Transcript Anemia – Crowe

ANEMIA
An Outpatient Diagnostic Approach
Matthew Crowe
PGY-2
5/4/2015
DISCLAIMER
 Anemia is broad
SOME COMMON CAUSES
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Microcytic
Sickle cell
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Autoimmune
Iron deficiency
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Thalassemia
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Drug induced
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Chronic disease
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Virus
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Sideroblastic
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Lymphoid d/o
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Idiopathic
Macrocytic
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Alloimmune
Drug induced
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Immediate transfusion rxn
B12 deficiency
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Delayed transfusion reaction
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Folate deficiency
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Neonatal hemolytic
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Myelodysplasia
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Mircoangiopathic (TTP/HUS)
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Aplastic anemia
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Infection (malaria)
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Large granular lymphocyte d/o
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Chemical agent
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Excess alcohol use
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Chronic disease
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Liver disease
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Primary bone marrow d/o
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Hemolytic anemia
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Aplastic anemia
Spurious
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Pure red cell aplasia
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Ineffective erythemropoiesis
Normocytic anemia
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Drugs, toxins, radiation
Iron deficiency
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Immune mediated
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Renal insufficiency
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Infiltrating process
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Spherocytosis
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G6PD deficiency
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OVERVIEW
 Introduction
 Definitions
 Classification
 Physiology
 Diagnostic approach
 History and physical
 Diagnostic tools
 Classification & workup
 Review
 Questions
ANEMIA
Pathologic state of insufficient
erythrocytes to carry oxygen to
peripheral tissues
Clinically, a reduction of one of the
major RBC components
Not a disease, but a sign of underlying
illness or pathology
ANEMIA
Blood loss
Production defect
Destruction
PHYSIOLOGY
Lifespan
Production
Erythropoietin
Components
Nutrition
PHYSIOLOGY
PHYSIOLOGY
PHYSIOLOGY
DIAGNOSTIC APPROACH
Symptoms
Exam
CBC?
Other labs?
DIAGNOSTIC APPROACH
History
 Duration
 Medical history
 Procedures
 Family history
 Medications
 Diet
Exam
DIAGNOSTIC APPROACH
Different approaches, categorizations
MCV
Underutilized
 Reticulocyte count
 Peripheral smear
DIAGNOSTIC APPROACH
LABORATORY
Reticulocyte count
 Measure of new cells being produced
 1% is normal (daily cell turnover)
Absolute count or corrected/index
Most helpful if extremely low, or >3%
Production vs blood loss or hemolysis
LABORATORY
 Peripheral smear
MICROCYTIC
Rule out iron deficiency
 Low ferritin diagnostic of iron-depletion
 Iron, TIBC, % saturation
 RDW, anisocytosis (vs ACD)
 Reactive thrombocytosis
 Severe: cigar-shaped cells, elliptocytes
MICROCYTIC
Normal ferritin?
 Pre-existing microcytosis?
 Smear: polychromasia, basophilic stippling,
target cells (not IDA)
 Thalassemic syndrome
 Decreased production of globin chain
 Structural abnormality of globin chain
 Hemoglobin electrophoresis
MICROCYTIC
Sideroblastic anemia
 Not IDA or thalassemia
 Increased RDW
 Dimorphic RBCs
 Marrow with ringed sideroblasts
MICROCYTIC
Anemia of chronic disease
 Usually normocytic
 Rheumatoid, PM, DM, CTD, HL, RCC,
chronic infection
 Normal RDW
 Unremarkable smear
 Diagnosed on clinical grounds
NORMOCYTIC
Rule out treatable causes
 Nutritional
 Renal disease
 Hemolysis
Chronic disease?
Bone marrow disorder?
NORMOCYTIC
Nutritional anemia
 Iron deficiency
 B12 / cobalamin deficiency
 Folate deficiency
NORMOCYTIC
Anemia in renal disease
 Unremarkable smear
 Normal erythropoietin level
 Inappropriate
 May not be noticeable until more
advanced disease
NORMOCYTIC
Hemolytic anemia
 Cell destruction (LDH)
 Hemoglobin catabolism (indirect bili)
 Clearing hemoglobin (hapto)
 Bone marrow regeneration (retic)
None of these are specific
 LDH + hapto 90% specific
 Normal LDH + hapto >25 92% sensitive r/o
NORMOCYTIC
Hemolytic anemia
 Process inherent to RBC vs extrinsic
