Treatment of Anemia CIS

Question 1

Case 1: 5 year hx of peptic ulcer disease, heavy menstruation, blood in stools, low ferritin, low HCT, low Hgb. She has been taking NSAIDs. What should be given to pt orally?

Answer 1

NSAIDs and peptic ulcer disease can reduce iron absorption

heavy menstruation - can predispose to anemia

Ferrous Sulfate: given orally

• since she has children, need to warn her about poisoning from iron if they get into the bottle.
• she should take it separately from tetracycline and be taken with food.

Question 2

when would parenteral iron therapy be indicated?

Answer 2

malabsorption - parenteral iron is given in ferric form,

other indications: intolerance to oral therapy, advanced chronic renal disease, small bowel resection, inflammatory bowel disease, malabsorption syndromes

Question 3

what to give when suffering acute iron toxicity?

Answer 3

deferoxamine - its an iron chelator

activated charcoal is not effective in iron poisoning

Question 4

case 2: 38 y/o female with cancer that is in the middle of chemo. She c/o SOB and her Hgb is low, Hct is low, MCV and MCHC are normal. peripheral smear shows normochromic, normocytic RBCs. What kind of anemia?

Answer 4

Anemia of chronic disease

Question 5

Which agent will stimulate an increase in the production of retics and is most appropriate tx for this patient?

Answer 5

Epoetin alpha

Question 6

Cyanocobalamin?

Answer 6

used for B12 deficiency

Question 7

Oprelvekin

Answer 7

Megakaryocyte growth factor

Question 8

Pegfilgrastim

Answer 8

G-CSF

Question 9

Filgrastim

Answer 9

G-CSF

Question 10

what drug should you not choose if pt. is on chemotherapy?

Answer 10

erythrocyte stimulating agents: Epoetin alph and darbepoetin alpha - see increased risk of progression or recurrence of anemic pts with cancer, and is not recommended

Question 11

megaloblastic anemia tx?

Answer 11

assoc. with Vit B12 deficiency or folic acid deficiency.

Give either cyanocobalamin, hydroxocobalamin or folic acid

an anemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production.[1] When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis. Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias. The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically a deficiency of vitamin B12 and/or folic acid.

Question 12

vit B12 deficiency?

Answer 12

often see neurological problems, if give folic acid, will probably rescue the anemia, but the neurologic sx will most likely progress

Question 13

signs of anemia?

Answer 13

pallor, fatigue, dizziness, exertional dyspnea, hypoxia, tachycardia, increased CO and vasodilation

Question 14

inadquate iron intake?

Answer 14

microcytic hypochromic anemia

Question 15

ferrous sulfate, ferrous gluconate, ferrous fumarate

Answer 15

oral preparations of iron

• should be taken with water
  AE’s= nausea, epigastric discomfort, ab cramps, constipation, black stools, diarrhea

Question 16

free iron levels

Answer 16

if have high iron levels, then see increase in apoferritin (stimulate apoferritin synthesis)

if have low iron levels, then see increase in transferrin (low levels inhibit apoferritin synthesis)

Question 17

parenteral iron therapy

Answer 17

iron dextran, iron-sucrose complex, sodium ferric gluconate complex

Use: given to pts that are unable to tolerate/absorb oral iron or with extensive chronic anemia (i.e. advanced CRD, small bowel resection, IBD, malabsorption syndromes)

AE’s: (esp. of iron dextran) = h/a, light headedness, fever, arthralgias, back pain, flushing, urticaria, bronchospasm * anaphlylaxis, death!

• = less likely to cause hypersensitivity rxns

Question 18

Acute iron toxicity

Answer 18

seen in children who ingest iron tablets => necrotizing gastroenteritis, vomiting, bloody diarrhea –> shock, lethargy, dsypnea –> severe met. acidosis, death

** give parenteral deferoxamine (iron chelating that promotes excretion)**

Question 19

chronic iron toxicity

Answer 19

deposits in heart, liver, pancreas –> organ failure and death

(2) Toxicity is most common in patients with inherited hemochromatosis, a disorder characterized by excessive iron absorption, and in patients who receive many red cell transfusions over a long period of time
(3) Efficiently treated with intermittent phlebotomy (deferoxamine is not effective, only used in last case effort)

(4) Oral iron chelator deferasirox reduces liver iron concentrations but data in removing iron from heart is lacking

Question 20

what does VitB12 deficiency lead to? tx?

