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Anemia Flashcards

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1
Q

What is anemia?

A

Anemia is a decrease in hemoglobin (Hgb) and hematocrit (Hct) concentrations below the normal range for age and gender

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2
Q

What is Hgb and what is its main purpose?

A

Hgb is an iron-rich protein found in red blood cells (RBCs); its main purpose is to carry oxygen from the lungs to the tissues

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3
Q

Describe the life cycle of RBCs

A

RBCs are formed in the bone marrow, where they take up Hgb and iron before being released into the circulation as immature RBCs, known as reticulocytes. After 1-2 days, the reticulocytes mature into erythrocytes, which have a lifespan of about 120 days. Erythrocytes are removed from circulation by macrophages, mainly in the spleen

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4
Q

When can anemia occur?

A

Anemia can occur due to impaired RBC production, increased RBC destruction (hemolysis) or blood loss

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5
Q

What is the danger of anemia?

A

A decrease in Hgb or RBC volume results in decreased oxygen carrying capacity of the blood

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6
Q

What can anemia result from?

A

Anemia can result from nutritional deficiencies (e.g. iron, folate, vitamin B12), or it can occur as a complication of another medical disorder, such as chronic kidney disease (CKD) or a malignancy

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7
Q

What are some symptoms that can occur when anemia becomes severe and/or prolonged?

A

If anemia becomes severe and/or prolonged, the lack of oxygen in the blood can lead to classic symptoms of fatigue, weakness, shortness of breath, exercise intolerance, headache, dizziness, anorexia and/or pallor

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8
Q

What are some symptoms that can occur with sudden blood loss?

A

If sudden blood loss occurs, the patient can experience acute symptoms, such as chest pain, fainting, palpitations and tachycardia

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9
Q

What are some symptoms that can occur with iron deficiency anemia?

A

Glossitis (an inflamed, sore tongue), koilonychias (thin, concave, spoon-shaped nails) or pica (craving and eating non-foods such as chalk or clay)

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10
Q

What are some symptoms that occur with vitamin B12 deficiency?

A

Vitamin B12 deficiency can present with neurologic symptoms, including peripheral neuropathies, visual disturbances and/or psychiatric symptoms

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11
Q

What are some symptoms that can occur with chronic anemia?

A

In chronic anemia, the heart tries to compensate for low oxygen levels by pumping faster (tachycardia) which can increase the mass of the ventricular (hypertrophy) and lead to heart failure

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12
Q

What is the mean corpuscular volume (MCV)?

A

The mean corpuscular volume (MCV), which reflects the size or average volume of RBCs, can help determine the type of anemia and the possible underlying cause

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13
Q

What does a low MCV and high MCV mean?

A

A low MCV means that RBC’s are smaller than normal (microcytic) and a high MCV means that RBCs are larger than normal (macrocytic)

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14
Q

What is the most likely cause of anemia if MCV < 80 fL (microcytic)?

A

Iron deficiency

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15
Q

What are the most likely causes of anemia if MCV is 80-100 fL (normocytic)?

A

Acute blood loss, malignancy, CKD, bone marrow failure (aplastic anemia), hemolysis

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16
Q

What are common laboratory tests in anemia?

A
  • Relevant CBC components: hemoglobin (Hgb), hematocrit (Hct), red blood cell (RBC) count, reticulocyte count
  • RBC indices: mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW)
  • Iron studies: serum iron, serum ferritin, total iron binding capacity (TIBC), transferrin saturation (TSAT)
  • Additional tests: serum folate, serum vitamin B12, methylmalonic acid, homocysteine
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17
Q

What do iron studies further evaluate?

A

Iron studies further evaluate microcytic anemia

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18
Q

What do Vitamin B12 and folate levels further evaluate?

A

Vitamin B12 and folate levels further evaluate macrocytic anemia

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19
Q

What is the reticulocyte count and what does it indicate?

