Anormalidades hematológicas en enfermedad hepática, fisiopatología y consideraciones terapéuticas / Hematologic disorders in liver failure: pathophysiology and therapeutic considerations

RESUMEN Las alteraciones en los recuentos celulares sanguíneos representan los hallazgos clínicos más notorios y recurrentes en pacientes que padecen enfermedad hepática, tanto aguda como crónica. Estos cambios constituyen un marcador importante de la disfunción hepática y, a menudo, desempeñan un papel crucial en la evaluación y manejo de estos pacientes. En conjunto con el alargamiento de las pruebas de coagulación, la trombocitopenia es la irregularidad más prevalente en estos individuos. Esta condición, así como las leucopenias, se le atribuye en gran medida al hiperesplenismo, una alteración en la que el bazo retiene y destruye las células sanguíneas, incluidas las plaquetas. Sin embargo, cuando el conteo plaquetario desciende por debajo de 10 x 103/µl, es fundamental considerar otras causas, como factores autoinmunitarios que pueden estar contribuyendo con la trombocitopenia. La anemia, definida como una disminución en el número de glóbulos rojos o en los niveles de hemoglobina, es otra característica constante que acompaña a la enfermedad hepática. Aunque en la mayoría de los casos la anemia es macrocítica, en algunas situaciones puede ser secundaria a eventos hemolíticos, como lo observado en el síndrome de Zieve. Esta diversidad en las manifestaciones de la anemia en pacientes hepáticos subraya la complejidad de las interacciones entre el hígado y los componentes sanguíneos. A pesar de los avances en la comprensión de las causas subyacentes de estas citopenias, las opciones del tratamiento siguen siendo limitadas. Generalmente, las opciones terapéuticas se enfocan en la administración de transfusiones de hemocomponentes para compensar las deficiencias en los recuentos celulares o en el uso de análogos de trombopoyetina (TPO) para estimular temporalmente la producción de las plaquetas en la medula ósea. No obstante, estos tratamientos tienden a abordar los síntomas más que las causas fundamentales de las alteraciones hematológicas en la enfermedad hepática. La persistencia y el empeoramiento de estas alteraciones pueden servir como indicadores tempranos de la progresión de la disfunción hepática. La relación intrincada entre el hígado y la homeostasis hematológica continúa siendo objeto de investigación, la compresión más profunda de estos mecanismos podría abrir potencialmente la puerta hacia enfoques terapéuticos más específicos y efectivos para abordar las citopenias en el contexto de la enfermedad hepática.

ABSTRACT Alterations in blood cell counts are the most prominent and recurrent clinical findings among patients suffering from both acute and chronic liver disease. These changes are an important marker of liver failure and often play a key role in the evaluation and management of these patients. Together with the prolongation of coagulation tests, thrombocytopenia is the most common disorder among these individuals. This condition, as well as leukopenia, is largely attributable to hypersplenism, a disorder in which the spleen retains and destroys blood cells, including platelets. However, when the platelet count drops below 10x103/µl, it is essential to consider other causes, such as autoimmune factors that may be contributing to the development of thrombocytopenia. Anemia, defined as a decrease in red blood cell count or hemoglobin levels, is another common characteristic of liver disease. Although in most cases macrocytic anemia occurs, in some situations it can be secondary to hemolytic events, as observed in Zieve's syndrome. This wide range of manifestations of anemia among liver patients highlights the complex interaction between liver and blood components. Despite advances in understanding the underlying causes of these cytopenias, treatment options remain limited. Therapeutic options generally focus on the transfusion of blood products to compensate for deficiencies in cell counts or on the use of thrombopoietin (TPO) analogues to temporarily stimulate platelet production in the bone marrow. However, these treatments tend to address the symptoms rather than the root causes of hematologic disorders in liver disease. The persistence and worsening of these disorders may serve as early indicators of the progression of liver failure. The complicated relationship between liver and hematological homeostasis remains the subject of research. A deeper understanding of these mechanisms could potentially open the door toward more targeted and effective therapeutic approaches to address cytopenias in the context of liver disease.

Cross-Training and Resistance Training in Adults with Type B Acute Lymphoblastic Leukemia during the Induction Phase: A Randomized Blind Pilot Study.

