Anemia Flashcards
What is anemia?
- decreased # of RBC or hemoglobin results in less oxygen binding
- all the symptoms of anemia are related to the tissues having depleted oxygen stores
Describe the Anemia Assessment - 5 steps
See How Many Red Cells
S = Signs and Symptoms
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?
C = Check reticulocytes and likely deficiencies
What are the 3 types of anemia?
- Iron-deficiency
- Folate-deficiency
- B12-deficiency
Anemia symptoms:
CNS
- fatigue
- malaise
- weakness
- headache
- dizziness
- irritability
- difficulty concentrating
Anemia symptoms:
HEENT (head, ears, eyes, nose, throat)
Pallor (skin, conjunctivae, nail beds), vertigo
Anemia symptoms:
RESP
dyspnea on exertion
Anemia symptoms:
CVS
Palpitations, tachycardia, angina
Anemia symptoms:
GI
Anorexia
Anemia symptoms:
Other
cold intolerance, loss of skin tone
What labs are typically ordered to assess anemia?
- CBC: Hbg, Hct (including RBC indices: MCV, MCHC, RDW)
- Iron indices (ferritin), vitamin B12 and folate levels
- Reticulocyte index
- Stool sample for occult blood (in older adults to rule out colon cancer)
- +/- peripheral blood smear
What is the laboratory definition of anemia in males?
Hgb < 130 g/L
What is the laboratory definition of anemia in females?
Hgb < 120 g/L
*lower for females due to monthly menstruation
Microcytic anemia = what deficiency?
iron
Macrocytic anemia = what deficiency?
B12/folate
What MCV = microcytic ?
< 80
What MCV = normocytic ?
80-100
What MCV = macrocytic ?
> 100
see diagram on page 2
ok
What is the most common cause of anemia?
iron deficiency
What are the clinical presentations of iron deficiency anemia?
- dry rough skin
- brittle nails
- dry, damaged hair or hair loss
- restless leg syndrome
Other possible symptoms (unlikely unless Hgb < 90):
- Glossal pain, smooth tongue (atrophy of tongue papillae)
- Reduced salivary flow
- Pica (compulsive eating of nonfood items - ex. clay, starch)
- Pagophagia (compulsive eating of ice)
What are signs of advanced tissue iron deficiency?
Cheilosis - cracking at corners of mouth
Koilonychia - spooning of fingernails
What is Serum Ferritin?
- Reflects tissue iron stores (liver, spleen, bone marrow)
- Acute phase reactant - may be elevated in infection, inflammation, malignancy
- If < 15-30, iron deficiency anemia is likely
- If > 100, iron deficiency is unlikely
What is TSAT (%) ?
Serum iron/TIBC x 100
- Amount of iron that is readily available
- Normal range is 14-50%
What is TIBC?
indirect measure of iron-binding capacity of serum transferrin
What is Serum Iron?
- concentration of iron bound to transferrin
- must be interpreted together with TIBC to obtain TSAT
Iron Deficiency Anemia:
Hgb
low
Iron Deficiency Anemia:
MCV
Low
Iron Deficiency Anemia:
MCH
Low
Iron Deficiency Anemia:
MCHC
Low
Iron Deficiency Anemia:
RDW
High (wide variation in size of RBCs)
Iron Deficiency Anemia:
Reticulocytes
Low
Iron Deficiency Anemia:
Serum Ferritin
Low
What are some risk factors for IDA (iron deficiency anemia)?
1) Inadequate intake/increased requirements:
- adolescents (poor diet, rapid growth)
- menorrhagia, pregnancy/lactation
- vegetarians (especially vegans)
- endurance runners/other athletes (increase RBC production, iron loss, through injury/”foot strike” damage to RBCs, sweat)
- Chronic renal failure patients
2) Blood loss:
- Regular blood donors
- Surgery
- Drugs (ex. ASA/NSAIDs, anticoagulants - GI blood loss)
3) Genetic:
- Family Hx of hematologic disorders
- Ethnicity (first nations, indo-Candian)
What are the goals of treatment?
- To improve clinical signs and symptoms of anemia
- To restore Hgb levels and MCV to normal and replenish iron stores
What are the principles of treatment?
- Determine cause of iron deficiency and treat underlying disease if possible
- Fecal occult blood test (FOBT) to check for GI bleeding/colon cancer screening
- Replenish iron stores
What are some options for treatment?
- Increase dietary iron
- Oral iron supplementation
- IV iron supplementation
- Blood transfusions
- Menses
- GI neoplasms
- Blood donations
- Bleeding disorder
- UC(ulcerative colitis)/IBD
- Peptic ulcer
- Hemorrhoids
- Diverticulosis
- Drugs (ASA, NSAIDs, anticoagulants)
All examples of what cause ?