A

A reticulocyte count measures production of RBCs. The reticulocyte count is low in untreated anemia due to iron, folate or B12 deficiency and with bone marrow suppression. The reticulocyte count is high in acute blood loss or hemolysis

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20
Q

What is the most common nutritional deficiency in the United States?

A

Iron deficiency is the most common nutritional deficiency in the United States

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21
Q

What are common causes of iron deficiency?

A

Inadequate dietary intake (iron-poor diets, malnutrition, disease-related), blood loss (acute, chronic, or drug-induced), decreased iron absorption (high gastric pH, GI diseases), increased iron requirements (pregnancy, lactation, infants, rapid growth)

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22
Q

What are the two available forms of dietary iron and which is more readily absorbed?

A

Two available forms of dietary iron includes heme iron (found in meat and seafood) and non-heme iron (found in nuts, beans, vegetables and fortified grains). Heme iron is more readily absorbed than non-heme iron, which is affected by gastric pH and other foods being consumed

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23
Q

What increases the absorption of non-heme iron?

A

Meat, seafood, poultry and ascorbic acid increase the absorption of non-heme iron while foods that contain phytate and polyphenols can decrease non-heme iron absorption

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24
Q

What are some laboratory findings associated with iron deficiency anemia?

A

Decreased Hgb, MCV < 80 fL, decreased RBC production (low reticulocyte count), decreased serum iron, ferritin and TSAT, increased TIBC

