anemia cbc, retic count hypoproliferative retics normal or increased
TRANSCRIPT
Anemia
CBC, retic count
Hypoproliferative Retics normal or increased
Hypoproliferative
Clues from morphology
microcytic, normocytic, or macrocytic
poikilocytosis
anisocytosis
nucleated red cells
target cells
Howell-Jolly bodies
hypersegmented polys
Marrow damage > Infiltration; fibrosis > Aplasia > Myelodysplasia > Drug or radiation injury
Iron deficiency
B12 deficiency
Folate deficiency
Stimulus > Inflammation > Endocrine defect > Renal disease
Hypersplenism
Retics normal or increased
Hemorrhage and Hemolysis
Blood loss
Hemolysis > Antibody-mediated > Membrane defect > Metabolic defect > Red cell fragmentation
Hemoglobinopathy
Clues from morphology
microcytic, normocytic, or macrocytic
red cell fragmentation
red cell clumping
nucleated red cells
target cells
IRF = immature reticulocyte fraction
= immature retics / total retics
HLR% = high light scatter retics
= Retics% x IRF
Foucade, Belaouni. Lab Hematol 1999; 5:153-8
IRF and Anemia
Foucade, Belaouni. Lab Hematol 1999; 5:153-8
Direct anti-globulin test
Gut lumen
Fe+++ Fe++ Heme Fe
Enterocyte DMT1
Ferritin Fe++
Fe+++
MTP1
Plasma transferrin
Enterocyteprecursor
Hepcidin
Transferrin Receptor
HFE
Regulation of iron absorption
•Marrow iron stores
•1 - 3+ •0 - 1+ •0 •0
•Ferritin •50 - 200 •<20 •<15 •0
•TIBC •300 - 360 •>360 •>380 •>400
•Serum iron
•50 - 150 •50 - 150
•<50 •<30
•Red cells •normal •normal •normal •microcytic, hypochromic
Iron stores
Erythron iron
Gastrointestinal absorption1 mg/day
Storage iron
Liver, RES
1 gram
Functional iron
Blood, marrow,
myoglobin2 grams
Plasma transferrin2 mg
Daily physiologic loss1 mg
Serum iron after oral iron in patients with iron deficiency
WH Crosby, Arch Int Med; circa 1970
20
40
60
80
1 2 3 4
Ser
um
iro
n
Hours
Kaltwasser, Gottschalk. Kidney Int. 1999; 55(suppl): S49 - S56
Serum ferritin and total body iron
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
Ratio of serum transferrin receptor to ferritin as a measure of total body iron
Cook, Flowers, Skikne. Blood 2003; 101: 3359 - 64
Erythropoietin response in iron deficiency
Spivak JL. Lancet 2000; 355:1707 - 12
Schreiber, Howalt, et at. NEJM 1996; 334: 619 - 23
Controls = normal volunteers and patients with traumatic blood loss
Serum erthyropoietin levels in patients with inflammatory bowel disease
Schreiber, Howalt, et at. NEJM 1996; 334: 619 - 23
IL-1 and anemia in patients with inflammatory bowel disease
Schreiber, Howalt, et at. NEJM 1996; 334: 619 - 23
Treatment with oral iron ± rEPO in patients with inflammatory bowel disease
Anemia of chronic disease
Inflammation
Tissue necrosis
Infection
Neoplasia
Congestive heart failure
Acute myocardial infarction
Anemia of chronic disease
Typical lab findings:
Serum iron < 50
TIBC < 150
Normochromic or hypochromic red cells
Normal ferritin
Normal serum transferrin receptor
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
Anemia of chronic disease
Mediators:
IL-1
IL-6
-interferon
TNF-
Mortality and initial hematocrit in PRAISE
Mozaffarian, Levy, et al. J Am Coll Cardiol 2003; 41(11): 1933 - 9
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
Mortality and initial hematocrit in PRAISE
Mozaffarian, Levy, et al. J Am Coll Cardiol 2003; 41(11): 1933 - 9
Prospective, randomized study of erythropoietin and i.v. iron in patients with CHF
Silverberg DS, Wexler D, et al. J Am Coll Cardiol 2001; 37: 1775 - 80
32 patients
NYHA Class III or IV
LVEF < 40%
Hgb 10 - 11.5
Random
ized
Sq epo twice a week
i.v. iron sucrose weekly
Continue standard therapy
Prospective, randomized study of erythropoietin and i.v. iron in patients with CHF
Silverberg DS, Wexler D, et al. J Am Coll Cardiol 2001; 37: 1775 - 80
NYHA class
LVEF
Days in hospital
Hgb
Ferritin
Creatinine
epo and i.v. iron
observation
+ 48%
+ 5 %
- 79%
10.312.9
221 366
1.7 1.7
- 11%
- 5 %
+ 28%
10.910.8
264 283
1.4 1.8
After 8 months:
Anemia of chronic disease
In IBD study and in CHF study response to treatment was not predicted by:
serum erythropoietin
serum iron
ferritin
Goodnough, Skikne, Brugnara. Blood, 2000; 96: 823 - 833
Effectiveness of treatment with erythropoietin
Safety of intravenous iron
Faich, Strobos. Am J Kidney Dis 1999: 33(3):464-70
Sodium ferric gluconate in sucrose (Ferrlecit)
Available in Europe > 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
Safety of intravenous iron
Faich, Strobos. Am J Kidney Dis 1999: 33(3):464-70
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
Safety of intravenous iron
Faich, Strobos. Am J Kidney Dis 1999: 33(3):464-70
Other theoretical risks:
iron overload
sepsis
accleration of athersclerosis
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.
Medicare warning :(