Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Blood transfusion in children at a university hospital in a middle-income country: The need to reinforce adherence to current guidelines.

OBJECTIVES: Blood component transfusion is a common procedure used during hospital admissions; however, it is not risk-free. The evaluation of correct use of blood products (BP) is of vast importance considering the risks and costs implied in their use. Our principal objective was to evaluate the adherence to national guidelines for blood transfusion in pediatric patients at a third level university hospital. MATERIAL AND METHODS: A prospective and retrospective descriptive analytical study was conducted to report the incidence of incorrect use of BP in pediatric patients (1 month to 16 years of age). In a timeline period of 4 years, 579 medical records were randomly selected from a total of 6575 transfusions realized to create a statistically significant sample. The variables studied were volume, infusion time, and transfusion criteria. Indications were evaluated in patient's medical records according to national guidelines. RESULTS: Of the transfusions analyzed, 54% were classified as incorrect mainly due to lack of transfusion criteria fulfillment. Blood transfusion indications in pediatric patients adhered poorly to national guidelines. CONCLUSION: The implementation of effective programs for education and information on the use of BP are needed to increase compliance with current guidelines.

Percepción de la calidad de vida en pacientes adultos mayores con diabetes mellitus tipo II / Quality of life in elder adult patients with diabetes mellitus type II

Introducción: la calidad de vida es un parámetro dependiente de la autopercepción que tenga cada individuo. Objetivo: evaluar la percepción de la calidad de vida por pacientes adultos mayores con padecimiento de diabetes mellitus tipo II. Métodos: se realizó un estudio cualitativo del tipo investigación-acción participativa en 37 adultos mayores del área de salud 11, Policlínico Universitario René Vallejo Ortiz, Manzanillo, noviembre 2016 - junio 2017. La calidad de vida se midió utilizando el cuestionario de WHOQOL-BREF realizando una visita pormenorizada a las viviendas. Resultados: predominó el sexo femenino (75.68 por ciento) con una media de edad de 71.24 años. El 27,03 por ciento de los adultos mayores eran divorciados o viudos, 62.16 por ciento convivían en familias extensas, 59.46 por ciento convivían en familias funcionales mientras que 51.35 por ciento convivían en familias con ingresos económicos medios. La comorbilidad fue prevalente a expensas de la hipertensión arterial (67.47 por ciento). El tiempo medio de evolución de la enfermedad fue de 11.37 años. La calidad de vida fue autopercibida como deficiente en el 67.57 po r ciento de los adultos mayores a expensas de la satisfacción con su salud (75.68 por ciento). La dependencia de sustancias médicas resultó ser el dominio de mayor puntuación y el que mayor incidencia tuvo en el resultado final de la percepción de la calidad de vida. Conclusiones: se hace necesario una estrategia coordinada entre los distintos sectores de la sociedad que busquen una mayor calidad de vida en adultos mayores con enfermedades crónicas como la diabetes mellitus tipo II(AU)

Introduction: life quality is a dependent parameter of the auto perception of each individual. Objective: to evaluate the perception of life quality in elderly patients who suffer from diabetes mellitus type II. Methods: a qualitative study of the type participative investigation-action in 37 elderly adults from health area # 11 was carried out at René Vallejo Ortiz University Policlinic, Manzanillo, from November, 2016 to June, 2017. Life quality was measured using the WHOQOL-BREF questionnaire performing a detailed visit to the houses. Results: female sex prevailed (75.68 percent) with a mean age of 71.24 years old. The 27.03 percent 5 of the elderly adults was divorced or widowers, 62.16 percent cohabited in extensive families, 59,46 percent cohabited in functional families while 51.35 percent cohabited in families with average economic means. The prevalent comorbidity was related to hypertension (67.47 percent). The half time of evolution of the illness was of 11.37 years. The life quality was autoperceived as poor in 67.57 percent of the elderly adults in relation to the satisfaction with their health (75,68 percent). Dependence to medical substances resulted the highest and the highest incidence was in the final result of the perception life quality. Conclusions: it is necessary a coordinated strategy among the different sectors of the society to look for a higher life quality in elderly adults with chronic diseases as diabetes mellitus type II(AU)