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25
What is the treatment for iron deficiency anemia?
- Oral iron therapy with recommended dose of 100-200 mg elemental iron per day - Take iron on an empty stomach - Avoid H2RAs and PPIs, separate from antacids - Sustained-release or enteric-coated formulations cause less GI irritation but are not recommended due to poor absorption
26
How much percent of elemental iron is in ferrous gluconate?
12%
27
What percentage of elemental iron is in ferrous sulfate?
20%
28
What percentage of elemental iron is in ferrous sulfate, dried?
30%
29
What percentage of elemental iron is in ferrous fumarate?
33%
30
What are some oral products that have 100% elemental iron?
Carbonyl ion, polysaccharide iron complex, ferric maltol
31
What are the goals of treating iron deficiency anemia?
Increase serum Hgb by 1 g/dL every 2-3 weeks; continue treatment for 3-6 months after anemia has resolved until iron stores return to normal
32
What is a boxed warning of oral iron products?
Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6; keep iron out of the reach of children; in the case of an accidental overdose, go to the emergency department or call a poison control center immediately (even if asymptomatic)
33
What are contraindications of oral iron?
Hemochromatosis, hemolytic anemia, hemosiderosis
34
What are side effects of oral iron?
Constipation (dose-related), dark and tarry stools, nausea, stomach upset
35
What are some monitoring parameters or oral iron?
Hgb, iron studies, RBC indices, reticulocyte count
36
What are some notes associated with oral iron?
A stool softener such as docusate is often recommended to prevent iron-induced constipation. The antidote for iron overdose is deferoxamine (Desferal)
37
What do antacids, H2RAs and PPIs do to oral iron and what is the recommendation with concomitant use?
Antacids, H2RAs and PPI decrease iron absorption by increasing gastric pH. Patients should take iron 2 hours before or 4 hours after taking antacids. H2RAs and PPIs raise gastric pH for up to 24 hours so separating administration of these agents from iron supplements does not improve absorption
38
Describe how iron affects absorption of other drugs.
Iron is a polyvalent cation that can decrease the absorption of other drugs by binding with them in the GI tract to form nonabsorbable complexes so separate administration is recommended
39
How long should administration of iron supplements be separated from quinolone and tetracycline antibiotics?
Less of a concern with doxycycline and minocycline but take iron two hours before or 4-8 hours after these agents
40
How long should administration of iron supplements be separated from bisphosphonates?
Take iron 60 minutes after oral ibandronate or 30 minutes after alendronate/risedronate
41
How long should administration of iron supplements be separated from cefdinir, dolutegravir, levothyroxine, levodopa and methyldopa?
Separate from iron by 2-4 hours
42
What increases the absorption of iron?
Vitamin C increases the absorption of iron (by providing an acidic environment). Giving iron with ascorbic acid (vitamin C 200 mg may enhance the absorption to a minimal extent)
43
What is the advantage of parenteral iron over oral adminnistration?
Parenteral iron increases Hgb faster than oral iron and reduces gastrointestinal issues seen with oral administration. The total dose needed to replenish iron stores (e.g. 1000 mg) can be provided in a single infusion
44
Why is IV administration of iron restricted?
Due to the risk of more severe adverse reactions, as well as the cost of therapy, IV iron administration is typically restricted
45
Which patients can get IV iron administration?
CKD on hemodialysis, CKD receiving ESA, unable to tolerate oral iron or failure of oral therapy, losing iron too fast for oral replacement, as an alternative when blood transfusions are not accepted by the patient
46
What are some examples of intravenous (parenteral) iron?
Iron sucrose (Venofer), Ferumoxytol (Feraheme), Iron dextran complex (INFeD), Sodium ferric gluconate (Ferrlecit), ferric carboxymaltose (injectafer), ferric derisomaltose (monoferric), ferric pyrophosphate citrate (Triferic)
47
What is the boxed warning of iron dextran and ferumoxytol?
Serious and sometimes fatal anaphylactic reactions have occurred with the use of iron dextran or ferumoxytol; all patients receiving iron dextran should be given a test dose prior to the first full therapeutic dose; fatal reactions have occurred even in patients who tolerated the test dose; a history of drug allergy or multiple drug allergies may increase this risk
48
What are some side effects of IV iron?
Muscle aches, flushing, hypotension, hypertension, tachycardia, chest pain and peripheral edema *All parenteral iron products carry a risk for hypersensitivity reactions
49
What are monitoring parameters of IV iron?
Hgb, iron studies, reticulocyte count, vital signs, signs and symptoms of anaphylaxis
50
What are some notes associated with IV iron?