Patients with acute lymphoblastic leukemia (ALL) undergoing induction decrease their physical capacity, lose muscle mass, and decrease their quality of life (QOL). The safety, feasibility, and benefits of exercise during chemotherapy have been proven, but the effects of cross-training activities have yet to be analyzed. To measure the effects of cross-training on body composition, physical performance, and QOL, a blind randomized clinical trial was carried out. A total of 33 patients were included and randomized into a cross-training exercise group (CEG), a resistance exercise group (REG), and a control group (CG). During induction, patients received an exercise routine three to five days a week for 30 to 50 min each. Body composition, QOL, and physical performance were measured at baseline, up to discharge, and at a follow-up of two months. Body composition improved in the REG and CEG. In the CG, muscle mass decreased and fat mass increased (p = 0.020 and 0.020, respectively). The REG and CEG had significant positive improvements in physical performance compared to the CG. QOL showed no differences in any group (p = 0.340). Cross-training and resistance exercise are essential to improve body composition and physical performance during induction. Considering the prognostic value of physical performance, we propose integrated training exercises as adjuvant therapy in adult patients with ALL.

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

Obesidad y riesgo de recaídas en pacientes con Leucemia Linfoblástica Aguda: Estudio retrospectivo / Obesity and risk of relapse in patients with Acute Lymphoblastic Leukemia: A retrospective study

ANTECEDENTES: La obesidad se ha asociado con estado proinflamatorio de bajo grado que se ha relacionado con el desarrollo del cáncer en general incluyendo el hematológico. OBJETIVOS: El presente trabajo tiene el objetivo de identificar la asociación del diagnóstico de obesidad acorde al índice de masa corporal (IMC) con indicadores pronóstico de pacientes adultos con Leucemia Linfoblástica Aguda (LAL). PACIENTES Y MÉTODO: Se trata de un estudio observacional, retrospectivo que incluyó pacientes hospitalizados con diagnóstico de LAL de linaje de células B. Se estimó el IMC con base al peso y talla registrado al ingreso de los pacientes. Se determinó el riesgo de recaídas, recaídas a médula ósea y supervivencia. Se utilizó el método de Kaplan-Meier mediante el test log-Rank en el análisis estadístico. RESULTADOS: Se incluyeron 128 pacientes. El peso y el IMC no mostraron una asociación significativa con el riesgo de recaídas. La frecuencia de recaída a médula ósea fue del 43,8%. La obesidad no impactó con la supervivencia global (p = 0,640) ni en la supervivencia libre de enfermedad (p = 0,527). La presencia de obesidad no se comportó como una variable de riesgo de recaída (p = 0,873). El IMC con punto de corte de 30 kg/m2 no se comportó como un factor de riesgo de recaída (OR 1.078). Conclusión: La obesidad no es un factor de riesgo independiente para el pronóstico de los pacientes adultos portadores de Leucemia Linfoblástica Aguda de linaje B.

BACKGROUND: Obesity has been associated with a low-grade proinflammatory state, and it has been related to the development of cancer in general, including hematologic cancer. AIM: The present work aimed to identify the association of the diagnosis of obesity according to the body mass index (BMI) with prognostic factors of adult patients with Acute Lymphoblastic Leukemia (ALL). PATIENTS AND METHOD: This observational, retrospective study included hospitalized patients diagnosed with ALL of the B-cell lineages. BMI was estimated based on the weight and height registered on clinical records at the admission of the patients. The relapse risk and bone marrow relapse were determined, and the survival rate was measured. The statistical analysis included the Kaplan-Meier method using the log-Rank test. Results: This study included 128 clinical records of patients. Weight had no significant association with relapse risk. The frequency of bone marrow relapse was 43.8%. Obesity did not impact overall survival (p = 0.640) or disease-free survival (p = 0.527). The presence of obesity does not behave as a relapse risk variable (p = 0.873). BMI with a 30 kg/m2 cut-off point did not influence relapse risk (OR 1.078). CONCLUSION: Obesity is not an independent risk factor for the prognosis of adult patients with Acute Lymphoblastic Leukemia B-lineage.

Leucemia promielocítica aguda durante el embarazo: reporte de 17 casos de un país en desarrollo / Acute promyelocytic leukemia during pregnancy: report of 17 cases from a developing country

Resumen OBJETIVO: Recopilar casos atendidos en centros oncológicos de México y reportar los tratamientos exitosos, con respuestas completas y las complicaciones del embarazo. MATERIALES Y MÉTODOS: Estudio retrospectivo de serie de casos que incluyó a pacientes con leucemia promielocítica aguda asociada con el embarazo atendidas en diferentes hospitales de la zona metropolitana de la Ciudad de México entre 1999 y 2021. RESULTADOS: Se identificaron 17 pacientes con leucemia promielocítica aguda asociada con el embarazo, con mediana de edad de 23 años (14-40 años); 7 correspondieron a madres menores de 20 años. En relación con su entorno social 9 tenían baja escolaridad, 12 se dedicaban al hogar y 13 tenían una pareja al momento de la concepción. Por último, 11 eran originarias de una zona urbana. Las pacientes atendidas entre 1999-2010 se trataron con interferón plus citarabina (7 de 17) o mediante soporte transfusional y esteroide (2 de 17), en 8 de los 17 casos el tratamiento se inició con tretinoína en combinación con quimioterapia (daunorrubicina) como tratamiento de inducción. CONCLUSIONES: El tratamiento de pacientes embarazadas y con leucemia promielocítica aguda representa un reto debido al riesgo trombótico y hemorrágico. Si bien la adición de tretinoína ha modificado el pronóstico de las pacientes con esta leucemia, su indicación a las embarazadas sigue siendo motivo de controversia, sobre todo por el riesgo de teratogenicidad.

