Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus.

OBJECTIVE: To assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. METHODS: A cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. RESULTS: The mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8-315.9) vs 158.1 (113.4-201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. CONCLUSION: Patients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Principales modificaciones asociadas a la esplenectomía / Main modifications associated with splenectomy

Introducción. El bazo es un órgano linfoide implicado en el reconocimiento antigénico, la depuración de patógenos y la remoción de eritrocitos envejecidos o con inclusiones citoplasmáticas. La esplenectomía es una técnica utilizada tanto para el diagnóstico (linfomas), el tratamiento (trombocitopenia inmune, anemia hemolítica adquirida) y la curación (microesferocitosis hereditaria) de diversas enfermedades. Métodos. Describir los principales cambios hematológicos y complicaciones asociadas al procedimiento de esplenectomía. Discusión. Los cambios posteriores a la esplenectomía pueden ser inmediatos, como la aparición de cuerpos de Howell-Jolly, la trombocitosis y la presencia de leucocitosis durante las primeras dos semanas. Otras complicaciones tempranas incluyen la presencia de trombosis, en especial en pacientes con factores de riesgo secundarios (edad, sedentarismo, manejo hospitalario, obesidad) o un estado hipercoagulable (diabetes, cáncer, trombofilia primaria), siendo tanto el flujo de la vena porta como el volumen esplénico los principales factores de riesgo para su aparición. Las complicaciones tardías incluyen la alteración en la respuesta inmune, aumentando el riesgo de infecciones por bacterias encapsuladas, en conjunto con una reducción en los niveles de IgM secundario a la ausencia de linfocitos B a nivel de bazo. Debido al riesgo de infecciones, principalmente por Streptococcus pneumoniae, la esplenectomía parcial se ha considerado una opción. Conclusión. Una adecuada valoración de la indicación de esplenectomía y la identificación precoz de complicaciones posoperatorias son fundamentales para reducir la mortalidad asociada a la esplenectomía

Introduction. The spleen is a lymphoid organ involved in antigen recognition, pathogen clearance, and removal of aged erythrocytes or those with cytoplasmic inclusions. Splenectomy is a technique used for diagnosis (lymphomas), treatment (immune thrombocytopenia, acquired hemolytic anemia), and cure (hereditary microspherocytosis) of various diseases. Methods. To describe the main hematological changes and complications associated with the splenectomy procedure. Discussion. Changes after splenectomy can be considered immediate: the appearance of Howell-Jolly bodies, thrombocytosis, and leukocytosis during the first two weeks. Other complications include the presence of thrombosis, especially in patients with risk factors (age, sedentary lifestyle, long hospital stay, obesity) or a hypercoagulable state (diabetes, cancer, primary thrombophilia), with both portal vein flow and splenic volume being the main risk factors for its appearance. Late complications include altered immune response, increased risk of infections by encapsulated bacteria, and a reduction in IgM levels secondary to the absence of B lymphocytes in the spleen; due to the risk of diseases mainly by Streptococcus pneumoniae, partial splenectomy has been considered an option. Conclusion. An adequate assessment of the indication for splenectomy and the early identification of complications are essential to reduce the mortality associated with splenectomy

Leucemia y Covid-19 (Leucovid-19): efecto de la pandemia sobre el diagnóstico de leucemia aguda en la Ciudad de México previo a Ómicron.

No disponible.

Overexpression of BCL2, BCL6, VEGFR1 and TWIST1 in Circulating Tumor Cells Derived from Patients with DLBCL Decreases Event-Free Survival.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignant lymphoid neoplasm and is the most common subtype of non-Hodgkin lymphoma in adults. More than half of patients with DLBCL can achieve remission with standard R-CHOP regimes; however, approximately 30-40% of patients are still failing this standard therapy, which remains as an important cause of progression and mortality of this disease. It is necessary to have diagnostic and monitoring tools that allow us to improve the accuracy of prognosis in these patients. Circulating tumor cells (CTCs) identification through molecular biomarkers is one of the novel strategies that have been used in other types of cancer, and we aim to use this tool to analyze the potential role in DLBCL. Patients and Methods: We analyzed 138 blood samples of patients with DLBCL, of which CTCs were isolated by density gradient for subsequent detection and quantitation of molecular biomarkers using RT-qPCR with TaqMan probes. Survival analysis was performed using Kaplan-Meier curves. Results: We found overexpression of ABCB1, αSMA, BCL2, BCL6 and VEGFR1 genes, as well as the presence of CK19, EpCAM, KI67, MAGE-A4, SNAIL and TWIST1 genes. CK19 and EpCAM expression were associated with a minor OS (85.7% vs 98.1%, p = 0.002). The overexpression of BCL2, BCL6, VEGFR1 and TWIST1 was related to a minor EFS (p = 0.001). Conclusion: This study showed that in liquid biopsies analyzed, the presence of CTCs can be confirmed through molecular biomarkers, and it has an impact on OS and EFs, making this detection useful in the follow-up and prognosis of patients with DLBCL.

