clinical pharmacy-therapeutics of anemia

1. ANEMIA

2.  Definition
 Clinical manifestations
 Diagnosis
 Classifications
 Treatment

3. Anemias are a group of diseases characterized by a
decrease in hemoglobin(Hb) or the volume of red blood
cells (RBCs) , resulting in decreased oxygen-carrying
capacity of blood.

4.  Anemias are generally a sign of underlying pathology;
therefore, determining the cause of the anemia is
important
Possible consequences of chronic anemia include
reduced quality-of-life, decreased survival, and increased
risk of cardiac complications, neurologic dysfunction, and
surgical complications.
 Awareness of anemia, its detection, investigation, and
management must be raised.

5. Clinical presentation of anemia
■Patients may be asymptomatic or have vague
complaints.
■Patients with vitamin B12 deficiency may develop
neurologic consequences.
■In anemia of chronic disease, signs and symptoms
of the underlying disorder often overshadow those of
the anemia .

6. Symptoms
■Decreased exercise tolerance
■Fatigue
■Dizziness
■Irritability
■Weakness
■Palpitations
■Vertigo
■Shortness of breath
■Chest pain
■Neurologic symptoms in vitamin B12 deficiency
Signs
■Tachycardia
■Pale appearance (most prominent in conjunctivae)
■Decreased mental acuity
■Increased intensity of some cardiac valvular murmurs
■Diminished vibratory sense or gait abnormality in vitamin B1

7. Classification system of anemia

8. I. Morphology
Macrocytic anemias
Megaloblastic anemias
Vitamin B12 deficiency
Folic acid deficiency anemia
Microcytic hypochromic anemias
Iron-deficiency anemia
Genetic anomaly
Sickle cell anemia
Thalassemia
Other hemoglobinopathies (abnormal
hemoglobins)
Normocytic anemias
Recent blood loss
Hemolysis
Bone marrow failure
Anemia of chronic disease
Renal failure
Endocrine disorders
Myelodysplastic anemias

9. II. Etiology
Deficiency
Iron
Vitamin B12
Folic acid
Pyridoxine
Central, caused by impaired bone marrow
function
Anemia of chronic disease
Anemia of the elderly
Malignant bone marrow disorders
Peripheral
Bleeding (hemorrhage)
Hemolysis (hemolytic anemias)

10. III. Pathophysiology
Excessive blood loss
Recent hemorrhage
Peptic ulcer
Gastritis
Hemorrhoids
Chronic hemorrhage
Vaginal bleeding
Peptic ulcer
Intestinal parasites
Aspirin and other NSAID
Excessive RBC destruction
Drugs
Excessive sequestration in the
spleen
Heredity
Disorders of hemoglobin synthesis
Inadequate production of mature
RBCs
Deficiency of nutrients (B12
, folic acid, iron, protein)
Deficiency of erythroblasts
Aplastic anemia
Folic acid antagonists
Antibodies
Leukemia
Carcinoma
Endocrine abnormalities
Hypothyroidism
Adrenal insufficiency
Pituitary insufficiency
Chronic renal disease
Chronic inflammatory disease
Collagen vascular diseases
Hepatic disease

11. DIAGNOSIS OF ANEMIA
History, physical examination and laboratory testing
are used in the evaluation of anemia

12. LABORATORY EVALUATION
1. RBC production failure (hypoproliferative)
2. Cell maturation ineffectiveness
3. Increase in RBC destruction

14. Hemoglobin
Hb represent the amount of Hb per volume of whole
blood.
 The higher values seen in males are due to stimulation
of RBC production by androgenic steroids, whereas the
lower values in females are due to decrease in Hb as a
result of blood loss during menstruation.
 The Hb estimate of the oxygen-carrying capacity of
blood.
 Hb levels may be diminished because of a decreased
quantity of Hb per RBC or because of a decrease in the
actual number of RBCs.
 In pregnancy Hb may not reflect red cell mass
changes.

15. Hematocrit
Expressed as a percentage.
 hematocrit (Hct) is the actual volume of RBCs in a
unit volume of whole blood .
abnormal cell size or shape and indicates the
pathology.
 A low Hct indicates a reduction in either the number
or the size of RBCs or an increase in plasma volume.
The RBC count is an indirect
estimate of the Hb content of the
blood; it is an actual count of
RBCs per unit of blood.