Comparison of conventional cytomorphology, flow cytometry immunophenotyping, and automated cell counting of CSF for detection of CNS involvement in acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVE: Cytospin conventional cytomorphology (CCC) is the standard method for detecting lymphoblasts in cerebrospinal fluid (CSF) of patients with acute lymphoblastic leukemia (ALL) and for guiding treatment decisions. We evaluated flow cytometry immunophenotyping (FCI) performance for improving detection of central nervous system (CNS) involvement in ALL. METHODS: This prospective study included analysis of consecutive CSF samples of patients of all ages with ALL at 3 clinical stages: new diagnosis, relapse suspicion, and after relapse treatment. Manual, cytospin, automated, and FCI methods were compared and their performance statistically assessed. Using FCI as the reference method, optimal CSF cutoff cell count that better correlated with presence of lymphoblasts was established by receiver operating characteristic (ROC) curve analysis. RESULTS: Seventy-seven CSF samples were investigated, 35 (45.4%) from newly diagnosed cases, 30 (39%) suspicion of relapse, and 12 (15.6%) after treatment for relapse. Median manual WBC count in patients with CNS involvement detected by FCI was 3.75 cells/µL (0.0-1280), and this was also the count that best correlated with CNS infiltration (sensitivity, 50.0%; specificity, 82.2%). Compared with FCI, CCC sensitivity and specificity were 28.6% and 100%. Automated CSF WBC count in patients with CNS involvement detected by FCI was 5 (0.0-1578). For automated count, optimal WBC cutoff was 4.5 cells/µL (sensitivity, 62.5%; specificity, 70.5%). CONCLUSION: Flow cytometry immunophenotyping complements conventional cytospin analysis for detection of lymphoblasts in the CSF of ALL patients at any clinical stage.

Latin America: the next region for haematopoietic transplant progress.

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009-2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11 519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5-8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3-4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.

The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants.

We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III-IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II-IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1-5.6, P=0.02) and aGvHD III-IV (HR 8.3 CI 3.4-20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.

Therapeutic choices in patients with Ph-positive CML living in Mexico in the tyrosine kinase inhibitor era: SCT or TKIs?

A total of 72 patients with Ph-positive CML in first chronic phase were followed during a 6-year period in two different institutions in México. Among them, 22 were given a reduced-intensity allogeneic SCT, whereas 50 were given a tyrosine kinase inhibitor (TKI), mainly imatinib mesylate. The 6-year overall survival (OS) after the therapeutic intervention for patients allografted or given a TKI was 77 and 84%, respectively (P, NS); the median OS for both groups has not been reached, being above 90 and 71 months, respectively (P, NS). The freedom from progression to blast or accelerated phases was also similar for both groups, as well as the overall OS after diagnosis. Most patients allografted (91%) chose this treatment because they were unable to afford continuing treatment with the TKI, whereas most treated with the TKI (84%) were given the treatment without charge, through institutions able to pay for their treatment. The median cost of each nonmyeloablative allograft was US$18,000, an amount that is enough to cover 180 days of treatment with imatinib (400 mg per day) in México. Cost considerations favor allogeneic SCT as a 'once only' procedure whereas lifelong treatment with an expensive drug represents an excessive burden on resources.

Non-myeloablative stem cell transplantation in patients with relapsed acute lymphoblastic leukemia: results of a multicenter study.

Using non-myeloablative conditioning, allogeneic hematopoietic stem cell transplantation (HSCT) was conducted in 43 ALL patients in a CR2. The median age of the patients was 19 years. Patients received oral busulfan 4 mg/kg/day for 2 days; i.v. cyclophosphamide 350 mg/m(2)/day for 3 days; and i.v. fludarabine 30 mg/m(2)/day for 3 days. Oral cyclosporin A 4 mg/kg was started and methotrexate 5 mg/m(2) was delivered on days 1, 3, 5 and 11. The median CD34+ cell dose received was 5.0 x 10(6)/kg. The medium time to achieve a granulocyte count above 0.5 x 10(9)/l was 14 days. Thirteen patients were alive 30-1050 days after the HSCT. The 3-year overall survival rate was 30%. Ten patients (23%) developed acute GVHD, whereas eight patients (18.6%) developed chronic GVHD. Thirty patients died between days 47 and 1050 after the HSCT, most of them (70%) because of an ALL relapse. One hundred-day mortality was 15%, whereas transplant-related mortality was 21%. These results are inferior to those obtained using the same allografting method in other leukemias, probably as a consequence of poor susceptibility to the graft-versus-leukemia effect of the ALL cells beyond first remission as compared with other hematological malignancies.

