Anemias - Dr. Smith

What are the 4 oral iron options?

▪Ferrous sulfate

▪Ferrous gluconate

▪Ferrous fumarate

▪Iron polysaccharide complex

What are the 6 injectable iron options?

▪Iron dextran

▪Iron sucrose

▪Ferumoxytol

▪Ferric carboxymaltose

▪Sodium ferric gluconate

▪Ferric derisomaltose

What are the 3 erythropoiesis stimulating agents?

▪Erythropoietin

▪Darbepoetin

▪Methoxy polyethylene glycol (PEG)-epoetin beta

What percentage of cancer patients are anemic at diagnosis?

40%

What percentage of cancer patients become anemic during treatment?

65%

•Delays in receiving therapy

•Dose reduction

•Discontinuation

What 3 implications does anemia have on cancer outcomes?

•Independent predictor of poorer survival

•Higher risk of mortality

•Higher risk of cancer progression

What is anemia and what does it result from?

Decrease in either Hgb or circulating red blood cells (RBCs) which leads to reduced oxygen-carrying capacity

Results from

•Inadequate RBC production

•Increased RBC destruction

•Blood loss

What hormone stimulates RBC production?

Erythropoietin (EPO) stimulates RBC production

•90% produced by kidneys

Why are folic acid and vitamin B12 needed by RBCs?

Needed for DNA and RNA

What is the lifespan of a RBC?

120 days

What are some signs and symptoms of acute development of anemia? (7)

•Palpitations

•Angina

•Shortness of breath

•Syncope

•Lightheadedness

•Tachycardic

•Hypotensive

What are some signs and symptoms of chronic development of anemia? (7)

•Fatigue

•Headache

•Malaise

•Exertional dyspnea

•Pale

•Angina

•Weakness

What is the goal dose of oral iron in iron-deficiency anemia?

150 - 200 mg elemental iron per day in divided doses

Oral iron should be taken with food

(T/F)

False,

Best on empty stomach, but patient may need to take with food

What type of environment does oral iron need to be absorbed? (acidic or basic)

Acidic environment; only 10% gets absorbed (in duodenum/ upper jejunum)

What are the adverse effects of oral iron administration?

GI such as nausea/vomiting, constipation, black stools

What are some medications which DECREASE iron absorption? (4)

-Polyvalent cations: aluminum, magnesium, calcium

-Histamine 2 antagonists

-Proton pump inhibitors

-Tetracyclines (oral)

What are some medications in which oral iron DECREASES the availability? (4)

-Fluoroquinolones

-Levodopa

-Levothyroxine

-Tetracyclines (oral)

Regarding oral iron, vitamin -- is a beneficial drug interaction as co-administration increases absorption of iron

Vitamin C is a beneficial drug interaction as co-administration increases absorption of iron

What are the brand names for ferrous sulfate?

Feratab, Feosol, FeroSul, Slow-FE

What percentage of elemental iron is in ferrous sulfate tablets?

20%

65 mg in 325 mg tab

What is the brand name of ferrous gluconate?

Ferate

What percentage of elemental iron is in ferrous gluconate tablets?

12%

38 mg in 324 mg tab

What are the brand names for ferrous fumarate?

Ferrimin, Ferretts

What percentage of elemental iron is in ferrous fumarate tablets?

33%

106 mg in 324 mg tab

What are the brand names for iron polysaccharide complex?

Nu-iron, Ferrex, Poly-Iron

What percentage of elemental iron is in iron polysaccharide complex tablets?

100%

150 mg in 150 mg tab

What is the brand name for ferric citrate?

Auryxia

What percentage of elemental iron is in ferric citrate tablets?

21%

210 mg in 1000 mg

What is the goal dose for injectable iron supplementation?

1 gm, can be given in divided doses

What routes of administration can be used for injectable iron?

IV (can be given with dialysis)

IM

What are the adverse reactions of injectable iron?

•Anaphylaxis - iron dextran requires test dose

•Infusion reactions - hypotension, fever, flushing, arthralgias/myalgias

•Iron overload

What are the 4 scenarios where injectable iron should be used?

•Unable to tolerate oral iron

•Non-adherent to oral iron

•Malabsorption issues

•Iron replacement needed more quickly

IV iron dosing is indication-specific

(T/F)

True

IV iron preparations are dark red to black

(T/F)

True

What are the brand names for iron dextran and how is it administered?

DexFerrum, InFeD

IV or IM

What is the BBW associated with iron dextran?

BBW: Anaphylactic-type reactions

What is the dose of iron dextran given?

25 mg test dose then remaining dose based on equation

What is the brand name of iron sucrose?

Venofer

What is the BBW for iron sucrose?

BBW: Anaphylactic-type reactions

What is the dose for iron sucrose?

Chemotherapy-associated anemia = 200 mg IV every 3 weeks x 5 doses

What is the brand name for ferumoxytol?