16. Red Blood Cell Indices
indices describe the size and Hb content of the RBCs
and are calculated from the Hb, Hct, and RBC count.
RBC indices, such as mean corpuscular volume (MCV)
and mean corpuscular Hb (MCH), are single mean
values that do not express the variation that can occur
in cells.
.

17. Mean Corpuscular Volume (Hct/RBC Count)MCV
represents the average volume of RBCs.
It may reflect changes in MCH, but it can be confounded.
Cells are considered macrocytic if they are larger than normal,
microcytic if they are smaller than normal, and normocytic if their
size falls within normal limits.
Folic acid and vitamin B12 deficiency anemias yield macrocytic
morphology, whereas iron deficiency and thalassemia are
examples of microcytic anemias.
MCV is falsely elevated in the presence of cold agglutinins and
hyperglycemia.
When IDA (decreased MCV) is accompanied by folate deficiency
(increased MCV), failure to understand that the MCV represents an
average RBC size creates the potential for overlooking the real
cause of the anemia.

18. Mean Corpuscular Hemoglobin (Hb/RBC Count)MCH
Is defined as the volume of Hb in an RBC.
It reflects the adequacy of iron supply to developing
erythron.
Two morphologic changes, microcytosis and
hypochromia, can reduce MCH .

19. Mean Corpuscular Hemoglobin Concentration
(Hb/Hct)
The weight of Hb per volume of cells is the mean
corpuscular Hb concentration (MCHC).
Because MCHC is independent of cell size, it is more
useful than MCH in distinguishing between
microcytosis and hypochromia.
A low MCHC always indicates hypochromia; a
microcyte with a normal Hb concentration will have a
low MCH but a normal MCHC.
A decreased MCHC is seen most often in
association with IDA.

20. Total Reticulocyte Count
Although an indirect assessment, the total reticulocyte
count is an indication of new RBC production.
It measures how quickly immature RBCs
(reticulocytes) are produced by bone marrow and
released into the blood.
the reticulocyte count usually are low.
Reticulocytes circulate in the blood approximately 2
days before maturing into RBCs

21. Red Blood Cell Distribution Width
The higher the red blood cell distribution width (RDW),
the more variable the size of the RBCs.
The RDW increases in early IDA because of the release
of large, immature, nucleated RBCs to compensate for
the anemia, but this change is not specific for IDA.
The RDW also can be helpful in the diagnosis of a mixed
anemia. A patient can have a normal MCV yet have a
wide RDW.
This finding indicates the presence of microcytes and
macrocytes, which would yield a “normal” average RBC
size.

22. Serum Iron
The level of serum iron is the concentration of iron bound to
transferrin. Normally, transferrin is approximately one-third bound
(saturated) to iron.
Total Iron-Binding Capacity
An indirect measurement of the iron-binding capacity of serum
transferrin, TIBC evaluation is performed by adding an excess
of iron to plasma to saturate all transferrin with iron .
Folic Acid
The results of folic acid measurements vary depending on the
assay method used.
Vitamin B12
Low levels of vitamin B12(cyanocobalamin) indicate vitamin B12
deficiency.

23. Coombs Test
Antiglobulin tests, also called Coombs tests ,
indicate hemolytic anemia caused by an immune
response.
Schilling Test
The purpose of the rarely used Schilling urinary
excretion test is to diagnose vitamin B12 deficiency
anemia caused by a B12 absorption defect resulting
from a lack of intrinsic factor (pernicious anemia) .

24. Erythropoietin Levels
Healthy individuals require 10 to 30 milliunits/mL of EPO to
maintain normal Hb and Hct concentrations

25. Homocysteine
Vitamin B12 and folate both are required for conversion of
homocysteine to methionine. Increased serum homocysteine
may suggest vitamin B12 or folate deficiency.
Homocysteine levels also can be elevated in patients with
vitamin B6 deficiency, renal failure and hypothyroidism .
Methylmalonic Acid
A vitamin B12 coenzyme is needed to convert methylmalonyl
coenzyme A to succinyl coenzyme A. Patients with vitamin B12
Deficiency may have increased concentrations of serum
methylmalonic acid (MMA), which is a more specific marker for
vitamin B12 deficiency .

26. ■Hb, hematocrit (Hct), and RBC indices may remain normal early in
the disease and then decrease as the anemia progresses .
■Serum iron is low in IDA and ACD .
■Ferritin levels are low in IDA and normal to increased in ACD
■TIBC is high in IDA and is low or normal in ACD .
■Mean corpuscular volume is elevated in vitamin B12 deficiency and
folate deficiency .
■Vitamin B12 and folate levels are low in their respective types of
anemia .
■Homocysteine is elevated in vitamin B12 deficiency and folate
deficiency .
■Methylmalonic acid is elevated in vitamin B12 deficiency .

