28 - Anemia Flashcards
1
Q
What is anemia?
A
- Group of diseases characterized by decrease in either hemoglobin or volume of RBCs which results in decreased oxygen-carrying capacity of the blood
- Sign of underlying pathology rather than a disease
2
Q
How is anemia characterized?
A
- Can be characterized by RBC size (macrocytic, normocytic, or microcytic)
- Vitamin B12 & folate deficiencies are both macrocytic anemias
- Microcytic = iron deficiency
- Normocytic = recent blood loss or chronic disease
3
Q
Main causes of anemia
A
- Inadequate RBC production
- Ineffective RBC maturation (iron deficiency, vitamin B12 & folic acid deficiency)
- Increased RBC destruction
- Increased RBC loss
- More than 1 anemia & etiology can occur at the same time
4
Q
Describe the assessment for anemia
A
- 5 steps -> See How Many Red Cells (SHMRC)
- S = signs & sx (look for first)
- H = hemoglobin or hematocrit (if low = anemic)
- M = MCV (indication of average RBC size)
- R = RDW (or peripheral blood smear) – are all cells the same size? Do you believe the MCV? – normal RDW = 11-14%
- – If MCV is normocytic, might assume that RBC’s are normal w/o anemia
- – If RDW is high, means big difference between size of RBC’s => anemia
- – Iron deficiency anemia produces microcytic MCV, but may start off as normal & RDW will be high (above normal) b/c don’t have all the same size RBCs
- C = check reticulocytes & likely deficiencies
- – Reticulocytes = immature RBC’s released from bone marrow
- Be aware of mixed anemias
5
Q
General clinical presentation of anemia
A
- CNS = fatigue, headache, dizziness
- HEENT (head, eyes, ears, nose, throat) = pale skin, conjunctivae, & nail beds; vertigo
- Respiratory = dyspnea on exertion
- CVS = tachycardia, palpitations
- GI = anorexia
- Other = cold intolerance, loss of skin tone
6
Q
What labs are used to assess anemia?
A
- CBC (Hbg, Hct including RBC indices – MCV, MCHC, RDW)
- Iron indices (ferritin), vitamin B12, folate
- Reticulocyte index
- Stool sample for occult blood
7
Q
Lab definition of anemia
A
- Males = Hgb < 130 g/L
- Females = Hbg < 120 g/L
8
Q
What do the values of MCV and RDW mean in regards to anemia?
A
- Microcytic (MCV < 80 fL)
- Normal RDW = ACD (anemia of chronic disease)
- High RDW = iron deficiency (ferritin < 20 mcg/L)
- *Don’t use RDW to differentiate between IDA & ACD
- Normocytic (MCV 80-100 fL)
- Normal RDW = CKD; ACD; hypothyroidism
- High RDW = hemolytic anemia; sickle cell anemia
- *Check reticulocytes
- Macrocytic (MCV > 100 fL)
- Normal RDW = liver disease; EtOH
- High RDW = B12/folate deficiency
9
Q
What is the most common cause of anemia?
A
Iron deficiency
10
Q
Presentation of iron deficiency anemia
A
- Clinical presentation = dry rough skin, brittle nails, dry damaged hair or hair loss, restless leg syndrome (b/c epithelial cells that rapidly divide need iron, so w/ iron deficiency they can’t divide as quickly & will dry up)
- Signs of advanced tissue iron deficiency = cheilosis (cracking at corners of mouth) & koilonychia (spooning of fingernails)
11
Q
Describe how to determine severity of anemia sx
A
- Mild = little to no sx
- Moderate = sx affecting life; fatigue, weakness, difficulty concentrating
- Severe = unable to tolerate mild exercise, may be symptomatic at rest
12
Q
Describe the lab values measured in regards to iron
A
- Serum ferritin (20-300 mcg/L)
- Reflects tissue iron stores (liver, spleen, bone marrow)
- Acute phase reactant (may be elevated in infection, inflammation, malignancy)
- If ferritin is low (< 20) probably deficient in iron
- If ferritin high (> 100) likely have a chronic disease & must check TSAT
- TSAT (%) = serum iron/TIBC * 100%
- Amount of iron readily available (how much iron is in blood & available to bone marrow to make new RBCs)
- Normal = 14-50%
- Usually only measured if ferritin is normal (or in CKD)
- Basically, saying how much transferrin is bound to iron in the blood
- TIBC total iron binding capacity (47-72 umol/L) – indirect measure of iron-binding capacity of serum transferrin
- Serum iron (7-27 umol/L) – concentration of iron bound to transferrin
13
Q
What are the lab findings of iron deficiency anemia?
