Anemia

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Anemia
CBC, retic count
Retics normal or increased
Hypoproliferative
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Hypoproliferative
Marrow damage gt Infiltration fibrosis gt
Aplasia gt Myelodysplasia gt Drug or radiation
injury Iron deficiency B12 deficiency Folate
deficiency Stimulus gt Inflammation gt
Endocrine defect gt Renal disease Hypersplenism
Clues from morphology
microcytic, normocytic, or macrocytic poikilocyto
sis anisocytosis nucleated red cells target
cells Howell-Jolly bodies hypersegmented polys
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Retics normal or increased
Hemorrhage and Hemolysis
Clues from morphology
Blood loss Hemolysis gt Antibody-mediated gt
Membrane defect gt Metabolic defect gt Red cell
fragmentation Hemoglobinopathy
microcytic, normocytic, or macrocytic red cell
fragmentation red cell clumping nucleated red
cells target cells
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IRF immature reticulocyte fraction immature
retics / total retics HLR high light scatter
retics Retics x IRF
Foucade, Belaouni. Lab Hematol 1999 5153-8
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IRF and Anemia
Foucade, Belaouni. Lab Hematol 1999 5153-8
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Direct anti-globulin test
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Regulation of iron absorption
Gut lumen
Heme Fe
DMT1
Enterocyte
Ferritin


Fe
Fe
MTP1
Enterocyte precursor
Plasma transferrin
Transferrin Receptor
HFE
Hepcidin
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Iron stores
Erythron iron
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Gastrointestinal absorption 1 mg/day
Functional iron Blood, marrow, myoglobin 2 grams
Storage iron Liver, RES 1 gram
Plasma transferrin 2 mg
Daily physiologic loss 1 mg
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Serum iron after oral iron in patients with iron
deficiency
80
60
Serum iron
40
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1
2
3
4
Hours
WH Crosby, Arch Int Med circa 1970
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Serum ferritin and total body iron
Kaltwasser, Gottschalk. Kidney Int. 1999
55(suppl) S49 - S56
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Serum transferrin receptor
Storage iron 107 mg
Storage iron 335 mg
Storage iron 1,102 mg
Serial measurement of sTfr during phlebotomy in 3
individuals
Goodnough, Skikne, Brugnara. Blood, 2000 96 823
- 833
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Ratio of serum transferrin receptor to ferritin
as a measure of total body iron
Cook, Flowers, Skikne. Blood 2003 101 3359 - 64
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Erythropoietin response in iron deficiency
Spivak JL. Lancet 2000 3551707 - 12
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Serum erthyropoietin levels in patients with
inflammatory bowel disease
Controls normal volunteers and patients with
traumatic blood loss
Schreiber, Howalt, et at. NEJM 1996 334 619 - 23
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IL-1 and anemia in patients with inflammatory
bowel disease
Schreiber, Howalt, et at. NEJM 1996 334 619 - 23
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Treatment with oral iron rEPO in patients with
inflammatory bowel disease
Schreiber, Howalt, et at. NEJM 1996 334 619 - 23
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Anemia of chronic disease
Inflammation Tissue necrosis Infection Neoplasia C
ongestive heart failure Acute myocardial
infarction
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Anemia of chronic disease
Typical lab findings Serum iron lt 50 TIBC lt
150 Normochromic or hypochromic red
cells Normal ferritin Normal serum transferrin
receptor
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Anemia of chronic disease
Mechanisms blunted erythropoietin
response diminished response of erythroid
precursors to erythropoietin decreased delivery
of iron from RES, increased intracellular
ferritin in macrophages decreased
gastrointestinal iron absorption
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Anemia of chronic disease
Mediators IL-1 IL-6 g-interferon TNF-a
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Mortality and initial hematocrit in PRAISE
Prospective randomized amlodipine survival
evaluation 1130 patients 15 month
follow-up Results adjusted using multivariant Cox
model for age, gender, diabetes, smoking, heart
failure etiology, EF, NYHA class, systolic BP,
WBC, creatinine, and 18 additional factors
Mozaffarian, Levy, et al. J Am Coll Cardiol 2003
41(11) 1933 - 9
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Mortality and initial hematocrit in PRAISE
Mozaffarian, Levy, et al. J Am Coll Cardiol 2003
41(11) 1933 - 9
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Prospective, randomized study of erythropoietin
and i.v. iron in patients with CHF
Sq epo twice a week i.v. iron sucrose weekly
32 patients NYHA Class III or IV LVEF lt 40 Hgb
10 - 11.5
Randomized
Continue standard therapy
Silverberg DS, Wexler D, et al. J Am Coll Cardiol
2001 37 1775 - 80
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Prospective, randomized study of erythropoietin
and i.v. iron in patients with CHF
epo and i.v. iron
observation
After 8 months
NYHA class LVEF Days in hospital Hgb Ferritin Crea
tinine
48 5 - 79 10.3 ?12.9 221 ? 366 1.7 ? 1.7
- 11 - 5 28 10.9 ?10.8 264 ? 283 1.4 ? 1.8
Silverberg DS, Wexler D, et al. J Am Coll Cardiol
2001 37 1775 - 80
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Anemia of chronic disease
In IBD study and in CHF study response to
treatment was not predicted by serum
erythropoietin serum iron ferritin
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Effectiveness of treatment with erythropoietin
Goodnough, Skikne, Brugnara. Blood, 2000 96 823
- 833
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Safety of intravenous iron
Sodium ferric gluconate in sucrose
(Ferrlecit) Available in Europe gt 30 years 2.7 x
106 doses/year in Germany Italy in 1995 Iron
dextran (Imferon until 1992, InFed since 1992) 3
x 106 doses/year in US in 1996
Faich, Strobos. Am J Kidney Dis 1999 33(3)464-70
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Safety of intravenous iron
Reported severe adverse reactions (1976 -
1996) SFGS 3.3 severe allergic reactions/106
doses, no fatalities ID 8.7 severe allergic
reactions/106 doses, 31 fatalities
Faich, Strobos. Am J Kidney Dis 1999 33(3)464-70
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Safety of intravenous iron
Other theoretical risks iron overload sepsis a
ccleration of athersclerosis
Faich, Strobos. Am J Kidney Dis 1999 33(3)464-70
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Medicare warning (
Recombinant human erythropoietin is approved only
for treatment of anemia caused by renal failure
or by cancer treatment and for certain
hematologic malignancies. Sodium ferric
gluconate in sucrose is approved only for
treatment of anemia in patients on hemodialysis
and for patients who have had a severe reaction
to iron dextran.