Harrison’s Hour:

Chapter 59
Anemia and
Templo, Allain Joseph S., MD

Polycythemia
Mary Mediatrix Medical Center
Internal Medicine - 1st year Resident
 Objectives
• Present a case about anemia

• Provide a brief background on erythropoiesis

• To give focus on the approach to anemia

• To give a brief background on polycythemia

• Present a Concept Map of the case

DISCLAIMER
Case
GB
93F
CC: Dislodged PEG Tube

Labs
CBC –
WBC 6.9
Previously admitted for LGIB sec to Colonic Hgb 7.1
Mass t/c malignancy. Discharged Hct 23.3
stable/Improved. Plt 355
Neu 62
1 day PTA, PEG tube noted to be dislodged, no Lymph 19
bleeding/discharge at stoma. No fever, abdominal Microcytic Hypochromic
pain, melena/hematochezia associated.
Na 125 K 4.3 BUN 18 Crea 0.6 SGPT 12 RBS 120
PMH: Alzheimer’s Disease (no maintenance) Trop T <50
Bronchial Asthma(No Maintenance) PT 14.3/10.6/65.8%/1.35
Baseline: Bedridden PTT 35.2/35.5
PSH: (-)Vices/Travel/exposure history 12L ECG NSR TWI V3-5
FH: (-) CXR Consolidation Left Lower Lobe
Feeding History: Milk Formula Ensure 2-3 scoops (-)FOBT
TID

PE: 120/70 36C 69 20 96

 Impression: Anemia prob. sec. to: Plan:
1. Severe Iron Deficiency Keep on NPO temporarily
Hydration w/ D5NSS w/ congestion prec.
2. Chronic Inflammation For Blood Transfusion, 2 units pRBC properly
Colonic Mass prob. Malignant typed and crossmatched
Hyponatremia sec. poor intake For Reinsertion of PEG Tube once Anemia is
Alzheimer’s Disease corrected.
Bronchial Asthma not in Exacerbation
s/p PEG Insertion March 2019
5th Hospital Day
Currently still admitted
Admission: For 2 more units of
Patient unable to pRBC transfusion
secure Blood Products. 4th Hospital Day Still for PEG Insertion
NGT Feeding Started. Comfortable
Still for PEG insertion. (-)Abd. Pain
(-)Bleeding Episodes
s/p 1 unit pRBC
Repeat CBC
Hgb 7.9(7.1)
HCT 23.3
Plt 355
WBC 7.67
Neu 82
Discussion
 Hematopoiesis
• Process by which the formed elements of blood are
produced.

• Hematopoietic Stem Cell

• Erythropoiesis - process of formation of RBC

Erythropoiesis
Yolk Sac (6-10 weeks of gestation) Bone Marrow

Liver and Spleen (10weeks- Second

trimester)

Bone Marrow( from 4th month)

 Erythrocytes
• RBC Development is characterized by:
•

1. Decrease in cell size

2. Disappearance of Nucleus

3. Appearance of Hemoglobin
 Erythrocytes
•

• Circular,
Biconcave,
and non-
•
nucleated
• Flexible
and readily
 Erythrocytes
• Normal Red Cell Production
•

• Erythron - organ responsible for red cell production

•

• Dynamic organ, made up of rapidly proliferating

pool of marrow erythroid precursor cells and a
large mass of mature circulating RBCs

• Daily Replacement of 0.8-1% of all circulating red

 Erythropoetin
• Primary regulatory hormone

• produced by the Peritubular Capillary Lining of the

Kidneys

• Small amounts produced by the liver

• Maintenance of erythroid progenitor cells

•

• Absence leads to apoptosis

 Erythropoetin
• Normal Level: 10-25 U/L

• Increase in proportion w/ severity of anemia

• Half-time: 6-9h

• Triggers an increase of 4-5 fold in RBC production

within 1-2 weeks
•

• ONLY in the presence of adequate nutrients (Fe2+)

 Erythropoiesis

Critical Elements:
1. EPO production
2. Iron Availability
3. Proliferative Capacity of the Bone Marrow
4. Effective Maturation of Red Cell Precursor
 Anemia
• Defined by WHO as Hgb Level:
•

• <13g/dL in men
• <12g/dl in women
 Clinical Presentation
• Most often recognized by abnormal screening laboratory
tests.

• Usually present w/ fatigue, breathlessness and

tachycardia

• Acute Anemia (Hemolysis or Blood Loss) -

Hypovolemia dominates the clinical feature; CBC
picture does not reflect volume status.
•

• 10-15% - usually presents w/ vascular instability,

vascular contraction and changes in regional blood
 Clinical Presentation
• Chronic or Progressive Anemia - depend on the age
and adequacy of blood supply to critical organs.
•

• Intrinsic Compensatory Mechanisms play a role

(Oxygen-Hemoglobin Dissociation Curve)

• Symptoms typical in anemia appear later in younger

patients and are only obvious when the anemia is
severe (<7g/dL)
No Direct Effects in Hemoglobi
effects on Tissue Perfusion in th
Anemia
Anemia
 Approach to Anemia
• Careful history and physical exam
•

• Age

• Nutritional History

• Blood Transfusion History

• Family History

• Geographic Background and ethnic origins

• Exposure to toxic agents

 Approach to Anemia
• Physical Findings:
•

• Pallor expected if Hgb is <8-10g/dL

• Forceful heart beat, strong peripheral pulses, systolic murmur

• Splenomegaly and Lymphadenopathies suggest an

underlying Lymphoproliferative disease

• Past Laboratory Measurements are helpful to determine a

time of onset
Laboratory Evaluation
Laboratory Evaluation
Laboratory Evaluation
 Peripheral Blood Smear
• Provides information about defects in red cell
production.

