How much do you know about anemia? here is a case-based approach presentation.

1. Week
Anemia
Part One
Anas Bahnassi
1

2. Lecture Outline
Definition
Pathophysiology
Detection
Iron Deficiency Anemia
Predisposing Factors
Signs and Symptoms
Management

3. Definition
Anemia is a reduction in red cell mass.
It often is described as a decrease in the number of
(RBC/mm3)
Or
A decrease in the hemoglobin concentration in blood to a
level below the normal physiologic requirement for
adequate tissue oxygenation.
The term anemia is not a diagnosis, but rather an objective
sign of a disease.

4. Pathophysiology
A symptom of many pathologic conditions
It is associated with nutritional deficiencies, acute and chronic diseases; it also can
be drug induced.
It can be caused by slower cell production or increased destruction (Secondary to
hemolysis) or loss (Bleeding).

5. Pathophysiology
Blood Loss
•
•
Acute: trauma, ulcer, hemorrhoids
Chronic: ulcer, vaginal bleeding, aspirin ingestion
Inadequate
RBC
Production
•
•
Nutritional deficiency: B12, folic acid, iron
Erythroblast deficiency: bone marrow failure (aplastic anemia,
irradiation, chemotherapy, folic acid antagonists) or bone marrow
infiltration (leukemia, lymphoma, myeloma, metastatic solid tumors,
myelofibrosis)
Endocrine deficiency: pituitary, adrenal, thyroid, testicular
Chronic disease: renal, liver, infection, granulomatous, collagen
vascular
Intrinsic factors: hereditary (G6PD), abnormal hemoglobin
synthesis
Extrinsic factors: autoimmune reactions, drug reactions, infection
(endotoxin)
•
•
Excessive
RBC
Destruction
•
•

6. Detection
Onset of anemia can be acute or can develop slowly, resulting in tissue hypoxia.
Slowly developing anemias can be asymptomatic initially or include symptoms such as:
Slight exertional dyspnea, increased angina, fatigue, or malaise.
Uncorrected tissue hypoxia can lead to a number of complications in quality of life,
cognition, and respiratory and gastrointestinal (GI) systems.
May lead to changes in the kidney tissue oxygen tension.

7. Detection
In severe anemia, a hemoglobin (Hgb) <8 mg/dL,
Systolic murmurs,
Angina pectoris,
heart rate, and stroke volume often increased  Congestive heart failure,
Pulmonary congestion,
Ascites,
Edema.
Skin and mucous membrane pallor, jaundice, smooth or beefy tongue, cheilosis, and
spoon-shaped nails (koilonychia) also may be associated with severe anemia of
different causes of anemia.

8. Patient History
A time line, which begins with the onset of symptoms (and
surrounding events) and extends to current status, is important.
Because longstanding anemias can indicate hereditary
disorders, the family history should be noted.
Past Hgb or hematocrit (Hct) determinations, transfusion
history, as well as occupational, environmental, and social
histories may be valuable.
A medication history can help eliminate drug reactions or
interactions as the cause of the anemia.

9. Physical Examination
Pallor is most easily observed in the conjunctiva, mucous
membranes, nail beds, and palmar creases of the hand.
Postural hypotension and tachycardia can be seen when
hypovolemia (acute blood loss) is the primary cause of anemia.
Patients with B12 deficiency may exhibit neurologic findings, which
include changes in deep tendon reflexes, ataxia, and loss of
vibration and position sense; all are consistent with nerve fiber
demyelination.
Patients may be slightly jaundiced from bilirubin release.

10. Laboratory Evaluation
The cornerstone of this evaluation is the complete blood count
(CBC).
Male patients have higher hematocrit (Hct) values than do female
patients.
The Hct is increased in individuals living at altitudes above 4,000
feet in response to the diminished oxygen content of the
atmosphere and blood.
The morphologic appearance of the RBC provides useful
information about the nature of the anemia.