Pattern of Adiponectin, Osteocalcin, Irisin, FGF-21, and MCP-1 According to the Body Size Phenotype: Could They Be Markers of Metabolic Health in Mexican-Mestizo Middle-Aged Women?

Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype of middle-aged women, and their associations with BMI, visceral adipose tissue (VAT), and HOMA-IR. A cross-sectional study in 265 women aged from 40 to 65 years was performed. The biochemical characteristics were evaluated in metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy obese, and metabolically unhealthy obese women. There was an association of OCN with BMI (r = -0.107; p = 0.047); adiponectin with BMI (r = -0.217; p = 0.001), insulin (r = -0.415; p = 0.0001), HOMA-IR (r = -0.429; p = 0.0001), and VAT (r = -0.134; p = 0.025); irisin with BMI (r = 0.604; p = 0.001), insulin (r = 0.446; p = 0.0001), HOMA-IR (r = 0.452; p = 0.0001), and VAT (r = 0.645; p = 0.0001); FGF-21 with insulin (r = -0.337; p= 0.030) and HOMA-IR (r = -0.341; p = 0.03); and MCP-1 with BMI (r = 0.481; p = 0.0001), VAT (r = 0.497; p = 0.001), insulin (r = 0.298; p= 0.001), and HOMA-IR (r = 0.255; p = 0.004). A multivariate analysis showed that an elevation of OCN (OR 1.4 (95%CI 1.06-1.81)) and a reduction of adiponectin (OR 0.9 (0.84-0.96)) were associated factors for a metabolic unhealthy phenotype in normal weight participants. Likewise, higher irisin (OR 1.007 (1.003-1.011)) and MCP-1 (1.044 (1.008-1.083)) were risk factors for a metabolic unhealthy phenotype in woman with obesity. OCN, adiponectin, irisin, FGF-21, and MCP-1 are associated with some metabolic parameters such as BMI, HOMA-IR, and VAT, and could be possible biomarkers of an unhealthy metabolic phenotype in middle-aged women.

COVID-19 in a country with a very high prevalence of diabetes: The impact of admission hyperglycaemia on mortality.

Aims: To evaluate the frequency of diabetes and admission hyperglycaemia in Mexican COVID-19 patients, to describe the clinical and biochemical characteristics of patients with admission hyperglycaemia and to determinate the impact of diabetes and admission hyperglycaemia on COVID-19 severity and mortality. Methods: A multicentric study was performed in 480 hospitalized patients with COVID-19. Clinical and biochemical characteristics were evaluated in patients with admission hyperglycaemia and compared with non-hyperglycaemic patients. The effect of diabetes and admission hyperglycaemia on severity and risk of death were evaluated. Results: Age was 50.7 ± 13.6 years; 68.3% were male. Some 48.5% (n = 233) had admission hyperglycaemia; 29% (n = 139) of these patients had pre-existing diabetes. Patients with admission hyperglycaemia had more requirement of invasive mechanical ventilation (IMV), higher levels of urea, D-dimer and neutrophil-lymphocyte ratio (NLR), as well as lower lymphocyte count. An association between admission hyperglycaemia with IMV and D-dimer with glucose was found. Age ≥50 years (OR 2.09; 95%CI 1.37-3.17), pre-existing diabetes (OR 2.38; 95%CI 1.59-5.04) and admission hyperglycaemia (OR 8.24; 95%CI 4.74-14.32) were risk factors for mortality. Conclusions: Admission hyperglycaemia is presented in 48.5% of COVID-19 patients. Diabetes and admission hyperglycaemia are associated with the severity of disease and mortality. This study shows the devastating conjunction of hyperglycaemia and COVID-19. Clinical trial registration: Clinical characteristics of patients with COVID-19, DI/20/204/04/41 (Hospital General de Mexico) and NR-13-2020 (Hospital Regional de Alta Especialidad Ixtapaluca).

COVID-19 en pacientes con patologías hematológicas / COVID-19 in patients with hematological diseases

Resumen Los informes iniciales sugirieron que los pacientes con antecedentes o malignidad activa podrían tener un mayor riesgo de contraer el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) y desarrollar complicaciones relacionadas con la enfermedad por coronavirus 2019 (COVID-19). Pacientes con patologías hematológicas benignas y malignas pueden estar inmunocomprometidos por los efectos de la terapia antineoplásica, medicamentos de apoyo como los esteroides y las propiedades inmunosupresoras del cáncer en sí. También podrían tener una respuesta inmunitaria aumentada a la infección secundaria a fármacos inmunomoduladores. Se espera que la COVID-19, causada por el SARS-CoV-2, sea una infección devastadora en muchos pacientes con enfermedades hematológicas. En México se reportaron los primeros casos confirmados el 1 de marzo de 2020; en nuestro servicio de hematología el primer caso reportado y confirmado fue en abril de 2020. Realizamos un estudio de serie de casos de 33 pacientes hospitalizados con patologías benignas y malignas que desarrollaron COVID-19. Las tasas de casos de COVID-19 en sujetos hospitalizados con patologías hematológicas fue del 15.7%. La mortalidad por COVID-19 fue del 54.54%. En pacientes con patologías hematológicas parece deberse principalmente a que los pacientes con cáncer activo sin respuesta completa que recibieron quimioterapia citotóxica u otro tratamiento contra el cáncer tienen un mayor riesgo de mortalidad por la COVID-19 en comparación con aquellos que no reciben tratamiento activo, pacientes de novo sin quimioterapia, pero en estadios avanzados de la enfermedad con comorbilidades y asociadas principalmente con coinfecciones bacterianas.