28. Anemia therapeutics

29. IRON-DEFICIENCY ANEMIA
• Oral iron therapy with soluble ferrous iron salts, which are not enteric
coated and not slow- or sustained-release, is recommended at a daily
dosage of 200 mg elemental iron in two or three divided doses .
Slow-release or sustained-release iron preparations do not undergo
sufficient dissolution until they reach the small intestines, which
significantly reduces iron absorption and can attenuate the hematinic
effects .
• Diet plays a significant role because iron is poorly absorbed from
vegetables, grain products, dairy products, and eggs; iron is best
absorbed from meat, fish, and poultry.
Meat, orange juice, and other ascorbic acid–rich foods should be
included with meals, whereas milk and tea should be consumed in
moderation between meal
Adverse reactions dark discoloration of feces, constipation or diarrhea,
nausea, and vomiting .

30. • Parenteral iron may be required for patients with iron
malabsorption, intolerance of oral iron therapy, or
noncompliance.
The replacement dose depends on etiology of anemia
and Hb concentration
• Available parenteral iron preparations have similar
efficacy but different pharmacologic, pharmacokinetic,
and safety profile.
The newer products, sodium ferric gluconateand iron
sucrose, appear to be better tolerated than iron dextran.

31. Comparison of Parenteral Iron Preparations

32. Equations for Calculating Doses of
Parenteral Iron

33. Drugs That Decrease Iron Absorption
Al-, Mg-, and Ca+2 -containing antacids
Tetracycline and doxycycline
Histamine2 antagonists
Proton pump inhibitors
Cholestyramine
Object Drugs Affected by Iron
Levodopa↓ (chelates with iron)
Methyldopa↓ (decreases efficacy of methyldopa)
Levothyroxine↓(decreased efficacy of Levothyroxine)
Fluoroquinolones↓(forms ferric ion– quinolone complex)
Tetracycline and doxycycline ↓(when administered within 2
hours of iron salt)

34. TRANSFUSIONS
indicated in acute situations of blood loss when hemodynamic
support is needed.
Once Hct decreases to <30%, the oxygen-carrying capacity in
patients with coronary disease is dangerously compromised,
and ischemia can occur.
patients who have developed low Hct values over extended time
periods, These patients often demonstrate cardiac compromise
after transfusion despite Hct levels in the 20% range.
These patients should receive iron therapy , followed by
transfusion only if necessary.

35. VITAMIN B12-DEFICIENCY ANEMIA
The goals of treatment for vitamin B12 deficiency include reversal
of hematologic manifestations, replacement of body stores, and
prevention or resolution of neurologic manifestations .
Oral cobalaminis initiated at 1 to 2 mg daily for 1 to 2 weeks,
followed by 1 mg daily.
• Oral vitamin B12 supplementation appears to be as effective as
parenteral, even in patients with pernicious anemia, because the
alternate vitamin B 12 absorption pathway is independent of
intrinsic factor, but in much larger doses than those used to treat
other causes of vitamin B 12 deficiency .

36. • Parenteral therapy is more rapid acting than oral therapy
and should be used if neurologic symptoms are present.
A popular regimen is cyanocobalamin 1,000 mcg daily for 1
week, then weekly for 1 month, and then monthly.
When symptoms resolve, daily oral administration can be
initiated.
• Adverse events are rare with vitamin B 12 therapy,
Uncommon side effects include hyperuricemia and
hypokalemia due to marked increase in potassium utilization
during production of new hematopoietic cells.

37. FOLATE-DEFICIENCY ANEMIA
folic acid deficiency include inadequate intake, decreased
absorption, hyperutilization, and inadequate utilization .
Hyperutilization of folic acid may occur when the rate of cellular
division is increased, as seen in pregnant women; patients with
hemolytic anemia, myelofibrosis, malignancy, chronic
inflammatory disorders such as Crohn disease, rheumatoid
arthritis, or psoriasis; patients undergoing long-term dialysis;
burn patients; and
in adolescents and infants during their growth spurts .