A
- Hgb = low
- MCV = low (microcytic)
- MCH = low (microcytosis or hypochromia)
- MCHC = low (hypochromic = less pigment, so pale)
- Normochromic or hypochromic = Hgb content
- Independent of cell size, so more useful than MCH in distinguishing between microcytosis & hypochromia
- Low MCHC = hypochromia (microcyte w/ normal hemoglobin concentration will have low MCH but normal MCHC); most often seen in iron-deficiency anemia
- RDW = high (variation in size of RBCs)
- Reticulocytes = low-normal (impaired RBC production)
- Serum ferritin = low (< 20 mcg/L)
- Serum ferritin is proportional to total iron stores, so is the best indicator of iron deficiency or iron overload
- Low serum ferritin is basically diagnostic of IDA
14
Q
What is MCH and what is the most common cause of elevated MCH?
A
- Amount of hemoglobin in an RBC & usually increases or decreases w/ the MCV
- Most common cause of elevated MCH is macrocytosis (vit B12 or folate deficiency)
15
Q
What is MCHC?
A
Concentration of hemoglobin per volume of cells
16
Q
Risk factors for IDA
A
- Inadequate intake/increased requirements
- Adolescents (poor diet, rapid growth)
- Menorrhagia, pregnancy/lactation
- Vegetarians (especially vegans)
- Athletes (increased RBC production, iron loss, sweat)
- Chronic renal failure px
- Blood loss – regular blood donors, surgery, drugs (NSAIDs, ASA, anticoagulants; antacids can decrease iron absorption)
- Genetic – family history of hematologic disorders; ethnicity
17
Q
Goals of tx for IDA
A
- Improve clinical signs & sx of anemia
- Restore Hgb levels & MCV to normal & replenish iron stores
18
Q
Principles of tx for IDA
A
- Determine cause of iron deficiency & treat underlying disease if possible
- Fecal occult blood test (FOBT) to check for GI bleeding/colon cancer screening
- Replenish iron stores
- Options = increase dietary iron (very hard to get rid of deficiency w/ just dietary intake), oral iron supplementation, IV iron supplementation, blood transfusions
19
Q
Causes of IDA
A
- Increased iron loss (ex: menses, GI neoplasms, blood donation, peptic ulcer, hemorrhoids, drugs like ASA, NSAIDs, anticoagulants)
- Increased demand for iron (ex: rapid growth in infancy/adolescence, pregnancy, EPO deficiency)
- Decreased iron intake/absorption (ex: inadequate diet, gastric surgery, Crohn’s disease, celiac disease, achlorhydria/low gastric acid, acute or chronic inflammation, H. pylori infection)
20
Q
What is the difference between heme iron and non-heme iron and what are sources of each?
A
- Heme iron Fe2+ (ferrous iron)
- Meat, poultry, seafood
- 3x more absorbable vs. non-heme iron (has different receptor that it binds to in gut & less things block its absorption)
- Absorption decreased by content of calcium in meal (Ca2+ supplements, milk/dairy)
- Non-heme iron Fe3+ (ferric iron)
- Vegetables, fruits, dried beans, nuts, grains
- Absorption increased by gastric acid & ascorbic acid-rich foods
21
Q
What decreases non-heme iron absorption?
A
- Phytates (bran, oats, rye fiber)
- Tannins (herbal teas) – don’t recommend tea if trying to keep iron levels up
- Phosphates
- Polyphenols (tea/coffee)
- Calcium supplements
- Milk/dairy
- Antacids, PPIs, H2 blockers
22
Q
Recommended dose of oral iron for IDA? How should it be taken?
A
- Recommended dose for IDA = 150-200 mg elemental Fe/day (or 2-3 mg/kg/day)
- Elderly = 15-50 mg/day may be effective (especially if mild deficiency)
- Take on empty stomach or at least 1 h before meal or 2 h after meal
- May need to take w/ meals to decrease GI side effects (decreases absorption)
23
Q
SE and drug interactions of oral iron?