Abstract OBJECTIVE: To collect cases attended in oncology centers in Mexico and to report successful treatments, with complete responses and complications around gestation. MATERIALS AND METHODS: Retrospective case series study including patients with pregnancy-associated acute promyelocytic leukemia attended in different hospitals in the metropolitan area of Mexico City between 1999 and 2021. RESULTS: Seventeen patients with pregnancy-associated acute promyelocytic leukemia were identified, with a median age of 23 years (14-40 years); 7 corresponded to mothers younger than 20 years. In relation to their social environment, 9 had low schooling, 12 were homebased and 13 had a partner at the time of conception. Finally, 11 were originally from an urban area. Patients seen between 1999-2010 were treated with interferon plus cytarabine (7 of 17) or by transfusion support and steroid (2 of 17), in 8 of the 17 cases treatment was initiated with tretinoin in combination with chemotherapy (daunorubicin) as induction therapy. CONCLUSIONS: Treatment of pregnant patients and patients with acute promyelocytic leukemia represents a challenge due to thrombotic and hemorrhagic risk. Although the addition of tretinoin has modified the prognosis of patients with this leukemia, its indication in pregnant women remains controversial, especially because of the risk of teratogenicity.

Effect of a Cross-Training and Resistance Exercise Routine on IL-15 in Adults with Type B Acute Lymphoblastic Leukemia during the Induction Phase: Randomized Pilot Study.

IL-15 is a proinflammatory myokine essential for activating NK cells and CD8+ T lymphocytes, and its overexpression has been related to reducing overall survivorship in patients with acute lymphoblastic leukemia (ALL). Physical exercise has been shown to be safe, feasible, and beneficial in hematological cancers. Exercise requires the activation of muscles that secrete cytokines, such as IL-15, causing immune mobilization. The objective was to compare the outcomes of two training routines on IL-15 and survival prognosis in adult patients diagnosed with ALL. A blind randomized clinical study was carried out where twenty-three peripheral blood samples were obtained pre and postexercise intervention from patients categorized into three types of intervention: the resistance exercise group (REG), the cross-training exercise group (CEG), and the control group (CG). Changes in IL-15 levels during the intervention were not significant in any of the groups (CG p = 0.237, REG p = 0.866, and CEG p = 0.678). However, 87.5% of patients who received an exercise intervention achieved remission, while only 21.73% experienced a relapse. There were no deaths during the study. Although IL-15 level adaptation in the REG and the CG performed similarly, the REG induced a better clinical outcome. Resistance exercises may help improve survival prognosis and reduce relapses in patients with ALL.

[Obesity and risk of relapse in patients with Acute Lymphoblastic Leukemia: A retrospective study]. / Obesidad y riesgo de recaídas en pacientes con Leucemia Linfoblástica Aguda: Estudio retrospectivo.

BACKGROUND: Obesity has been associated with a low-grade proinflammatory state, and it has been related to the development of cancer in general, including hematologic cancer. AIM: The present work aimed to identify the association of the diagnosis of obesity according to the body mass index (BMI) with prognostic factors of adult patients with Acute Lymphoblastic Leukemia (ALL). PATIENTS AND METHOD: This observational, retrospective study included hospitalized patients diagnosed with ALL of the B-cell lineages. BMI was estimated based on the weight and height registered on clinical records at the admission of the patients. The relapse risk and bone marrow relapse were determined, and the survival rate was measured. The statistical analysis included the Kaplan-Meier method using the log-Rank test. RESULTS: This study included 128 clinical records of patients. Weight had no significant association with relapse risk. The frequency of bone marrow relapse was 43.8%. Obesity did not impact overall survival (p = 0.640) or disease-free survival (p = 0.527). The presence of obesity does not behave as a relapse risk variable (p = 0.873). BMI with a 30 kg/m2 cut-off point did not influence relapse risk (OR 1.078). CONCLUSION: Obesity is not an independent risk factor for the prognosis of adult patients with Acute Lymphoblastic Leukemia B-lineage.

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.