Caracterización de pacientes con trombosis portal sobre hígado no cirrótico en un hospital universitario de Medellín, Colombia / Characterization of patients with portal vein thrombosis on non-cirrhotic liver at a university hospital in Medellín, Colombia

Introducción. La trombosis de la vena porta es la oclusión parcial o completa de la luz de la vena porta o sus afluentes por la formación de trombos. Se asocia a desenlaces adversos y a un peor pronóstico. La frecuencia de aparición viene en aumento, a menudo de manera incidental, debido al uso cada vez mayor de imágenes diagnósticas. Metodología. Estudio observacional de una serie de casos de pacientes mayores de 18 años a quienes se les documentó trombosis venosa portal en hígado no cirrótico en el periodo comprendido entre enero de 2012 y diciembre de 2019 en un hospital de cuarto nivel de la ciudad de Medellín, Colombia. Resultados. Se documentaron 94 trombosis portales, la media de edad fue 44 ± 15 años, el 56 % eran mujeres. El promedio de aparición de síntomas fue de 14 días. La presentación de la trombosis fue aguda en un 41 %, crónica en 44 % y de instauración aguda sobre una trombosis crónica en un 15 %. La presentación clínica fue asintomática en el 33 %, el dolor abdominal fue la presentación más común con el 62 %. La trombofilia adquirida de mayor ocurrencia fueron las neoplasias mieloproliferativas crónicas en un 18 %, seguida del síndrome antifosfolípido en un 6 %. El método diagnóstico más usado fue la TAC trifásica en un 58 % seguido de la ultrasonografía en un 35 %. El 66 % de los pacientes fueron anticoagulados, siendo la warfarina el principal anticoagulante usado en un 56 %. El 16 % presento algún tipo de sangrado, aunque ninguno fue sangrado mayor. Conclusiones. La trombosis portal sigue siendo en muchos casos un hallazgo incidental. Se encontró un número inusual de neoplasias mieloproliferativas crónicas. La anticoagulación es segura y eficaz, aunque los anticoagulantes orales directos aún tienen un uso restringido.

Introduction. Portal vein thrombosis is the partial or complete occlusion of the lumen of the portal vein or its tributaries by thrombus formation. It is associated with adverse outcomes and a poorer prognosis. Its frequency is increasing, often incidentally, due to the growing use of diagnostic imaging. Methodology. This is an observational study of a case series of patients over 18 years old who were documented with portal vein thrombosis in a non-cirrhotic liver between January 2012 and December 2019 in a fourth-level hospital in the city of Medellín, Colombia. Results. Ninety-four cases of portal vein thrombosis were documented. The mean age was 44 ± 15 years, and 56 % were women. The average onset of symptoms was 14 days. Thrombosis presentation was acute in 41 %, chronic in 44 %, and acute on chronic in 15 %. Clinically, 33 % were asymptomatic, and abdominal pain was the most common presentation at 62 %. The most common acquired thrombophilia was chronic myeloproliferative neoplasms at 18 %, followed by antiphospholipid syndrome at 6 %. The most used diagnostic method was triphasic CT at 58 %, followed by ultrasonography at 35 %. Sixty-six percent of the patients received anticoagulation, with warfarin being the main anticoagulant used at 56 %. Sixteen percent experienced some type of bleeding, although none were major. Conclusions. Portal vein thrombosis remains, in many cases, an incidental finding. An unusual number of chronic myeloproliferative neoplasms were found. Anticoagulation is safe and effective, although the use of direct oral anticoagulants remains restricted.

Etiology and diagnostic approach of recurrent miscarriage at a reference center in Bucaramanga, Colombia.

OBJECTIVE: The purpose of this study was to determine the etiologies of recurrent miscarriage in our hospital and whether its diagnostic approach followed the recommendations of the American Society of Reproductive Medicine (ASRM) guidelines published in 2012 and the National Institute for Health and Care Excellence (NICE) guidelines published in 2011. METHODS: This was a retrospective study. The medical records of 158 patients diagnosed with recurrent miscarriage between 2013 and 2018 at Santander University Hospital were reviewed. The Institutional Review Board of HUS approved the study in May 2020. RESULTS: The most common etiologies identified were protein S deficiency, thrombophilia, and cervical insufficiency, with incidence rates of 25.9%, 10.7%, and 3.8%, respectively. Moreover, the most frequently requested diagnostic tests were for protein S, protein C, and anti-phospholipid IgG. Abnormal results for protein S were obtained in 49% of the patients, whereas lupus anticoagulant was abnormal in 12.8%, and Factor V Leiden gene mutations in 8.5% of the patients. Three substantial deviations from the recommended diagnostic approach for recurrent miscarriage by international guidelines were identified in our population: the lack of request for cytogenetic analysis of pregnancy tissue, request for cytogenetic analysis for the parents in only 0.6% of the study sample, and the request for imaging tests to assess uterine anatomy in only 6.3% of the studied population. Both the ASRM and NICE guidelines were only partially followed with a combined adherence rate of 66.5%. CONCLUSION: The diagnostic approach for recurrent miscarriage poses important clinical challenges when compared to the recommendations of international guidelines. Therefore, the development of a local recurrent miscarriage assessment protocol is proposed in our institution.