Non-myeloablative hematopoietic stem cell transplantation is of limited value in advanced or refractory acute myeloblastic leukemia. The Mexican experience.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective strategy for preventing relapse of acute myelogenous leukemia (AML). We analyzed the outcome of 31 primary AML patients who received a reduced-intensity conditioning regimen for allogeneic HSCT in first or second remission. Thirty-one AML patients, 20 in first complete remission (FCR), 8 in second complete remission (SCR) and 3 in a partial remission (SPR) were included. All received busulfan 4 mg/kg/d/2 days, fludarabine 30 mg/m(2)/d/3 days and cyclophosphamide 350 mg/m(2)/d/3 days as conditioning regimen. The median number of CD34+ cells infused was 5.6 x 10(6)/kg and 5.2 x 10(6) in FCR and SCR group, respectively. All patients received cyclosporine-A (CsA) and methotrexate as graft vs. host disease (GvHD) prophylaxis. All patients showed myeloid engraftment (neutrophils >0.5 x 10(9)/l) after a median of 13 days in FCR group and 15 days in SCR group. Platelet recovery >20 x 10(9)/l was achieved after a median of 13 days in both groups. Relapse for 20 patients in FCR was 35% compared to 91% for 11 in SCR/SPR (p < 0.05). Conclusions. Reduced-intensity conditioning followed by allogeneic HSCT can induce stable remission in primary AML patients transplanted in FCR. A high relapse rate was documented in patients with refractory or relapsed AML.

Outpatient allografting using non-myeloablative conditioning: the Mexican experience.

A group of 132 patients with both malignant and nonmalignant conditions was allografted using the 'Mexican' method of non-ablative conditioning. The conditioning was delivered on an outpatient basis and the procedure was planned to be conducted on outpatients in all cases. While 103 patients (78%) were able to complete the procedure totally as outpatients, 29 (22%) were hospitalized because of fever, mucositis or acute graft-versus-host disease. In a multivariate analysis, although differences were not statistically significant, it was found that the patients who were allografted as outpatients had higher levels of hemoglobin (12 versus 11.8 g/dl), higher platelet counts (248 versus 191 x 10(9)/l), lower white blood cell counts (11.7 versus 12.4 x 10(9)/l), higher Karnofsky scale scores (100 versus 90%) and lower creatinine levels (0.9 versus 0.93 mg/dl). A total of 86% of the patients with normal values for these variables could be allografted as outpatients, whereas only 67% of those with abnormal values completed the entire procedure as outpatients. It is concluded that allografting can be accomplished totally on an outpatient basis using the 'Mexican' reduced intensity-conditioning regimen.

Autologous peripheral blood stem cell transplantation in multiple myeloma using oral versus I.V. melphalan.

Autologous peripheral blood stem cell transplantation is the therapy of choice for the treatment of multiple myeloma (MM) patients younger than 70 years old. Between August 1993 and November 2004, 54 patients with MM were autografted after conditioning with high-dose oral melphalan 140 mg/m(2) in combination with etoposide and carmustine (28 patients) or with high-dose melphalan 200 mg/m(2) I.V. (26 patients). The oral and IV melphalan groups were comparable. There were no significant differences in disease-free survival (DFS) and overall survival (OS) between the groups; however, in patients transplanted in remission, OS and DFS were better in the I.V. melphalan group. Four good-prognostic factors were identified: interval between diagnosis and transplant <18 months, number of prior chemotherapy lines < or =2, remission status (complete or partial), and the use of I.V. melphalan. In conclusion, I.V. melphalan is the therapy of choice for conditioning patients with MM who are in remission.

The early referral for reduced-intensity stem cell transplantation in patients with Ph1 (+) chronic myelogenous leukemia in chronic phase in the imatinib era: results of the Latin American Cooperative Oncohematology Group (LACOHG) prospective, multicenter study.