38. Dose: Oral folate1 mg daily for 4 months is usually sufficient for
treatment of folate-deficiency anemia, unless the etiology cannot
be corrected.
If malabsorption is present, the daily dose should be increased to
5 mg.
Several drugs have been reported to cause a folic acid deficiency
megaloblastic anemia. Some drugs (e.g., azathioprine, 6-
mercaptopurine, 5-fluorouracil, hydroxyurea, and zidovudine) directly
inhibit DNA synthesis.
Other drugs are folate antagonists; the most toxic is methotrexate
(other examples include trimethoprim, and triamterene).
A number of drugs (e.g., phenytoin and phenobarbital ) antagonize
folate via poorly understood mechanisms but are thought to reduce
vitamin absorption by the intestine

39. humans are unable to synthesize sufficient folate to meet total
daily requirements, they depend on dietary sources.
Major dietary sources of folate include fresh, green, leafy
vegetables, citrus fruits, yeast, mushrooms, dairy products, and
animal organs such as liver and kidney
Because the body stores approximately 5 to 10 mg of
folate, primarily in the liver, cessation of dietary folate
intake can result in megaloblastosis within 4 to 5 months.
Periconceptional folic acid supplementation is
recommended to decrease the occurrence and recurrence of
neural tube defects, specifically anencephaly and spina bifida.

40. Hemolytic anemia

41. Hemolytic anemia results in decreased survival time of
RBCs secondary to destruction in the spleen or
circulation.
Hemolytic anemias usually are normocytic and
normochromic, with increased levels of reticulocytes,
lactate dehydrogenase, and indirect bilirubin.
Treatment is directed toward correcting or controlling the
underlying pathology.

42. Common classes of hemolytic anemia

43. • Treatment of hemolytic anemia should focus on
correcting the underlying cause.
There is no specific therapy for G6PD deficiency, so
treatment consists of avoiding oxidant medications
and chemicals.
Steroids, other immunosuppressants, and even
splenectomy can be indicated to reduce RBC
destruction.

45. Patients with sickle cell disease( SCD) require lifelong
multidisciplinary care.
All patients should receive regularly scheduled comprehensive
medical evaluations.
The goal of comprehensive care is to reduce hospitalizations,
complications, and mortality.
Because of the complexity of the disease, a multidisciplinary
team is needed to provide medical care, education, counseling,
and psychosocial support.
Appropriate comprehensive care can have a positive impact on
both longevity and general quality of life. This care includes the
use of traditional prophylactic and general symptomatic
supportive care and the use of newer, more specific therapies
aimed at altering hematologic capacity and function.

46. Treatment for patients with SCD involves the use of
general measures to meet the unique demands for
increased erythropoiesis.
Additional interventions can be aimed at preventing or
treating complications of the disease.
When crises occur, the type and severity of the crisis
determine the appropriate therapeutic plan .

47. Hemolysis and Vaso-occlusion
Vaso-occlusion:
Occurs when the rigid
sickle shaped cells fail to
move through the small
blood vessels, blocking
local blood flow to a
microscopic region of
tissue. Amplified many
times, these episodes
produce tissue hypoxia.
The result is pain, and
often damage to organs.
Hemolysis:
The anemia in SCD is
caused by red cell
destruction, or hemolysis,
and the degree of anemia
varies widely between
patients. The production of
red cells by the bone
marrow increases
dramatically, but is unable
to keep pace with the
destruction.

49. Hemolysis and Vaso-occlusion
Acute Manifestations:
 Bacterial Sepsis or
meningitis*
 Recurrent vaso-occlusive
pain (dactylitis, muscoskeletal
or abdominal pain)
 Splenic Sequestration*
 Aplastic Crisis*
 Acute Chest Syndrome*
 Stroke*
 Priapism
 Hematuria, including papillary
necrosis
Chronic Manifestations:
 Anemia
 Jaundice
 Splenomegaly
 Cardiomegaly and functional
murmurs
 Proteinemia
 Cholelithiasis
 Delayed growth and sexual
maturation
 Restrictive lung disease*
 Pulmonary Hypertension*
 Avascular necrosis
 Proliferative retinopathy
 Leg ulcers
 Transfusional hemosiderosis*
*Potential cause of mortality

50. TREATMENT
GENERAL PRINCIPLES
• Patients with SCD require lifelong multidisciplinary care.
Interventions include general measures, preventive strategies,
and treatment of complications and acute crises.
• Patients with SCD should receive routine immunizations plus
influenza, meningococcal, and pneumococcal vaccinations.
• Prophylactic penicillinis recommended for children with SCD
until they are 5 years old. Beginning at age 2 months or earlier,
the dosage is penicillin V potassium, 125 mg orally twice daily
until 3 years of age and then 250 mg twice daily until age 5
years, or benzathine penicillin, 600,000 units intramuscularly
every 4 weeks from age 6 months to 6 years.
• Folic acid, 1 mg daily, is recommended in adult patients.