Increased iron loss
- Rapid growth, infancy, adolescence
- Pregnancy
- EPO deficiency
All examples of what cause ?
Increased demand for iron
- Inadequate diet
- Gastric surgery
- Crohn’s disease
- Celiac disease
- Achlorhydria
- Acute or chronic inflammation
- H. pylori infection
All examples of what cause ?
Decreased iron intake/absorption
You need ____ in the stomach to absorb iron.
acid
*so antacids affect iron absorption
Examples of Heme Iron (ferrous iron)
- Meat, poultry, seafood
- 3x more absorbable vs. non-heme iron
- Absorption decreased by content of calcium in meal (Ca2+ supplements, dairy)
Examples of Non-Heme Iron (ferric iron)
- Vegetables, fruits, dried beans, nuts, grains
- Absorption increased by gastric acid and ascorbic acid-rich foods, heme iron
What decreases non-heme iron absorption?
- Phytates (bran, oats, rye, fibre)
- Tannins (herbal teas)
- Phosphates
- Polyphenols (tea/coffee)
- Calcium supplements
- Milk/dairy
- Antacids, PPI, H2Bs
What is the recommended dose of iron for IDA for adults and elderly?
Adults: 150-200 mg elemental FE/day (or 2-3 mg/kg/day) usually divided BID/TID
Elderly: lower 15-50mg/day dose may be effective
How should iron be spaced from food?
- on an empty stomach or at least 1 hr before meal or 2 hrs after meals
- may need to take with meals to decrease GI SE (decreases absorption of iron though)
SE of iron?
- nausea, vomiting, dyspepsia, constipation, diarrhea, dark stools, metallic taste
- generally dose related and resolve with time (except dark stools)
How do you start iron?
Start with 1 tab and work up gradually (every 3-7 days) to improve GI tolerability
Start low and titrate up
Liquid preps of iron may do what?
Stain teeth
-Mix with juice/water & drink through straw, rub teeth with baking soda)
Drug interactions with iron?
- Antacids, PPIs, H2B, cholestyramine, calcium/milk (decrease absorption of Fe)
- Levodopa, levothyroxine, quinolones, tetracyclines, bisphosphates (also decrease absorption) - Take iron at least 3 hours before or 2 hours after these drugs
Consider holding iron until _______ completed
antibiotics
Describe the differences between oral preparations
- Various iron salts contain different amounts or iron (all absorbed similarly)
- SR formulations (no controlled studies to indicate less GI SE, slow release past duodenum may decrease chance for absorption
- Enteric coated (more poorly absorbed than standard film-coated)
gluconate
green
sulphate
red
% of elemental iron in Ferrous Gluconate ?
11%
35/300 mg tab
% of elemental iron in Ferrous Sulphate ?
20%
60/300 mg tab
% of elemental iron in Ferrous fumarate ?
33%
100/300 mg tab
When should you consider parenteral iron?
- Evidence of iron malabsorption
- Intolerance to oral iron
- Patient with significant blood loss who refuses blood transfusion and cannot take oral iron
- Chronic dialysis patients
- Some patients receiving chemotherapy and erythropoiesis stimulating agents (ESAs)
All parenteral iron preparations carry a risk for ______ rxns
anaphylactic
What is the formula for calculating IV iron dose?
Dose of iron (mg) = weight (kg) x (140-Hgb) x 0.22
- An additional quantity of iron to replenish stores should be added (about 600 mg for women and 1000 mg for men)
- Usually given in divided doses
Can you give oral and IV iron together?
No way man
-Don’t give IV and oral iron together bc GI absorption would be impaired
What are the transient side effects of IV iron that usually resolve within 48 hours ?
- nausea, vomiting, pruritus, headache and flushing
- myalgia, arthralgia
- back and chest pain
What are some other side effects of IV iron?
- Hypersensitivity reactions (rare)
- Severe or life-threatening reactions (rare). Risk factors: rapid infusions, history of atopy and drug allergy
- Must be given by trained HCP in an environment with access to resuscitation equipment.
- Patients are monitored closely during administration
How much iron is in 1 mL of packed RBC’s?
1 mg iron
How many mL is in 2 units of PRBC’s?
500 mL = 500 mg iron
How much does 1 unit of PRBC increase Hgb by ?
10 g/L
Describe the concerns with safety and availability of blood transfusions?
Bloodborne infections, development of autoantibodies, transfusion reactions and iron overload
Who are blood transfusions considered for?
severe anemia with Hgb < 70-80 g/L
IDA:
Therapeutic doses of iron should increase Hgb by ____g/L per week
*Response of < 20 g/L over 3 weeks - further evaluation
10
When are CBC, Ferritin, and may eTSAT ordered?
CBC every month and 3-6 months
Ferritin +/- TSAT in 3-6 months
When do reticulocytes rise?
