da droga causando resistência à aspirina (RA). Objetivos Realizar uma revisão sistemática da literatura para determinar o impacto das variantes genéticas na resistência à aspirina. Métodos Artigos publicados nos bancos de dados MEDLINE/PubMed, Cochrane, Scopus, LILACS e SCIELO foram sistematicamente selecionados. Foram identificados 290 artigos e, destes, 269 artigos foram excluídos por não atenderem aos critérios de inclusão previamente estabelecidos. Um total de 20 estudos caso-controles e 1 coorte foi incluído. Resultados As variantes genéticas rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2) e rs5918 (ITGB3) foram as mais estudadas. Quanto à relevância, das 64 variantes genéticas avaliadas pelos artigos, 14 tiveram significância estatística (p< 0,05; intervalo de confiança [IC] de 95%) em pelo menos um artigo. Entre eles, os seguintes tiveram resultados unânimes: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 e rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 e rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP) e rs662 (PON1), enquanto estes diferiram na interferência real na RA: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1) e rs20417 (PTGS2). Como limitações do estudo, destacam-se as metodologias não uniformes dos artigos analisados e as diferenças populacionais. Conclusão Vale ressaltar que a farmacogenética é uma área em expansão. Portanto, mais estudos são necessários para entender melhor a associação entre variantes genéticas e RA. cardiovasculares acetilsalicílico entanto RA . (RA) MEDLINEPubMed MEDLINE PubMed MEDLINE/PubMed Cochrane Scopus selecionados 29 destes 26 estabelecidos 2 casocontroles caso controles incluído rs rs112664 ITGA2, ITGA2 ITGA , (ITGA2) rs384278 PTGS1, PTGS1 PTGS rs2041 PTGS2 (PTGS2 rs591 ITGB3 ITGB (ITGB3 estudadas relevância 6 p< p (p 0,05 005 0 05 IC [IC 95% 95 artigo eles unânimes rs137109 P2RY1, P2RY1 PRY P RY (P2RY1) rs104564 MDR1, MDR1 MDR (MDR1) rs105193 rs775693 PLA2G7, PLA2G7 PLAG PLA G (PLA2G7) rs207174 HO1, HO1 HO (HO1) rs113188 rs452 TBXA2R, TBXA2R TBXAR TBXA R (TBXA2R) rs43447 ALOX12, ALOX12 ALOX (ALOX12) rs931504 ALOX5AP ALOXAP AP (ALOX5AP rs66 PON1, PON1 PON (PON1) ITGB3, rs224309 GP1BA, GP1BA GPBA GP BA (GP1BA) rs133034 (PTGS1 PTGS2. estudo destacamse destacam se populacionais expansão Portanto (RA rs11266 (ITGA2 rs38427 rs204 (PTGS rs59 (ITGB 0,0 00 9 rs13710 P2RY (P2RY1 rs10456 (MDR1 rs10519 rs77569 PLA2G (PLA2G7 rs20717 (HO1 rs11318 rs45 (TBXA2R rs4344 ALOX1 (ALOX12 rs93150 rs6 (PON1 rs22430 (GP1BA rs13303 rs1126 (ITGA rs3842 rs20 rs5 0, rs1371 (P2RY rs1045 (MDR rs1051 rs7756 (PLA2G rs2071 (HO rs1131 rs4 rs434 (ALOX1 rs9315 (PON rs2243 rs1330 rs112 rs384 rs2 rs137 rs104 rs105 rs775 rs207 rs113 rs43 (ALOX rs931 rs224 rs133 rs11 rs38 rs13 rs10 rs77 rs93 rs22 rs1 rs3 rs7 rs9