Paternal thrombophilia and recurrent implantation failure: an exploratory case-control study.

OBJECTIVE: Many pieces of literature have reported that inherited and acquired thrombophilia might be a risk factor for recurrent implantation failure (RIF), however, most studies have only focused on RIF patients and not their male partners. We studied the possible association of paternal thrombophilia with RIF risk. METHODS: Forty-two male partners aged 20-45 suffered from RIF compared with 42 males from couples with at least one successful pregnancy. All participants were investigated for thrombophilia markers. RESULTS: The prevalence of coagulation Factor V activity was significantly higher in the case group (42.9%) than in the control group (16.7%) (p=0.008) (OR=3.75; 95% CI, 1.38, 10.12). The prevalence of protein C and protein S deficiencies in RIF patients were 4.8% and 2.4%, respectively, and 0% in the controls. The prevalence of antithrombin III (ATIII) deficiency was significantly higher in the case group (19%) than in the control group (2.4%) (p=0.01). None of MTHFR C677T and MTHFR A1298C were statistically significant between the two groups. Combined thrombophilia was 45.2% in the men of the RIF group when compared with the control, 14.2% (p=0.001) (OR = 4.95; 95% CI, 1.75-13.86). CONCLUSIONS: Paternal thrombophilia may be related to recurrent implantation failure, so evaluation of this factor in RIF patients could be used to identify relevant risk groups and may help in the proper management of these cases to enhance the chance of implantation.

Isquemia intestinal, una manifestación inusual de la embolia paradójica. Un reporte de caso / Intestinal ischaemia as a rare manifestation of a paradoxical embolism. A case report

Introducción. La embolia paradójica es un evento trombótico originado en la circulación venosa, que se manifiesta como embolismo arterial por medio de un defecto anatómico a nivel cardíaco o pulmonar. Se asocia principalmente a eventos cerebrovasculares, aunque se han encontrado casos de infarto agudo de miocardio, infarto renal y otros eventos isquémicos. Caso clínico. Paciente de 47 años, quien consultó por cuadro de dolor abdominal, que requirió manejo quirúrgico de urgencia, donde identificaron isquemia intestinal importante. Los estudios adicionales hallaron déficit de proteína S y persistencia de foramen oval permeable. Resultados. La presencia de trombosis arterial se conoce como trombosis de sitios inusuales y requiere de estudios para descartar trombofilias asociadas u otros estados protrombóticos. El déficit de proteína S es una trombofilia infrecuente, la cual se asocia en la vida adulta a eventos trombóticos de origen venoso. En presencia de defectos anatómicos, como un foramen oval permeable, puede progresar a embolia arterial, configurando un cuadro de embolismo paradójico. La estratificación de estos pacientes requiere imágenes que demuestran el defecto mencionado, así como el posible origen de los émbolos. El manejo se basa en anticoagulación plena, manejo de soporte, resolver las manifestaciones trombóticas existentes y un cierre temprano del defecto anatómico. Conclusiones. El embolismo paradójico debe sospecharse en caso de trombosis de sitios inusuales. Requiere de un estudio exhaustivo con imágenes y su manejo debe basarse en anticoagulación y cierre del defecto.

Introduction. Paradoxical embolism is a thrombotic event originating in the venous circulation, which manifests as arterial embolism through an anatomical cardiac or pulmonary defect. It is mainly associated with stroke, also presenting as acute myocardial infarction, renal infarction, and other ischemic events. Clinical case. A 47-year-old patient was admitted due to abdominal pain, which required emergency surgical management, finding significant intestinal ischemia. Additional studies found protein S deficiency and evidence of a patent foramen ovale. Discussion. Arterial thrombosis is known as unusual thrombosis; this situation requires to rule out associated thrombophilia or other prothrombotic diseases. Protein S deficiency is a rare thrombophilia, which in adults causes venous thrombosis. In the presence of anatomical defects, such as a patent foramen ovale, it can progress to arterial embolism, presenting a picture of paradoxical embolism. The study work of these patients requires imaging that demonstrates the aforementioned defect, as well as the possible origin of the emboli. Management is based on full anticoagulation, treatment of existing thrombotic manifestations, and management of the anatomical defect. Conclusions. Paradoxical embolism should be suspected in case of unusual thrombosis. It requires exhaustive studies based on imaging, and management should consist of anticoagulation and closure of the defect.

Trastornos de la coagulación: factor V Leiden, panorama biológico, clínico y epidemiológico / Coagulation Disorders: Factor V Leiden, Biological, Clinical, and Epidemiological Overview