 Mebranopathies, enzymopathies,
hemoglobinopathies
 Immune, micoangiopathic, infection,
chemical
 Intravascular vs extravascular
NORMOCYTIC
 Intravascular vs extravascular
NORMOCYTIC
Ruled out the above?
History, history, history
 Meds, alcohol, radiation, chemical
exposure, recent trauma or surgery?
Anemia of chronic disease
Primary bone marrow disorder
NORMOCYTIC
Anemia of chronic disease
 Cytokine mediated process
 Inhibition RBC production or function
 Support
 Comorbid conditions
 Unremarkable smear
 Maybe ESR elevation
 Often mistaken for IDA given iron studies
 Ferritin
NORMOCYTIC
NORMOCYTIC
Primary bone marrow disorder
 Smear is most helpful
 CBC for other cell lines
 May need bone marrow
 Myelodysplastic syndrome
 Pure red cell dysplasia
 Aplastic anemia
 Marrow infiltration
MACROCYTIC
Rule out drug-induced causes
 Review medications, alcohol, treatments
 Hydroxyurea, MTX, TMP, zidovudine
 5-FU, chemotherapy agents
 Alcohol
Rule out nutritional causes
 B12 / cobalamin
 Folate
MACROCYTIC
Folate deficiency
 Folate level usually low
 RBC-folate level (chronicity)
 Homocysteine level
 Increased
 Conversion to methionine
Must also check B12
MACROCYTIC
B12 deficiency
 B12 level usually low
 Pregnancy, elderly, leukopenia,
borderline level?
 Methylmalonic acid level
 Cofactor in conversion to succinyl CoA
 Specific? Renal insufficiency, metabolic
disorders
 Homocysteine also elevated
MACROCYTIC
B12 deficiency
 Confirmed?
 Screen for intrinsic factor antibodies
 Pernicious anemia?
 Schilling test can differentiate pernicious
anemia from malabsorptive disorders
 Sprue, IBD, amyloidosis, intestinal
lymphoma
MACROCYTIC
No drug or nutrition related etiology?
 Bone marrow disease?
 May need biopsy
 Other clues on smear?
 Substantial polychromasia (retic)
 Hemolysis
 Round RBC morphology
 Liver disease (target cells)
 Hypothyroidism
REVIEW
 What is anemia
 Physiology
 How is it classified
 Diagnostic approach
 History and physical
 Diagnostic tools
REVIEW
Anemia is not a disease, but a sign of
underlying pathology
Do not rely on any one data piece
Anemia is dynamic
Beware of multiple causes
TEST YOUR KNOWLEDGE
A 22-year-old woman undergoes a new patient evaluation. She was recently diagnosed
with systemic lupus erythematosus manifesting as painful joints, malar photosensitive
rash, oral aphthous ulcers, and a positive antinuclear antibody and anti-Smith antibody
titer. Her menstrual pattern is normal, and her medical history is otherwise
noncontributory. Her only medications are hydroxychloroquine and a multivitamin.
On physical examination, temperature is 37.2 °C (99.0 °F), blood pressure is 126/78 mm
Hg, pulse rate is 88/min, and respiration rate is 17/min. BMI is 20. The patient has a malar
rash and thinning hair, but no joint abnormalities, oral lesions, pericardial or pleural rubs,
or heart murmurs.
Laboratory studies:
Hemoglobin
Leukocyte count
Ferritin
Iron
Reticulocyte count
Total iron-binding capacity
Transferrin saturation
Creatinine
8.2 g/dL (82 g/L)
3900/µL (3.9 × 109/L)
556 ng/mL (556 µg/L)
18 µg/dL (3.2 µmol/L)
2%
180 µg/dL (32 µmol/L)
10%
1.0 mg/dL (88.4 µmol/L)
Which of the following is the most likely diagnosis?
A
Inflammatory anemia
B
Iron deficiency
C
Microangiopathic hemolytic anemia
D
Warm antibody-associated hemolysis
TEST YOUR KNOWLEDGE
A 32-year-old man is evaluated for fatigue, dyspnea, lethargy, and yellowing of the
eyes of 1 week's duration. Medical history is significant for a recent communityacquired methicillin-resistant Staphylococcus aureus skin infection of the right forearm
treated with a 14-day course of trimethoprim-sulfamethoxazole. Treatment concluded
yesterday, and his infection has resolved.
On physical examination, temperature is 36.8 °C (98.4 °F), blood pressure is 103/53 mm
Hg, pulse rate is 112/min, and respiration rate is 16/min. He has scleral icterus. On
cardiopulmonary examination, he is tachycardic. The remainder of the physical
examination is normal.
Laboratory studies:
Hemoglobin
Leukocyte count
Mean corpuscular volume
9.6 g/dL (96 g/L)
8900/µL (8.9 × 109/L) with a normal differential
104 fL (compared with a value of 85 fL 3 years ago)
Platelet count
259,000/µL (259 × 109/L)
Reticulocyte count
6.4%
Three years ago, the routine complete blood count was normal.
Which of the following is the most likely diagnosis?
A
Cold agglutinin disease
B
Glucose-6-phosphate dehydrogenase deficiency
C
Hereditary spherocytosis
D
Sickle cell disease
E
Thalassemia
REFERENCES

Tefferi, Ayalew. "Anemia in Adults: A Contemporary Approach to Diagnosis." Mayo Clinic Proceedings
78.10 (2003): 1274-280. Web. 3 May 2015.

DeLoughery, Tom. Anemia: An Approach To Diagnosis. Rep. N.p.: Oregon Health & Science U, 2010. Print.

MKSAP 16, ACP

UpToDate: “Approach to the adult patient with anemia”

Armando Hasudungan, Armando. "Haematology - Red Blood Cell Life Cycle." YouTube. YouTube, 29 Sept.
2014. Web. 03 May 2015. <https://www.youtube.com/watch?v=cATQFej6oAc>.

Image of RBC & components. Digital image. Air We Breathe: Air Composition. Chemistryland, n.d. Web. 3
May 2015. http://www.chemistryland.com/CHM107/AirWeBreathe/Comp/AirComposition.html.