9. An Approach to Anemia Retic Hi Retic Low Anemia MCV Hi MCV Nl MCV Lo
10. An Approach to Anemia Retic Hi Retic Low Anemia Destruction Loss MCV Hi MCV Nl MCV Lo Intrinsic Extrinsic Splenic Mechanical Recovery Tissue On Floor Occult Iron (Lead) Thal Frags B12 Folate Liver ETOH Thyroid Toxic MDS Chronic Disease Renal Mixed Mild/Treated Early Transfused Endocrine Intrinsic BM Dilution
11. An Approach to Anemia Retic Hi Retic Low Anemia Destruction Loss MCV Hi MCV Nl MCV Lo Intrinsic Hgb’opathy Enzymopathy Membrane HS PNH Extrinsic Splenic Mechanical Recovery Tissue On Floor Occult
12. Retic Hi Retic Low Anemia Destruction Loss MCV Hi MCV Nl MCV Lo Intrinsic Extrinsic AIHA cold warm Drug/Toxins Sepsis Burns Splenic/Hepatic Mechanical MAHA Tissue On Floor Occult Recovery
27. “ African” G6PD Deficiency hemolysing with oxidant stress Average G6PD Act. Time in Circulation Hemolyzed New Average G6PD Activity Young Retics with more G6PD
28. Retic Hi Retic Low Anemia Destruction Loss MCV Hi MCV Nl MCV Lo B12 Folate Toxic AZT,DDC Chemo Dilantin MDS Hepatic ETOH Thyroid Other Nuclear Maturation Lipid Bilayer
32. An Approach to Anemia Retic Hi Retic Low Anemia Destruction Loss MCV Hi MCV Nl MCV Lo Iron (Lead) Thalassemia Fragmentation Sideroblastic Anemia acquired congenital
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35. Iron Metabolism Plasma Fe-Tf Hepcidin Hepcidin Hepcidin Iron Signal? Erythropoiesis Signal anemia, hypoxia RBC Bone Marrow Duodenum Spleen Tomas Ganz ASH 2006 Inflammation IL-6 Dec. Hep Inc. Hep Hepcidin
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37. Retic Hi Retic Low Anemia Destruction Loss MCV Hi MCV Nl MCV Lo Early Anything Mild/Treated Transfused Chronic Disease Renal Mixed Endocrine Intrinsic BM Aplastic Myeloma True Lymphoma Drug Infection Anorexia Malignancy Parvovirus
43. Hgb and Quality of Life Quality of Life (LASA) 7 9 11 13 Hgb Crawford. Cancer 2002;95:888, Soignet. Semin Hematol. 2000
44. Risks of PRBC Tx vs. EPO Erythropoietin RBC Transfusion
45.
Notas del editor
Kaplan-Meier progression to death for patients in the EuroSIDA study, according to baseline hemoglobin level, in multivariate analysis [20]. Normal was defined as a hemoglobin level of 114 g/dL for men and 112 g/dL for women; mild anemia was defined as a hemoglobin level of 8–14 g/dL for men and 8–12 g/dL for women; and severe anemia was defined as a hemoglobin level of !8 g/dL for both men and women.
30% + coombs w/o hemolysis
Note macrocytosis and hyperseg
23 yo Thai, 13 weeks Pregnant Hgb 11, MCV 72 What Tests? Iron Studies first , may mask beta-Thal By decreasing Hgb A 2 If Hemoglobin Electropheresis is normal? If iron nl, then not beta-thal BUT alpha-thal carrier state has normal HPLC Evaluating Iron Ferritin Sensitive/specific Except increased in inflammation, liver disease, malignancy Fe/TIBC (Transferrin) and Saturation Decreased in inflammation, malignancy THEREFORE: Iron Trial Serum (soluble) Transferrin Receptor Mediates iron transfer into cell Increased in Fe-def, rapid cell production CHR-Retic Hemoglobin Concentration? Follow-up GI Eval 10 -15% with malignancy ?Only if ferritin <100?
Anemia of chronic disease and iron deficiency anemia, the most common forms of anemia, are differentiated primarily by estimates of iron status. Standard measures of iron status, such as ferritin, total iron-binding capacity, and serum iron are directly affected by chronic disease. In contrast, soluble transferrin receptor (sTfR) is elevated in iron deficiency but is not appreciably affected by chronic disease. sTfR is elevated in subjects with hyperplastic erythropoiesis (eg, hemolytic anemia, beta-thalassemia, polycythemia, etc) and depressed in subjects with hypoplastic erythropoiesis (eg, chronic renal failure, aplastic anemia, or post-transplant anemia). Transferrin receptor (TfR) is the major mediator of iron uptake by cells. TfR is a transmembrane, disulfide-linked dimer of two identical subunits that binds and internalizes diferric transferrin, thereby delivering iron to the cell cytosol. When a cell needs iron, TfR expression is increased to facilitate iron uptake. Since the major use of iron is for hemoglobin synthesis, about 80% of total TfR is on erythroid progenitor cells. Soluble transferrin receptor arises from proteolysis of the intact protein on the cell surface, leading to monomers that can be measured in plasma and serum. Thus, the concentration of sTfR in plasma or serum is an indirect measure of total TfR. The serum level of sTfR reflects either the cellular need for iron or the rate of erythropoiesis. The concentration of sTfR in plasma or serum is elevated in iron deficiency. The concentration of sTfR in plasma or serum is correlated with erythron transferrin uptake, a ferrokinetic measure of erythropoietic activity. Postgraduate Medical Journal 2004;80:405-410 risk of colon CA with iron deficiency
Increased Hepcidin in inflammation blocks the marked iron movements Iron replacement at low doses: Am J Med Volume 118, Issue 10, Pages 1142-1147 (October 2005)
Iron replacement at low doses: Am J Med Volume 118, Issue 10, Pages 1142-1147 (October 2005)
Flunker G, Peters A, Wiersbitzky S, Modrow S, Seidel W. Persistent par- vovirus B19 infections in immnol (Berl). 1998;186:189–194.
In a review of 3 open-label community-based studies of >7000 cancer patients, the effects of recombinant human erythropoietin (rHuEPO) on quality-of-life (QOL) outcomes and hemoglobin (Hgb) were summarized. Dosing was 3 times weekly in 2 studies (Glaspy et al and Demetri et al) and once weekly in the study by Gabrilove et al. In each study, the final Hgb significantly improved from baseline with mean increases of 1.8 g/dL, 2.0 g/dL, and 2.0 g/dL in the studies by Glaspy, Demetri, and Gabrilove, respectively (p<0.001). QOL data collected in these open-label assessments were compiled by the Functional Assessment of Cancer Therapy (FACT) scale and the Linear Analogue Self-Assessment (LASA) test. Key parameters assessed included energy, activity, and overall QOL. As shown in this slide, very similar results, captured as percent change from baseline, were obtained by Demetri et al (1998) and Gabrilove et al (1999) who, between them, noted an approximate 30% increase in energy level, an approximate 28% increase in activity, and an approximate 20% increase in overall QOL. An earlier study reported by Glaspy (1997) with a smaller initial pool of patients (N=1498) reported slightly better improvements in energy (38%), activity (32%), and overall QOL (24%).
NEJM ICU pt study, 0.4 g difference at 29 days ICU Pts with trauma Decreased Mortality (4.8 vs 10.4%, 1400 pts) Increased Thrombosis