5-7 days after iron therapy started, reaching a max on day 10-14, then decreases
How long should you treat IDA for after anemia is resolved?
For 3-6 months after anemia resolved to allow for repletion of iron stores and prevent relapse (approx 6-12 months)
Which 2 tests are used to differentiate between B12 deficiency and folate deficiency?
- Homocysteine
- MMA (methylmalonic acid)
- Both are high in B12 deficiency
- Only homocysteine is high in folate deficiency
Which symptoms can help you differentiate between B12 deficiency and folate deficiency?
Neurologic symptoms:
-If present = B12 deficiency
*Folic acid deficiency does not cause neurologic symptoms
What are neurologic symptoms?
parasthesias, numbness, tingling
What is the role of vitamin B12 (cobalamin) ?
- Required along with folic acid in synthesis of DNA, RNA
- Essential for maintaining integrity of NEUROLOGIC system
- Role in fatty acid synthesis and energy production
Dietary sources of Vitamin B12
meat, fish, poultry, diary, fortified cereals
B12 deficiency takes several years to develop due to efficient ??
enterohepatic circulation and body stores
B12 Deficiency Anemia:
Hgb
Low
B12 Deficiency Anemia:
MCV
High (microcytic)
B12 Deficiency Anemia:
Serum vitamin B12
Low
B12 Deficiency Anemia:
Homocysteine
High
B12 Deficiency Anemia:
MMA
High
B12 Deficiency Anemia:
WBC, platelets
Low (mild)
B12 Deficiency Anemia:
Reticulocyte count
Low
In additional to general symptoms of anemia:
What neurologic symptoms are there for B12 deficiency anemia?
Early: numbness & paresthesias
Later: peripheral neuropathy, ataxia, imbalance, decrease vibratory sense, decreased proprioception
In additional to general symptoms of anemia:
What neuropsychiatric symptoms are there for B12 deficiency anemia?
Irritability, personality changes, memory impairment, dementia, depression, psychosis (uncommon)
In additional to general symptoms of anemia:
What GI symptoms are there for B12 deficiency anemia?
- glossitis (inflammation of tongue)
- dysphagia (difficulty swallowing)
- anorexia
In additional to general symptoms of anemia:
What MSK symptoms are there for B12 deficiency anemia?
muscle weakness
Patients with unexplained ____ should be evaluated for vitamin B12 deficiency
neuropathies
- Strict vegans (and their breast-fed infants)
- Chronic EtOH
- Elderly (tea and toast diet)
Are all types of what cause of Vitamin B12 deficiency?
inadequate intake (rare)
- Pernicious anemia (no intrinsic factor)
- Cobalamin malabsorption (inadequate gastric acid production)
- Rx acid suppression (chronic use)
- Overgrowth of bacteria in the bowel that use vitamin B12
Are all types of what cause of Vitamin B12 deficiency?
Malabsorption
- Lack of transport protein
- Transcobalamin 2 deficiency
Are all types of what cause of Vitamin B12 deficiency?
Inadequate utilization (uncommon)
Pernicious anemia is a type of _____ deficiency anemia
B12
Pernicious anemia is absence of ?
absence of intrinsic factor
Causes of pernicious anemia?
- Autoimmune destruction of gastric parietal cells
- Atrophy of gastric mucosa
- Stomach surgery
Risk factors for pernicious anemia?
- age (increase over age 60)
- women > men
- europeans of northern descent, african americans
Pernicious anemia:
What antibodies are positive in 50%
anti-intrinsic factor antibodies
Pernicious anemia:
What is the Schilling test? (no longer used)
Oral dose of ratio-labelled B12, then IM injection of non-labelled B12 to saturate plasma transport proteins, 24 hour urine collection
List some common drugs that can cause drug-induced megaloblastic anemia
- carbamazepine
- phenytoin
- valproic acid
- colchicine
- H2B, PPIs
- metformin
- oral contraceptives
Describe the treatment for vitamin B12 deficiency anemia (SC/IM)
SC/IM vitamin B12 (cyanocobalamin):
- 800-1000 mpg daily for 1-2 weeks to saturate stores then;
- 100-1000 mpg weekly until Hgb/Hct normal then;
- 100-1000 mpg monthly to maintain normal erythrocyte count
*only really need 100mcg but pack size is 1000 mcg so you give that and then the rest will be excreted in the urine
Describe the treatment for vitamin B12 deficiency anemia (oral)
Oral vitamin B12 (cyanocobalamin or methylcobalamin):
- Treat early to reduce risk of irreversible neurologic damage
- Life time therapy if underlying cause not corrected
Why do you want to treat vitamin B12 deficiency early?
to reduce risk of irreversible neurologic damage
Is oral B12 as effective as IM for hematologic/neurologic response even in pernicious anemia?
Yes
Who is IM B12 injection recommended for?