Abstract Initial reports suggested that patients with a history or active malignancy may be at increased risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing complications related to coronavirus disease 2019 (COVID-19). Patients with benign and malignant hematological pathologies may be immunocompromised by the effects of antineoplastic therapy, supportive medications such as steroids, and the immunosuppressive properties of the cancer itself. They may also have an increased immune response to infection secondary to immunomodulatory drugs. COVID-19, caused by SARS-CoV-2, is expected to be an infection devastating in many patients with hematologic diseases. The first confirmed cases in Mexico were on March 1, 2020; In our hematology service, the first case reported and confirmed was in April 2020. We conducted a case series study of 33 hospitalized patients with benign and malignant pathologies that developed COVID-19. The COVID-19 case rates in hospitalized subjects with hematological pathologies was 15.7%. The mortality from COVID-19 was 54.54%. In patients with hematological pathologies it seems to be mainly due to the fact that patients with active cancer without a complete response who received cytotoxic chemotherapy or other anti-cancer treatment cancer have a higher risk of mortality from COVID-19 compared to those who do not receive active treatment, patients de novo without chemotherapy, but in advanced stages of the disease with comorbidities and associated mainly with bacterial coinfections.

Dímeros D e hiperglucemia y mortalidad en COVID-19 en un centro hospitalario de México / D-dimers, hyperglycemia and mortality in COVID-19 in a hospital in Mexico

Resumen Objetivo: Evaluar la asociación entre la concentración de glucosa al ingreso y los niveles circulantes de dímeros D en pacientes hospitalizados por enfermedad por coronavirus 2019 (COVID-19). Pacientes y métodos: Se estudiaron 187 pacientes hospitalizados por COVID-19. Se evaluaron las características bioquímicas, la concentración de glucosa y dímeros D, la gravedad de la enfermedad definida por la presencia de neumonía y/o insuficiencia respiratoria que ameritó ventilación mecánica invasiva (VMI) y la causa del egreso hospitalario. Resultados: La edad promedio de los pacientes fue 52 años, el 68% eran hombres, un 40.8% con obesidad y un 23.5% con hipertensión. Del total de pacientes hospitalizados, el 45.5% presentaba diabetes o hiperglucemia a la admisión. La concentración de proteína C reactiva y de dímeros D (1,134 [646.5-4,135.0] vs. 755 [548.7-1,780.0] ng/ml; p = 0.04] fue superior en pacientes con diabetes e hiperglucemia, en comparación con los pacientes con glucosa normal. Los pacientes que requirieron VMI presentaron también mayor concentración de dímeros D. Se observó una correlación directa entre las concentraciones de glucosa inicial y dímeros D (r: 0.239; p = 0.003). Conclusión: En los pacientes con COVID-19 el estado hiperglucémico se asocia directamente con un incremento de la concentración de dímeros D. Los resultados de este estudio deben conducir a insistir en el control glucémico como estrategia fundamental en los pacientes con COVID-19.

Abstract Objective: To evaluate the association between glucose level at admission and circulating levels of D-dimers in patients hospitalized for coronavirus disease 2019 (COVID-19). Methods: 187 patients hospitalized for COVID-19 were studied. Biochemical characteristics, glucose and D-dimers levels, severity of disease, defined by the presence of pneumonia and/or respiratory failure that required invasive mechanical ventilation (IVM) and the cause of hospital discharge were evaluated. Results: Age was 52 years, 68% were male, 40.8% with obesity and 23.5% with hypertension. Of the total of hospitalized patients, 45.5% had diabetes or hyperglycemia upon admission. Patients with diabetes and/or admission hyperglycemia had higher levels of protein C-reactive and D-dimers [(1134 (646.5-4135.0) vs. 755 (548.7-1780.0) ng/ml, p = 0.04], compared to patients with normal glucose level. Patients who required IMV also had a higher concentration of D-dimers. A correlation between glucose and D-dimers levels was evidenced (r=0.239, p=0.003). Conclusions: In patients with COVID-19, the hyperglycemic state is directly associated with an increase in the concentration of D-dimers and severity of disease. The results of this study should lead to insisting on glycemic control as a fundamental strategy in patients with COVID-19.