• Complement to the red cell indices

• reveals changes in shape (poikilocytosis) and size

(anisocytosis)
 Reticulocyte Count
• An accurate reticulocyte count is
the key to the initial
classification of anemia

• Red cells that have been recently

released from the bone marrow

• Appear blue or black punctate

spots using methylene blue stain

• Usually metabolized over the

first 24-36h of the reticulocyte’s
life span
 Reticulocyte Count
• Corrected Reticulocyte Percentage or absolute number
of reticulocytes
•

• Provides a reliable measure of effective red cell

production.

• Use of 2 Corrections to provide a true index of effective

red cell production
•
Reticulocyte Count
First Correction - Adjusts the reticulocyte count based on
the reduced number of circulating red cells.
•

• Provides an estimate of the reticulocyte count

corrected for anemia

ARC = Reticulocyte Count(%) X (Actu

Hct/Expected Hgb or Hct)
 Reticulocyte Count
• Second Correction

• PBS examined for shift cells

(Polychromatophilic macrocytes) -
represent prematurely released
reticulocytes

• Prematurely released cells survive

as reticulocytes in circulation for >
1day, leading to a falsely high
estimate of red cell production
•

•
Reticulocyte Count
Reticulocyte Production Index

• In general, a maturation time correction of 2 is used

• “2” accounts for the average time for RBCs to mature from Reticulocytes to Mature RBCs

RI = Reticulocyte Count(%) X (Actual Hgb or Hc

Hct)
Maturation Time Correction
•

•
Reticulocyte Count
Reticulocyte Production Index

• In general, a maturation time correction of 2 is used

• “2” accounts for the average time for RBCs to mature from Reticulocytes to Mature RBCs

RI = Reticulocyte Count(%) X (Actual Hgb or Hc

Hct)
Maturation Time Correction

Interpretation: Marrow respons

is Appropriate
Appropriate
 Iron Studies
A. Serum Iron
B.

• Represents the amount of circulating iron bound to

transferrin

• Normal Range: 50-150 ug/dL

C. Total Iron Binding Capacity

D.

• Indirect Measure of Circulating Transferrin

 Iron Studies
C. Transferrin Saturation(%)
•

• (Serum Fe/TIBC)100

• Normally 25-50%

• <20% associated w/ Iron Deficiency Anemia

• >50% disproportionate amount of iron bounded, may

result to Iron Overload

• D. Ferritin
 Bone Marrow Examination
• Can diagnose primary marrow disorders such as:
•

• Myelofibrosis

• Red Cell Maturation Defects

• Infiltrative Disease

• In patient’s w/ Hypoproliferative anemia and Normal Iron

stores, Bone Marrow Examination is indicated.
 Bone Marrow Examination
• Indications (International Council for
Standardization in Hematology)
•

1. Investigation of unexplained anaemia, abnormal red cell indices,

cytopenias or cytoses

2. Investigation of abnormal peripheral blood smear morphology

suggestive of bone marrow pathology

3. Diagnosis, staging and follow-up of malignant haematological

disorders (e.g. acute and chronic leukaemias, myelodysplastic
syndromes, chronic myeloproliferative disorders, lymphomas,
plasma cell myeloma, amyloidosis, mastocytosis)
 Classification of Anemia
• 3 Major Categories
•

• Marrow production defects

(hypoproliferation)

• Maturation defects
(Ineffective Erythropoiesis)

• Decreased Survival (Blood

loss/Hemolysis)
 Hypoproliferative Anemia
• Low RPI
• Little or no change in red cell indices
• Reflect Absolute or Relative Marrow
Failure
• Most Common: Iron Deficiency Anemia
•
 Hypoproliferative Anemia
• Low RPI
• Little or no change in red cell indices
• Reflect Absolute or Relative Marrow
Failure
• Most Common: Iron Deficiency Anemia
•
•
Iron Deficiency Anemia
Most Common Type of Anemia
•
Iron Deficiency Anemia
Iron Source - Mainly from Dietary and Iron
Stores(Senescent Cells)
•
Iron Deficiency Anemia
Iron Source - Mainly from Dietary and Iron
Stores(Senescent Cells)
•
Iron Deficiency Anemia
Iron Source - Mainly from Dietary and Iron
Stores(Senescent Cells)
•
Iron Deficiency Anemia
Most Common Type of Anemia
 Hypoproliferative Anemia
• Low RPI
• Little or no change in red cell indices
• Reflect Absolute or Relative Marrow
Failure
• Most Common: Iron Deficiency Anemia
•
 Maturation Disorder
• Inappropriately low RPI
• Macro-Microcytic
• Bone Marrow may show Erythroid
Hyperplasia
• 2 types:
•