Resumen El sistema de coagulación mantiene la sangre en estado fluido en todo momento y, por tanto, está incesantemente activa durante toda la vida. Sin embargo, en el momento en que ocurre una lesión del sistema vascular, el sistema de coagulación inmediatamente gira 180° y transforma la sangre en un cuerpo sólido perfectamente localizado, al que llamamos coágulo. Este proceso, mediante el cual se forma un coágulo, se conoce como hemostasia, que es uno de los componentes del sistema de coagulación. La importancia de la mutación Leiden del factor V se basa en lo siguiente: el factor V de la coagulación es una proteína que se sintetiza en el hígado y el gen que lo codifica está situado en la región 23 del brazo largo del cromosoma 1, este factor circula en sangre periférica de manera inactiva hasta que interactúa con el factor X activado, formando un complejo que convierte al factor II (protrombina) en trombina, que va a tener su acción sobre el fibrinógeno convirtiéndolo en fibrina. La regulación del factor V activado se da por la actividad de la proteína C activada, cuando el factor V tiene una mutación (nombrada Leiden) que es ocasionada por el cambio de una adenina por una guanina en el nucleótido 1691 del factor V (G1691A), que causa que se sustituya una arginina por una glutamina en el residuo 506 de la proteína factor V; la proteína resultante es un factor V anómalo, mismo que no puede inactivarse por la proteína C activada, por lo que el factor V continúa activado y no puede impedir que el proceso de coagulación se detenga. En nuestro país (considerando varias afecciones) se ha descrito en diversas publicaciones de investigadores mexicanos que las mutaciones Leiden del factor V y la G20210A de la protrombina no son frecuentes, como lo son en los países europeos.

Abstract The coagulation system always keeps the blood in a fluid state and is therefore incessantly active throughout life. However, the moment an injury to the vascular system occurs, the coagulation system immediately rotates 180° and transforms the blood into a perfectly localized solid body, which we call a clot. This process, by which a clot forms, is known as hemostasis, which is one of the components of the coagulation system. The importance of the Leiden mutation of factor V is based on the following: coagulation factor V is a protein that is synthesized in the liver and the gene that encodes it is located in region 23 of the long arm of chromosome 1, this factor circulates in peripheral blood inactively until it interacts with activated factor X forming a complex that converts factor II (prothrombin) into thrombin, which will have its action on fibrinogen turning it into fibrin. The regulation of activated factor V is given by the activity of activated protein C, when factor V has a mutation (named Leiden) that is caused by the exchange of an adenine for a guanine in the nucleotide 1691 of factor V (G1691A), which causes arginine to be replaced by a glutamine in the 506 residue of the factor V protein, the resulting protein is an abnormal factor V, which cannot be inactivated by activated protein C, so factor V remains activated and cannot prevent the clotting process from stopping. In our country (considering several conditions) it has been described in various publications of Mexican researchers that Leiden mutations of factor V and G20210A of prothrombin are not frequent, as they are in European countries.

Prophylactic low-molecular-weight heparin in women with thrombophilia undergoing in vitro fertilization.

OBJECTIVE: To verify whether low-molecular-weight heparin (LMWH) could increase pregnancy rates and/or decrease abortion rates in women with thrombophilia undergoing assisted reproduction cycles. METHODS: Cross-sectional study with patients undergoing in vitro fertilization (IVF) (N = 104). Women without thrombophilia (control group, n = 20), women with thrombophilia who did not receive LMWH (untreated group, n = 30), and women with thrombophilia, treated with daily enoxaparin from the day of embryo transfer until week 36 of gestation (treated group, n = 54). All women underwent controlled ovarian hyperstimulation. IVF was performed by intracytoplasmic sperm injection, and embryos were transferred on day 3. Pregnancy was detected by ß-human chorionic gonadotropin (biochemical pregnancy) and fetal heartbeat at week 5 to 6. Ongoing pregnancy was determined by ultrasound on week 12. RESULTS: Patients in the untreated thrombophilia group presented with significantly lower ongoing pregnancy rates and live birth rates and significantly higher early pregnancy loss and abortion rates when compared with the control and the treated thrombophilia groups. CONCLUSIONS: In women with diagnosed coagulation disorders, use of LMWH is important to avoid miscarriages.

Estudio de las trombofilias por el laboratorio clínico

La trombofilia se define como una predisposición individual a padecer episodios tromboembólicos. Debido a la elevada y creciente incidencia tanto mundial como en Cuba de eventos cardiovasculares, cerebrovasculares y vasculares periféricos, cuya patogenia involucra la trombofilia, se hace necesaria una actualización de la utilidad de las pruebas de laboratorio clínico para su estudio. Esta revisión tiene como objetivo actualizar la información sobre la indicación e interpretación de los exámenes de laboratorio clínico útiles en el estudio de las trombofilias. Se realizaron búsquedas en las bases de datos PubMed, SciELO, LILACS y ClinicalKey, con las palabras clave "trombofilia" y "laboratorio clínico", en inglés y español. La búsqueda reveló 120 artículos, de los cuales 27 fueron novedosos y relevantes para el tema. Se debe investigar el estado trombofílico en cualquier paciente que presente trombosis venosa antes de los 45 años -recurrente o en sitios inusuales-, trombosis neonatal inexplicable, necrosis cutánea por cumarínicos, resistencia a anticoagulantes, trombosis arterial antes de los 30 años, historia familiar trombofílica, pérdida recurrente de embarazos, púrpura trombocitopénica trombótica o lupus eritematoso sistémico. Las investigaciones iniciales serán: hemograma completo, observación de extensión coloreada de sangre periférica y tiempo parcial de tromboplastina activada. Los exámenes más específicos incluirán el estudio genético del factor V Leiden, ensayos para detectar déficits de antitrombina, proteína C o proteína S; análisis del ADN para el alelo G20210A de la protrombina, determinación del factor VIII y de homocisteína, y detección de anticoagulante lúpico, anticuerpos anti-β2-glicoproteína I y anticardiolipina.