ABSTRACT Snake venom disintegrins are low molecular weight, non-enzymatic proteins rich in cysteine, present in the venom of snakes from the families Viperidae, Crotalidae, Atractaspididae, Elapidae, and Colubridae. This family of proteins originated in venom through the proteolytic processing of metalloproteinases (SVMPs), which, in turn, evolved from a gene encoding an A Disintegrin And Metalloprotease (ADAM) molecule. Disintegrins have a recognition motif for integrins in their structure, allowing interaction with these transmembrane adhesion receptors and preventing their binding to proteins in the extracellular matrix and other cells. This interaction gives disintegrins their wide range of biological functions, including inhibition of platelet aggregation and antitumor activity. As a result, many studies have been conducted in an attempt to use these natural compounds as a basis for developing therapies for the treatment of various diseases. Furthermore, the FDA has approved Tirofiban and Eptifibatide as antiplatelet compounds, and they are synthesized from the structure of echistatin and barbourin, respectively. In this review, we discuss some of the main functional and structural characteristics of this class of proteins and their potential for therapeutic use. weight nonenzymatic non enzymatic cysteine Viperidae Crotalidae Atractaspididae Elapidae Colubridae SVMPs, SVMPs , (SVMPs) which turn ADAM (ADAM molecule cells functions activity result diseases Furthermore barbourin respectively review (SVMPs

Abstract Introduction: Plasmatic fibrinogen is known as a main risk factor to cardiometabolic diseases through mechanisms such as thrombin formation, platelet aggregation and inflammation, part of the endothelial dysfunction leading to Acute Coronary Syndrome. Elevated fibrinogen levels may be present in subjects with obesity; however, there is no enough information on whether this is also the same among metabolically obese normal-weight subjects (MONW). Objective: To determine the association between being MONW and fibrinogen levels in a sample of Peruvian inhabitants. Methodology: Cross-sectional analytical study. Secondary data analysis of the PERU MIGRANT study (2007, 989 participants). For the diagnosis of MONW, it was considered if it presented two or more characteristics such as: waist circumference (anthropometric evaluation), triglycerides, fasting glucose, systolic blood pressure or diastolic blood pressure, HDL-cholesterol, insulin resistance through HOMA-IR, C-reactive protein. Elevated fibrinogen ≥450 mg/dL was considered. For regression analysis we used generalized linear model with link log and family Poisson with robust variance. We present crude prevalence ratio and adjusted by mentioned variables, as association parameter. We considered confidence interval 95%. Results: Of the 393 selected participants, 46.3% were women, the median of age was 47(37-56), only 13.5% had elevated fibrinogen levels. The prevalence of the MONW subject was 32.67%. In the correlation analysis, there was only a statistically significant relationship between fibrinogen and plasma CRP (rho= 0.54; p<0.001). In multiple regression, association was found between being MONW and high plasma fibrinogen levels (PR=1.93, 95%CI: 1.44-2.57; p<0.001). Conclusions: There is an association between high levels of plasmatic fibrinogen and MONW. These results can serve as a first step for future prospective research, either to be a risk factor or as an additional marker of consideration for monitoring and diagnosis in normal-weight people.

Resumen Introducción: El fibrinógeno plasmático es reconocido como un factor de riesgo importante para eventos cardiometabólicos a través de mecanismos como la formación de trombina, agregación plaquetaria e inflamación, todos partes de la disfunción endotelial conducentes al Síndrome Coronario Agudo. Elevados niveles pueden estar presentes en sujetos con obesidad, sin embargo, no hay información suficiente sobre si esto también es igual en los sujetos delgados metabólicamente obesos (DMO). Objetivo: Determinar la asociación entre el DMO y niveles de fibrinógeno en una muestra de pobladores peruanos. Metodología: Estudio transversal analítico. Análisis de datos secundarios del estudio PERU MIGRANT (2007, 989 participantes). Para el diagnóstico de DMO se consideró si presentaba dos o más características de siete criterios metabólicos: circunferencia de la cintura (mediante evaluación antropométrica), triglicéridos, glucosa en ayunas, presión arterial sistólica y diastólica, colesterol-HDL, HOMA-IR, proteína C reactiva (PCR). Se consideró fibrinógeno (elevado ≥450 mg/dL). Para el análisis de regresión, se realizó un modelo lineal generalizado con enlace log y familia Poisson con varianza robusta. De esa forma, se obtuvo como medida de asociación las razones de prevalencia crudas (RPc) y ajustadas (RPa) por las covariables mencionadas, se consideró intervalos de confianza al 95% (IC95%). Resultados: De los 393 participantes seleccionados, el 46,3% fueron mujeres, la mediana de edad fue 47(37-56), 13,5% presentó niveles de fibrinógeno elevado. La prevalencia de DMO fue 32,67%. Solo hubo una relación estadísticamente significativa entre fibrinógeno y el PCR-plasmático (rho=0,54; p<0,001). La regresión múltiple, encontró asociación entre el DMO y el nivel altos fibrinógeno plasmático (RP=1,93 IC95%: 1,44-2,57; p<0,001). Conclusiones: Existe asociación entre los niveles altos de fibrinógeno plasmático y el DMO. Estos resultados pueden servir para futuras investigaciones prospectivas, ya sea para considerarlo un factor de riesgo o como un marcador adicional para el seguimiento y diagnóstico en personas delgadas.