51. FETAL HEMOGLOBIN (HbF) INDUCERS
Increases in HbF correlate with decreased RBC sickling
and adhesion. Patients with low HbF levels have more
frequent crises and higher mortality.
• Hydroxyurea, a chemotherapeutic agent, has many
effects on blood cells, including the stimulation of HbF
production.
It is indicated for patients with frequent painful episodes,
severe symptomatic anemia, acute chest syndrome, or
other severe vasoocclusive complications.
The dosage should be individualized based on response
and toxicity.

52. TREATMENT OF COMPLICATIONS
• Patients should be educated to recognize conditions that
require urgent evaluation.
To avoid exacerbation during acute illness, patients should
maintain balanced fluid status and oxygen saturation of at
least 92%.
• RBC transfusions are indicated for acute exacerbation of
baseline anemia (e.g., aplastic crisis, hepatic or splenic
sequestration, severe hemolysis), severe vasoocclusive
episodes, and procedures requiring general anesthesia or
ionic contrast .

53. Fever of 38.5°C (101.3°F) or higher should be evaluated
promptly. A low threshold for empiric antibiotic therapy with
coverage against encapsulated organisms is recommended
(e.g., ceftriaxonefor outpatients and cefotaximefor inpatients).
• Patients with acute chest syndrome should receive incentive
spirometry; appropriate fluid therapy; broad-spectrum
antibiotics including a macrolideor quinolone; and, for hypoxia
or acute distress, oxygen therapy.
Steroids and nitric oxide are being evaluated.
• Priapism has been treated with analgesics, antianxiety
agents, and vasoconstrictors to force blood out of the corpus
cavernosum (e.g., epinephrine), and vasodilators to relax
smooth muscle (e.g., hydralazine).

54. TREATMENT OF SICKLE CELL CRISIS
• Treatment is primarily supportive. Blood transfusions may be indicated for
severe or symptomatic anemia. Antibiotic therapy is not warranted because the
most common etiology is viral, not bacterial, infection.
• Treatment options for splenic sequestrationinclude observation alone,
especially for adults because they tend to have milder episodes; chronic
transfusion to delay splenectomy; and splenectomy after a life-threatening
crisis, after repetitive episodes, or for chronic hypersplenism.
• Hydration and analgesics are the mainstays of treatment for vasoocclusive
(painful) crisis. Fluid replacement should be 1.5 times the maintenance
requirement, can be administered IV or orally, and should be monitored to avoid
volume overload. An infectious etiology should be considered; if appropriate,
empiric therapy should be initiated.

55. • Mild to moderate pain should be treated with nonsteroidal
antiinflammatory drugs or acetaminophen.
• Severe pain should be treated aggressively with an opioid, such as
morphine, hydromorphone, fentanyl,and methadone. Moderate pain
should be treated with a weak opioid, such as codeineor
hydrocodone.
• Severe pain should be treated with an IV opioid titrated to pain
relief and then administered on a scheduled basis with as-needed
dosing for breakthrough pain. Patient-controlled analgesia is
commonly utilized.
• Suspicion of addiction commonly leads to suboptimal pain control.
Factors that minimize dependence include aggressive pain control,
frequent monitoring, and tapering medication according to response.

56. Glucose-6-phosphate dehydrogenase
(G6PD) deficiency

57. A hereditary condition, drug-induced oxidative hemolytic anemia,
most often accompanies a glucose-6-phosphate dehydrogenase
(G6PD) enzyme deficiency, but it can occur because of other
enzyme defects .
A G6PD deficiency is a disorder of the hexose monophosphate
shunt, which is responsible for producing NADPH in RBCs,
which in turn keeps glutathione in a reduced state.
Reduced glutathione is a substrate for glutathione peroxidase,
an enzyme that removes peroxide from RBCs, thus protecting
them from oxidative stress.
Without reduced glutathione, oxidative drugs can oxidize
the sulfhydryl groups of hemoglobin, removing them prematurely
from the circulation (i.e., causing hemolysis).

58. Although severe hemolysis is rare, any drug that places
oxidative stress on RBCs can cause drug-induced
oxidative hemolytic anemia.
One case of drug-induced oxidative hemolytic anemia
has been reported in a child when dapsone (an oxidizing
agent) was transferred through the breast milk of the
mother, who was taking the drug.