• Cytoplasmic Defect
•

• Microcytic
• Nuclear Defect
•

• Microcytic
 Maturation Disorder
• Inappropriately low RPI
• Macro-Microcytic
• Bone Marrow may show Erythroid
Hyperplasia
• 2 types:
•

• Cytoplasmic Defect
•

• Microcytic
• Nuclear Defect
•

• Microcytic
 Maturation Disorder
• Inappropriately low RPI
• Macro-Microcytic
• Bone Marrow may show Erythroid
Hyperplasia
• 2 types:
•

• Cytoplasmic Defect
•

• Microcytic
• Nuclear Defect
•

• Microcytic
 Hemolysis/Hemorrhage
•

• RPI >2.5
• Hemolysis
•

• Least Common
• Red cell indices typically normocytic
or slightly macro
• Increase in Polychromatophilic
Macrocytes
• Hemorrhage
•

• Acute Blood Loss

•

• Hypovolemia predominates
• CBC picture does not reflect
volume status
• not associated with an increased
 Treatment
• Correct the underlying cause eg. IDA, Folate/Vit. B12
Deficiency, etc.

• If symptomatic or w/ cardiac complications, a lower

threshold for Blood Transfusion is indicated.
 Treatment
• Iron Deficiency Anemia
•

• 200mg taken per day

• Oral

• Should be taken in an empty stomach

• GOAL is to correct anemia while providing Fe stores

0.5-1g for 6-12months.

• Parenteral Iron if oral doses cannot be tolerated

 Treatment
• Anemia of Inflammation
•

• EPO can be given

• Blood Transfusion
 Treatment
• Megaloblastic Anemia
•

• Treat underlying cause

• Cobalamin Deficiency - Usually require lifelong

regular cobalamin injections

• Folate Deficiency - 5-15mg folic acid daily is

satisfactory
 Treatment
•

• Thalassemia
•

• Supportive Blood Transfusion

• Splenectomy if transfusion requirement

increases by 50% per year
 Treatment
•

• Autoimmune Hemolytic Anemia

•

• Steroids

• Some spontaneously resolved

 Blood Transfusion
• Packed Red Blood Cell Transfusion
•

• Inc. O2 carrying capacity in anemic patients

• Given as drip to run for 4-6hrs

• Should be properly Typed and Cross-Matched

• 1 unit = Inc. Hgb by 1g/dL or Hct by 3%

 Blood Transfusion
• Indications
•

• <6g/dL

• 6-10g/dL - based on clinical complications and

inadequate oxygenation states

• >10 g/dL - Indicated for those w/ Cardiac

Complications
 Iron Overload
• Adverse Effect of Chronic Transfusions

• 1 unit= 250-300mg Fe

• Signs/Symptoms: Endocrine Dysfunction(Glucose

intolerance, Delayed Growth), Cirrhosis,
Cardiomyopathy, Ferritin elevation

• Treatment: Deferoxamine/Deferasirox(20-30mg/kg)
 Polycythemia
• Hgb >17g/dL in men; >15g/dL in women

• Hct >50% in men; >40% in women

• May be Asymptomatic
• Clinical Manifestation (Hyperviscosity/Thrombosis):
Headache, Vertigo, Tinnitus, Visual Disturbances
•

• Blood Viscosity increases logarithmically at Hct

>55%

• Clinical Clues: Smoking history, Living in High

Altitude Areas, Diuretic use, Congenital Heart Disease,
Sleep Apnea, or Chronic Lung Disease
 Prolonged
depleted Fe Stores

93F
Poor Intake
Hepcidin Dec. Fe
Colonic Mass
Absorption/Release
from stores

Chronic Microcytic
Inflammatory Hypo chromic
state Anemia

Inflammatory Dec. EPO

Cytokines
Interleukins
 Take Home Message
• Not all anemia is Iron Deficiency Anemia

• Look at the whole picture of the CBC

•

• if Anemic, look at the Red Cell Indices

• Transfusion Guidelines, are only used as a guide.

Decision to Transfuse depends on Clinical Judgement of
the Physician.
 Sources
• Adamson, J. and Longo, D., 2020. Anemia and
Polycythemia. Harrison’s Principles Of Internal
Medicine. 20th ed. New York City: McGraw Hill,
pp.385-394.

• Guyton, A., 2011. Red Blood Cells, Anemia, and

Polycythemia. Guyton And Hall Textbook of Medical
Physiology. 12th ed. Philadelphia, PA:
Saunders/Elservier, 413-420

• Erber, W., 2010. Morphology. Diagnostic Techniques in

Hematologic Malignancies. Cambridge: Cambridge
University Press, pp. 14-15
Thank Yo