Resumen El síndrome de Marfan clásicamente se presenta con aneurismas de la raíz de la aorta. La ectasia aórtica produce alteraciones en el flujo sanguíneo que influyen sobre el comportamiento de los factores de la coagulación y la actividad de las plaquetas. También se ha reportado resistencia a la heparina asociada al Síndrome de Marfan en un menor número de pacientes, probablemente debido a deficiencia de antitrombina III (ATIII) o a diversas mutaciones. La aorta ascendente y la válvula aórtica se reemplazan con material prostético en los procedimientos Bentall- de Bonno. La resistencia a la anticoagulación durante circulación extracorpórea significa un enorme desafío tanto para los anestesiólogos, como para el equipo quirúrgico. Se observó resistencia a la heparina en un paciente con Síndrome de Marfan sometido a un procedimiento de Bentall. No había disponibilidad de concentrado ATIII y no aumentó el Tiempo de Coagulación Activada a pesar de las elevadas dosis de heparina. Se utilizó exitosamente un abordaje alterno de anticoagulación.

Abstract Marfan syndrome classically presents with aortic root aneurysms. Aortic ectasia causes diverse blood flow alterations, influencing the behavior of coagulation factors and platelet activity. Heparin resistance has also been reported associated with Marfan Syndrome in a small number of patients, probably due to antithrombin III (ATIII) deficiency or various mutations. The ascending aorta and the aortic valve are replaced with prosthetic material during Bentall- de Bonno procedures. Resistance to anticoagulation during extracorporeal circulation, represents a significant challenge for both anesthesiologists and the surgical team. Resistance to heparin was observed in a patient with Marfan syndrome undergoing a Bentall procedure. ATIII concentrate was not available, and Activated Coagulation Time did not increase despite high doses of heparin. An alternate anticoagulation approach was used successfully.

Abstract Introduction: Plasmatic fibrinogen is known as a main risk factor to cardiometabolic diseases through mechanisms such as thrombin formation, platelet aggregation and inflammation, part of the endothelial dysfunction leading to Acute Coronary Syndrome. Elevated fibrinogen levels may be present in subjects with obesity; however, there is no enough information on whether this is also the same among metabolically obese normal-weight subjects (MONW). Objective: To determine the association between being MONW and fibrinogen levels in a sample of Peruvian inhabitants. Methodology: Cross-sectional analytical study. Secondary data analysis of the PERU MIGRANT study (2007, 989 participants). For the diagnosis of MONW, it was considered if it presented two or more characteristics such as: waist circumference (anthropometric evaluation), triglycerides, fasting glucose, systolic blood pressure or diastolic blood pressure, HDL-cholesterol, insulin resistance through HOMA-IR, C-reactive protein. Elevated fibrinogen ≥450 mg/dL was considered. For regression analysis we used generalized linear model with link log and family Poisson with robust variance. We present crude prevalence ratio and adjusted by mentioned variables, as association parameter. We considered confidence interval 95%. Results: Of the 393 selected participants, 46.3% were women, the median of age was 47(37-56), only 13.5% had elevated fibrinogen levels. The prevalence of the MONW subject was 32.67%. In the correlation analysis, there was only a statistically significant relationship between fibrinogen and plasma CRP (rho= 0.54; p<0.001). In multiple regression, association was found between being MONW and high plasma fibrinogen levels (PR=1.93, 95%CI: 1.44-2.57; p<0.001). Conclusions: There is an association between high levels of plasmatic fibrinogen and MONW. These results can serve as a first step for future prospective research, either to be a risk factor or as an additional marker of consideration for monitoring and diagnosis in normal-weight people.

