Agents Used in Anemia

Question 1

What is anemia?

Answer 1

Reduction in red cell mass

Question 2

What is the role of Iron in anemia?

Answer 2

Stored in intestinal mucosal cells as ferritin until needed by the body
Deficiency:
–results from acute or chronic blood loss
–insufficient intake during periods of accelerated growth in children, heavy menstruation or pregnant women
Iron deficiency is Hypochromic Microcytic Anemia

Question 3

How do you treat iron deficiency?

Answer 3

Oral or parenteral iron preparations

–dont use oral if malabsorption is causing the problems

Question 4

What are the oral iron therapies available?

Answer 4

Ferrous Iron is most efficiently absorbed, therefore only ferrous iron salts should be used
Ferrous sulfate, ferrous gluconate and ferrous fumarate can all be used
–patients taking oral iron can develop black stools

Question 5

What are the parenteral iron therapies?

Answer 5

Used in patients who are unable to tolerate or absorb oral iron and for patients with extensive chronic anemia who cannot be maintained with oral iron alone
–iron dextran, sodium ferric gluconate complex and iron sucrose

Question 6

Acute iron toxicity is seen exclusively in young children who ingest iron tablets. What are the symptoms in these kids?

Answer 6

Necrotizing Gastroenteritis with vomiting, abd pain and bloody diarrhea followed by shock, metabolic acidosis, coma and death

Question 7

What is the treatment for acute iron toxicity?

Answer 7

1. Bowel Irrigation

2. Deferoxamine (iron chelator): binds iron and promote its excretion in urine and feces

Question 8

What is chronic iron toxicity?

Answer 8

Aka hemochromatosis
–excess iron is deposited in the heart, liver, pancreas, and other organs.
Occurs usually in inherited hemochromatosis: excessive iron absorption and in patients who receive many red cell transfusions over a long period

Question 9

What is the treatment for chronic iron toxicity?

Answer 9

without anemia use phlebotomy

Iron chelation therapy using IV deferoxamine or deferasirox used to retard accumulation of iron

Question 10

Moving on to vitamin B12 what does deficiency in this lead to?

Answer 10

Vit B12 (Cobalamin)
--leads to megaloblastic anemia and neurologic abnormalities

Question 11

What are the active forms and the forms found in food in terms of vit B12?

Answer 11

Deoxyadenosylcobalamin and Methylcobalamin
–active forms in the human
Cyanocobalamin and Hydroxocobalamin
–found in food and converted to active form
Ultimate source is from microbial synthesis in meat, eggs and dairy products

Question 12

What are some of the pharmacokinetics for vitamin B12?

Answer 12

Stored in the liver
takes 5 years for all the stored vitamin B12 to be exhausted and for megaloblastic anemia to occur
Vitamin B12 is absorbed only after it complexes with intrinsic factor (glycoprotein secreted by the parietal cells of the gastric mucosa)
Complex is absorbed in the distal ileum by a receptor mediated transport system

Question 13

Vitamin B12 deficiencies are usually do to what?

Answer 13

Malabsorption of B12 due to
–lack of intrinsic factor or
–loss or malfunction of the transporter in the distal ileum
Nutritional deficiency is rare
Excessive B12 again is stored in the liver

Question 14

There are two essential enzymatic reactions in humans require vitamin B12. What is the first?

Answer 14

Methylcobalamin serves as an intermediate in the transfer of a methyl group from N5-methyltetrahydrofolate to homocysteine, forming methionine.
–in the process, N5-Methyltetrahydrofolate is converted to tetrahydrofolate, the precursor of folate cofactors

Question 15

As a result, a deficiency of folate cofactors necessary for several biochemical reactions involving the transfer of one carbon group develops. In particular depletion of tetrahydrofolate prevents what?

Answer 15

Synthesis of adequate supplies of the dTMP and purines required for DNA synthesis in rapidly dividing cells

Question 16

The accumulation of folate as N5-methyltetrahydrofolate and the associated depletion of tetrahydrofolate cofactors in vitamin B12 are called what?

