EVALUATION OF THE ANEMIC PATIENT Slide 2 Is the patient really
anemic? Hemoglobin declines with advanced ageHemoglobin declines
with advanced age African heritage - 0.5 g/dl lower hgbAfrican
heritage - 0.5 g/dl lower hgb Hematocrit lower by a mean of 4
points in recumbent vs standing position Edematous pts have 12%
drop in Hct/Hgb after one hour of recumbenceEdematous pts have 12%
drop in Hct/Hgb after one hour of recumbence Slide 3 Blood
2004;104:2263-2268 Data from the Third National Health and
Nutrition Examination Survey (1988-1994) Prevalence of anemia rises
rapidly after age 50, prevalence 20% over age 85 11% of men, 10.2%
of women over 65 anemic 1/3 due to nutritional deficiency, 1/3 to
chronic inflammation or renal disease, 1/3 unexplained Most cases
mild; only 2.8% of women and 1.6% of men had Hgb < 11 g
Unexplained mild anemia in elderly people may simply be an effect
of aging in some cases Slide 4 Slide 5 Slide 6 Slide 7 Clinical
Clues History Family history Timing of symptoms Medications
Occupation/Hobbies Diet Mouth problems GI symptoms
Bruising/bleeding GU symptoms Exam Mouth Sternal tenderness Lymph
nodes Cardiac murmurs Liver/Spleen size Skin exam Pelvic/rectal
Always consider/rule out blood loss! Slide 8 Look hardest for
readily treatable causes of anemia Nutritional deficiency (iron,
B-12, folate) Endocrinopathy (esp thyroid) Low-EPO state (more
common than you think) GI blood loss Most treatable causes of
anemia can be diagnosed without marrow biopsy Slide 9 Confirm
laboratory data CBC performed by machine, including differentialCBC
performed by machine, including differential Quality of flagging
abnormal values variesQuality of flagging abnormal values varies
All flagged results should be reviewed when diagnosis is not
known.All flagged results should be reviewed when diagnosis is not
known. Blood smear from abnormal CBC should be reviewed by a
humanBlood smear from abnormal CBC should be reviewed by a human
Slide 10 KINETICS OF ERYTHROPOIESIS Hyporegenerative (marrow not
working well) Hyperregenerative (marrow working) Calculating the
reticulocyte index will usually tell you which category your
patient is in Slide 11 Reticulocytes Reticulin - insoluble
ribosomal RNA Present after extrusion of nucleus until degradation
of rRNA. Retics normally spend 3.5 days in marrow, 1 day in blood
Normal 28 -115 thousand per microliter Reticulocytes demonstrated
by Crystal Violet stain of blood smear (most labs now use
flourescent dye and automated cell counter) Slide 12 Measuring
Reticulocytes Maturation Mature RBC * False positive -
Howell-Jolly, Heinz, & Pappenheimer bodies, Malaria, Babesia,
porphyria High fluorescenceLow fluorescence Slide 13 Reticulocyte
Response Reticulocyte count = % retics Reticulocyte Index
correlates best with RBC production Correct for low RBC count
(absolute retic count) Correct for immature retics if present
(factor of 2) Normal RI = 1 but should go up in anemia if marrow
function normal Normal or low RI in anemia implies hyporegenerative
state Very high RI (>4) suggests hemolysis Misleading results
possible if not in steady state Slide 14 Retic Index When Hct 25 or
less, use 1/2 for maturation time term Slide 15 Example 75 yo with
osteomyelitis receiving extended antibiotic therapy poor appetite,
weight loss Labs: Hct 25, WBC 12.0, Platelets 545, MCV 92, Retic
5.8% (normal 0.5 to 2.2%) RI = 1.6 too low Slide 16
Hyporegenerative anemia Nutritional deficiency (iron, B-12, folate)
Marrow dyscrasia (leukemia, myelodysplasia, aplastic anemia etc)
Thalassemia Low EPO state (renal disease, inflammation,
endocrinopathy, ? old age) Retic index not appropriately increased
Slide 17 Hyperregenerative anemia Hemolysis Hemolysis Blood loss
Blood loss Retic count increase generally less striking than in
hemolysis Retic index increased Slide 18 Interpreting the MCV The
MCV reflects the average size of RBCThe MCV reflects the average
size of RBC Macrocytic (MCV >95) Microcytic (MCV TESTS OF IRON
STATUS TESTS OF IRON STATUS Practical aspects Low serum ferritin
almost always indicates iron deficiency Low serum iron and high
TIBC almost always indicate iron deficiency Ferritin > 100
rarely found in iron deficiency Exception - liver
inflammation/necrosis Normal serum iron rarely found in iron
deficiency Exception - iron deficiency recently treated with oral
iron When TIBC is low or normal, low serum iron not a reliable
indicator of iron deficiency! Iron deficiency may be hard to
diagnose via blood tests in setting of inflammation (eg, low iron,
low TIBC, intermediate ferritin level) Therapeutic trial of iron
+/- EPO a reasonable alternative to marrow biopsy Slide 32
Macrocytic, hyporegenerative anemia Megaloblastic: B12/folate
deficiency Myelodysplastic syndrome Drug-induced Non-megaloblastic:
Liver disease AlcoholHypothyroidismReticulocytosis Slide 33
Macrocytic Anemia - Causes Colon-Othero; Med Clin North Am: 581,
1992 Slide 34 B-12/Folate deficiency Therapeutic trial reasonable
if blood level of vitamin borderline In equivocal cases consider
confirmatory tests: TESTDEFICIENCY MethymalonateB-12
HomocysteineB-12 or folate Slide 35 Megaloblastic Anemia - Drugs
Folate antagonistsFolate antagonists methotrexate trimethoprim Most
cancer chemotherapyMost cancer chemotherapy Anti-retroviral
agentsAnti-retroviral agents zidovudine delavirdine lamivudine
zalcitabine Nitrous oxideNitrous oxide ArsenicArsenic
ChlordaneChlordane AnticonvulsantsAnticonvulsants Dilantin
Valproate Lamotrigine Slide 36 Normocytic, hyporegenerative anemia
Marrow disorders Aplastic anemia Pure red cell aplasia Inherited
anemia (Diamond-Blackfan) Myelophthisic state Myelodysplasia
Leukemia and other heme malignancy Low EPO state Uremia,
inflammation, endocrinopathy, HIV infection, etc Relatively common
in elderly Slide 37 Expected EPO Levels in Uncomplicated Anemia
Hematocrit Serum EPO Slide 38 Anemia of Renal Insufficiency Due to
low EPO, shortened RBC survival, and altered iron kinetics.Due to
low EPO, shortened RBC survival, and altered iron kinetics. Anemia
begins to develop when CrCl is below 40ml/min/1.73M 2Anemia begins
to develop when CrCl is below 40ml/min/1.73M 2 Common problem in
elderly, can be improved with EPO, often given with po or iv
ironCommon problem in elderly, can be improved with EPO, often
given with po or iv iron Example: 70yo woman, 52, 110 lbs, Cr
1.6Example: 70yo woman, 52, 110 lbs, Cr 1.6 CrCl = 22ml/min/1.73M 2
Slide 39 ANEMIA WITH IMPAIRED ERYTHROPOIETIN RESPONSE IN DIABETIC
PATIENTS Subjects: 722 patients with diabetes mellitus
Measurements/data collection: Clinical data, lab measurements
including CBC, iron studies, EPO Findings: 23.3% of patients were
anemic. 77.4% of these had inappropriately low (ie, normal) EPO
levels EPO levels inappropriately low in 69% of anemic diabetic
patients with apparently normal renal function. Most of these
patients had albuminuria and only mild anemia. CONCLUSIONS:
Diabetic renal disease can cause mild anemia in the absence of
renal impairment. Most diabetics with anemia could benefit from EPO
treatment Arch Intern Med. 2005;165:466-469 Slide 40 ERYTHROPOIETIN
AND AGING In 143 initially healthy subjects followed for 8-30
years, serum erythropoietin levels rose steadily with age, while
hemoglobin levels remained constant or declined slightly. This
suggests that older individuals are more dependent on EPO to
maintain the Hgb, and are at greater risk for anemia if there is
even slight impairment in EPO production. Ershler et al, J Am
Geriatr Soc 2005;53:1360 Slide 41 Hyperregenerative anemia Blood
loss HemolysisImmuneMechanical/microangiopathic Hereditary
(hemoglobinopathy, membrane defect, enzyme deficiency) Acquired
membrane defect (PNH, spur cells) Infection (malaria, Clostridia,
babesiosis) Slide 42 Hemolytic anemia laboratory evaluation Blood
smear (fragments, spherocytes, sickle cells, malaria, etc)Blood
smear (fragments, spherocytes, sickle cells, malaria, etc)
Nonspecific indicators of hemolysis: LDH, bilirubinNonspecific
indicators of hemolysis: LDH, bilirubin Direct Coombs testDirect
Coombs test Warm antibody = IgG C3 Cold antibody = C3 only (cold
agglutinin) Indicators of intravascular hemolysis: haptoglobin,
urine hemosiderin, plasma or urine hemoglobinIndicators of
intravascular hemolysis: haptoglobin, urine hemosiderin, plasma or
urine hemoglobin Other: Hgb electrophoresis, rbc enzyme levels,
G6PD, osmotic fragility, PNH testing etcOther: Hgb electrophoresis,
rbc enzyme levels, G6PD, osmotic fragility, PNH testing etc Slide
43 INDICATIONS FOR BONE MARROW BIOPSY Retic index not appropriately
increasedRetic index not appropriately increased No evidence of
iron/B-12/folate deficiency, renal failure, endocrinopathy,
inflammation or other low EPO stateNo evidence of iron/B-12/folate
deficiency, renal failure, endocrinopathy, inflammation or other
low EPO state Poor response to EPO, iron or vitamin replacementPoor
response to EPO, iron or vitamin replacement WBC/plts/diff
abnormal, monoclonal gammopathy, or other peripheral blood evidence
of marrow disorderWBC/plts/diff abnormal, monoclonal gammopathy, or
other peripheral blood evidence of marrow disorder Would you treat
leukemia/MDS or other neoplastic disorder if you found it? Slide 44
ALGORITHM FOR EVALUATION OF ANEMIA ANEMIC PATIENT
Hyper-regenerative Evaluate for hemolysis and bleeding
Hypo-regenerative Rule out treatable nutritional deficiency,
endocrinopathy, etc Low-EPOHigh-EPO Trial of EPO Consider
BMBxContinue EPO Retic index Epo level Response No response