- Give by slow IV injection or infusion to decease the risk of hypotension - All agents are stable in NS; feraheme is stable in NS or D5W - Triferic is only indicated for iron replacement in patients with hemodialysis-dependent CKD; it should be added to the bicarbonate concentrate of the hemodialysate for patients receiving hemodialysis
51
What is macrocytic anemia caused by?
Macrocytic anemia is caused by vitamin B12 or folate deficiency
52
Why does pernicious anemia occur?
Pernicious anemia, the most common cause of vitamin B12 deficiency, occurs due to lack of intrinsic factor (IF)
53
What is the significance of intrinsic factor (IF)?
IF is required for adequate vitamin B12 absorption in the small intestine; without IF, vitamin B12 deficiency will occur
54
If pernicious anemia is suspected, what test can be used to diagnose?
If pernicious anemia is suspected, patients can be diagnosed with a positive test for autoantibodies to IF *Testing for autoantibodies has replaced the Schilling test, which was previously used to diagnose pernicious anemia
55
What is the treatment for pernicious anemia?
This type of anemia requires lifelong parenteral vitamin B12 replacement
56
What are other causes of macrocytic anemia?
Other causes of macrocytic anemia include alcoholism, poor nutrition, gastrointestinal disorders and pregnancy
57
What medications can cause Vitamin B12 deficiency?
The long-term use (>2 years) of Metformin, H2RAs or PPIs can decrease the absorption of vitamin B12
58
What are consequences of Vitamin B12 deficiency?
Vitamin B12 deficiency can result in serious neurologic dysfunction, including cognitive impairment and peripheral neuropathies. If vitamin B12 deficiency goes undiagnosed for more than three months, neurological symptoms can become irreversible
59
What are the consequences of folic acid deficiency?
Folic acid deficiency does not result in neurologic symptoms; it causes ulcerations of the tongue and oral mucosa and changes to skin, hair and fingernail pigmentation
60
What lab values show a diagnosis of macrocytic anemia?
In addition to low Hgb and high MCV, reticulocyte counts and serum levels of vitamin B12 and/or folate will be low. Since vitamin B12 is required for enzyme reactions involving methylmalonic acid and homocysteine, they accumulate when vitamin B12 is deficient. Homocysteine levels can also be elevated in folate deficiency
61
What is the initial treatment of vitamin B12 deficiency?
The initial treatment of vitamin B12 deficiency typically involves vitamin B12 injections, to bypass absorption barriers, followed by oral supplements, if appropriate. Vitamin B12 injections are recommended first-line for anyone with a severe deficiency or neurological symptoms
62
What are examples of vitamin B12 and folic acid products?
Cyanocobalamin, vitamin B12, folic acid, folate, vitamin B9
63
What are contraindications to cyanocobalamin?
Allergy to cobalt or vitamin B12 (an intradermal test dose is recommended for any patient suspected of vitamin B12 sensitivity prior to intranasal or injectable administration)
64
What are some warnings associated with cyanocobalamin and folic acid?
Parenteral products may contain aluminum (which can accumulate and cause CNS and bone toxicity if renal function is impaired) or benzyl alcohol (which can cause fatal toxicity and "gasping syndrome" in neonates)
65
What are some side effects associated with cyanocobalamin?
Pain with injection, rash, polycythermia vera, pulmonary edema (all rare)
66
What are monitoring parameters of cyanocobalamin?
Hgb, Hct, vitamin B12, reticulocyte count
67
What are side effects associated with vitamin B12?
Bronchospasm, flushing, rash, pruritus, malaise (all rare)
68
What are monitoring parameters of folic acid?
Hgb, Hct, folate, reticulocyte count
69
What are some vitamin B12 and folic acid drug interactions?
- Chloramphenical can decrease the efficacy of vitamin B12; Colchicine can decrease the absorption of vitamin B12 - The efficacy of raltitrexed (a chemotherapeutic agent) can be decreased by folic acid; avoid combination - Folic acid can decrease the serum concentration of fosphenytoin, phenytoin, primidone, phenobarbital - Green tea and sulfasalazine may decrease the serum concentration of folic acid
70
What is erythropoietin (EPO)?
Erythropoietin (EPO) is a hormone produced by the kidneys that stimulates the bone marrow to produce RBCs
71
What does a deficiency of EPO case?
A deficiency of EPO causes anemia of chronic kidney disease (CKD)
72
What are the treatments for anemia of CKD?
Iron therapy and erythropoiesis-stimulating agents (ESAs) are the treatments for anemia of CKD
73
What is the first-line treatment of anemia of CKD for hemodialysis patients?
IV iron is the first-line for hemodialysis patients
74
What is the first line treatment for anemia of CKD for non-HD patients?
Non-HD CKD patients with anemia can be treated with oral iron supplements
75
What is the KDIGO and what do the guidelines recommend?