Answer 16

Methylfolate trap
–this is the step where vitamin B12 and folic acid metabolism are linked and it explains why the megaloblastic anemia of vitamin B12 deficiency can be partially corrected by ingestion of large amounts of folic acid.

Question 17

Administration of folic acid in the setting of vitamin B12 deficiency will not prevent neurologic manifestations, but what will it due?

Answer 17

Largely correct the anemia caused by the vitamin B12 deficiency

Question 18

What is the second reaction that required vitamin B12?

Answer 18

Isomerization of methylmalonyl-CoA to succinyl-CoA by the enzyme methylmalonyl-CoA mutase
–therefore methylmalonyl-CoA and methylmalonate accumulate

Question 19

What is the most characteristic clinical manifestation of vitamin B12?

Answer 19

Megaloblastic, macrocytic anemia

-the neurologic syndrome usually begins with paresthesias in peripheral nerves and weakness

Question 20

Once a diagnosis of megaloblastic anemia is made, it must be determined whether vitamin B12 or folic acid deficiency is the cause

Answer 20

done through serum levels

Question 21

Folic acid can partially reverse some of the hematologic abnormalities of vitamin B12 deficiency and thus mask the B12 deficiency. As a consequence, what happens?

Answer 21

Neurologic complications of untreated vitamin B12 deficiency will proceed to severe neurologic dysfunction

Question 22

If initiation of treatment is urgently required, blood samples should be obtained for the appropriate assays and the patient should be treated how??

Answer 22

With both folic acid and vitamin B12

Question 23

What is the most common vitamin B12 deficiency?

Answer 23

Pernicious Anemia
Other causes: partial or total gastrectomy, and conditions that affect the distal ileum, such as malabsorption syndromes, inflammatory bowel disease or small bowel resection

Question 24

Pernicious anemia results form what?

Answer 24

Defective secretion of intrinsic factor by the gastric mucosal cells

Question 25

Vitamin B12 deficiency also occurs when the region of the distal ileum that absorbs the vitamin b12 intrinsic factor is damaged, as when?

Answer 25

the ileum is involved with inflammatory bowel disease or when the ileum is surgically resected

Question 26

What is required for therapy of vit B12 deficiency?

Answer 26

Parenteral injection of vitamin B12 (cyanocobalamin or hydroxocobalamin)
–due to malabsorption of the vitamin

Question 27

Moving on to folate deficiency, it is not uncommon. Folate deficiency is implicated as a cause of what?

Answer 27

Congenital malformations in newborns

Question 28

Folate stores are low in the body, so how long without folate will the body need start showing symptoms?

Answer 28

Folic Acid deficiency and megaloblastic anemia can develop within 1-6 months after the intake of folic acid stops

Question 29

Tetrahydrofolate cofactors participate in one carbon transfer reactions. Vitamin B12, one of theses essential reactions produces the dTMP needed for DNA synthesis. dTMP synthase, dihydrofolate reductase and serine transhydroxmethylase are referred to as what?

Answer 29

dTMP cycle

Question 30

Folate deficiency results in what?

Answer 30

Megaloblastic Anemia

–indistinguishable from B12 deficiency

Question 31

How is folate status assessed?

Answer 31

with assays for serum folate or red blood cells folate.

–red blood cell folate levels are better diagnostically

Question 32

Folate acid deficiency is often caused by inadequate dietary intake of folates. What kind of people have inadequate intake of folate?

Answer 32

1. Alcohol dependence and patients with liver disease: due to poor diet and diminished hepatic storage
2. Pregnant women and patients with hemolytic anemia
3. Malabsorption syndromes
4. Methotrexate, trimethoprim and pyrimethamine: inhibit dihydrofolate reductase
5. Phenytoin: long term use

Question 33

Evidence implicates maternal folic acid deficiency in the occurrence of what?

Answer 33

Fetal neural tube defects (spina bifida)

Question 34

What should be given for patients with folic acid deficiency?

Answer 34

Folic acid supplements