RESUMO
BACKGROUND: Little recent data are available describing fresh frozen plasma (FFP) use in neonates. The purpose of this study was to determine the outcomes of FFP transfusions in neonates. PATIENTS AND METHODS: A single institution, observational, and retrospective review of each transfusion of FFP given to neonates admitted to a neonatal intensive care unit over a 2-year period. RESULTS: One hundred and seventy-three neonates were identified as having received FFP, giving a prevalence of FFP use at 12%. By far the most common determining factor for FFP use was an association with an abnormal activated partial thromboplastin time or prothrombin time (52%). Other factors included bleeding, invasive procedures, volume expansion, necrotizing enterocolitis, cardiopulmonary bypass, and hydrops fetalis. Of objectively accessible responses, FFP was able to correct abnormal coagulation tests into the normal range only 40% of the time. Twenty-four neonates received recombinant factor VIIa (rFVIIa) after first receiving FFP. The prevalence of thrombotic events was not higher in neonates receiving rFVIIa than those receiving FFP alone. CONCLUSIONS: FFP was widely used in this neonatal unit. As data showing the predictive value of coagulation tests in neonates are discrepant, it is unclear if FFP was being appropriately used. Prospective, controlled data are required.
Assuntos
Transfusão de Componentes Sanguíneos , Fator VIIa/uso terapêutico , Plasma , Transtornos da Coagulação Sanguínea/terapia , Idade Gestacional , Hemorragia/terapia , Humanos , Recém-Nascido , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The principal alpha subunit of voltage-gated sodium channels is associated with auxiliary beta subunits that modify channel function and mediate protein-protein interactions. We have identified a new beta subunit termed beta4. Like the beta1-beta3 subunits, beta4 contains a cleaved signal sequence, an extracellular Ig-like fold, a transmembrane segment, and a short intracellular C-terminal tail. Using TaqMan reverse transcription-PCR analysis, in situ hybridization, and immunocytochemistry, we show that beta4 is widely distributed in neurons in the brain, spinal cord, and some sensory neurons.beta4 is most similar to the beta2 subunit (35% identity), and, like the beta2 subunit, the Ig-like fold of beta4 contains an unpaired cysteine that may interact with the alpha subunit. Under nonreducing conditions, beta4 has a molecular mass exceeding 250 kDa because of its covalent linkage to Nav1.2a, whereas on reduction, it migrates with a molecular mass of 38 kDa, similar to the mature glycosylated forms of the other beta subunits. Coexpression of beta4 with brain Nav1.2a and skeletal muscle Nav1.4 alpha subunits in tsA-201 cells resulted in a negative shift in the voltage dependence of channel activation, which overrode the opposite effects of beta1 and beta3 subunits when they were present. This novel, disulfide-linked beta subunit is likely to affect both protein-protein interactions and physiological function of multiple sodium channel alpha subunits.
Assuntos
Subunidades Proteicas/química , Subunidades Proteicas/fisiologia , Canais de Sódio/química , Canais de Sódio/fisiologia , Sequência de Aminoácidos , Animais , Adesão Celular , Linhagem Celular , Clonagem Molecular , Dissulfetos/química , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Canal de Sódio Disparado por Voltagem NAV1.2 , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Análise de Sequência de Proteína , Homologia de Sequência de Aminoácidos , Canais de Sódio/genética , Canais de Sódio/metabolismo , Distribuição Tecidual , Subunidade beta-2 do Canal de Sódio Disparado por Voltagem , Subunidade beta-4 do Canal de Sódio Disparado por VoltagemRESUMO
BACKGROUND: Voltage-gated sodium channels composed of pore-forming alpha and auxiliary beta subunits are responsible for the rising phase of the action potential in cardiac muscle, but their localizations have not yet been clearly defined. METHODS AND RESULTS: Immunocytochemical studies show that the principal cardiac alpha subunit isoform Na(v)1.5 and the beta2 subunit are preferentially localized in intercalated disks, identified by immunostaining of connexin 43, the major protein of cardiac gap junctions. The brain alpha subunit isoforms Na(v)1.1, Na(v)1.3, and Na(v)1.6 are preferentially localized with beta1 and beta3 subunits in the transverse tubules, identified by immunostaining of alpha-actinin, a cardiac z-line protein. The beta1 subunit is also present in a small fraction of intercalated disks. The recently cloned beta4 subunit, which closely resembles beta2 in amino acid sequence, is also expressed in ventricular myocytes and is localized in intercalated disks as are beta2 and Na(v)1.5. CONCLUSIONS: Our results suggest that the primary sodium channels present in ventricular myocytes are composed of Na(v)1.5 plus beta2 and/or beta4 subunits in intercalated disks and Na(v)1.1, Na(v)1.3, and Na(v)1.6 plus beta1 and/or beta3 subunits in the transverse tubules.