Answer 20

megaloblastic macrocytic anemia (often associated with mild/moderate leukopenia/thrombocytopenia),

GI sx, neurologic abnormalities

iv) Neurologic syndrome associated with B12 deficiency usually begins with paresthesias in peripheral nerves and weakness and progresses to spasticity, ataxia, and other CNS dysfunctions (B12 treatment stops the progression of neurologic disease but may not fully reverse neurologic symptoms)

obtained in meat, eggs, dairy products

defiency usually due to malabsorption due to lack of intrinsic factor or loss of distal ileum function
- seen in pernicioius anemia, gastrectomy, IBD, small bowel resection

tx: Cyanocobalamin, Hydroxocobalamin

Question 21

deferoxamine

Answer 21

iron chelator used to tx acute iron toxicity

Question 22

deferasirox

Answer 22

iron chelator used to tx chronic iron overload

Question 23

Cyanocobalamin, Hydroxocobalamin

Answer 23

tx of Vit B12 deficiency

reqd for synthesis of amino acid methionine and synth of succinyl CoA

almost all cases are due to malabsorption - so these are given parenterally

Question 24

Folic Acid

Answer 24

Folic acid is reqd for synth. of amino acids, purines, and DNA

**Major consequence of deficiency is anemia; folic acid deficiency is implicated as a cause of congenital malformations in newborns and may play a role in vascular disease

Obtained through yeast, liver, kidney and green veggies!

folic acid deficiency results in megaloblastic anemia! (same as B12) - but does not cause the neurologic sx as seen in B12 deficiency

deficiency seen in : inadequate dietary intake of folates (e.g., alcoholics with poor diet and diminished hepatic storage, pregnant women and patients with hemolytic anemia with increased folate requirements, patients with malabsorption syndromes, patients undergoing renal dialysis have folates removed from plasma)

iv) Drugs that can cause folic acid deficiency include methotrexate, trimethoprim, and pyrimethamine (all inhibit dihydrofolate reductase) and long-term therapy with phenytoin

Question 25

Erythropoietin (EPO)

Answer 25

i) Expressed primarily in peritubular interstitial cells of the kidney
ii) Binds to a receptor on the surface of committed erythroid progenitors in the marrow after secretion (erythropoietin receptors are members of the cytokine receptor superfamily and initiate the JAK/STAT signal transduction pathway (kinase signaling cascade))
iii) With anemia or hypoxemia, synthesis rapidly increases by 100-fold or more, serum erythropoietin levels rise, and marrow progenitor cell survival, proliferation, and maturation are stimulated (can be disrupted by kidney disease, marrow damage, or a deficiency in iron or an essential vitamin)
iv) Inflammatory cytokines, released due to an infection or an inflammatory state, suppress erythropoietin secretion, iron delivery, and progenitor proliferation (inflammation also affects iron metabolism)

Question 26

Epoetin alpha, Darbepoetin alpha

Answer 26

erythrocyte-stimulating agents that act like EPO - induces the release of reticulocytes from the bone marrow into the bloodstream, where they mature to erythrocytes

Results in an increase in reticulocyte counts (10 days) followed by a rise in hematocrit and hemoglobin levels (2-6 weeks)

Use:

1. used decrease the need for RBC transfusions in patients with anemia secondary to chronic kidney disease (endogenous erythropoietin levels are low because the kidneys cannot produce the growth factor) - nearly always coupled with iron supplementation as well
   (1) Treatment of anemia due to concurrent myelosuppressive chemotherapy in patients with cancer (nonmyeloid malignancies) receiving chemotherapy (palliative intent) for a planned minimum of 2 additional months of chemotherapy
   (2) Treatment of anemia associated with HIV (zidovudine) therapy when endogenous erythropoietin levels ≤ 500 mUnits/mL
   (3) Reduction of allogenic RBC transfusion for elective, noncardiac, nonvascular surgery when perioperative Hgb is 10-13 g/dL and there is a high risk for blood loss