Thrombophilia is defined as an individual predisposition to suffer thromboembolic episodes. Due to high and growing incidence both worldwide and in Cuba of cardiovascular, cerebrovascular and peripheral vascular events whose pathogenesis involves thrombophilia, it becomes necessary an update of the usefulness of clinical laboratory tests used for their study. The review aims to update information on indication and interpretation of clinical laboratory tests useful in the study of thrombophilia. Searches were carried out in the databases PubMed, SciELO, LILACS and ClinicalKey with key words thrombophilia and clinical laboratory, in English and Spanish, the search reveled 120 articles, of which 27 were novel and relevant to the topic. Thrombophilic status should be investigated in any patient who presents venous thrombosis before the age of 45-recurrent or in unusual sites-unexplained neonatal thrombosis, coumarin skin necrosis, resistance to anticoagulant, arterial thrombosis before the age of 30, thrombophilic familiar history, recurrent pregnancy loss, thrombotic thrombocytopenic purpura or systemic lupus erythematosus. Initial tests should be: complete blood count, observation of colored smear of peripheral blood, and activated partial of thromboplastin time. More specific tests will include the genetic study of factor V Leiden, tests to detect antithrombin, protein C or protein S deficiencies; DNA analysis for the G20210A allele of prothrombin, factor VIII and homocysteine measurement, and detection of lupus anticoagulant, anti-β2-glycoprotein I and anticardiolipin antibodies.

Experiencing pregnancy in the context of lupus and antiphospholipid syndrome: a grounded theory / Experimentando el embarazo en el contexto del lupus y del síndrome antifosfolípido: una teoría fundamentada / Vivenciando a gestação no contexto do lúpus e da síndrome antifosfolípide: uma teoria fundamentada

ABSTRACT Objective: To understand the meanings attributed to pregnancy in the context of Lupus and antiphospholipid syndrome by women and healthcare professionals. Method: Qualitative research, using Symbolic Interactionism as a theoretical framework and Grounded Theory, a constructivist perspective. Data were collected between January and August 2022, through online interviews with 27 women with Lupus located on the social network Facebook and in-person or remote interviews with 12 healthcare professionals. Results: The theoretical model constructed has two categories: "Equal conditions, distinct experiences: experiencing the gestational process" shows that obstetric complications and lack of connection with healthcare professionals trigger negative meanings to the experience; and "Therapeutic management interfering in the attribution of meanings to the experience", demonstrates that the way women interact with healthcare professionals and how they manage treatment favors a positive reframing. Final considerations: The meanings attributed to pregnancy are elaborated and modified according to the interpretation of previous and current experiences, healthcare trajectory and interactions with healthcare professionals. Previous guidance, planning, bonding and trust in healthcare professionals enable positive meanings, while obstetric complications, unqualified assistance and lack of bonding with professionals provide negative meanings.

RESUMEN Objetivo: Comprender los significados atribuidos al embarazo en el contexto del Lupus y del síndrome antifosfolípido por mujeres y profesionales de la salud. Método: Investigación cualitativa, que utilizó como marco teórico el Interaccionismo simbólico y metodológico, la Teoría Fundamentada, una vertiente constructivista. Los datos fueron recolectados entre enero y agosto de 2022, a través de entrevistas online a 27 mujeres con Lupus ubicadas en la red social Facebook y entrevistas presenciales o remotas a 12 profesionales de la salud. Resultados: El modelo teórico construido tiene dos categorías: "Condiciones iguales, experiencias diferentes: vivir el proceso gestacional" muestra que las complicaciones obstétricas y la falta de conexión con los profesionales de la salud desencadenan significados negativos a la experiencia; y Gestión terapéutica interfiriendo en la atribución de significados", demuestra que la forma en que las mujeres interactúan con los profesionales de la salud y cómo conducen el tratamiento favorece la resignificación positiva.. Consideraciones finales: Los significados atribuidos al embarazo son elaborados y modificados según la interpretación de experiencias pasadas y actuales, trayectoria de atención e interacciones con profesionales de la salud. La orientación previa, la planificación, la vinculación y la confianza en los profesionales de la salud posibilitan significados positivos, mientras que las complicaciones obstétricas, la asistencia no calificada y la falta de vínculo con los profesionales proporcionan significados negativos.

RESUMO Objetivo: Compreender os significados atribuídos à gravidez, no contexto do Lúpus e da Síndrome Antifosfolípide, por mulheres e profissionais de saúde. Método: Pesquisa qualitativa, que utilizou como referencial teórico o Interacionismo simbólico e metodológico, a Teoria Fundamentada nos Dados, vertente construtivista. Os dados foram coletados entre janeiro e agosto de 2022, mediante entrevistas on-line com 27 mulheres com Lúpus, localizadas na rede social Facebook e em entrevistas presenciais ou remotas com 12 profissionais de saúde. Resultados: O modelo teórico construído possui duas categorias: "Condições iguais, experiências distintas: vivenciando o processo gestacional" mostra que complicações obstétricas e ausência de vínculo com os profissionais de saúde desencadeiam significados negativos à experiência; e "O manejo terapêutico interferindo na atribuição dos significados à experiência" demonstra que a forma com que a mulher interage com os profissionais de saúde e conduz o tratamento favorece a ressignificação positiva. Considerações finais: Os significados atribuídos à gestação são elaborados e modificados conforme a interpretação de experiências anteriores e atuais, trajetória assistencial e interações com os profissionais de saúde. A orientação prévia, o planejamento, o vínculo e a confiança nos profissionais de saúde possibilitam significados positivos. Já, as complicações obstétricas, a assistência não qualificada e ausência de vínculo com os profissionais produzem significados negativos.