Resumen Introducción: El fibrinógeno plasmático es reconocido como un factor de riesgo importante para eventos cardiometabólicos a través de mecanismos como la formación de trombina, agregación plaquetaria e inflamación, todos partes de la disfunción endotelial conducentes al Síndrome Coronario Agudo. Elevados niveles pueden estar presentes en sujetos con obesidad, sin embargo, no hay información suficiente sobre si esto también es igual en los sujetos delgados metabólicamente obesos (DMO). Objetivo: Determinar la asociación entre el DMO y niveles de fibrinógeno en una muestra de pobladores peruanos. Metodología: Estudio transversal analítico. Análisis de datos secundarios del estudio PERU MIGRANT (2007, 989 participantes). Para el diagnóstico de DMO se consideró si presentaba dos o más características de siete criterios metabólicos: circunferencia de la cintura (mediante evaluación antropométrica), triglicéridos, glucosa en ayunas, presión arterial sistólica y diastólica, colesterol-HDL, HOMA-IR, proteína C reactiva (PCR). Se consideró fibrinógeno (elevado ≥450 mg/dL). Para el análisis de regresión, se realizó un modelo lineal generalizado con enlace log y familia Poisson con varianza robusta. De esa forma, se obtuvo como medida de asociación las razones de prevalencia crudas (RPc) y ajustadas (RPa) por las covariables mencionadas, se consideró intervalos de confianza al 95% (IC95%). Resultados: De los 393 participantes seleccionados, el 46,3% fueron mujeres, la mediana de edad fue 47(37-56), 13,5% presentó niveles de fibrinógeno elevado. La prevalencia de DMO fue 32,67%. Solo hubo una relación estadísticamente significativa entre fibrinógeno y el PCR-plasmático (rho=0,54; p<0,001). La regresión múltiple, encontró asociación entre el DMO y el nivel altos fibrinógeno plasmático (RP=1,93 IC95%: 1,44-2,57; p<0,001). Conclusiones: Existe asociación entre los niveles altos de fibrinógeno plasmático y el DMO. Estos resultados pueden servir para futuras investigaciones prospectivas, ya sea para considerarlo un factor de riesgo o como un marcador adicional para el seguimiento y diagnóstico en personas delgadas.

Abstract The hypercoagulable state continues after the Coronavirus 2019 (Covid 19) infection and prophylactic anticoagulants are recommended in this period. However, arterial and venous thromboembolic events can be observed during the convalescence period after the Covid 19. Here, we present the case of acute lower extremity arterial and venous thromboembolism developed in the post-Covid 19 period in a 77-years-old patient, under therapeutic doses of anticoagulant therapy (enoxparin 1mg/kg of weight every 12 hours). The patient, who had no previous history of arterial or venous thrombosis, was taken to emergency surgery with the diagnosis of ALI (acute limb ischemia) due to acute arterial thrombosis. An arterial thrombectomy was performed with the help of a 4F Fogarty catheter inserted from the left femoral artery under local anesthesia. All distal pulses of the patient were palpable in the postoperative period. After the platelet count became >100,000 mm3, 100 mg of acetylsalicylic acid daily was added to the therapeutic dose of enoxaparin sodium treatment. The patient was discharged, uneventfully, except for a minimal diameter increase secondary to deep venous thrombosis (DVT) on the fifth postoperative day, with a combination of enoxaparin and acetylsalicylic acid treatment. Endothelial injury, chronic immuno-thrombogenicity, and increased platelet aggregation in the post-Covid 19 recovery period can cause major thrombotic events, even weeks after the recovery. Anticoagulant therapy is recommended for thromboprophylaxis when the following statuses exist: ≥65 years, critical illness, cancer, prior VTE, thrombophilia, severe immobility, and elevated D- dimer. Combination treatment with long-term antiaggregant therapy may be prudent in thromboembolic events developed under anticoagulant therapy.