A
- SE = N/V, dyspepsia, constipation, diarrhea, dark stools (remember to warn px)
- Generally, dose related & resolve w/ time
- Start w/ 1 tab and work up gradually to improve GI tolerability
- Drug interactions = antacids, PPIs, H2 blockers, calcium/milk, levodopa, levothyroxine, quinolones, tetracyclines, bisphosphonates
- Consider holding iron until antibiotics completed (iron is a growth factor for bacteria & don’t want antibiotic to not be absorbed, so easiest to hold iron)
- For px w/ CKD, often are on calcium at meals as a phosphate binder, so give iron 3 tabs HS b/c better absorbed on empty stomach
24
Q
Which oral iron preparation should you choose? know this
A
- Various iron salts contain different amounts of iron (all absorbed similarly)
- SR formulations not good b/c release past duodenum may decrease chance for absorption
- Enteric coated more poorly absorbed than standard film-coated (b/c iron needs to be exposed to acid to be absorbed)
- Ferrous gluconate (11% Fe, 35 mg/300 mg tab), sulphate (20% Fe, 60 mg/300 mg tab), & fumarate (33% Fe, 100 mg/300 mg tab)
- Rarely start someone who’s never had iron supplement w/ fumarate
- Generally, start on 1 sulfate & titrate up to 3 tabs
- If someone says they used iron supplements & had horrible side effects, start w/ 1 gluconate & slowly titrate up
25
Q
When should parenteral iron be considered? What is a disadvantage to this type of iron?
A
- Evidence of iron malabsorption, intolerance to oral iron, pt w/ significant blood loss who refuses blood transfusion & can’t take oral iron, chronic dialysis px, some px receiving chemotherapy & erythropoiesis stimulating agents (ESAs)
- All parenteral iron preparations carry a risk for anaphylactic reactions
26
Q
How is IV iron dose calculated?
A
- For iron deficiency anemia (adults) not px requiring iron replacement for blood loss
- Dose of iron (mg) = weight (kg) * (140 – Hgb) * 0.22
- “Desired Hbg” can adjust to 120 or 130
- Additional quantity of iron to replenish stores should be added (~600 mg for women & 1,000 mg for men)
- Usually given in divided doses
- *Don’t give w/ oral iron as GI absorption would be impaired
27
Q
Possible adverse reactions w/ IV iron
A
- Transient side effects (usually resolve w/in 48 h) = N/V, pruritus, headache, flushing, myalgia, back & chest pain
- Hypersensitivity reactions (rare)
- Severe or life-threatening reactions (rare) – risk factors = rapid infusions, history of atopy & drug allergy
- Px are monitored closely during administration
28
Q
Describe the use of blood transfusions for anemia
A
- Indicated if acute blood loss w/ hemodynamic compromise
- 1 mL packed RBCs ~ 1 mg iron (ex: 2 units of PRBCs = 500 mL = 500 mg iron)
- 1-unit PRBC increases Hgb by ~ 10 g/L
- Concerns = safety, availability
- Considered for those w/ severe anemia (Hgb < 70-80 g/L)
29
Q
What is monitored w/ IDA?
A
- Therapeutic doses of iron should increase Hgb by 10 g/L per week (response of < 20 g/L over 3 weeks = further evaluation needed)
- CBC (Hgb) q1month x 3-6 months (increase of Hgb by 2 weeks, normalization of Hgb by 6-8 weeks)
- Ferritin, +/- TSAT in 3-6 months
- Treat for 3-6 months after anemia resolved to allow for repletion of iron stores & prevent relapse (~6-12 months)
- Important to monitor for SE & sx improvement
30
Q
Describe vitamin B12 deficiency anemia
A
- IF (intrinsic factor) = main receptor for vit B12 to be absorbed (some people lack IF b/c formed antibodies against & destroy it) => pernicious anemia is type of vitamin B12 deficiency
- MMA = methylmalonic acid & homocysteine tests can determine this anemia
- These are expensive tests & rarely used; only used if B12 levels are borderline & need more info
- Conversion of MMA to succinyl-CoA requires B12 & conversion of homocysteine to methionine requires vitamin B12 and folate
- *Know that major sx difference between folate & B12 deficiency = neurologic sx (tingling, numbness, dementia, ataxia) only in B12 deficiencies b/c B12 required to produce myelin for neurons
- Role of vitamin B12 (cobalamin) – required w/ folic acid in synthesis of DNA & RNA, essential for maintaining integrity of neurologic system, role in fatty acid synthesis & energy production
31
Q
What are some dietary sources of vitamin B12?
A
- Meat, fish, poultry
- Dairy
- Fortified cereals
32
Q
How long does vitamin B12 deficiency take to develop? Why?
A
- Several years (5-10 years)
- Due to efficient enterohepatic circulation & body stores (hence why more common in elderly)
33
Q
What are the lab findings in vitamin B12 deficiency?