Evaluación de parámetros inflamatorios, trombóticos y variantes genéticas en pacientes con ataque cerebrovascular isquémico que se asisten en un hospital de Uruguay

Introducción: El ataque cerebrovascular es la segunda causa de muerte en adultos en el mundo occidental y una de las principales causas de discapacidad permanente, aumentando su frecuencia con la edad, el 85 % es de tipo isquémico. Objetivos: Analizar parámetros trombofílicos, hipofibrinolíticos y genéticos en pacientes con ataque cerebrovascular isquémico y evaluar la posible asociación de estos con factores de riesgo cardiovascular. Metodología: Se utilizó un cuestionario para evaluar la presencia de factores de riesgo cardiovascular en 114 pacientes incluidos en el estudio con diagnóstico de ataque cerebrovascular isquémico. Proteína C y antitrombina fueron determinados mediante métodos cromogénicos, resistencia a la proteína C activada e inhibidor lúpico mediante métodos coagulométricos y proteína S libre, inhibidor del activador del plasminógeno-1, homocisteína y lipoproteína (a) por métodos inmunoquímicos. Fibrinógeno fue determinado por coagulometría y proteína C reactiva por inmunoturbidimetría, ambos contra un grupo control. Las variantes genéticas factor V Leiden, protrombina G20210A, rs1205 (gen PCR), rs1800779 (gen NOS3) y rs2257073 (gen ASB10) fueron analizadas mediante real-time PCR, comparando los últimos tres con una población de referencia. La alteración de las frecuencias de las variables fue determinada por análisis estadístico chi-cuadrado. Resultados: Tres de los cuatro pacientes jóvenes estudiados presentaron indicadores de trombofilia. El resto de los parámetros alterados fueron homocisteína 30.1% (22.4-39.1), lipoproteína (a) 32.1% (24.1-41.4), inhibidor del activador del plasminógeno-1 36.0% (27.8-45.1), fibrinógeno 12.3% (7.5-19.6) y proteína C reactiva 78.1% (69.6-84.7). Se encontró asociación (p < 0.05) entre ciertos factores de riesgo cardiovascular y los parámetros evaluados como hipertensión/proteína C reactiva, dislipemia/lipoproteína (a), arritmia/lipoproteína (a) y arritmia/fibrinógeno. Para pacientes con ataque cerebrovascular isquémico solo la variante rs1205 mostró una frecuencia más alta del alelo T. Conclusiones: Este estudio revela la importancia de analizar la trombofilia en pacientes jóvenes, especialmente en aquellos sin factores de riesgo cardiovascular, así como el rol de la hipofibrinolisis, inflamación y algunas variantes genéticas en el desarrollo de ataque cerebro vascular isquémico.

Introduction: Stroke is the second cause of death in adults in the Western world and one of the main causes of permanent disability, increasing in frequency with age; 85% are ischemic. Objectives: To analyze thrombophilic, hypofibrinolytic, inflammatory, and genetic parameters in patients with ischemic stroke and evaluate possible associations with vascular risk factors. Methodology: Questionnaires were used to evaluate vascular risk factors in 114 patients included in the study with ischemic stroke diagnosis. Protein C and Antithrombin were determined by chromogenic assays, Activated Protein C Resistance and Lupus Anticoagulant were determined with by coagulometry and Free Protein S, Plasminogen activator inhibitor-1, Homocysteine and Lipoprotein (a) by immunochemistry. Fibrinogen was assayed by coagulometry and C-reactive protein by immunoturbidimetry, both against a control group. Factor V Leiden, Prothrombin G20210A, rs1205 (CRP gene), rs1800779 (NOS3 gene) and rs2257073 (ASB10 gene) genetic variants were analyzed by Real-Time PCR, comparing the last three with a reference population. Alteration frequencies of the variables were determined by chi-square statistical analysis. Results: Three out of four of the young patients studied presented indicators of thrombophilia. The rest of the altered parameters were Homocysteine 30.1% (22.4-39.1), Lipoprotein (a) 32.1% (24.1-41.4), Plasminogen activator inhibitor-1 36.0% (27.8-45.1), Fibrinogen 12.3% (7.5-19.6) and C-reactive protein 78.1% (69.6-84.7). Associations were found (p<0.05) between certain vascular risk factors and parameters evaluated, namely hypertension/C-reactive protein, dyslipidemia/lipoprotein (a), arrhythmia/lipoprotein (a) and arrhythmia/fibrinogen. For ischemic stroke patients only the genetic variant rs1205 showed higher frequency of the T allele. Conclusions: This study reveals the importance of analyzing thrombophilia in young patients, especially those without vascular risk factors, as well as the role of hypofibrinolysis, inflammation and some genetic variants in the development of ischemic stroke.

