To evaluate the usefulness of flow cytometric detection of intracellular antigens (Ags) in establishing proper lineage affiliation and its contribution to the diagnosis of acute leukemia, we studied 100 consecutive patients in whom acute leukemia was diagnosed between January 1997 and July 1998. Immunological classification was assessed using a three-line panel of monoclonal antibodies for phenotypic characterization of leukemic blast cells as proposed at the First Latin American Consensus Conference for Flow Cytometric Immunophenotyping of Leukemia. We found 74 cases of B-cell lineage acute lymphoblastic leukemia (ALL), seven cases of T-cell ALL, and 19 cases of acute myeloid leukemia (AML). In this study cytoplasmic (cy) CD79a, cyCD22, cyCD3, and cyMPO were highly sensitive, specific B, T, and myeloid markers that were expressed in virtually all cases of B and T cell ALL and in all subtypes of AML. Applied in combination with immunophenotyping this knowledge led to improvement in diagnostic precision and refinement of immunological classification, ensuring the selection of the most appropriate therapy for the patients studied. In conclusion, intracellular Ags detection was of utmost importance in establishing correct lineage affiliation in cases lacking expression of B, T, or myeloid surface Ags or disclosing equivocal or ambiguous immunophenotypic features and in identifying biphenotypic acute leukemia. In combination with FAB morphology and immunophenotyping, we were able to reliably classify all patients with acute leukemia in this study. Am. J. Hematol. 68:69-74, 2001.

To assess the incidence, clinical features at presentation, hematologic, immunophenotypic, and cytogenetic characteristics of AMKL in children we prospectively studied 834 consecutive non selected children with newly diagnosed acute leukemia (AL) admitted to the Hematology Department at the Instituto Nacional de Pediatría (INP), Mexico, D.F. We found 682 cases (81.8%) with a typical ALL immunophenotype, and the remaining 152 (18.2%) were considered to have AML. In 29 of the 152 patients with AML studied, a diagnosis of AMKL was established. These 29 cases represented 19.1% of the cases of AML and 3.48% of the total cases of AL during the time span covered by the study. Twenty-four percent of the cases occurred in infants 2 years old or younger and 41.4% occurred in children 41 months of age or younger. In contrast, in only 18.6% of the patients with AML (M0-M6), the diagnosis was established before 42 months of age and in 17% before their second year of life. Clinical presentation was not strikingly different than that observed in patients with other types of AML, and the time interval from onset of symptoms to diagnosis was also similar, though in a small subset of patients, the clinical course was characterized by a chronic slowly progressive disorder extending over weeks or months resembling smoldering leukemia or chronic myelofibrosis with agnogenic myeloid metaplasia. Bone marrow (BM) fibrosis was a constant features in our patients; 75% of the patients studied showed this complication at the time of diagnosis. Some rather unusual findings in this study were intense skeletal pains from multiple osteolytic lesions, the presence of soft-tissue tumor, and the presence of cohesive scanty clusters of primitive-looking blast cells in BM aspirates. Several interesting cytogenetic findings in our study were t(1;22)(p13;q13) in a 14-year-old boy, t(9;22)(q34;q11) in one patient, and monosomy 7 in two patients. Another important finding in our study was the clinical association with colonic adenocarcinoma in one patient, an association that to our knowledge has not been reported previously. In conclusion, our data suggest that the incidence of AMKL in Mexico might be higher than those reported in Caucasian white pediatric population, and that biologic and cytogenetic profile may differ from those of western countries, but more studies are needed to corroborate cytogenetic heterogeneity, ethnic and geographic diversity. Early onset of the disease, low WBC counts, slight thrombocytopenia or normal platelet counts, and BM fibrosis were characteristic distinctive features of at least half of the patients with this subtype of AML. Am. J. Hematol. 73:71-80, 2003.

von Willebrand's disease (VWD) is the most commonly inherited bleeding disorder. For a long time, it has been said that VWD was absent in some countries due to ethnical differences. Information about the prevalence of VWD in Mexico remains unclear, owing largely to poor awareness and diagnosis of the disease. The aim of this study was to objectively diagnose VWD in a cohort of highly selected Mexican patients with a chronic history of bleeding. Mexican Mestizos were recruited between July 2010 and August 2011. Included were 133 adult and paediatric patients with a high suspicion of VWD. Fifty-three were diagnosed with VWD: 47 (88.7%) with type 1 VWD, four (7.5%) with type 2a VWD and two (3.8%) with type 3 VWD. Mean age for female patients was 19.5 years (range 3-44 years) and 18.5 years (range 4-63 years) for male patients. Mean age at start of bleeding symptoms was 8.8 years (range 1-61). The most frequent clinical symptoms were epistaxis (84.9%), ecchymosis (79.2%), haematomas (71.7%), gum bleeds (62.3%) and petechia (50.9%). Severe transoperative or postoperative bleeding was found in 17 patients (32.1%). Twenty-six women at childbearing age had a history of abnormal gynaecological bleeding. Our results clearly demonstrate the presence of VWD in Mexican and underscore the importance of a more detailed description of VWD. Efforts to increase the awareness and diagnosis of VWD could help in better identification of patients with bleeding disorders and lead to early, appropriate management with safe and efficacious therapies such as desmopressin and plasma concentrates.

Novel biomarkers for risk refinement and stratification in childhood acute lymphoblastic leukemia (ALL) are needed to optimize treatment results. We studied the expression of CASP8AP2 and H2AFZ associated with relapse and survival in bone marrow samples from newly diagnosed children with ALL. We found: (a) an increased risk for early relapse in those patients with low expression of CASP8AP2 (odds ratio [OR] 3.93, 95% confidence interval [CI] 1.40-11.02, p < 0.05) confirming its usefulness as a predictive risk marker, although H2AFZ did not present the same effect; (b) patients with low expressions of CASP8AP2 and H2AFZ had inferior survival rates (p < 0.001); (c) the predictive values regarding low expressions of H2AFZ and CASP8AP2 and high white blood cell count suggest that these features could help to identify more accurately patients at greater risk of relapse.

Este artículo debe citarse comoLa coagulación es el resultado de una interacción coordinada de las proteínas sanguíneas, las células circulantes, células de la vasculatura y las proteínas de la matriz extracelular en la pared de los vasos. Este complejo mecanismo hace difícil su evaluación en el laboratorio, que sólo se limita a medir las proteínas de la coagulación circulantes y células circulantes, mientras que los elementos vasculares no son medibles. La Figura 1 esquematiza la activación de la coagulación.Actualmente se dispone de pruebas de laboratorio que evalúan diferentes vías de la coagulación: el tiempo de sangrado, de acuerdo con la técnica de Duke, consiste en la medición de la duración de la hemorragia producida por la punción hecha en el lóbulo de la oreja con una lanceta; normalmente dura de tres a siete minutos. En una forma muy general permite evaluar la retracción del capilar, la cantidad y calidad de las plaquetas; con cifras menores de plaquetas el tiempo de sangrado se prolonga, pero su mayor utilidad es para evaluar la función de las plaquetas cuando la cifra es normal como sucede en trombastenia de Glanzman, enfermedad de von Willebrand, uremia, uso de aspirina.Para evaluar la función plaquetaria es indispensable tener la cuenta plaquetaria que se obtiene con la realización de la biometría hemática. Las técnicas automatizadas que actualmente se utilizan permiten conocer también el volumen plaquetario medio que normalmente va de 5 a 12 fentolitros (fL). Una cuenta normal es de 150 a 450,000/mL. La disminución de las plaquetas puede ser consecuencia de un anticuerpo sensible a ácido etilendiaminotetracético que propicia la aglutinación