Anormalidades hematológicas en pacientes con el SARS-CoV-2 (COVID-19) y sus implicaciones pronósticas / Hematological abnormalities in patients with the SARS-CoV-2 (COVID-19) and its prognostic implications

Resumen La infección por coronavirus 2 del síndrome respiratorio agudo grave condiciona un gran número de anormalidades pulmonares y sistémicas que basan su fisiopatogenia en la inmunotrombosis. Específicamente para el área de la hematología desde los primeros estudios de caracterización clínica y paraclínica se identificaron anormalidades hematológicas y de la hemostasia que se han documentado de forma consistente en diferentes publicaciones y cuyo conocimiento es trascendente desde el punto de vista de pronóstico. Durante el curso de la enfermedad, la evaluación longitudinal de algunos parámetros hematológicos es primordial para la identificación temprana de pacientes potencialmente complicables. El conteo absoluto de leucocitos, la depleción linfoide y la trombocitopenia son los marcadores hematológicos principalmente alterados. La linfopenia severa es un hallazgo cardinal en la fase temprana de la infección y su persistencia durante la progresión de la enfermedad tiene mayor impacto pronóstico adverso. La determinación de los índices hemáticos neutrófilo:linfocito y linfocito:plaqueta también ha demostrado su utilidad como predictores de complicaciones respiratorias y mortalidad. Un estado de hipercoagulabilidad demostrado por niveles altos de dímero D y/o productos de degradación de fibrinógeno y diversas alteraciones hemostásicas en el perfil de coagulación se asocian a una mayor tasa de morbimortalidad. Otros biomarcadores inflamatorios, incluidos proteína C reactiva, procalcitonina y ferritina, podrían identificar tempranamente aquellos casos que requieren de soporte ventilatorio y/o hemodinámico avanzado. En esta revisión se abordan los antecedentes históricos de la patología y las principales alteraciones hematológicas y de la hemostasia y sus implicaciones pronósticas.

Abstract Severe acute respiratory syndrome coronavirus 2 infection conditions a large number of pulmonary and systemic abnormalities that base its physiopathogenesis on immunothrombosis. Specifically, for the area of hematology, from the first clinical and paraclinical characterization studies, hematological and hemostasis abnormalities have been identified that have been consistently documented through different publications and whose knowledge is transcendent from the prognostic point of view. During the course of the disease, longitudinal evaluation of some hematological parameters is essential for the early identification of potentially complicated patients. Absolute leukocyte count, lymphoid depletion, and thrombocytopenia are the principally altered hematologic markers. Severe lymphopenia is a cardinal finding in the early phase of infection, and its persistence during disease progression has a greater adverse prognostic impact. The determination of the neutrophil/ lymphocyte and lymphocyte/ platelet hematic indices have also shown their usefulness as predictors of respiratory complications and mortality. A state of hypercoagulability demonstrated by high levels of D-dimer and or fibrinogen degradation products and various hemostatic alterations in the coagulation profile are associated with a higher rate of morbidity and mortality. Other inflammatory biomarkers including C-Reactive Protein, procalcitonin and ferritin can early identify those cases that require advanced ventilatory and/or hemodynamic support. In this review, the historical antecedents of the pathology and the main hematological and hemostasis alterations and their prognostic implications are addressed.

Coagulopatía, tratamiento anticoagulante en COVID-19 y trombosis posvacunación / Coagulopathy, anticoagulant treatment in COVID-19 and thrombosis postvaccine

Resumen La coagulopatía y la trombosis son situaciones graves que afectan a los pacientes con enfermedad por coronavirus 2019 (COVID-19) que requieren hospitalización. En estos pacientes se alteran mecanismos procoagulantes y fibrinolíticos que condicionan un estado procoagulante progresivo y grave. La anticoagulación oportuna en estos pacientes es importante, pero han surgido preguntas sobre el tipo, la dosis y el momento adecuado de la anticoagulación. Las directrices y documentos de consenso existentes ofrecen sugerencias generales sobre la dosis de heparinas de bajo peso molecular en función de la gravedad de la enfermedad y el riesgo de trombosis, pero todavía falta una relación entre los marcadores de coagulación y el régimen de anticoagulación. Se están llevando a cabo muchos ensayos clínicos que abordan estas cuestiones; se alienta la participación en estos ensayos para determinar las mejores estrategias de tratamiento para los pacientes de COVID-19. Es necesario aumentar los conocimientos con un rápido intercambio para atender adecuadamente a los pacientes en esta pandemia.

Abstract Coagulopathy and thrombosis are serious situations that COVID-19 patients require hospitalization. In these patients, procoagulant and fibrinolytic mechanisms are altered that condition a progressive and severe procoagulant state. Timely anticoagulation in these patients is important, but questions have been raised about the type, dose, and timing of anticoagulation. The guidelines and consensus documents offer general suggestions on the dose of LMWH based on the severity of the disease and the risk of thrombosis, but a relationship between coagulation markers and anticoagulation regimen is still lacking. Many clinical trials are underway that address these issues; Participation in these trials to determine the best treatment strategies for COVID-19 patients is encouraged. Increasing knowledge with rapid exchange is necessary to adequately care for patients in this pandemic.