A
- Hgb = low
- MCV = high (macrocytic)
- MCV changes can precede low B12 levels by months
- Serum B12 = low
- Vit B12 levels may be falsely low w/ folate deficiency
- Homocysteine = high
- MMA = high
- WBC, platelets = low (mild)
- Reticulocytes = low (want it to be high)
34
Q
Signs and sx of vitamin B12 deficiency anemia
A
- In addition to general sx of anemia
- Neurologic = early (numbness, paresthesia’s) or later (peripheral neuropathy, ataxia, imbalance)
- If elderly px has unexplained/acute dementia or neuropathy, must rule out vitamin B12 deficiency b/c if not treated will be irreversible
- Muscle weakness
- Irritability, personality changes, memory impairment
35
Q
Causes of vitamin B12 deficiency
A
- Inadequate intake (rare) – strict vegans, chronic EtOH, elderly diet (tea & toast)
- Malabsorption – pernicious anemia (no intrinsic factor), cobalamin malabsorption (inadequate gastric acid production; needed for cleavage of vit B12 from proteins in diet), Rx acid suppression
- Inadequate utilization (uncommon) – lack of transport protein
36
Q
Pernicious anemia - what is it? Causes? Risk factors?
A
- Absence of intrinsic factor
- Anti-intrinsic factor antibodies – positive in 50%
- Causes = autoimmune destruction of gastric parietal cells, atrophy of gastric mucosa, stomach surgery
- Risk factors = age (increases over age 60), women > men
37
Q
What can cause drug-induced megaloblastic anemia?
A
- Direct inhibitors of DNA synthesis (azathioprine, hydroxyurea, chemotherapy)
- Folate antagonists (carbamazepine, phenytoin, valproic acid, methotrexate, trimethoprim)
- Reduced folate/vitamin B12 absorption (excessive EtOH, ASA, colchicine, metformin, oral contraceptives)
38
Q
Tx of vitamin B12 deficiency anemia
A
- Subcut/IM vitamin B12 (cyanocobalamin) *start this when pt experiencing neurologic sx
- 800-1000 mcg daily for 1-2 weeks to saturate stores, then
- 100-1000 mcg weekly until Hgb/Hct normal, then
- 100-1000 mcg monthly to maintain normal erythrocyte count
- Oral vitamin B12 (cyanocobalamin or methylcobalamin) 1000-2000 mcg daily
- Treat early to reduce risk of irreversible neurologic damage
- Life time therapy if underlying cause not corrected
39
Q
How to decide IM vs. oral vitamin B12
A
- Daily PO (1000-2000 mcg) vit B12 as effective as IM for hematologic/neurologic response even in pernicious anemia
- IM/subcut recommended for:
- Neurologic sx, until resolved, then may switch to PO
- Hospitalized px
- Poor GI absorption
- Unable to take PO
- Diarrhea/vomiting
- Noncompliance
40
Q
Monitoring for vitamin B12 deficiency anemia
A
- Reticulocytosis in 3-5 days (peaks at 7 days)
- Hematologic improvement (Hgb, WBC) in 5-7 days
- MMA, homocysteine decreases start at 1-2 weeks
- Vitamin B12 deficiency resolves in 3-4 weeks (improved strength & well-being w/in a few days)
- 6 months or longer required for improvement of neurologic signs/sx
- Check CBC & vitamin B12 levels at 1-2 months, then at 3-6 mo
- Check homocysteine & MMA at 2-3 months
41
Q
Describe folic acid deficiency anemia
A
- Role of folic acid = production of DNA & RNA, necessary to form methylcobalamin which converts homocysteine to methionine
- Humans unable to synthesize sufficient folate, so dietary sources needed
42
Q
Dietary sources of folic acid
A
- Fresh green leafy vegetables
- Citrus fruits
- Mushrooms
- Dairy products
- *Cooking > 15 min in lots of water destroys high proportion of folate
43
Q
How much folate does the body store and where?