60. ANEMIA OF CHRONIC DISEASE
Anemia of chronic disease is a diagnosis of exclusion, It results
from chronic inflammation, infection, or malignancy and can occur as
early as 1 to 2 months after the onset of these processes.
The serum iron level usually is decreased, but in contrast to IDA , the
serum ferritin concentration is normal or increased and TIBC is normal
or decreased.
• Treatment of anemia of chronic disease is less specific than that of
other anemias and should focus on correcting reversible causes
. Iron therapy is not effective when inflammation is present.
RBC transfusions are effective but should be limited to episodes
of inadequate oxygen transport and Hb of 8 to 10 g/dL .

61. • Epoetin alfa (recompinant human erythropoitin)can be considered,
especially if cardiovascular status is compromised, but the
response can be impaired in patients with anemia of chronic
disease (off-label use).
The initial dosage is 50 to 100 units/kg three times weekly.
If Hb does not increase after 6 to 8 weeks, the dosage can be
increased to 150 units/kg three times weekly.
• Epoetin alfa is usually well tolerated. The hypertension seen in
patients with end-stage kidney disease is less common in patients
with acquired immune deficiency syndrome.

62. Diseases Causing Anemia of Chronic
Disease
Less common causes
Alcoholic liver disease
Congestive heart failure
Thrombophlebitis
Chronic obstructive pulmonary
disease
Ischemic heart disease
Common causes
Chronic infections
Tuberculosis
HIV
Subacute bacterial endocarditis
Osteomyelitis
Chronic UTI
Chronic inflammation
Rheumatoid arthritis
SLE
Inflammatory bowel disease
Inflammatory osteoarthritis
Gout
Chronic inflammatory liver diseases
Malignancies

63. OTHER TYPES OF ANEMIAS
• Patients with other types of anemias require appropriate
supplementation depending on the etiology of anemia.
• In patients with anemia of critical illness, parenteral iron is often utilized
but is associated with a theoretical risk of infection.
Routine use of epoetin alfa or RBC transfusions is not supported by
clinical studies.
• Anemia of prematurity is usually treated with RBC transfusions. The
use of epoetin is controversial.
• In the pediatric population, the daily dose of elemental iron,
administered as iron sulfate, is 3 mg/kg for infants and 6 mg/kg for older
children for 4 weeks.
If response is seen, iron should be continued for 2 to 3 months. The
dose and schedule of vitamin B 12 should be titrated according to
clinical and laboratory response.
The daily dose of folate is 1 to 3 mg.

64. EVALUATION OF THERAPEUTIC OUTCOMES
In iron-deficiency anemia, iron therapy should cause reticulocytosis
in 5 to 7 days and raise Hb by 2 to 4 g/dL every 3 weeks.
The patient should be reevaluated if reticulocytosis does not occur
or if Hb does not increase by 2 g/dL within 3 weeks.
Iron therapy is continued until iron stores are replenished, which
usually requires at least 3 to 6 months.
bleeding may require iron replacement therapy
for only 1 month after correction of the underlying lesion.

65. In megaloblastic anemia, signs and symptoms usually improve
within a few days after starting vitamin B12 or folate therapy.
 Neurologic symptoms can take longer to improve or can be
irreversible, but they should not progress during therapy.
 Reticulocytosis should occur within 2 to 5 days.
A week after starting vitamin B12 therapy, Hb should rise and
leukocyte and platelet counts should normalize .
A CBC count and serum cobalamin level usually are drawn 1 to 2
months after initiation of therapy and 3 to 6 months thereafter for
surveillance monitoring .

66. Slow response to therapy or failure to observe
normalization of laboratory results may suggest the
presence of an additional abnormality such as iron
deficiency, thalassemia trait, infection, malignancy, or
misdiagnosis .

67. Folic acid
Symptomatic improvement, as evidenced by increased alertness,
appetite, and cooperation, often occurs early during the course of
treatment.
Reticulocytosis occurs within 2 to 3 days and peaks
within 5 to 8 days after beginning therapy. Hct begins to rise within 2
weeks and should reach normal levels within 2 months.
MCV initially increases because of an increase in reticulocytes but
gradually decreases to normal .

68. In anemia of chronic disease, reticulocytosis should occur a few
days after starting epoetin alfa therapy.
Iron, TIBC, transferrin saturation, or ferritin levels should be
monitored periodically because iron depletion is a major reason for
treatment failure.
If clinical response does not occur by 8 weeks, epoetin should be
discontinued.