Atención integral y manejo del paciente con hemofilia en el contexto de la pandemia de COVID-19 / Comprehensive care and patient management with hemophilia, in the context of COVID-19 pandemic

Resumen El espectro clínico de la hemofilia severa ha evolucionado a lo largo de la historia desde una condición catastrófica y altamente fatal a principios del siglo xx, hasta un trastorno crónico y «manejable¼ en las últimas décadas, gracias a los notables avances en el tratamiento alcanzados en los últimos 40 años, avances impulsados y reforzados por algunas experiencias catastróficas pasadas, como lo fue el desastre biológico en la década de 1980 debido a infecciones virales fatales transmitidas por trasfusión, como hepatitis y virus de la inmunodeficiencia humana/sida, a partir de lo cual la aparición de nuevos agentes infecciosos son una preocupación constante para la comunidad de hemofilia, como lo es actualmente el caso al que nos enfrentamos con la pandemia de enfermedad por coronavirus 2019, que ha creado una situación extremadamente desafiante para los miembros de la comunidad mundial de trastornos hemorrágicos. Ante esta pandemia han surgido interrogantes sobre la posibilidad de si los pacientes con hemofilia tendrán mayor riesgo de infección y si la deficiencia de factor y su tratamiento podrían influir en las manifestaciones de la infección, su curso natural, tratamiento y complicaciones; aunado a la preocupación de que parece claro que la pandemia actual tendrá consecuencias definitivas sobre el manejo de la hemofilia en todo el mundo. Tales interrogantes han dado lugar a la revisión de la literatura, guías, consensos de expertos, incluyendo las recomendaciones de la Federación Mundial de Hemofilia, en un intento de responder a dichas interrogantes, generando así tanto pautas para la atención como ampliando algunas de ellas, impulsando el desarrollo de nuevos protocolos de investigación.

Abstract The clinical spectrum of severe hemophilia has evolved throughout history from a catastrophic and highly fatal condition in the early 20th century to a chronic and “manageable” disorder in recent decades, thanks to the remarkable advances in treatment achieved. in the last 40 years, advances driven and reinforced by some past catastrophic experiences, such as the biological disaster in the 1980s due to fatal viral infections transmitted by transfusion, such as hepatitis and HIV/AIDS, from which, the appearance of new infectious agents are an ongoing concern for the hemophilia community, as is currently the case facing us with the coronavirus disease 2019 pandemic, which has created an extremely challenging situation for members of the global bleeding disorders community. Faced with this pandemic, questions have arisen regarding the possibility of whether patients with hemophilia will have a higher risk of infection and whether factor deficiency and its treatment could influence the manifestations of the infection, its natural course, treatment and complications; coupled with the concern that it seems clear that the current pandemic will have definitive consequences on the management of hemophilia around the world. Such questions have led to a review of the literature, guidelines, and expert consensus, including the recommendations of the World Federation of Hemophilia, in an attempt to answer these questions, thus generating both guidelines for care, and expanding some of them, promoting the development of new research protocols.

Trombocitopenia inmune primaria. Tratamiento y recomendaciones ante la pandemia por COVID-19 / Primary immune thrombocytopenia. Treatment and recommendations for the COVID-19 pandemic

Resumen La trombocitopenia inmune primaria (TIP) es una trastorno autoinmune adquirido caracterizado por el recuento bajo de plaquetas como resultado de la destrucción de plaquetas y la producción de plaquetas deteriorada. La falta de ensayos aleatorizados sobre el manejo de la TIP ha dado como resultado controversias significativas y gran variación en la práctica clínica para su diagnóstico y tratamiento. Aunado a esto, la pandemia actual de enfermedad por coronavirus 2019 (COVID-19), causada por el nuevo coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2), plantea una serie de dilemas para el estudio y tratamiento de los pacientes con trombocitopenia inmune, incluyendo las ventajas y desventajas de las opciones terapéuticas estándar para la TIP de reciente diagnóstico o en recaída y cronicidad, en cada uno de los enfoques de manejo: observación, corticosteroides, inmunoglobulina intravenosa, inmunoglobulina anti-D (anti-DIg), rituximab, esplenectomía y agonistas de los receptores de trombopoyetina, así como el reconocimiento de los desafíos planteados al manejo de pacientes con TIP con manifestaciones hemorrágicas y riesgo trombótico observado en pacientes hospitalizados con infección por SARS-CoV-2. Por tal motivo, el presente trabajo tiene como objetivo plasmar y ofrecer recomendaciones y pautas a seguir tanto en niños como en adultos con y sin COVID-19, ante el riesgo y beneficio en cada escenario, basado en consenso de expertos y guías ya establecidas (sobre todo para pacientes adultos) para el manejo, tratamiento y seguimiento de la TIP en el contexto de la actual pandemia.

Abstract Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet count as a result of platelet destruction and impaired platelet production. The lack of randomized trials on the management of IPT has resulted in significant controversy and great variation in clinical practice for its diagnosis and treatment. In addition to this, the current coronavirus disease 2019 (COVID-19) pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a series of dilemmas for the study and treatment of patients with immune thrombocytopenia, including the advantages and disadvantages of therapeutic options standard for newly diagnosed or relapsed and chronic IPT, in each of the management approaches: observation, corticosteroids, IV immunoglobulin, anti-D immunoglobulin, rituximab, splenectomy and thrombopoietin receptor agonists, as well as recognition of the challenges posed to the management of patients with IPT with hemorrhagic manifestations and thrombotic risk observed in hospitalized patients with SARS-CoV-2 infection. For this reason, the present work aims to capture and offer recommendations and guidelines to follow in both children and adults with and without COVID-19, given the risk and benefit in each scenario, based on consensus of experts and already established guidelines (on all for adult patients) for the management, treatment and follow-up of IPT in the context of the current pandemic.

