Anemia 101

1. Santosha Vardhana, MD PHD

2. New anemia: H&P
History
• Fatigue
• Exertional dyspnea,
palpitations, angina,
claudication
• Dizziness/Syncope
• Remember to ask about:
– Ethnicity
– Medications (NSAIDs)
– EtOH use
Physical
• VS/General
– Orthostasis, hypotension,
– Lethargy, dizziness
– Back or leg pain
• Skin:
– Conjunctival rim pallor
– Delayed capillary refill
– Petechiae or purpura
• CV:
– Bounding pulses
– Ejection murmur
– Clinical heart failure

3. New Anemia: Labs (Basic)
What lab What’s normal Who cares
Hgb >12 (F), >13 (M) You do – it’s the topic of this lecture
WBC 3.5-10.5 Increase may indicate MPD
Decrease may indicate bone marrow failure
Platelets 150-450 Decrease may indicate bone marrow failure or
platelet consumption (TTP)
Red Cell Indices
MCV 80-96 fL Identifies microcytic/macrocytic anemia
MCHC 27.5-33.2 pg Decreased when there is less Hgb/cell (IDA,
thalassemia), increased when there is more
Hgb/cell (hemolytic anemia, spherocytosis)
RDW 11.5-14.5 Microcytic/normal RDW: suspect thalassemia
Microcytic/high RDW: suspect IDA
Macrocytic/high RDW: suspect B12/Folate def.

4. My approach to anemia
Reticulocyte
Index
RI>2
(normal)
RBC loss
RBC
destruction
RI<2 (low)
Check MCV

5. Step 1: the reticulocyte index
• How do I calculate the RI?
– RI = retic count x [Pt Hct/45] x correction factor
– Correction factor is determined by pt Hct
• RI normal (>2): normal production
– Evaluate for occult blood loss
– Evaluate for hemolysis
• RI decreased (<2): impaired production
– Evaluate RBC morphology

6. My approach to anemia
Reticulocyte
Index
RI>2
(normal)
RBC loss
RBC
destruction
RI<2 (low)
Check MCV

7. Step 1b (normal RI): look for blood loss
Other areas: menorrhagia, post-surgical, traumatic, iatrogenic

8. Step 1b (normal RI): workup RBC
destruction
Test Interpretation
LDH Elevated in any hemolysis
Haptoglobin Decreased with intravascular hemolysis
Coombs Positive in any immune-mediated hemolysis
(includes drugs that induce immune-mediated
hemolysis)
Smear
Review
Can reveal microspherocytes (hemolytic
anemia), schistocytes (MAHA)

9. Destruction: immune vs. non-immune mediated
Immune (agglutinin+)
Cold PNH
Post-mycoplasma
Warm Drug-induced
AIHA
Transfusion rxn
Non-Immune
Macro-
circulatory
Hypersplenism
Mechanical valve
Micro-
circulatory
DIC
TTP
HUS
Intra-RBC G6PD
Strutural defects (spherocytosis,
elliptocytosis, HbS, HbC)

10. Obligatory slide of peripheral smears
MAHA AIHA

11. My approach to anemia
Reticulocyte
Index
RI>2
(normal)
RBC loss
RBC
destruction
RI<2 (low)

12. Inadequate Materials
Heme IDA, ACD, Copper deficiency
Globin Thalassemia
Nucleotides B12, Folate, nucleoside analogs, lead poisoning
Inadequate precursors
Maturation
arrest
MDS, Leukemia, aplastic anemia, PRCA, viral infections, drugs,
toxins
Destruction of
precursors
Sideroblastic anemia, PNH
Inadequate stimulus
EPO Anemia of CKD
T4 Hypothyroidism
Step 2 (decreased RI): what is causing
the failure?

13. My approach to anemia
Reticulocyte
Index
RI>2
(normal)
RBC loss
RBC
destruction
RI<2 (low)
Check MCV

14. Step 2b (decreased RI): check the MCV
• Microcytosis (<80)
– IDA, ACD, thalassemia
• Macrocytosis (>100)
– B12/Folate
– Medication review
– Liver, EtOH disease
• Normocytosis (80-100)
– Bone marrow disorders
– Toxins, drugs
– Chronic inflammation
– Renal failure
– Thyroid disease

15. Step 2c (decreased RI): order the
appropriate “anemia labs”
Normal IDA ACD Mixed
Fe 60-170 mcg/dl   
TIBC 240-450
mcg/dl
 Normal/ Variable
Ferritin 12-300 ng/mL   Normal
sTfR 1.8-4.6 mg/L  Normal 
Normal B12 deficiency Folate deficiency
Serum B12 180-914 ng/L <200-300 Normal
Serum Folate >4 mcg/L Normal <4
Serum MMA 70-270 nmol/L  Normal
Serum homocysteine 5-15 umol/L  

16. Anemia of chronic disease: hepcidin

17. Homocysteine and MMA metabolism