The KDIGO (Kidney Disease Improving Global Outcomes) guidelines recommend iron therapy in both non-HD and HD patients if TSAT is <30% and ferritin levels are <500 ng/mL
76
What is the KDOQI and what do the guidelines recommend?
The KDOQI (Kidney Disease Outcome Quality Initiative) guidelines recommend iron therapy if TSAT <20% (non-HD and HD patients) and ferritin levels are <100 ng/mL in non-HD patients and <200 ng/mL in HD patients
77
What are ESAs?
ESAs or erythropoiesis-stimulating agents help maintain Hgb levels and reduce the need for blood transfusions, but they are ineffective if iron stores are low
78
What are some examples of ESAs?
Epoetin alfa (Epogen, Procrit) and Darbepoetin (Aranesp)
79
What are some boxed warnings associated with ESAs?
- Increased risk of death, MI, stroke, VTE, thrombosis of vascular access - Use the lowest effective dose to reduce the need for blood transfusions - CKD: increased risk of death, serious cardiovascular events and stroke when Hgb level > 11 g/dL - Cancer: shortened overall survival and/or increased risk of tumor progression or recurrence in clinical studies of patients with some cancers. Not indicated when the anticipated outcome is cured; discontinue when chemotherapy is completed - Perisurgery (epoetin alfa): DVT prophylaxis is recommended due to increased risk of DVT
80
What are contraindications of ESAs?
- Uncontrolled hypertension, pure red cell aplasia (PRCA) that begins after treatment - Epoetin alfa: multidose vials contain benzyl alcohol (contraindicated in neonates, infants, pregnancy and lactation)
81
What are some warnings associated with ESAs?
- Hypertension, seizures, serious allergic reactions, serious skin reactions (SJS/TEN) - Epoetin alfa: contains albumin from human blood (remote risk for transmission of viral diseases)
82
What are some side effects of ESAs?
Arthralgia/bone pain, fever, headache, pruritus/rash, N/V, cough, dyspnea, edema, injection site pain, dizziness
83
What are some monitoring parameters of ESAs?
Hgb, Hct, TSAT, serum ferritin, BP
84
What are some notes associated with ESAs?
- IV route is recommended for patients on hemodialysis - Store in refrigerator; protect from light; discard multidose vials 21 days after initial entry - Do not shake - The darbepoetin t1/2 is a 3-fold longer than epoetin alfa (it can be given weekly)
85
How does aplastic anemia occur?
Aplastic anemia (AA) occurs when the bone marrow fails to make enough RBCs, WBCs and platelets. It can be caused by drugs, infectious diseases, hereditary conditions or autoimmune disorders
86
What are the consequences of aplastic anemia?
Patients with AA are at risk for life-threatening infections or bleeding
87
What are some treatment options for aplastic anemia?
Treatment can include immunosuppresants, blood transfusions or a stem cell transplant. Eltrombopag (Promacta), a thrombopoietin nonpeptide agonist, increases platelet counts and is approved for the treatment of severe aplastic anemia in patients who are unresponsive to immunosuppresive therapy
88
How does hemolytic anemia develop?
Hemolytic anemia develops when RBCs are destroyed and removed from the blood stream before their normal lifespan of 120 days. This type of anemia can be acquired or inherited
89
What is the most common MOA of drug-induced hemolytic anemia?
The medication binds to the RBC surface and triggers the development of antibodies that attack the RBC
90
What tests are used to detect antibodies that are stuck to the surface of RBCs?
The Direct Coombs test
91
What select drugs that can cause hemolytic anemia?
Cephalosporins, Dapsone*, Isoniazid, Levodopa, Methyldopa, Methylene blue*, Nitrofurantoin*, Pegloticase*, Penicillins, Primaquine*, Quinidine, Quinine, Rasburicase*, Rifampin, Sulfonamides* *Avoid in G6PD deficiency
92
Who does a glucose-6-phosphate dehydrogenase (G6PD) deficiency most commonly affect?
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked inherited disorder that most commonly affects person of African, Asian, Mediterranean or Middle Eastern descent
93
What is the importance of G6PD?
The G6PD enzyme protects RBCs from harmful substances (e.g. reactive oxygen species). Without sufficient levels of G6PD, RBCs hemolyze (break apart) 24-72 hours after exposure to oxidative stress
94
What can increase the risk of hemolysis in a patient with G6PD deficiency?
Infections, certain foods, (e.g. fava beans), severe stress and certain drugs can increase the risk of hemolysis in a patient with G6PD deficiency
95
What are some key counseling points for oral iron?
- Take on an empty stomach. If stomach upset occurs, it can be taken with food, but avoid cereals, tea, coffee, eggs, milk and high-fiber products, as these decrease iron absorption - Drug interactions due to binding and/or high gastric pH - Can cause dark stools (which is expected) and/or constipation
96
What are some key counseling points of ESAs?
- Can cause blood clots and/or hypertension | - Do not shake the vial or syringe; this will ruin the medication and it will not work

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