Introdução: O AVC é a segunda causa de morte em adultos no mundo ocidental e uma das principais causas de incapacidade permanente, aumentando de frequência com a idade; 85% são isquémicos. Metas: Analisar os parâmetros trombofílicos, hipofibrinolíticos e genéticos em pacientes com acidente vascular cerebral isquêmico e avaliar a possível associação com fatores de risco cardiovascular. Metodologia: Um questionário foi utilizado para avaliar a presença de fatores de risco cardiovascular em 114 pacientes incluídos no estudo com diagnóstico de acidente vascular cerebral isquêmico. Proteína C e antitrombina foram determinadas por métodos cromogênicos, resistência à proteína C ativada e inibidor de lúpus por métodos coagulométricos e proteína S livre, inibidor do ativador do plasminogênio-1, homocisteína e lipoproteína (a) por métodos imunoquímicos. O fibrinogênio foi determinado por coagulometria e a proteína C-reativa por imunoturbidimetria, ambos contra um grupo controle. As variantes genéticas fator V Leiden, protrombina G20210A, rs1205 (gene PCR), rs1800779 (gene NOS3) e rs2257073 (gene ASB10) foram analisadas por PCR em tempo real, comparando as três últimas com uma população de referência. As frequências de alteração das variáveis ​​foram determinadas pela análise estatística qui-quadrado. Resultados: Três dos quatro pacientes jovens estudados apresentaram indicadores de trombofilia. O resto dos parâmetros alterados foram homocisteína 30,1% (22,4-39,1), lipoproteína (a) 32,1% (24,1-41,4), inibidor do ativador de plasminogênio-1 36,0% (27,8-45,1), fibrinogênio 12,3% (7,5-19,6) e proteína C reativa 78,1% (69,6-84,7). Foi encontrada associação (p<0,05) entre alguns fatores de risco cardiovascular e os parâmetros avaliados como hipertensão/proteína C reativa, dislipidemia/lipoproteína (a), arritmia/lipoproteína (a) e arritmia/fibrinogênio. Para pacientes com acidente vascular cerebral isquêmico apenas a variante rs1205 apresentou maior frequência do alelo T. Conclusões: Este estudo revela a importância de analisar a trombofilia em pacientes jovens, especialmente aqueles sem fatores de risco cardiovascular, bem como o papel da hipofibrinólise, inflamação e algumas variantes genéticas no desenvolvimento do acidente vascular cerebral isquêmico.

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.

ACV isquémico en población joven: ¿existe un enfoque diferencial del riesgo? / Ischemic stroke in a young population: is there a differential approach to risk factors?

Introducción: El ataque cerebrovascular isquémico en el adulto joven se define como aquel que ocurre en la población entre los 18 y los 55 años, y representa el 15-18 % de todos los ACV isquémicos. Los factores de riesgo en jóvenes son comunes a los encontrados en adultos mayores. El objetivo de este trabajo es describir las características clínicas y los factores de riesgo de una población menor de 55 años con ACV isquémico atendida en un centro de referencia hospitalario en Colombia. Materiales y métodos: Estudio descriptivo, retrospectivo de corte transversal en pacientes entre los 18 y los 55 años; se incluyeron 100 pacientes sobrevivientes a un primer ACV isquémico agudo confirmado por neuroimagen, atendidos entre enero de del 2019 y noviembre del 2021. Resultados: De 1023 pacientes con diagnóstico de ACV isquémico agudo, el 9,8 % fueron adultos jóvenes. La media de edad fue de 45 ± 8,7 años, y el 59 % de estos pacientes fueron hombres. Discusión: Los factores de riesgo "tradicionales" se presentan en la mayoría de los jóvenes con ACV isquémico. La hipertensión arterial se mantiene como el antecedente más frecuente. Las mujeres presentan eventos de mayor severidad y peor desenlace funcional. Conclusión: Los pacientes mayores de 45 años tienen un perfil de factores de riesgo similar a lo observado en adultos mayores con ACV, mientras que en los menores de 45 años se encuentra un perfil de factores de riesgo diferente que plantea un diagnóstico etiológico particular de esta población.

Introduction: Ischemic stroke in young adults is defined as occurring in individuals between the ages of 18 and 55, representing 15-18 % of all ischemic strokes. Risk factors in young adults are similar to those found in older adults. The objective of this study is to describe the clinical characteristics and risk factors of a population under 55 years of age with ischemic stroke treated at a hospital reference center in Colombia. Materials and methods: Descriptive, retrospective cross-sectional study in patients between 18 and 55 years old. A total of 100 patients between 18 and 55 years old who survived a first confirmed acute ischemic stroke, as confirmed by neuroimaging, were included. The study period was from January 2019 to November 2021. Results: Out of 1023 patients diagnosed with acute ischemic stroke, 9.8 % occurred in young adults. The mean age was 45 ± 8.7 years, of which 59 % were male. Discussion: "Traditional" risk factors are present in the majority of young adults with ischemic stroke. Hypertension remains the most common antecedent. Women experience more severe events and worse functional outcomes. Conclusion: Patients over 45 years old have a risk factor profile similar to what is observed in older adults with stroke, while in those under 45, a different risk factor profile is found, which poses a particular etio-logical diagnosis for this population.

