Erythropoietin resistance contributes to anaemia in chronic heart failure and relates to aberrant JAK–STAT signal transduction

Okonko, Darlington O.; Marley, Stephen B.; Anker, Stefan D.; Poole‐Wilson, Philip A.; Gordon, Myrtle Y.

doi:10.1016/j.ijcard.2011.07.045

Cited by 24 publications

(18 citation statements)

References 34 publications

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“…These data concord with recent studies [33][34][35] attesting to the role of erythroid suppression in CHF and increment them significantly by showing, for the first time, a direct role for immune cells and TNFα in this process. Whilst haemodilution [3,28], iron store depletion [46,47], and other mechanisms [1,48] clearly contribute to low haemoglobin levels in CHF, the anaemia of chronic disease is increasingly emerging as a dominant substrate that is known to be amenable to erythropoietic agents. Whether such agents confer morbidity and mortality benefits in CHF awaits the results of an ongoing trial [49].…”

Section: Study Implications and Conclusionmentioning

confidence: 99%

Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

Okonko

Marley

Anker

et al. 2013

International Journal of Cardiology

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Section: Study Implications and Conclusionmentioning

confidence: 99%

Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

Okonko

Marley

Anker

et al. 2013

International Journal of Cardiology

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“…14 Moreover, there are substantial blood transfusion requirements outside of operative blood loss requirements, suggesting a hypoproliferative state as a major contributor to burn-induced anemia during critical illness. 19,20 Epo resistance in burn patients may be caused by Epo receptor (Epo-R) down-regulation, impaired transduction of the Epo signal, or a reduction in Eporesponsive cells. 16 Moreover, the administration of exogenous recombinant Epo has been ineffective in the treatment of anemia secondary to burn injury compared with its effects on most patients with anemia due to renal failure who are on hemodialysis and a subset of patients with myelodysplastic syndrome.…”

mentioning

confidence: 99%

Peripheral Blood Mononuclear Cell-Derived Erythroid Progenitors and Erythroblasts Are Decreased in Burn Patients

Williams

Szilágyi

Conrad

et al. 2013

Journal of Burn Care & Research

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Patients with large burns suffer from anemia of critical illness. Administration of exogenous erythropoietin is ineffective, and transfusion remains the only effective treatment. We have previously shown that erythroid precursors are decreased 1 week after burn in an animal model. Therefore, we have used a two-phase liquid culture system to quantify peripheral blood mononuclear cell (PBMC) compartment-derived erythroid progenitors (EPs) in burn patients. Institutional review board approval and informed consent were obtained. Blood samples were collected at 1 to 30 days after burn, with a mean TBSA of 37.7 ± 15.8% (n = 10; 90% men; age, 46.0 ± 18 years). Four healthy volunteers served as controls. PBMCs were isolated by Ficoll-Hypaque density-gradient centrifugation and were placed in serum-free expansion medium containing cyclosporine A (1 ng/ml), granulocyte macrophage colony-stimulating factor (20 ng/ml), stem cell factor (30 ng/ml), and interleukin-3 (5 ng/ml; phase I). On day 7, cells were reseeded in serum-free expansion medium containing erythropoietin (1 U/ml), holotransferrin (0.3 mg/ml), and stem cell factor (10 ng/ml; phase II). Aliquots from the phase II culture system on day 6 were incubated with anti-CD71, CD235a, and CD36. EPs (CD71 CD36) and erythroblast subpopulations (colony-forming unit erythroids, Proerythroblasts, and intermediate erythroblasts) were identified based on the expressions of CD71 and CD235a by flow cytometry, calculated per million expanded cells, and expressed as a percentage of controls. Total EPs were significantly decreased by days 28 to 31 after the burn (19%; P < .05). Among the erythroblast subpopulations, colony-forming unit erythroids (11%; P < .004) and proerythroblasts (24%; P < .05), were decreased significantly by days 28 to 31 after the burn. PBMCs of burn patients can be used to study impaired erythropoiesis and anemia of critical illness.

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“…High erythropoietin levels have previously been demonstrated and may suggest an adequate response to anemia in patients with HFrEF, where erythropoietin resistance is most likely involved. 16 Although the use of oral anticoagulants was higher in patients with anemia and HFrEF, this does not necessarily imply a causal relationship, particularly as iron deficiency anemia was infrequent in our cohort of patients.…”

Section: Discussionmentioning

confidence: 68%

Heart Failure With Anemia

O’Meara

Rouleau

White

et al. 2014

Circ: Heart Failure

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Background— Anemia is a highly prevalent and strong independent prognostic marker in heart failure (HF), yet this association is not completely understood. Whether anemia is simply a marker of disease severity and concomitant chronic kidney disease or represents the activation of other detrimental pathways remains uncertain. We sought to determine which pathophysiological pathways are exacerbated in patients with HF, reduced ejection fraction (HFrEF) and anemia in comparison with those without anemia. Methods and Results— In a prospective study involving 151 patients, selected biomarkers were analyzed, each representing proposed contributive mechanisms in the pathophysiology of anemia in HF. We compared clinical, echocardiographic, and circulating biomarkers profiles among patients with HFrEF and anemia (group 1), HFrEF without anemia (group 2), and chronic kidney disease with preserved EF, without established HF (chronic kidney disease control group 3). We demonstrate here that many processes other than those related to chronic kidney disease are involved in the anemia–HF relationship. These are linked to the pathophysiological mechanisms pertaining to left ventricular systolic dysfunction and remodeling, systemic inflammation and volume overload. We found that levels of interleukin-6 and interleukin-10, specific markers of cardiac remodeling (procollagen type III N-terminal peptide, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase 1, left atrial volume), myocardial stretch (NT-proBNP [N-terminal probrain natriuretic peptide]), and myocyte death (troponin T) are related to anemia in HFrEF. Conclusions— Anemia is strongly associated not only with markers of more advanced and active heart disease but also with the level of renal dysfunction in HFrEF. Increased myocardial remodeling, inflammation, and volume overload are the hallmarks of patients with anemia and HF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00834691.

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Erythropoietin resistance contributes to anaemia in chronic heart failure and relates to aberrant JAK–STAT signal transduction

Cited by 24 publications

References 34 publications

Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

Peripheral Blood Mononuclear Cell-Derived Erythroid Progenitors and Erythroblasts Are Decreased in Burn Patients

Heart Failure With Anemia

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