NOT indicated:

• cancer pts receiving hormonal therapy or radiation therapy unless its a myelosuppressive chemo
• pts with myelosuppressive chemo when expected outcome is curative
• surgery pts what are donating blood, or unergoing cardiac surgery

toxicity: hypertension and thrombotic complications

Question 27

when to use G-CSF and GM-CSF

Answer 27

meyloid growth factors currently available for clinical use to stimulate proliferation and differentiation of one or more myeloid cell lines and enhance the function of mature granulocytes and monocytes

G-CSF:

(1) Stimulates proliferation and differentiation of progenitors already committed to the neutrophil lineage
(2) Activates the phagocytic activity of mature neutrophils and prolongs survival
(3) Increases concentration of hematopoietic stem cells in peripheral blood (major advance in transplantation because peripheral blood stem cells (PBSCs) may be used rather than bone marrow stem cells)

GM-CSF:

(1) Broader biologic actions than G-CSF
(2) Primary therapeutic effect is to stimulate myelopoiesis
(a) Stimulates the proliferation and differentiation of early and late granulocytic progenitor cells as well as erythroid and megakaryocyte progenitors
(b) Stimulates the function of mature neutrophils
(c) Stimulates T-cell proliferation together with interleukin-2
(3) Increases concentration of peripheral blood stem cells to a lesser extent than G-CSF

Question 28

Filgrastim

Answer 28

(rHuG-CSF), G-CSF

tx: Cancer patients treated with myelosuppressive cancer chemotherapy (reduces infections and chemo related illnesses by boosting neutrophil levels)
Patients with severe chronic neutropenia
Patients recovering from bone marrow transplantation

i) Filgrastim and pegfilgrastim are used more frequently than GM-CSF because they are better tolerated
ii) Filgrastim and pegfilgrastim can cause bone pain, which clears when discontinued

Question 29

Pegfilbrastim

Answer 29

G-CSF

tx: Cancer patients treated with myelosuppressive cancer chemotherapy (reduces infections and chemo related illnesses by boosting neutrophil levels)
Patients with severe chronic neutropenia
Patients recovering from bone marrow transplantation

• (3) Pegfilgrastim may be administered less frequently and may shorten the period of severe neutropenia in comparison to filgrastim;

i) Filgrastim and pegfilgrastim are used more frequently than GM-CSF because they are better tolerated
ii) Filgrastim and pegfilgrastim can cause bone pain, which clears when discontinued

Question 30

Sargramostim

Answer 30

(rHUGM-CSF) - GM-CSF

iii) GM-CSF can cause fever, malaise, arthralgias, myalgias, and a capillary leak syndrome characterized by peripheral edema and pleural or pericardial effusions - not used as often

Question 31

when to use megakaryocyte growth factors?

Answer 31

patients with thrombocytopenia that have high risk of hemorrhage

b) Thrombopoietin and interleukin-11 (IL-11) are endogenous regulators of platelet production

Question 32

Oprelvekin

Answer 32

IL-11

activates specific cell surface cytokine receptors to stimulate the growth of multiple lymphoid and myeloid cells; acts synergistically with other growth factors to stimulate the growth of primitive megakaryocytic progenitors; increases the number of peripheral platelets and neutrophils

i) IL-11 is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for nonmyeloid cancers; reduces the number of platelet transfusions

Toxicity:

(1) Fatigue, headache, dizziness, and cardiovascular effects (e.g., anemia, dyspnea, transient atrial arrhythmias) are the most common
(2) Hypokalemia
(3) All adverse effects are reversible

Question 33

Romiplostim

Answer 33

(3) MOA: activates Mpl thrombopoietin receptor to cause a dose-dependent increase in platelet count that begins 5 days after SubQ injection and peaks at 12-15 days
ii) Romiplostim is approved for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia purpura (ITP) who have had insufficient response to corticosteroids, immune globulin, or splenectomy
(1) Well tolerated except for a mild headache on the day of administration