agents of anemia

Question 1

oral route of iron therapy- drugs ? how long ? what enhances it ?

Answer 1

Ferrous iron Fe2+ is best absorbed:
• Ferrous sulfate
• Ferrous gluconate
• Ferrous fumarate

Treat for 3-6 months after correction of the cause .
Ascorbic acid co-administered for optimal
absorption.

Question 2

parenteral route for iron absorption - PK ? drugs ? who do you give it to ?

Answer 2

• Chronic renal failure patients have a high iron
requirement.
• Parenteral iron is given to hemodialysis patients (in
combination with erythropoietin).
> also for people who dont respond to oral iron therapy

• Iron dextran – highest risk of type I
hypersensitivity reaction
• Sodium ferric gluconate complex
• Iron sucrose

Question 3

AE of iron therapy

Answer 3

• Black stools
• GI upset:
• Nausea
• Epigastric discomfort
• Abdominal cramps
• Constipation
• Diarrhea
--> can confound results of gastrointestinal bleeding

Question 4

acute iron toxicity effects on body ?

Answer 4

• Direct GI tract irritation:
• acute vomiting
• diarrhea
• abdominal pain
• mucosal ulceration and bleeding

Question 5

pathogenesis of acute iron toxicity

Answer 5

• Free iron disrupts critical cellular
processes, resulting in:
• Metabolic acidosis.
• Widespread organ toxicity which can
progress to shock, coma then death.

Question 6

acute iron toxicity dignosis

Answer 6

• Historical suspicion of ingestion.
• Abdominal radiographs often demonstrate
radio-opaque pills in the stomach.

Question 7

Acute Iron Toxicity - Treatment

Answer 7

• Note that activated charcoal is ineffective as
it does not bind iron.
• Treatment includes supportive care and iron
chelators

Deferoxamine
• Given IV to bind systemic iron.
• Promotes iron excretion in urine and feces.
• Indicated in moderate to severe iron toxicity.

Deferasirox
• Oral preparation.
• Only effective at reducing iron absorption if
given within one hour of iron ingestion.

Question 8

when does Chronic Iron Toxicity occur ? pro oxidant effect ? treatment ?

Answer 8

in • Inherited hemochromatosis and patients requiring
frequent blood transfusions (e.g. thalassemia
major).

Pro-oxidant effect:
• Cardiomyopathy
• Cirrhosis
• “Bronze Diabetes”

Chronic Iron Toxicity Treatment
Deferasirox –> Outpatient iron chelation in transfusion
dependent individuals.

for patients who dont require transfusions –> treatment is simple phlebotomy

Question 9

Vitamin B12 Deficiency Causes

Answer 9

• Insufficient ingestion :
• Vegan diet without B12 supplementation.

Defects in absorption of cobalamin :
• Autoimmune disease – Pernicious anemia
• Surgery – gastrectomy, ileal resection
• Small bowel disease – Crohn’s, Coeliac
disease, fish tapeworm infestation

Drugs inhibiting absorption of B12:
• metformin, neomycin – alter gut microflora
• nitrous oxide anesthesia – converts
cob(I)alamin to the inactive form cob(III)alamin
• proton pump inhibitors, histamine 2 receptor
antagonists – increase gastric pH

Question 10

Vitamin B12 Deficiency Presentation

Answer 10

Neurologic changes:
• Paresthesias in early disease.
• Subacute Combined Degeneration (SCD) of the
spinal cord due to abnormal myelin synthesis.
• Prolonged deficiency = irreversible nerve damage.

Skeletal changes
• Suppression of osteoblast activity may lead to
an increased risk of osteoporosis.

Question 11

Vitamin B12 Deficiency Lab Studies

Answer 11

• CBC & Peripheral Blood Smear
• Megalobastic, macro-ovalocytotic anemia
• Leukopenia and/or thrombocytopenia.

Serum vitamin B12 levels
• Reduced

Antibodies against intrinsic factor
• Positive in in pernicious anemia

Serum homocysteine
• Increased

Serum methylmalonate
• Increased

• Serum methylmalonyl-CoA levels
• Increased

Question 12

Folate Deficiency Risk Factors

Answer 12

• Advanced age
• Pregnancy
• Chronic hemolytic anemias eg. sickle cell anemia
• Alcohol abuse
• Impairs the enterohepatic circulation of folate within
four days and can lead to megaloblastosis within 5 to 10 weeks

Question 13

folate deficiency causes

Answer 13

methotrexate
phenytoin
trimethoprim
pyrimethamine

Question 14

Folate Deficiency Presentation

Answer 14

• Clinical features of anemia.
• No neurological signs or symptoms in contrast with
cobalamin deficiency.
• Fetal neural tube defects in the first trimester of
pregnancy.

Question 15

Folate Deficiency Lab Studies

Answer 15

CBC & Peripheral Blood Smear
• Macrocytic, megaloblastic anemia

Serum/ red cell folate levels
• Decreased

Serum homocysteine level
• Increased

Serum methylmalonate levels
• Normal

Question 16

Folate Therapy

Answer 16

• Folic acid given orally for 1– 4 months or
until complete hematological recovery
occurs
Should NEVER be initiated in isolation in persons
with a macrocytic, megaloblastic anemia.
• Both hydroxocobalamin and folic acid should be
started until serum assays of methylmalonate are
available to determine whether vitamin B12
deficiency is present

 Prophylactic supplementation should be given to
persons with the following risk factors :
• Pregnancy
• Alcohol dependence
• Hemolytic anemia
52
• Liver disease
• Exfoliative skin disease
• Renal dialysis

Question 17

erythrocyte growth factors ? PK? PD? AE

Answer 17

derbepoetin - ocne a week
erythropoeitin (epoetin alfa)-IV- 3 times a week

they both act via JAK/STAT receptor binding leading to 1) stimulation of erythroid proliferation and differentation
2) induction of reticulocyte release from bone marrow

given to pateints with chronic renal failure and bone marrow suppression

AE–> HTN, thrombosis

Question 18

Myeloid growth factors

Answer 18

filgrastim (G-CSF)
Sargramostim (GM-CSF)

for cancer chemotherapy nutropenia and bone marrow suppression

AE–> bone pain but filgrastim is better tolerated

Question 19

megakaryocyte growth factor ?

Answer 19

interleukin 11

acts via cell surface cytokine receptor
stimulate the growth of primitive megakaryocyte progenitors
incres count of peripheral platelets and neurtophils

reduces the need fro platelet transfusion in chemotherapy recipients with prior episodes of thrombocytopenia

Question 20

treatment for Sickle cell

Answer 20

hydroxyurea

increases HbF
decre expression of neutropihl adhesion molecule
increases production of endothelial NO