Parámetros de laboratorio de importancia en el manejo de pacientes con COVID-19 / Laboratory parameters of importance in the management of COVID-19 patients

Resumen El coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) detona el padecimiento la enfermedad por coronavirus 2019 (COVID-19), poniendo en riesgo de muerte a la población vulnerable. El laboratorio clínico enfrenta un reto para el diagnóstico, seguimiento, pronóstico y evaluación de los tratamientos, que se ofrecen a los enfermos de COVID-19. Nuestro objetivo es mostrar al lector un resumen de los principales cambios en los parámetros que se estudian en los laboratorios clínicos. Material y métodos: Se hizo una búsqueda bibliográfica cruzando los términos COVID-19 y laboratorio clínico. Se analizaron las publicaciones relevantes por los miembros del Comité de Trombosis y Hemostasia-AMEH A.C. y se plasmaron las pruebas que a criterio de los participantes destacan por la relación entre la información que proporcionan respecto al seguimiento, pronóstico y evaluación al tratamiento. Resultados: Se recomienda solicitar una citometría hemática (recuento de células blancas, relación neutrófilo:linfocito), química sanguínea (transaminasas, bilirrubinas, albúmina, urea, creatinina, glucosa, lactato deshidrogenasa), pruebas de coagulación (tiempo de protrombina, tiempo de tromboplastina parcial activado, fibrinógeno y dímeros D) y pruebas especiales (proteína C reactiva, ferritina, procalcitonina, troponina).

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers the coronavirus disease 2019 (COVID-19), putting the vulnerable population at risk of death. The clinical laboratory faces a challenge for the diagnosis, monitoring, prognosis and evaluation of therapy with low molecular weight heparin. Our objective in this article is to offer a brief discuss of the main changes in the clinical parameters, studied on behalf of COVID-19 patients by a clinical laboratory. Material and methods: A bibliographic search was made crossing the terms COVID-19 and clinical laboratory. Relevant publications were analyzed by the members of the Committee for Thrombosis and Hemostasis-AMEH A.C. The relevant articles were discussed, and the clinical tests discussed in the article are those, that meet the criteria of providing information referring to the follow-up, prognosis and evaluation of treatment against the lower cost. Results: It is recommended to request a blood count (white cell count, neutrophyl/ lymphocytes ratio), clinical chemistry (transaminases, bilirubin, albumin, urea, creatinine, glucose, lactate dehydrogenase), coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, DD dimers) and special tests (C-reactive protein, ferritin, procalcitonin, troponins).

Usefulness of the neutrophil-to-lymphocyte, monocyte-to-lymphocyte and lymphocyte-to-platelet ratios for the prognosis of COVID-19-associated complications.

INTRODUCTION: Various biomarkers based on blood counts have been useful for the prognosis of patients critically ill with COVID-19. OBJECTIVE: To describe the usefulness of the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR) and lymphocyte-to-platelet (LPR) ratios for the prognosis of mortality and ventilatory support requirement for COVID-19. METHOD: Retrospective cohort of clinical records of patients with COVID-19 who required hospital care. RESULTS: One-hundred and -twenty-five cases were analyzed; mean age was 51 years, and 60 % were of the male gender; 21.6 % had type 2 diabetes mellitus, and 18.4 % had hypertension. Mean leukocyte count was 9.5 x 103/µL, with a neutrophil mean of 8.0 x 103/µL. Mean NLR was 12.01, while for MLR it was 0.442, and for LPR, 373.07. Regarding the area under the curve, the following values were recorded for mortality: 0.594 for NLR, 0.628 for MLR and 0.505 for LPR; as for mechanical ventilation, the values were 0.581 for NLR, 0.619 for MLR and 0.547 for LPR. In the univariate analysis, an NLR value > 13 (OR: 2.750, p = 0.001) and an MLR of > 0.5 (OR: 2.069, p = 0.047) were associated with mortality; LPR showed no impact on mortality or respiratory support. CONCLUSION: NLR and MLR are useful for predicting mortality in patients with COVID-19.