Resumen El estado de hipercoagulabilidad continúa después de la infección por Coronavirus 2019 (Covid-19) y la anticoagulación profiláctica se recomienda durante este período. Sin embargo, eventos tromboembólicos arteriales y venosos se pueden observar durante el período de convalecencia posterior al Covid-19. Se presenta el caso de trombosis venosa profunda (TVP) y arterial agudas de una extremidad inferior en una paciente de 77 años, bajo terapia anticoagulante (enoxparin 1mg/kg de peso, cada 12 horas), en el período post- Covid 19. La paciente, sin historia previa de trombosis arterial ni venosa, fue llevada a cirugía de emergencia con el diagnóstico de isquemia aguda de extremidades por trombosis arterial aguda. Se le realizó trombectomía arterial con la ayuda de un catéter Fogarty 4F insertado desde la arteria femoral izquierda bajo anestesia local. Todos los pulsos distales del paciente fueron palpables en el periodo postoperatorio. Después de que las plaquetas llegaron a ser mayores a100.000 mm3, 100 mg de ácido acetilsalicílico diarios se añadieron a la dosis terapéutica del tratamiento con enoxaparina sódica. La paciente fue dada de alta sin incidencias, excepto por un mínimo aumento de diámetro secundario a la TVP, al quinto día postoperatorio con la combinación de enoxaparina y ácido acetilsalicílico. La lesión endotelial, la inmunotrombogenicidad crónica y la agregación plaquetaria aumentada en el período de recuperación posterior a Covid-19 pueden causar eventos trombóticos importantes incluso semanas después de la recuperación. La combinación con terapia antiagregante a largo plazo puede ser prudente en los casos de eventos tromboembólicos desarrollados en pacientes con terapia anticoagulante.

Resumen Las microangiopatías trombóticas (MAT) se caracterizan por la oclusión microvascular como consecuencia de una lesión endotelial difusa que produce inflamación, agregación plaquetaria y destrucción de glóbulos rojos, causando daño isquémico del órgano afectado. Se caracterizan clínicamente por anemia hemolítica microangiopática, Coombs negativo, daño multiorgánico (principalmente de riñones, sistema nervioso central, aparato cardiovascular y tracto gastrointestinal). Su presentación puede ser sistémica o localizada y sus etiologías son múltiples. En los pacientes con cáncer es un gran reto diagnóstico establecer la causa de la microangiopatía trombótica, siendo las etiologías más frecuentes la neoplasia maligna activa, la coagulación intravascular diseminada, infecciones y medicamentos antineoplásicos. Se presenta el caso clínico de una paciente con adenocarcinoma cáncer de páncreas irresecable, en manejo crónico con gemcitabina y se resalta la importancia de sospechar y distinguir la MAT inducida por quimioterapia, de la causada por la neoplasia ya que el pronóstico y tratamiento son muy diferentes. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2249).

Abstract Thrombotic microangiopathies (TMAs) are characterized by microvascular occlusion secondary to diffuse endothelial damage which produces inflammation, platelet aggregation and red blood cell destruction, causing ischemic injury to the affected organ. They are clinically characterized by Coombs-negative microangiopathic hemolytic anemia, and multiple organ damage (mainly of the kidneys, central nervous system, cardiovascular apparatus and gastrointestinal tract). They may occur systemically or locally, and they have multiple etiologies. In patients with cancer, determining the cause of thrombotic microangiopathy is a great diagnostic challenge, with the most frequent etiologies being active malignant neoplasms, disseminated intravascular coagulation, infections and antineoplastic drugs. We present the clinical case of a patient with unresectable pancreatic adenocarcinoma on chronic gemcitabine treatment, and highlight the importance of suspecting and distinguishing chemotherapy-induced TMAs from neoplasm-induced TMAs, as their prognosis and treatment are very different. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2249).