Characteristics of the post-surgical decrease in platelet counts in orthopedic surgery patients, observations and insights.

INTRODUCTION: A reduced platelet count (PLT) is a frequent post-operative finding in orthopedic surgery patients. Despite its prevalence, the characteristics of post-surgical thrombocytopenia have not been well described. METHODS: A retrospective chart review was conducted on patients who underwent a knee or hip replacement from 2012 to 2015. Patients who received heparin were excluded. RESULTS: A total of 56 patients were analyzed on post-operative days 0 to 4. By day 1, 90.9% of the patients experienced a reduction in their platelet counts. The lowest mean platelet count (nadir) occurred on day 2 (201.3 × 109/L). The average decrease in the platelet count from the baseline was 24% (95%CI: 20.6 - 27.2). The change in the platelet count from the baseline ranged from a 49.6% drop to a 14.2% increase. A substantial portion of patients experienced thrombocytopenia, with 28% occurring on day 2. Platelet counts less than 100 × 109/L occurred only once. The percent decrease in the platelet count from the baseline to any other time point was significantly larger in patients aged > 65 years, compared to patients aged ≤ 65 years (p = 0.007). Specifically, the average drop in the platelet count at the nadir (day 2) relative to the baseline was 27.8% in patients aged > 65 years, compared to 19.5% in patients aged ≤ 65 years. CONCLUSIONS: A reduction in the platelet count is a frequent post-operative finding in orthopedic surgery patients, even after removing confounding factors, such as heparin exposure, but clinical thrombocytopenia is uncommon. Alternative etiologies should be considered when the platelet count is less than 100 × 109/L. Vigilance should also be considered regarding elderly patients.

Complicaciones hemorrágicas y trombóticas del embarazo: diagnóstico, prevención y tratamiento

Las hemorragias y la enfermedad tromboembólica venosa (ETEV) figuran entre las cinco causas más frecuentes de morbilidad y mortalidad materna en el mundo. Revisamos la evaluación y el manejo actualizado de las causas obstétricas de la hemorragia posparto (HPP), así como el diagnóstico y manejo de condiciones hematológicas que pueden causar o agravar la HPP, por ejemplo: coagulación intravascular diseminada, enfermedad de von Willebrand, trombocitopenia autoinmune y las microangiopatías trombóticas. Revisamos el rol del síndrome antifosfolípido y las trombofilias hereditarias como factores predisponentes a pérdidas fetales recurrentes y la ETEV en el embarazo y las recomendaciones actuales para la prevención de ambas complicaciones. Asimismo, repasamos el abordaje diagnóstico y líneas de manejo de la ETEV. Un objetivo adicional fue enfatizar la importancia del trabajo colaborativo multidisciplinario para lograr el manejo exitoso de las gestantes con las complicaciones obstétricas y hematológicas descritas.

Bleeding and venous thromboembolism (VTE) are among the five most common causes of morbidity and mortality in pregnant women worldwide. This review describes the current evaluation and management of the obstetric causes of postpartum hemorrhage (PPH), as well as the diagnosis and management of hematologic conditions which can cause or worsen PPH, such as disseminated intravascular coagulation, von Willebrand disease, autoimmune thrombocytopenia and the thrombotic microangiopathies. It also describes the role of the antiphospholipid syndrome and inherited thrombophilia as predisposing factors for recurrent pregnancy loses and VTE, and the current recommendations for the prevention of both complications. As well, the current diagnostic approach and management of ETEV are described. An additional objective of this Review is to emphasize the importance of a collaborative multidisciplinary approach for the successful management of the obstetric and hematologic complications herein described.

Hereditary thrombophilia and low -molecular -weight heparin in women: useful determinants, including thyroid dysfunction, incorporating the management of treatment and outcomes of the entity

SUMMARY OBJECTIVE: Our study purposed to examine the complex relationship between low-molecular-weight heparin therapy, multiple pregnancy determinants, and adverse pregnancy outcomes during the third trimester in women with inherited thrombophilia. METHODS: Patients were selected from a prospective cohort of 358 pregnant patients recruited between 2016 and 2018 at the Clinic for Obstetrics and Gynecology, University Clinical Centre of Serbia, Belgrade. RESULTS: Gestational age at delivery (β=-0.081, p=0.014), resistance index of the umbilical artery (β=0.601, p=0.039), and D-dimer (β=0.245, p<0.001) between 36th and 38th weeks of gestation presented the direct predictors for adverse pregnancy outcomes. The model fit was examined using the root mean square error of approximation 0.00 (95%CI 0.00-0.18), the goodness-of-fit index was 0.998, and the adjusted goodness-of-fit index was 0.966. CONCLUSION: There is a need for the introduction of more precise protocols for the assessment of hereditary thrombophilias and the need for the introduction of low-molecular-weight heparin.

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.

Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México.

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.

Paciente joven con accidente cerebrovascular isquémico: ¿Se debe buscar una trombofilia? / Ischemic stroke in a young patient, is it needed to look for a thrombophilia?