11. Homework
?
You need to provide a handwritten
table of normal hematological values
Don’t forget to mention your reference

12. Laboratory diagnosis of Anemia
Macrocytic
Anemia
Hematocrit
Low B12, Schiling Test (+)
Defective nuclear maturation
with decreased production
Pernicious anemia
Or Low Serum Folate
Hemoglobin
Indices
RBC count
Peripheral
Blood
Smear
Low Hct, Low Hgb, Low
RBC, High MCV,
Red Cells
Morphology
Screening Procedure
Normoccytic
Anemia
Folate deficiency anemia
 Hct, Hgb,  reticulocyte
count,
Blood loss, renal failure
 Hgb,  Bilirubin,  relic
Coombs Test (+)
Microcytic
Hypochromic
Anemia
Hematolyte anemia
Autoimmune hymolysis
 Hct, Hgb,  MCV,
 Fe, MCHC,  TIBC
Fe:TIBC < 15%
Iron deficiency anemia

13. Iron deficiency anemia
The daily iron intake and stores are unable to
meet the RBC and other body tissue needs
2.5 g out of total 3.5 g found in Hgb
Only 0.5-1mg/day is lost
Menstruating women lose 0.5-2.5% more/day
Average diet contains 6mg Fe/1000Kcal.
We need 10-12 mg Fe/day
Menstruating, pregnant, and lactating mothers need 20mg Fe/day

14. Causes of iron deficiency anemia
Blood Loss
Menstruation, gastrointestinal (e.g., peptic ulcer), trauma
Decreased Absorption
Medications, gastrectomy, regional enteritis
Increased Requirement
Infancy, pregnant/lactating women
Impaired Utilization
Hereditary, Iron use

15. Predisposing Factors
A diet lacking in certain vitamins. iron, vitamin B-12 and
folate
Intestinal disorders. affects the absorption of nutrients:
Crohn's disease and celiac disease.
Menstruation.
Pregnancy.
Chronic conditions. cancer, kidney or liver failure or another
chronic condition
Family history.
Other factors. A history of certain infections, blood
diseases and autoimmune disorders, alcoholism, exposure to
toxic chemicals, and the use of some medications can affect
red blood cell production and lead to anemia.

16. A case approach understanding for iron deficiency anemia
A35-year-old woman, is seen in the clinic.
Chief complaints
include weakness, dizziness, and epigastric pain.
PMD
5-year history of peptic ulcer disease,
10-year history of heavy menstrual bleeding,
20-year history of chronic headaches.
FH
Patient has 3 children
Current Meds
Tetracycline (250 mg BID) for acne, ibuprofen (400 mg PRN)
headaches, and daily esomeprazole (40 mg).
Initial Physical Exam
Decreased exercise tolerance. Pale, lethargic, black woman appearing
older than her stated age. Her vital signs are within normal limits; HR100
beats/min. notable for pale nail beds and splenomegaly.

17. A case approach understanding for iron deficiency anemia
A35-year-old woman, is seen in the clinic.
Significant laboratory results
Hgb, 8 g/dL (normal, 14 to 18)
Hct, 27% (normal, 40% to 44%)
Platelet count, 800,000/mm3 (normal, 130,000 to 400,000)
Reticulocyte count, 0.2% (normal, 0.5% to 1.5%);
Mean corpuscular volume (MCV), 75 µm3 (normal, 80 to 94);
Mean corpuscular hemoglobin (MCH), 23 pg (normal, 27 to 31);
Mean corpuscular hemoglobin concentration (MCHC), 30% (normal, 33% to 37%);
Serum iron, 40 µg/dL (normal, 50 to 160);
Serum ferritin, 9 ng/mL (normal, 15 to 200);
Total iron-binding capacity (TIBC), 450 g/dL (normal, 250 to 400);
4+ guaiac stools (normal, negative).