Feraheme

What AE is associated with ferumoxytol?

Hypersensitivity

What is the dose of ferumoxytol?

510 mg IV x 2 doses 3-8 days apart OR 1.02 gm IV x 1

What is the brand name of Ferric carboxymaltose

Injectafer

What are the adverse reactions to ferric carboxymaltose? (2)

Hypersensitivity

Transient hypertension

What is the dose for ferric carboxymaltose?

Chemotherapy-associated anemia =

750 mg IV x 2 doses (separated by at least 7 days)

OR

15 mg/kg/dose (max 750 mg)

What is the brand name for Sodium Ferric Gluconate?

Ferrlecit

What AE is associated with sodium ferric gluconate?

Hypersensitivity

What is the dose of sodium ferric gluconate?

Chemotherapy-associated anemia = 125 mg IV weekly for 6-8 doses

What is the brand name of Ferric derisomaltose?

Monferric

What AE is associated with ferric derisomaltose?

Hypersensitivity

What is the dose of ferric derisomaltose?

1 g x 1 dose

OR

500 mg IV weekly for 1-3 doses

SLIDE 15 TO LEARN TO DOSE IRON DEXTRAN, WILL BE ASKED TO DO IT ON ASS.

SLIDE 15 TO LEARN TO DOSE IRON DEXTRAN, WILL BE ASKED TO DO IT ON ASS.

Regarding oral iron therapy:

•Reticulocyte increase within ----

•Hgb may begin to rise in -- to -- weeks; approach normal within --months

•Total duration often -- to -- months

•Discontinue therapy when ------ levels normal

•Reticulocyte increase within days

•Hgb may begin to rise in 2-3 weeks; approach normal within 2 months

•Total duration often 6-12 months

•Discontinue therapy when ferritin levels normal

Regarding IV iron therapy:

•Monitor within -- week: ferritin, transferrin saturation, hgb

•Monitor monthly: ---- and --------

•Monitor within 1 week: ferritin, transferrin saturation, hgb

•Monitor monthly: iron, ferritin

What are the 2 types of macrocytic anemia?

Megaloblastic

Non-megaloblastic

What are the 3 types of megaloblastic anemia?

•Vitamin B12 deficiency

•Folic acid deficiency

•Drug-induced

What are the 6 types of non-megaloblastic anemia?

•Alcoholism

•Liver disease

•Hypothyroidism

•Splenectomy

•Hemolytic anemia

•Myelodysplastic syndrome

How does vit. b12 deficiency present clinically?

•Neurologic

--Bilateral paresthesias in extremities

--Loss of perception to surrounding objects

--Loss of vibratory sensation

•Lack of muscle control (ataxia)

•Dementia

•Psychosis

•Vision loss

•Glossitis

•Stomatitis

How does folic acid deficiency present clinically?

•Few additional signs and symptoms beyond general signs and symptoms of anemia

•Glossitis

What drugs cause vit. b12 deficiency and why?

•Acid-suppressing agents such as PPI and H2RA reduce absorption

•Metformin: mechanism unknown but may be due to reduced uptake within small intestine, bacterial overgrowth, altered GI motility

What drugs cause folic acid deficiency?

DNA synthesis inhibitors:

•Azathioprine

•6-mercaptopurine

•5-fluorouracil (5-FU)

•Hydroxyurea

•Zidovudine

Folate antagonists:

•Methotrexate

•Pentamidine

•Trimethoprim

•Triamterene

Vit B12 ranges =

•Normal: ≥ --- pg/mL

•Borderline: --- to --- pg/mL

•Low: < --- pg/mL

•Alternative range: --- to --- ng/mL

•Normal: ≥ 400 pg/mL

•Borderline: 150-399 pg/mL

•Low: < 150 pg/mL

•Alternative range: 200-800 ng/mL

Folic acid ranges =

•Normal: > -- ng/mL

•Borderline: -- to -- ng/mL

•Low: < -- ng/mL

•Alternative range: -- to -- ng/mL

•Normal: > 4 ng/mL

•Borderline: 2-4 ng/mL

•Low: < 2 ng/mL

•Alternative range: 1.8-9 ng/mL

------------: high levels may indicate vitamin B12 or folate deficiency

-------- ---- (---): high levels may indicate vitamin B12 deficiency

Homocysteine: high levels may indicate vitamin B12 or folate deficiency

Methylmalonic acid (MMA): high levels may indicate vitamin B12 deficiency

If you find severe B12 deficiency - neuropsychiatric findings, symptomatic, very low levels - how should the patient be treated?

▪IM or SQ

Initial therapy

▪Common: 1000 mcg IM/SQ daily x 1 week, then 1000 mcg IM/SQ weekly x 4-8 weeks

▪Alternative: 1000 mcg IM/SQ 1 to 3 times a week for 1 week, then 1000 mcg IM/SQ weekly for 4-8 weeks

Maintenance

▪Continue IM/SQ 1000 mcg monthly until signs/symptoms resolved and no longer deficient. Can then switch to oral/SL 1000-2000 mcg po daily

If you find mild B12 deficiency (mild symptoms, asymptomatic) - how should patient be treated?