Resumen El accidente cerebrovascular isquémico es un evento de gran importancia debido a las implicaciones y el impacto en la calidad de vida de la población afectada. Su incidencia es más alta en adultos mayores y en personas con factores de riesgo cardiovascular. Existe un grupo de pacientes jóvenes (18-44 años) sin factores de riesgo que presentan dicho evento, por lo que, en la práctica clínica, se tiende a evaluar rutinariamente las trombofilias hereditarias y adquiridas como factor etiológico principal para los eventos isquémicos en este grupo etario. No obstante, son pocos los casos donde se documenta algún trastorno de este tipo, ya que es más frecuente la presencia de otras etiologías como el cardioembolismo y trastornos vasculares. La evaluación de las trombofilias es compleja, dado el alto costo, las limitaciones técnicas para hacerlo y el impacto clínico y terapéutico incierto al documentarse estos estados. Se realiza esta revisión de tema con el fin de orientar al clínico acerca de la pertinencia de objetivar estas condiciones en el paciente joven con accidente cerebrovascular isquémico.

Abstract Acute ischemic stroke is a pathology of great complexity due to the implications and impact on the quality of life of the affected population. The incidence of this pathology is higher in older adults and in people with cardiovascular risk factors. There is a group of young patients with no risk factors who present these events. Therefore, in clinical practice, hereditary thrombophilias tend to be frequently evaluated as the main etiological factor for this age group. However, there are few cases where a disorder of this type is documented and the presence of other etiologies such as cardioembolism and vascular disorders are more frequent. Thus, the evaluation of thrombophilia is complex due to its high cost, technical limitations when evaluating, and its uncertain clinical and therapeutic impact when documented. For this reason, this review is carried out in order to guide the clinician about the relevance of objectifying these conditions in young patient with acute ischemic stroke

Splanchnic vein thrombosis as a manifestation of latent myeloproliferative neoplasm associated with sticky platelet syndrome / Trombosis esplácnica como presentación de neoplasia mieloproliferativa latente asociada con síndrome de plaqueta pegajosa

Abstract Vein thrombosis of unusual sites such as the splanchnic region continues to be not only a diagnostic but also a therapeutic challenge for the clinician due to its manifestation and associated pathologies. Latent JAK2 (Janus kinase 2) positive myeloproliferative neoplasm associated with sticky platelet syndrome is unusual. We present a clinical case of a 38-year-old female patient who presented with sudden onset abdominal pain of a possible vascular origin. Splanchnic thrombosis was diagnosed in latent myeloproliferative neoplasm by identifying the JAK2V617F mutation and sticky platelet syndrome via platelet aggregometry. Off-label anticoagulation with rivaroxaban 20 mg/day was administered. During her outpatient follow-up, she did not suffer any new thrombotic episodes.

Resumen La trombosis venosa de sitios inusuales como la esplácnica continúa siendo un reto no solo diagnóstico sino también terapéutico para el clínico debido a su forma de presentación y las patologías asociadas. La neoplasia mieloproliferativa latente JAK2 (cinasa de Janus 2) positiva asociada con síndrome de plaqueta pegajosa es inusual. Se presenta un caso clínico de una paciente de 38 años de edad que debutó con dolor abdominal de inicio súbito que sugirió un posible origen vascular. Se diagnosticó trombosis esplácnica en relación con neoplasia mieloproliferativa latente por la identificación de la mutación de la JAK2V617F y síndrome de plaqueta pegajosa mediante agregometría plaquetaria. Se administró de manera off-label anticoagulación con rivaroxabán 20 mg/día. Durante su seguimiento ambulatorio no ha presentado nuevos episodios trombóticos.

Central retinal artery occlusion and subsequent amaurosis fugax in the contralateral eye associated with the G20210A prothrombin gene (F2) variant: a case report.

PURPOSE: Report the case of a patient with a history of central retinal artery occlusion in her right eye and amaurosis fugax associated with acute ischemic changes in her left eye related to a prothrombin G20210A gene variant, in which OCT-A was used as a diagnostic and therapeutic tool. CASE PRESENTATION: 55-year-old woman with a history of central retinal artery occlusion in her right eye and prothrombin gene G20210A (F2) variant diagnosis. She presented to our consultation with amaurosis fugax in her left eye. As medical history, she had an episode of bilateral posterior scleritis diagnosed asynchronously with the current episode. Vascular, autoimmune, and metabolic prothrombotic diseases were ruled out. OCT-A showed areas suggesting acute ischemia consistent with macular retinopathy in her left eye. Anticoagulant therapy with Apixaban was initiated, considering the risk for her vision. Control OCT-A showed perfusion improvement in the previous site of the occlusive vascular event. We also considered the extent of the inflammatory response due to posterior scleritis as a differential diagnosis. Nevertheless, it is less likely, considering the temporality between scleritis and the retinal-vascular episodes. CONCLUSIONS: While the G20210A prothrombin gene (F2) variant is a rare cause of retinal artery occlusion, it is important to consider it a differential diagnosis. Good visual outcomes can be achieved with prompt initiation of antithrombotic treatment. In addition, OCT-A is useful for diagnosing ischemic retinal changes that cannot be observed with other diagnostic methods and monitoring them.