INTRODUCCIÓN: Diversos biomarcadores basados en conteos sanguíneos han sido de utilidad para el pronóstico de los pacientes en estado crítico por COVID-19. OBJETIVO: Describir la utilidad de los índices neutrófilo/linfocito (INL), monocito/linfocito (IML) y linfocito/plaqueta (IPL) para el pronóstico de la mortalidad y necesidad de soporte ventilatorio por COVID-19. MÉTODO: Cohorte retrospectiva de registros clínicos de pacientes con COVID-19 que requirieron atención hospitalaria. RESULTADOS: Se analizaron 125 casos, la edad media fue de 51 años y 60 %, del sexo masculino; 21.6 % padecía diabetes mellitus tipo 2 y 18.4 %, hipertensión. La media de leucocitos fue 9.5 × 103/µL y la de neutrófilos, de 8.0 × 103/µL. La media del INL fue de 12.01; del IML, de 0.442 y del IPL, de 373.07. Respecto al área bajo la curva se registraron los siguientes valores en cuanto a mortalidad: INL, 0.594; IML, 0.628 e ILP, 0.505; en cuanto a ventilación mecánica: INL, 0.581; IML, 0.619 e ILP, 0.547. En el análisis univariado, INL > 13 (RM = 2.750, p = 0.001) e IML > 0.5 (RM = 2.069, p = 0.047) se asociaron a mortalidad; ILP no mostró impacto en la mortalidad ni en el soporte respiratorio. CONCLUSIÓN: INL e IML son de utilidad para predecir la mortalidad en pacientes con COVID-19.

Utilidad de los índices neutrófilo/linfocito, monocito/linfocito y linfocito/plaqueta para el pronóstico de complicaciones asociadas a COVID-19 / Usefulness of the neutrophil-to-lymphocyte, monocyte-to-lymphocyte and lymphocyte-to-platelet ratios for the prognosis of COVID-19-associated complications

Resumen Introducción: Diversos biomarcadores basados en conteos sanguíneos han sido de utilidad para el pronóstico de los pacientes en estado crítico por COVID-19. Objetivo: Describir la utilidad de los índices neutrófilo/linfocito (INL), monocito/linfocito (IML) y linfocito/plaqueta (IPL) para el pronóstico de la mortalidad y necesidad de soporte ventilatorio por COVID-19. Método: Cohorte retrospectiva de registros clínicos de pacientes con COVID-19 que requirieron atención hospitalaria. Resultados: Se analizaron 125 casos, la edad media fue de 51 años y 60 %, del sexo masculino; 21.6 % padecía diabetes mellitus tipo 2 y 18.4 %, hipertensión. La media de leucocitos fue 9.5 × 103/mL y la de neutrófilos, de 8.0 × 103/mL. La media del INL fue de 12.01; del IML, de 0.442 y del IPL, de 373.07. Respecto al área bajo la curva se registraron los siguientes valores en cuanto a mortalidad: INL, 0.594; IML, 0.628 e ILP, 0.505; en cuanto a ventilación mecánica: INL, 0.581; IML, 0.619 e ILP, 0.547. En el análisis univariado, INL > 13 (RM = 2.750, p = 0.001) e IML > 0.5 (RM = 2.069, p = 0.047) se asociaron a mortalidad; ILP no mostró impacto en la mortalidad ni en el soporte respiratorio. Conclusión: INL e IML son de utilidad para predecir la mortalidad en pacientes con COVID-19.

Abstract Introduction: Various biomarkers based on blood counts have been useful for the prognosis of patients critically ill with COVID-19. Objective: To describe the usefulness of the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR) and lymphocyte-to-platelet ([LPR) ratios for the prognosis of mortality and ventilatory support requirement for COVID-19. Method: Retrospective cohort of clinical records of patients with COVID-19 who required hospital care. Results: One-hundred and twenty-five cases were analyzed; mean age was 51 years, and 60 % were of the male gender; 21.6 % had type 2 diabetes mellitus, and 18.4 % had hypertension. Mean leukocyte count was 9.5 × 103/mL, with a neutrophil mean of 8.0 × 103/mL. Mean NLR was 12.01, while for MLR it was 0.442, and for LPR, 373.07. Regarding the area under the curve, the following values were recorded for mortality: 0.594 for NLR, 0.628 for MLR and 0.505 for LPR; as for mechanical ventilation, the values were 0.581 for NLR, 0.619 for MLR and 0.547 for LPR. In the univariate analysis, an NLR value > 13 (OR: 2.750, p = 0.001) and an MLR of > 0.5 (OR: 2.069, p = 0.047) were associated with mortality. LPR showed no impact on mortality or respiratory support. Conclusion: NLR and MLR are useful for predicting mortality in patients with COVID-19.

Differences between metabolically healthy and unhealthy obesity in PAI-1 level: Fibrinolysis, body size phenotypes and metabolism.

BACKGROUND: Different studies have recognized the existence of subtypes of obesity and normal weight, in which it is reported that not all patients show the same cardiometabolic risk, called "metabolically healthy" and "metabolically unhealthy". In several reviews, differences in the inflammatory profile have been studied, but there is not information on the relationship of body size phenotypes with thrombosis risk. OBJECTIVE: Determine the association between body size phenotypes and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). METHODS: A cross-sectional study was conducted in women aged 40 to 65 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Karelis criteria were used to define metabolic status. Four groups were formed: Metabolically healthy normal weight (MHNW), Metabolically unhealthy normal weight (MUNW), Metabolically healthy obese (MHO) and Metabolically unhealthy obese (MUO). RESULTS: 230 women were included in our study with a mean age 52.3 ±â€¯5.9 years. The concentration of PAI-1 showed a significant difference between the groups MHNW, MUNW, MHO, MUO [2.3 (0.08, 13.6), 12.7, (0.08, 33.1), 23.4 (2.6, 28.8) and 22.8 (2.0, 46.7) ng/mL, respectively, p = 0.006]. Multiple regression analysis identified that BMI and HOMA-IR were independent factors influencing PAI-1 levels. CONCLUSION: This study is the first one that recognizes differences in the fibrinolytic activity between body size phenotypes. The groups with the lowest fibrinolytic activity were MUO and MHO, however, MUNW also present alterations of fibrinolysis, thus suggesting a prothrombotic state.