A
~5-20 mg in the liver
44
Q
Causes of folic acid deficiency anemia
A
- Inadequate intake – elderly, alcoholics, poverty, chronic illness/dementia, teenager (junk food diet)
- Decreased absorption – Crohn’s disease, celiac disease, alcoholism, drugs
- Hyperutilization (increased requirement) – pregnancy, hemolytic anemia, malignancy, chronic dialysis
- Altered metabolism – drugs (folate antagonists, DNA synthesis inhibitors)
45
Q
Folic acid deficiency anemia – lab findings
A
- Hgb = low
- MCV = high (macrocytic)
- RBC = low
- Serum folate not tested in WPG b/c very inaccurate
- Homocysteine = high
- MMA = normal
- Vitamin B12 = normal
- *Must rule out vitamin B12 deficiency!!! Can’t treat folate deficiency w/o making sure they don’t have vit B12 deficiency
46
Q
Folic acid deficiency anemia – tx
A
- Oral folic acid (folate) – 1 mg daily, 5 mg daily if absorption compromised (ex: EtOH)
- Tx continued until cause of deficiency identified & corrected
- 4 months therapy in order for folate-deficiency RBCs to be cleared (life span of RBC)
47
Q
Monitoring for folic acid deficiency anemia
A
- Sx improvement (increased alertness & appetite) occurs early
- Reticulocytosis in 2-3 days (peaks at 5-8 days)
- Hgb, Hct increases w/in 2 weeks, normalizes in 2 months
- Measure CBC at 1 mo then at 3-6 mo; RBC folate at 4 mo; homocysteine & MMA at 2-3 mo
48
Q
Describe anemia of chronic disease (ACD). Common causes and goal of tx?
A
- AKA anemia of inflammation
- Most common normocytic anemia (also can be microcytic)
- Usually diagnosis of exclusion (nonspecific sx, important to rule out iron deficiency & blood loss)
- Common causes = chronic infection (HIV, UTIs, osteomyelitis), malignancy, chronic inflammation, CKD
- Generally, develops after 1-2 months of sustained disease
- Goal (if possible) treat underlying cause
49
Q
ACD – lab findings
A
- Hgb = mild (> 95 g/L) to moderate (> 80 g/L) – usually ~100-110 g/L
- MCV = normal or low
- RDW = normal
- Reticulocytes = low (b/c inflammatory mediators are suppressing bone marrow so not producing as many RBCs)
- TIBC (transferrin) – normal or low in ACD; high in IDA
50
Q
Describe when to initiate ESA
A
- If Hgb < 100 g/L, individualize based on:
- Rate of fall of Hgb
- Prior response to iron therapy
- Risk of needing a transfusion
- Risks related to ESA therapy
- Anemia sx
- Don’t maintain Hgb > 115 g/L
- Don’t intentionally increase Hgb > 130 g/L
- Caution w/ ESA use for active malignancy, recent stroke, hx of cancer
51
Q
Describe the iron targets in CKD
A
- All CKD px on ESAs should have adequate iron stores before initiation/increasing dose of ESA
- For any pt on ESA, if not on iron should be put on iron
- If no dialysis – try oral iron
- If on hemodialysis – use IV iron b/c probably won’t absorb oral
52
Q
Treatment of ACD
A
- Iron supplementation – required by most px receiving ESAs due to increased iron demand resulting from stimulation in RBC production
- ESAs – consider when Hgb 90-100 g/L
- Vitamin B12 & folate supplementation – vitamins B, C, & folic acid (water-soluble vitamins) often depleted w/ renal diet & hemodialysis therapy
53
Q
Erythropoiesis-stimulating agents (ESAs) available products and dosing
A
- Epoetin alfa (Eprex) – given subcut or IV 1-3 times/week
- Darbepoetin alfa (Aranesp) – subcut or IV q1-2weeks
- ESA dosage adjustments – usually 25% dosage increments; pay attention to Hgb trends
54
Q
Describe ESA resistance
A
- Iron deficiency (main cause)/folic acid or B12 deficiency
- Underlying infection, inflammatory condition, or malignancy
55
Q
What are some warnings w/ ESAs?
A
- High targets (> 120 g/L) associated w/ strokes, thromboembolic events, CV events, & possible increased risk of cancer
- Original Hgb targets were 110-120 g/L
- Don’t initiate unless Hgb < 100 g/L & use lowest ESA dose necessary to decrease need for RBC transfusions
56
Q
What are the available IV iron products? When should they not be used?
A
- Dextran, sucrose (Venofer), & sodium ferric gluconate complex (Ferrlecit) are the available products
- Avoid giving IV iron to px w/ active systemic infections
57
Q
Monitoring anemia in CKD
A
- CBC every month – acceptable rate of Hgb rise ~ 10-20 g/L per month
- Don’t increase dose more often than q4weeks
- Decrease dose by 25% if Hgb increases > 10 g/L in 2 weeks
- Increased dose by 25% if Hgb increases < 10 g/L in 4 weeks (rule out ESA resistance)
- Ferritin & TSAT every 1-3 months
- BP – HTN most common AE reported; caution if BP uncontrolled
