Subject(s)
Down Syndrome , Hydrops Fetalis , Leukemoid Reaction , Adult , Down Syndrome/blood , Down Syndrome/complications , Down Syndrome/diagnosis , Down Syndrome/genetics , Down Syndrome/physiopathology , Fatal Outcome , Female , Fetal Blood , Genetic Testing/methods , Gestational Age , Heart Failure/diagnosis , Heart Failure/etiology , Humans , Hydrops Fetalis/diagnosis , Hydrops Fetalis/etiology , Hydrops Fetalis/physiopathology , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Infant, Newborn , Leukemoid Reaction/blood , Leukemoid Reaction/complications , Leukemoid Reaction/diagnosis , Leukemoid Reaction/physiopathology , Pregnancy , Ultrasonography, Prenatal/methods , Umbilical Veins/diagnostic imagingABSTRACT
Infants with Down syndrome (DS) are at a high risk of developing transient abnormal myelopoiesis (TAM). A GATA1 mutation leading to the production of N-terminally truncated GATA1 (GATA1s) in early megakaryocyte/erythroid progenitors is linked to the onset of TAM and cooperated with the effect of trisomy 21 (Ts21). To gain insights into the underlying mechanisms of the progression to TAM in DS patients, we generated human pluripotent stem cells harbouring Ts21 and/or GATA1s by combining microcell-mediated chromosome transfer and genome editing technologies. In vitro haematopoietic differentiation assays showed that the GATA1s mutation blocked erythropoiesis irrespective of an extra chromosome 21, while Ts21 and the GATA1s mutation independently perturbed megakaryopoiesis and the combination of Ts21 and the GATA1s mutation synergistically contributed to an aberrant accumulation of skewed megakaryocytes. Thus, the DS model cells generated by these two technologies are useful in assessing how GATA1s mutation is involved in the onset of TAM in patients with DS.
Subject(s)
Down Syndrome/physiopathology , Hematopoiesis , Induced Pluripotent Stem Cells/physiology , Leukemoid Reaction/physiopathology , Animals , Cells, Cultured , Chromosomes, Human, Pair 21/genetics , Down Syndrome/genetics , GATA1 Transcription Factor/genetics , Genetic Engineering , Genome, Human , Humans , Leukemoid Reaction/genetics , Mice , TransfectionABSTRACT
Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) is characterized by the transient appearance of blast cells, which resolves spontaneously. Approximately 20 % of patients with TAM die at an early age due to organ failure, including liver disease. We studied 25 DS-TAM patients retrospectively to clarify the correlation between clinical and laboratory characteristics and liver diseases. Early death (<6 months of age) occurred in four of the 25 patients (16.0 %), and two of those four patients died due to liver failure. Although physiologic jaundice improved gradually after a week, all DS patients had elevated D-Bil levels during the clinical course of TAM, except one who suffered early death. The median peak day of the WBC count, total bilirubin (T-Bil) and D-Bil levels was: day 1 (range day 0-57), day 8 (range day 1-55), and day 17 (range 1-53), respectively. Our results reveal that all patients with DS-TAM may develop liver disease irrespective of the absence or presence of symptoms and risk factors for early death. In patients of DS-TAM, careful observation of the level of D-Bil is needed by at least 1 month of age for the detection of liver disease risk.
Subject(s)
Down Syndrome/physiopathology , Hepatic Insufficiency/etiology , Leukemoid Reaction/physiopathology , Liver/physiopathology , Disease Progression , Female , Hepatic Insufficiency/congenital , Hepatic Insufficiency/epidemiology , Hepatic Insufficiency/physiopathology , Hospitals, Pediatric , Humans , Infant, Newborn , Japan/epidemiology , Male , Multiple Organ Failure/epidemiology , Multiple Organ Failure/etiology , Retrospective Studies , Risk Factors , Severity of Illness IndexABSTRACT
The most important adverse effects of phenobarbital, an anticonvulsant drug, are behavior and cognitive alterations. Hypersensitivity syndrome caused by phenobarbital presenting with a leukemoid reaction is a rare side effect, which is rarely ever reported and needs to be known. We report on a 27-year-old Chinese woman who experienced hypersensitivity syndrome three weeks after the initiation of phenobarbital. The patient developed fever, skin rash, face swelling, lymphadenopathy, myalgia, hepatitis, eosinophilia, atypical lymphocytes and leukocytosis. Along with the pathological progress of the disease, the patient noticed a gradual exacerbation of her symptoms. And the highest leukocyte count was up to 127.2 x 10(9)/L. After discontinuing of phenobarbital and administration of methylprednisolone combined with the intravenous immunoglobulin shock therapy, all initial symptoms improved and the leukocyte count normalized. This case is reported because of its rarity of the leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital.
Subject(s)
Anticonvulsants/adverse effects , Drug Hypersensitivity/etiology , Leukemoid Reaction/chemically induced , Phenobarbital/adverse effects , Adult , Drug Hypersensitivity/physiopathology , Epilepsy/drug therapy , Female , Humans , Leukemoid Reaction/physiopathologySubject(s)
Bronchopulmonary Dysplasia/physiopathology , Chorioamnionitis/physiopathology , Infant, Premature, Diseases/physiopathology , Leukemoid Reaction/physiopathology , Bronchopulmonary Dysplasia/complications , Female , Humans , Infant, Newborn , Infant, Premature , Infant, Very Low Birth Weight , Inflammation Mediators/physiology , Leukemoid Reaction/complications , PregnancyABSTRACT
A 33-y-old male developed severe acidosis, renal failure, and profound neutrophilia after ingesting ethylene glycol. Workup for his neutrophilia excluded infectious and malignant causes. An elevated leukocyte alkaline phosphatase (LAP) level confirmed a leukemoid response, and the neutrophila resolved. Although several leukemoid reactions have been published due to therapeutic agents these reports are often incomplete or inaccurate; this is the first case of leukemoid response to a toxin. Leukemoid response is distinguishable from leukemia by the absence of clonally derived cells, although this is not easily apparent in extreme neutrophilia. Elevated LAP is useful in identifying leukemoid reaction from leukemia in cases of extreme neutrophila. If a patient develops extreme neutrophila in association with drug or toxin exposure, a leukemoid reaction should be considered and an LAP obtained.
Subject(s)
Ethylene Glycol/poisoning , Leukemoid Reaction/chemically induced , Adult , Humans , Leukemoid Reaction/physiopathology , Leukemoid Reaction/therapy , Male , Suicide, AttemptedSubject(s)
Leukemoid Reaction/diagnosis , Diagnosis, Differential , Female , Humans , Infant , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/physiopathology , Leukemoid Reaction/pathology , Leukemoid Reaction/physiopathologyABSTRACT
En la reacción leucemoide (RL) un aumento importante en la cantidad de leucocitos, así como la presencia de células inmaduras en la sangre periférica, obligan al médico a descartar una leucemia aguda o crónica. Las RL pueden ser linfocíticas, granulocíticas, eosinofilicas y monocíticas, siendo estas últimas las más raras. Se informa el caso de una paciente de 64 años de edad con combe, PPD y anticuerpos antituberculosis positivos, así como leucocitosis y monocitosis persistente y linfadenitis granulomatosa en el reporte histopatológico de dos biopsias ganglionares, por lo que se concluye en una RL monocítica asociada a tuberculosis ganglionar, máxime que las alteraciones hematológicas y las adenomegalias desaparecieron con el tratamiento antifimico