▪IM/SQ: 1000 mcg IM/SQ weekly x 4-8 weeks, then 1000 mcg IM/SQ monthly

▪PO/SL: 1000 to 2000 mcg PO daily

▪Continue until deficiency addressed

How long should B12 supplementation last?

Irreversible cause of deficiency (bariatric surgery, pernicious anemia) - may be indefinite

Reversible (dietary deficiency) has been addressed - may discontinue once deficiency addressed and levels normal

B12 monitoring steps:

1-2 days =

5 days =

1 week =

1-2 months =

1-2 days = sxs improve

5 days = reticulocytes improve

1 week = Hgb improves and normalizes within 2 months

1-2 months = B12 begins to improve

Check B12 again every 3-6 months

We should rule out B12 deficiency before assuming folic acid deficiency

(T/F)

True

What is initial therapy for folic acid supplementation?

•1 mg orally daily x 4 months ± chronic therapy

•5 mg orally daily if cause is due to malabsorption

•400-800 mcg daily in pregnancy

Folic acid monitoring steps:

7 days =

2 weeks =

7 days = Reticulocytes improve

2 weeks = Hgb improves and normalizes within 2 months

What foods are good for B12?

Eggs

Milk/dairy

Clams

Mutton and Chicken

Shitake mushrooms

Salmon

What foods are good for folate?

Greens

Legumes

Eggs

Beets

Fruits

Nuts and seed

What are the 6 types of normocytic anemia mentioned?

Hemolysis

Blood loss

Anemia of critical illness

Anemia of inflammation

Anemia of chronic illness

Cancers effecting bone marrow

What is the pathophysiology of anemia of chronic disease, inflammation, OR critical illness?

•Pro-inflammatory cytokines released

•Blunted EPO response

•Impaired erythroid proliferation

•Disturbance of iron homeostasis

•Shortened RBC life span

Regarding normocytic anemia, what are the labs for general anemia work up plus additional labs?

•Lactate dehydrogenase (LDH)

•Coombs test (direct antiglobulin test)

•Haptoglobin

•Fractionated bilirubin

•Stool guaiac

•Reticulocyte count

•Iron studies

•Folic acid

•B12

What 2 procedures can be done regarding normocytic anemia diagnosis?

•Colonoscopy

•Esophagogastroduodenoscopy (EGD)

What are the 5 treatment considerations for normocytic anemia?

•Treat underlying cause

•Consider blood transfusion when Hgb < 7 gm/dL

•Vitamin supplementation (B12, folic acid)

•Iron

•Erythropoiesis-stimulating agents (ESAs)

If we are looking to cure patients cancer, we should give them an ESA

(T/F)

False, never give ESA if the outcome is to cure; ESAs can progress malignancy

When can ESAs be used in anemia due to cancer?

When patient has anemia due to chemotherapy induced myelosuppression, cancer is non-myeloid, Hgb is

What is myeloid cancer?

▪Myeloid leukemia: involves myeloid cell line of blood cells: precursors to granulocytes, erythrocytes, platelets

▪A myeloid leukemia can be acute (AML), promyelocytic leukemia, or chronic (CML)

What is non-myeloid cancer?

Anything other than myeloid leukemias; a few examples (not all-inclusive):

▪Carcinomas

▪Sarcomas

▪Melanomas

▪Lymphomas

▪Multiple myeloma

▪ETC

What is non-myelosuppressive chemotherapy?

Treatment that does NOT impact blood-forming cells to a significant degree

What is myelosuppressive chemotherapy?

Treatment that stops or slows the growth of blood-forming cells in the bone marrow and decreases the production of

▪RBC - hemoglobin (anemia)

▪WBC (neutropenia)

▪Platelets (thrombocytopenia)

Patient with a nonmyeloid cancer can receive EPO if all of the following are true:

•Goal is NOT cure

•Patient is receiving a myelosuppressive chemotherapy regimen

•Duration of myelosuppression expected to be > 2 months

Patient with a nonmyeloid cancer can receive EPO if all of the following are true:

•Goal is NOT cure

•Patient is receiving a myelosuppressive chemotherapy regimen

•Duration of myelosuppression expected to be > 2 months

What are 2 considerations to remember in elderly patients with anemia?

•Consider lower doses of iron due to GI effects

•Recognize chronic blood loss common

What are the considerations for pediatric dosing in:

•Iron deficiency:

•B12 deficiency:

•Folic acid deficiency:

•Iron deficiency: treat for 9-12 months: ferrous sulfate 3-6 mg/kg/day elemental iron, divided

•B12 deficiency: treat according to clinical response (no data)

•Folic acid deficiency: 1 mg po daily