Resumo Plaquetopenia é frequentemente observada em pacientes em hemodiálise, e sua correta investigação e controle permanecem um desafio. Estima-se que, durante a sessão de hemodiálise, ocorra queda de até 15% da contagem de plaquetas, com recuperação após o término do tratamento. Essa queda de plaquetas é decorrente de adesão plaquetária e ativação do complemento, independentemente do material da membrana. Vários estudos com marcadores de superfície plaquetária demonstram aumento da ativação e agregação plaquetária secundários à exposição à circulação extracorpórea. Este relato de caso mostra um paciente dialítico que evoluiu com plaquetopenia severa durante internação. Realizada investigação e exclusão de causas mais comuns: plaquetopenia relacionada à heparina, reação adversa a medicamentos, hiperesplenismo e doenças hematológicas, foi então aventada a possibilidade de plaquetopenia relacionada à hemodiálise após observação de que a queda se acentuava durante as sessões de hemodiálise com recuperação parcial após. Mudança do dialisador, atenção ao método de esterilização e realização do reuso devem ser consideradas para correção. No presente caso, a utilização do reuso minimizou a plaquetopenia associada a hemodiálise.

Abstract Thrombocytopenia is frequently observed in hemodialysis patients, and its correct investigation and control remain a challenge. It is estimated that during the hemodialysis session there is a drop of up to 15% in the platelet count, with recovery after the end of treatment. This reduction in platelets is due to platelet adhesion and complement activation, regardless of the membrane material. Several studies with platelet surface markers demonstrate increased platelet activation and aggregation secondary to exposure to cardiopulmonary bypass. This case report describes a patient on hemodialysis who developed severe thrombocytopenia during hospitalization. Investigation and exclusion of the most common causes were carried out: heparin-related thrombocytopenia, adverse drug reaction, hypersplenism, and hematological diseases. Afterwards, the possibility of hemodialysis-related thrombocytopenia was raised, since the fall was accentuated during the sessions with partial recovery after the dialyzer change. Attention to the sterilization method and dialyzer reuse must be considered for correction. In the current case, reusing the dialyzer minimized the drop in platelet counts associated with hemodialysis.

Abstract Background Vitamin K antagonists (VKA) are indicated for the prevention of thromboembolic events and reduction of mortality in patients with atrial fibrillation and patients with valvular prostheses. However, their use is associated with bleeding complications and hospitalizations. Predictors of hospital admission for bleeding in these patients are poorly known. Objectives To define the predictors for hospitalization of VKA users who seek emergency care due to bleeding. Methods Single-center, cross-sectional study, with retrospective analysis of electronic medical records from 03/01/2012 to 02/27/2017. Clinical and laboratory variables were compared between patients who were hospitalized and those who were not. A logistic regression model as used, in which the variables were included using the Backward stepwise method, with a p value of 0.05 as the input criterion, a removal value of 0.20 and a confidence interval of 95%. The p-value was considered statistically significant when <0.05. Results A total of 510 patients with bleeding were included, of whom 158 were hospitalized. Predictors of hospitalization were: INR at supratherapeutic levels (OR 3.45; P <0.01; 95% CI 1.58 - 7.51), gastrointestinal bleeding (OR 2.36; P <0.01; CI 95% 1.24 - 4.50), drop in hemoglobin (OR 6.93; P <0.01; 95% CI 3.67 - 13.07), heart failure (OR 1.96; P 0.01; 95% CI 1.16 - 3.30) and need for blood transfusion (OR 8.03; P <0.01; 95% CI 2.98 - 21.64). Conclusion Drop in hemoglobin, heart failure, INR at supratherapeutic levels, gastrointestinal bleeding and need for blood transfusion were associated with hospitalization. Identification of these factors in the initial evaluation would help to define which patients will demand more intensive care.