18. A case approach understanding for iron deficiency anemia
What are the factors predisposing this patient to Iron Deficiency
Anemia?
Her history of heavy menstrual bleeding
The 4+ stool guaiac
The GI blood loss may be secondary to chronic use of nonsteroidal antiinflammatory drugs, recurrent peptic ulcer disease, or both.
Many women of childbearing age have a borderline iron deficiency that becomes
more evident during pregnancy because of the increased iron requirements.
Absorption of dietary iron may be compromised by her use of proton pump
inhibitors and tetracycline .

19. A case approach understanding for iron deficiency anemia
What subjective or objective signs, symptoms, and laboratory
tests are typical of this patient’s Iron Deficiency Anemia?
Subjective:
Weakness and dizziness could be a result of her severe anemia.
Generally, until the anemia is severe, such symptoms occur with equal
frequency in the nonanemic population.
Objective:
Increased heart rate, decreased exercise tolerance, and pale appearance are
consistent with tissue anoxia and the cardiovascular response that may be
seen in iron deficiency anemia.
Laboratory tests:
Low serum iron, low serum ferritin, and elevated TIBC are typical of the
laboratory findings associated with iron deficiency anemia

20. A case approach understanding for iron deficiency anemia
How can you manage this patient’s Iron Deficiency Anemia?
What is the dose of iron provided? and for how long?
Control of the underlying causes of anemia, which in this case are many:
Iron stores are low because of GI blood loss, multiple childbirths, heavy
menstrual flow, decreased dietary iron absorption, and perhaps, an inadequate
diet.
GI blood loss should be corrected, her dietary intake should be analyzed and
modified, and supplemental iron should be prescribed to replenish her stores
and correct the anemia.

21. A case approach understanding for iron deficiency anemia
How can you manage this patient’s Iron Deficiency Anemia?
What is the dose of iron provided? and for how long?
If no iron is being lost through bleeding, the required daily dose of elemental
iron can be calculated using a formula that assumes that 0.25 g/dL/day is the
maximal rate of hemoglobin regeneration.
Elemental iron (mg/d) = 0.25g Hgb/100mL blood/day.
(approx. 5000mL of Blood)
(3.4mg Fe/1g Hgb)

Daily elemental iron need is 42.5 mg Fe/day
Absorption rate for iron in iron deficient state is approx. 20%
Daily elemental iron oral intake should be approx. 2oomg/d.

22. A case approach understanding for iron deficiency anemia
How can you manage this patient’s Iron Deficiency Anemia?
What is the dose of iron provided? and for how long?
Ferrous Sulfate contains 20% elemental iron:
Daily ferrous sulfate dose is then 200X5 = 1000 mg FeSO4/day
Or 325mg TID.
What are the differences between different iron supplements?
The ferrous form of iron is absorbed three times more readily than the ferric
form. Although ferrous sulfate, ferrous gluconate, and ferrous fumarate are
absorbed almost equally, each contains a different amount of elemental iron.

23. A case approach understanding for iron deficiency anemia
The patient is asking if SR formulations will provide better
option, what would you tell her?
SR preparations fall into three groups:
(a) those claimed to increase GI tolerance or decrease side effects,
(b) those formulated to increase bioavailability,
(c) those with adjuvants claimed to enhance absorption.
These products can be given once daily, they increase compliance.
Claims that SR iron preparations cause fewer GI side effects have not
been substantiated by controlled studies. In fact, these products transport
iron past the duodenum and proximal jejunum, thereby reducing the
absorption of iron.
Poor absorption and poor hematologic responses might occur with ferrous
sulfate SR capsules, they should not be used for initial treatment.