Circulating levels of plasminogen activator inhibitor-1 are associated with metabolic syndrome rather than with menopause.

The plasminogen activator inhibitor type 1 (PAI-1) is the major determinant of fibrinolytic activity. PAI-1 concentrations are elevated in obesity, type 2 diabetes and metabolic syndrome (MetS). On the other hand, during menopause, fibrinolytic activity decreases and, consequently, PAI-1 concentration increases; however, it is debated whether menopause is an independent determinant factor of PAI-1 levels. The objective of this study was to evaluate the effect of hormonal and metabolic status on the concentration of PAI-1 in pre-and post-menopausal women. A case-control study was conducted in ninety pre-and post-menopausal women aged 45 to 55 years, matched by body mass index (BMI). Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Of all the women, 30% presented MetS. Women with MetS had higher values of PAI-1 (36.0 ± 19.1 vs 19.3 ± 14.8 ng/mL, p < .001); in contrast, no differences were observed when compared by hormonal status (20.7 ± 18.10 vs 20.2 ± 17.0 ng/mL, NS). The results of this study suggest that in women, MetS plays a more important role in the deterioration of the fibrinolytic mechanisms rather than their hormonal status. Therefore, the identification of cardio-metabolic factors is relevant to reduce the presence of thrombosis in post-menopausal women.

El incremento de la grasa epicárdica en mujeres se asocia a riesgo trombótico / An increase in epicardial fat in women is associated with thrombotic risk

Introducción: En pacientes con enfermedad coronaria se ha observado una disminución de la actividad fibrinolítica y aumento del grosor del tejido adiposo epicárdico. El objetivo del estudio fue determinar la relación entre la grasa epicárdica y la actividad fibrinolítica, midiendo la concentración del inhibidor del activador del plasminógeno tipo-1 (PAI-1). Métodos: Estudio transversal que incluyó a 56 mujeres aparentemente sanas, con edad de 45-60 años. A las participantes se les realizaron mediciones antropométricas y bioquímicas, la actividad fibrinolítica se determinó midiendo PAI-1 por la técnica de ELISA. El grosor epicárdico se evaluó por ecocardiografía transtorácica. Resultados: La concentración de PAI-1 se asoció directamente con el grosor del tejido adiposo epicárdico (r = .475, p = .001), glucosa, triglicéridos, resistencia a la insulina, IMC, tejido adiposo visceral y grasa corporal total. El análisis de regresión multivariado indicó que la grasa epicárdica predice en forma independiente el valor de PAI-1. Conclusiones: Las mujeres con incremento de tejido adiposo epicárdico muestran menor actividad fibrinolítica por presentar niveles aumentados de PAI-1 y, en consecuencia, un posible mayor riesgo trombótico

Introduction: A decrease in fibrinolytic activity and an increase in the thickness of the epicardial adipose tissue have been observed in patients with coronary artery disease. The aim of this study was to determine the association between epicardial adipose tissue and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). Methods: A cross-sectional study was conducted on 56 apparently healthy women aged 45 to 60 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Epicardial thickness was assessed by transthoracic echocardiography. Results: The concentration of PAI-1 was directly associated with the thickness of the epicardial adipose tissue (r = 0.475, P = .001), body mass index (BMI), visceral adipose tissue, insulin resistance, glucose, and HDL-cholesterol. The multivariate regression analysis indicated that epicardial fat independently predicts the concentrations of PAI-1. Conclusions: Women with thicker epicardial adipose tissue have reduced fibrinolytic activity, and consequently greater thrombotic risk

An increase in epicardial fat in women is associated with thrombotic risk. / El incremento de la grasa epicárdica en mujeres se asocia a riesgo trombótico.

INTRODUCTION: A decrease in fibrinolytic activity and an increase in the thickness of the epicardial adipose tissue have been observed in patients with coronary artery disease. The aim of this study was to determine the association between epicardial adipose tissue and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). METHODS: A cross-sectional study was conducted on 56 apparently healthy women aged 45 to 60 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Epicardial thickness was assessed by transthoracic echocardiography. RESULTS: The concentration of PAI-1 was directly associated with the thickness of the epicardial adipose tissue (r=0.475, P=.001), body mass index (BMI), visceral adipose tissue, insulin resistance, glucose, and HDL-cholesterol. The multivariate regression analysis indicated that epicardial fat independently predicts the concentrations of PAI-1. CONCLUSIONS: Women with thicker epicardial adipose tissue have reduced fibrinolytic activity, and consequently greater thrombotic risk.