Abstract This study aimed to evaluate the antioxidant potential of the Coffea arabica Lineu (L.) leaf extract and its effects on platelet aggregation of dyslipidemic rats. The extract was obtained by the percolation of C. arabica L. leaves in hydroethanolic solution 70% (v/v). The mass spectrometry FIA-ESI-MS² suggested the presence of chlorogenic acid, rutin acid, and quinic acid. The DPPH• radicals scavenging capacity was demonstrated (IC50 = 0.06 mg/mL). The extract was administered to rats by gavage (300 mg/kg/day) for 56 days. Dyslipidemia was induced by administering Triton WR-1339 (300 mg/kg body weight) on the 54th day. On day 56, blood was collected by puncturing the abdominal aorta artery and the aortic artery was removed. Lipid profile, markers of renal and hepatic injury, lipid peroxidation, and platelet aggregation tests were carried out. The ingestion of extract reduced the lipid peroxidation (aorta and plasma) and platelet aggregation in dyslipidemic rats. The extract did not affect markers of renal and hepatic function as analyzed in this study, suggesting neither impaired liver nor kidney function in these animals. Therefore, our results demonstrate that the extract of leaves of C. arabica L. show antioxidant potential in vitro and in vivo as well as anti-platelet aggregation in dyslipidemic animals.

Abstract Ligustrazine is widely used for the treatment of cardiovascular diseases in traditional Chinese medication. It has been reported that Ligustrazine decreases the concentration of intracellular calcium ions (Ca2+); however, the underlying mechanism remains unknown. In the present study, the effect of Ligustrazine on adenosine diphosphate (ADP)-induced platelet aggregation was evaluated using a turbidimetric approach. The changes in concentration of intracellular Ca2+ stimulated by ADP was measured using fluo-4, a fluorescent Ca2+ indicator dye. The mRNA expression of stromal interaction molecule l (STIM1) and Orai1, calcium sensor, was determined using real-time PCR. In addition, the protein expression of STIM1, Orai1, and serum/glucocorticoid-regulated protein kinase 1 (SGK1) was determined using Western blot analysis. The data demonstrated that Ligustrazine significantly suppressed platelet aggregation in a dose-dependent manner and reduced the concentration of intracellular Ca2+ triggered by ADP. Our data showed that Ligustrazine treatment inhibited the expression of STIM1 and Orai1 induced by ADP at both mRNA and protein levels, and suppressed the protein expression of SGK1. Taken together, our data indicated that Ligustrazine suppressed platelet aggregation by partly inhibiting the activities of calcium sensors, thereby suggesting that Ligustrazine may be a promising candidate for the treatment of platelet aggregation.

ABSTRACT Objective: Low platelet reactivity levels are associated with higher risk of bleeding in patients receiving dual antiplatelet therapy relative to patients with optimal platelet blockade. This study set out to evaluate the prevalence of low platelet reactivity in patients with acute myocardial infarction treated with ticagrelor and aspirin. Methods: Patients admitted with acute myocardial infarction who were already undergoing dual antiplatelet therapy with aspirin and ticagrelor were enrolled. Blood samples were collected 1 hour before and 2 hours after the maintenance dose of ticagrelor to investigate trough and the peak effects of the drug respectively. Platelet reactivity was measured by three methods: Multiplate®, PFA-100® with Innovance® PFA-P2Y cartridge and PFA-100® with Collagen/ADP cartridge. Platelet reactivity was assessed in the presence of peak levels of ticagrelor and defined according to previously validated cut-offs for each method (<19 AUC, >299 seconds and >116 seconds respectively). The level of significance was set at p<0.05. Results: Fifty patients were enrolled (44% with ST-elevation). Median duration of DAPT was 3 days (interquartile range, 2-5 days). On average, peak and trough platelet reactivity were markedly low and did not differ between different methods. Low platelet reactivity was common, but varied according to analytic method (PFA-100®/Innovance®PFA-P2Y: 86%; Multiplate®: 74%; PFA-100®/Collagen/ADP: 48%; p<0.001). Conclusion: Low platelet reactivity was very common in patients with acute myocardial infarction submitted to dual antiplatelet therapy with ticagrelor and aspirin. Findings of this study justify the investigation of less intensive platelet inhibition strategies aimed at reducing the risk of bleeding in this population, such as lower dose regimens or monotherapy with P2Y12 inhibitors.