24. A case approach understanding for iron deficiency anemia
The patient is asking if SR formulations will provide better
option, what would you tell her?
Adjuvants are incorporated into many iron preparations in an attempt to
enhance absorption or decrease side effects.
Products contain ascorbic acid (vitamin C), which maintains iron in the ferrous
state. Doses up to 1 g increase iron absorption by only 10%; however, smaller
doses of vitamin C (e.g., 100 mg) do not significantly alter iron absorption.
Stool softeners are added to iron preparations to decrease the side effect of
constipation. Generally, these combinations contain suboptimal doses of stool
softener and are unwarranted. If constipation does develop, appropriate doses
of stool softeners should be taken.
In general, generic preparations of iron salts without adjuvant agents provide the
best value.

25. A case approach understanding for iron deficiency anemia
What are the goals of therapy? How will you monitor her?
Normalize the Hgb and Hct concentrations and replete iron stores.
(a) If the doses of iron are adequate, the reticulocyte count will begin to
increase by the third to fourth day and peak by the seventh to tenth day
of therapy.
(b) By the end of the second week of iron therapy, the reticulocyte count
will fall back to normal.
(c) The Hgb response is a convenient index to monitor in outpatients.
(d) Hematologic response is usually seen in 2 to 3 weeks with a 1 g/dL
increase in hemoglobin and a 6% increase in the hematocrit

26. A case approach understanding for iron deficiency anemia
What are the goals of therapy? How will you monitor her?
(a) Anemia can be expected to resolve in 1 to 2 months; however, iron
therapy should be continued for 3 to 6 months after the hemoglobin is
normalized to replete iron stores.
(b) Therapy duration is related to the absorption pattern of iron.
(a) During the first month of therapy, as much as 35 mg of elemental
iron is absorbed from the daily dose.
(b) With time, the percentage of iron absorbed from the dose
decreases, and by the third month of therapy, only 5 to 10 mg of
elemental iron is absorbed.

27. A case approach understanding for iron deficiency anemia
What are the information that you need to provide to your
patient?
Oral iron therapy produces dark stools.
Take iron on an empty stomach.
Constipation does not appear to be dose related.
Oral iron therapy can be initiated with a single tablet of ferrous sulfate 325
mg/day; the dose is increased by increments of one tablet per day every 2
to 3 days until the full therapeutic dose of ferrous sulfate, 325 mg three
times daily, can be administered.

28. A case approach understanding for iron deficiency anemia
What are the information that you need to provide to your
patient?
Potential drug interactions
Proton pump inhibitor, inhibits serum iron absorption by increasing the pH
of the stomach and decreasing the solubility of ferrous salts.
Antacids can increase stomach pH and certain anions (carbonate and
hydroxide) also are thought to form insoluble complexes when combined with
iron.
What to do:
Take iron at least 1 hour before or 3 hours after the proton pump inhibitor
dose.
Absorptions of both iron and tetracycline are decreased when administered
concomitantly, the iron should be taken 3 hours before or 2 hours after the
tetracycline dose as well.

29. A case approach understanding for iron deficiency anemia
When would parenteral iron therapy be indicated for this
patient?
Failure to respond to oral iron therapy can be caused by:
1.
2.
3.
4.
5.
Nonadherence,
Misdiagnosis (e.g., inflammation),
Malabsorption : can be evaluated by measuring iron levels every 30 minutes for
2 hours after the administration of 50 mg of ferrous sulfate. If her plasma iron
levels increase by >50%, absorption is adequate.
Continuing blood loss equal to or greater than the rate of RBC production.
Other indications include intolerance to oral therapy, required antacid
therapy, or significant blood loss in patients refusing transfusion.
If malabsoription is documented, she would be a candidate for injectable
iron.

30. Megaloblastic anemia
It can have several causes:
(a) anemia associated with vitamin
B12 deficiency
(b) anemia associated with folic acid
deficiency
(c) anemia caused by metabolic or
inherited defects associated
with decreased ability to utilize
vitamin B12 or folic acid.
Megaloblastosis results from impaired
DNA synthesis in replicating cells,
which is signaled by a large immature
nucleus.
RNA and protein synthesis remain
unaffected, and the cytoplasm matures
normally.
Symptoms include fatigue; exaggeration of pre-existing cardiovascular
or pulmonary problems; a sore, pale, smooth tongue; diarrhea or
constipation; and anorexia. Edema and urticaria also may be present.

