Published ahead of print on March 30, 2006, doi:10.1164/rccm.200504-561OC Am. J. Respir. Crit. Care Med., Volume 174, Number 1, July 2006, 51-57 A more recent version of this article appeared on July 1, 2006
Submitted on April 11, 2005 Erythropoiesis Abnormalities Contribute to Early Onset Anemia in Septic Shock PatientsYann-Erick Claessens1,1 Medical Intensive Care Unit, Hopital Cochin, Paris, France; INSERM U567, Hopital Cochin, Paris, France; Department of Emergency Medicine, Hopital Cochin, Paris, France, 2 Faculte de Medecine, Universite Paris-Descartes, Paris, France; INSERM U567, Hopital Cochin, Paris, France; Laboratory of Hematology, Hopital Cochin, Paris, France, 3 Medical Intensive Care Unit, Hopital Cochin, Paris, France; Faculte de Medecine, Universite Paris-Descartes, Paris, France, 4 Medical Intensive Care Unit, Hopital Cochin, Paris, France; Faculte de Medecine, Universite Paris-Descartes, Paris, France; INSERM U567, Hopital Cochin, Paris, France, 5 Laboratory of Hematology, Hopital Cochin, Paris, France, 6 Ortho Biotech France Inc., Paris, France, 7 Laboratory of Hematology, Hotel-Dieu Hospital, Paris, France, 8 Medical Intensive Care Unit, Hopital Cochin, Paris, France; Faculte de Medecine, Universite Paris-Descartes, Paris, France; Department of Emergency Medicine, Hopital Cochin, Paris, France * To whom correspondence should be addressed. E-mail: alain.cariou{at}cch.ap-hop-paris.fr.
Rationale: The intimate mechanisms of early onset anemia observed in critically ill septic patients remain unclear.
Objectives: We investigated erythropoiesis abnormalities in this setting by studying morphological, functional and biochemical patterns of erythroid lineage.
Methods: Erythroid lineage in the bone marrow from septic shock patients who developed early onset anemia was compared to healthy controls. Survival and proliferation capacities were quantified in both groups. Biochemical and flow cytometry patterns of apoptosis were dissected by exploring anti-apoptotic (erythropoietin receptor-dependent) and pro-apoptotic (death receptor-dependent) pathways. Measurements and Main Results: Erythroid lineage was morphologically similar in both groups. Apoptosis of glycophorin A (GPA) positive erythroid precursors was increased in patients vs controls as assessed by labeling with annexin V (26.1±8.8% vs 3.1±2.9%, P<0.05) or 3-3'-dihexyloxacarbocyanine iodide (DiOC6(3)) (55.9±10.5 % vs 19.1±5.4 %, P<0.05), respectively. This was associated with significant overexpression of Fas on erythroid precursors and higher TNF- Key words: Anemia, Erythropoiesis, Septic shock, Apoptosis, Erythropoietin
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plasma levels in patients vs controls. Moreover, growth capacities of late erythroid progenitors of burst forming unit-erythroid (BFU-E)-type at day 10 was impaired in the presence of serum from patients as compared to the effect of control serum (27±12 vs 109±27 per 105 seeded cells, respectively, P<0.001). Saturating concentrations of recombinant human Epo (rHuEpo) restored growth capacity of patients BFU-E (72±14 per 105 seeded cells), in autologous conditions of serum. Conclusions: Early onset anemia that may be observed in septic patients is associated with defective erythropoiesis related to an excess of apoptosis that can be counterbalanced in vitro by rHuEPO.