Using a reduced-intensity stem cell transplantation (RIST) schedule, 24 patients with Philadelphia (Ph1) (+) chronic myelogenous leukemia (CML) in first chronic phase (CP) were prospectively allografted in four Latin American countries: México, Brazil, Colombia and Venezuela, using HLA-identical siblings as donors. The median age of the patients was 41 years (range 10-71 years); there were eight females. Patients received a median of 4.4 x 10(6)/kg CD34 cells. The median time to achieve above 0.5 x 10(9)/l granulocytes was 12 days, range 0-41 days, and the median time to achieve above 20 x 10(9)/l platelets was also 12 days, range 0-45 days. In all, 22 patients are alive 81-830 (median 497) days after RIST. The 830-day probability of survival is 92%, and the median survival has not been reached, being beyond 830 days. A total of 11 patients (46%) developed acute graft-versus-host disease (GVHD), and seven of 23 (30%) developed chronic GVHD. Two patients died 43 and 210 days after RIST, one as a result of sepsis and the other of chronic GVHD. The 100-day mortality was 4.4%, and transplant-related mortality was 8%. RIST for patients with CML in CP appears to be an adequate therapeutic option.

Role of bone marrow examination in staging Hodgkin's disease: experience in México.

We assessed the value of bone marrow biopsy prospectively in a group of 91 individuals with Hodgkin's disease. The median age of our population was 29 years (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing disease and most patients (44%) were in pathological stage II at diagnosis. The bone marrow biopsy showed infiltration by Hodgkin's disease in only three individuals (3.3%); two of these patients displayed constitutional symptoms and had been assigned to stage III before the biopsy. In one case, bone marrow biopsy was the diagnostic procedure, which was performed as part of the investigation of fever of unknown origin. Follow-up periods ranged between 1 and 117 months (median 16 months). All patients achieved complete remission, seven patients relapsed and four were given autologous stem cell transplants. The median survival of the whole group was 117 months, while the 3500-day survival was 76%. As bone marrow biopsy was the diagnostic procedure in one case, bone marrow biopsy was a useful staging procedure in only 2.2% of patients (two out of 90 patients). We suggest that bone marrow biopsy should be only be performed as a staging procedure in a selected subset of patients with Hodgkin's disease (clinical stage III, B symptoms, etc.).

Features of the engraftment of allogeneic hematopoietic stem cells using reduced-intensity conditioning regimens.

The features of the engraftment in 26 patients allografted using reduced-intensity conditioning regimen (8 with chronic myelogenous leukemia, 6 with acute myelogenous leukemia, 9 with acute lymphoblastic leukemia, 1 with hybrid acute leukemia, 1 with myelodysplasia and 1 with thalassemia major) were analyzed. Patients received a median of 10 x 10(8)/Kg mononuclear cells (range 1.6 to 22.9), and a median of 4.2 x 10(6)/Kg CD34 cells (range 0.3 to 14). There was a linear correlation between the number of infused mononuclear cells (MNC) and that of CD34 cells (r = 0.78, p = 0.002). Three patients (11%) failed to engraft; in those who engrafted, the median time to achieve > 500 granulocytes was 11 days (range 10 to 22), and the median time to achieve > 10,000 platelets was 12 days (range 10 to 41). The three patients who failed to engraft received less than 5 x 10(8)/Kg MNC (1.6, 4.6 and 4.9) and less than 0.5 x 10(6)/Kg CD34; however, five of eight patients who received less than 5 x 10(8)/Kg MNC still engrafted successfully. On the other hand, all the patients who received less than 0.5 x 10(6)/Kg CD34 cells failed to engraft. Within the group of patients who engrafted, it was found that those who received more than 7 x 10(6)/Kg CD34+ cells tended to earlier recover > 20 x 10(9)/L platelets (p = 0.02), and > 0.5 x 10(9)/L neutrophils (p = 0.06) before day 15, than those who received less than 7 x 10(6)/Kg CD34+ cells. No such association could be established between the number of MNC and the time for recovery. In these patients allografted using reduced-intensity conditioning regimens, the target doses of hematopoietic cell used were similar to those described for conventional allografts: The number of CD34 infused cells was significantly related to the possibility of failure to engraft and to the recovery rate of the hemopoiesis.