31. A case approach to vitamin B12 deficiency anemia
a 55-year-old woman,
Chief complains
Progressive confusion and lethargy 9 months ago.
A CBC at that time revealed only mild leukocytosis.
Today, she comes to the emergency department with a 4week history of frequent (three to five per day) stools
containing bright red blood.
She reports continued lethargy, dizziness, ataxia, and
paresthesias in her hands and feet.

32. A case approach to vitamin B12 deficiency anemia
a 55-year-old woman,
Laboratory findings of interest
Hgb, 12.8 g/dL (normal, 12 to 16);
MCV, 90 µm3 (normal, 76 to 100);
Iron, 150 mcg/dL (normal, 50 to 160);
B12, 94 pg/mL (normal, 200 to 1,000);
Folate, 21 ng/mL (normal, 7 to 25);
Bilirubin, 3.0 mg/dL (normal, 0.1 to 1.0);
Lactate dehydrogenase (LDH), 520 U/L (normal, 50 to 150).
A subsequent bone marrow aspirate demonstrates megaloblastic erythropoiesis, giant
metamyelocytes, and a low stainable iron.
A barium swallow and follow-through show numerous jejunal and duodenal diverticuli. Jejunal and
duodenal aspirates reveal aerobic and anaerobic bacterial overgrowth.

33. A case approach to vitamin B12 deficiency anemia
What signs, symptoms, and laboratory findings are
typical for vitamin B12 deficiency in this patient?
Signs and symptoms consistent with B12 deficiency include
confusion, dizziness, ataxia, and paresthesias. Other signs and
symptoms may be caused by other underlying conditions.
The patient initially presented with a mild leukocytosis.
Evaluation 9 months later shows a low Hgb, a low serum vitamin
B12 level,
Hypersegmented PMN.
The high LDH and bilirubin levels reflect intramedullary
hemolysis of megaloblastic RBC consistent with vitamin B12
deficiency, even though the MCV is within normal limits.

34. A case approach to vitamin B12 deficiency anemia
What signs, symptoms, and laboratory findings are typical for
vitamin B12 deficiency in this patient?
The presence of megaloblastic erythropoiesis and giant metamyelocytes in
the bone marrow also is consistent with vitamin B12 deficiency.
History of bloody stools and diverticuli suggests substantial long-term blood
loss, which increased demand for iron and vitamin B12 to replace RBC.
Concurrent iron deficiency can mask megaloblastic changes in RBC, which
explains the suspiciously normal MCV (dimorphic anemia).
The serum folate concentration is also falsely normal. Although the RBC
folate level is likely to be low, serum folate concentrations are normal because
monoglutamated folates leak from cells into the serum in vitamin B12 deficient
states

35. A case approach to vitamin B12 deficiency anemia
How should vitamin B12 deficiency be treated?
The cause of vitamin B12 malabsorption must be corrected before the patient
is given oral vitamin B12 therapy. Presence of diverticuli is not the cause of
vitamin B12 malabsorption because diverticuli typically do not extend into the
distal ileum. Instead, given patient's medical history, the most likely cause of
vitamin B12 malabsorption is bacterial usurpation of luminal vitamin B12.
Patient should first be treated with a broad-spectrum antibiotic (e.g.,
tetracycline) or a sulfonamide for 7 to 10 days, then begin daily oral vitamin
B12 supplementation to replenish her body stores. In this case, normal levels of
intrinsic factor permit oral therapy.
The recommended daily dose of vitamin B12 is 25 to 250 mcg.
Patient o should begin to absorb vitamin B12 in her diet after the antibiotic
therapy.

36. Pharmacottherapy
Anas Bahnassi PhD CDM CDE
abahnassi@gmail.com
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