- Neurologic symptoms, until resolved, then switch to PO
- Inadequate evidence for use of PO B12 if severe neurologic impairment
- Hospitalized patients
- Poor GI absorption (ex. ileectomy)
- Unable to take PO
- Diarrhea/vomiting
- Noncompliance
What do you need to monitor for B12 deficiency anemia? Include timeframes.
- Reticulocytosis in 3-5 days (peaks at 7 days)
- Hematologic improvement (Hgb, WBC, platelets) in 5-7 days (normal by 1-2 months)
- Hypersegmented PMNs persistent for 2 weeks
- MMA, homocysteine decreases start at 1-2 weeks
- Vitamin B12 deficiency resolves in 3-4 weeks
- Improved strength and well-being within a few days
- 6 months or longer required for improvement of neurologic signs/symptoms
What is the role of folic acid?
- Production of DNA and RNA
- Necessary to form methylcobalamin which converts homocysteine to methionine
- Humans unable to synthesize sufficient folate - dietary sources needed
What are dietary sources of folic acid?
- fresh green leafy vegetables
- citrus fruits
- yeast
- mushrooms
- dairy products
- animal organs
Does cooking foods increase or decrease amount of folate in foods?
decrease
Folic acid:
5-10 mg mainly in ____ (4-6 month supply of folic acid)
liver
Folic acid:
Severely deficient diet can result in clinically significant deficiency within __ weeks
6
Causes of folic acid deficiency anemia?
- Inadequate intake
- Decreased absorption
- Hyperutilization (increased requirement)
- Altered metabolism
Who is at risk of folic acid deficiency anemia caused by inadequate intake?
elderly, alcoholics, poverty, chronic illness/dementia, teenager (junk food diet)
Who is at risk of folic acid deficiency anemia caused by decreased absorption?
Chron’s disease, celiac disease, alcoholism, drugs (ex. phenytoin)
Who is at risk of folic acid deficiency anemia caused by hyper utilization (increased requirement)?
pregnancy, hemolytic anemia, malignancy, chronic dialysis, chronic inflammatory disorders
Who is at risk of folic acid deficiency anemia caused by altered metabolism?
Drugs: folate antagonists (methotrexate, trimethoprim), DNA synthesis inhibitors (azathioprine, hydroxyurea, zidovudine)
What are the signs and symptoms of folic acid anemia?
Exact same as B12 deficiency anemia (except neurological symptoms)
Folic Acid Deficiency Anemia:
Hgb
Low
Folic Acid Deficiency Anemia:
MCV
High (macrocytic)
Folic Acid Deficiency Anemia: RBC folate (reflects total body stores)
Low
Folic Acid Deficiency Anemia:
Homocysteine
High
Folic Acid Deficiency Anemia:
MMA
Normal !!!
Folic Acid Deficiency Anemia:
Vitamin B12
Normal !!!
Folic Acid Deficiency Anemia:
Must rule out ?
vitamin B12 deficiency
What is the treatment for Folic Acid Deficiency Anemia?
Oral folic acid (folate)
- 1 mg daily
- 5 mg daily if absorption compromised (ex. EtOH)
How long is the treatment continued for Folic Acid Deficiency Anemia?
- until cause of deficiency is identified and corrected (ex. improve diet)
- 4 months therapy in order for folate-deficient RBCs to be cleared (life span of RBC)
What happens if you accidentally treat pernicious anemia with folate?
- Anemia symptoms will improve
- Partial hematologic response
- Neurologic symptoms WILL NOT BE REVERSED - may progress or become irreversible if not treated
*Remember that pernicious anemia is B12 deficiency
What do you need to monitor for Folic Acid Deficiency Anemia?
- Reticulocytosis in 2-3 days (peaks at 5-8 days)
- Hgb, Hat increases within 2 weeks, normalizes in 2 months
- RBC folate after 4 months (life cycle of RBC)
- Symptomatic improvement (increase altertness, increase appetite) occurs early
Anemia of Chronic Disease (ACD):
Is it microcytic or macrocytic?
Neither - normocytic
Anemia of Chronic Disease (ACD):
Usually a diagnosis of _____
Exclusion
- non-specific symptoms
- important to rule out IDA and blood loss
Anemia of Chronic Disease (ACD):
Common causes?
- Chronic infection (HIV, chronic UTIs, osteomyelitis)
- Malignancy
- Chronic inflammation (RA, lupus)
- CKD
Anemia of Chronic Disease (ACD):
Generally develops when?
after 1-2 months of sustained disease
Anemia of Chronic Disease (ACD):
Goal?
treat underlying cause if possible
Anemia of Chronic Disease (ACD):
AKA ?
anemia of inflammation
What is erythropoietin ?
hormone made by the kidney that signals for more RBCs to be made
Anemia of Chronic Disease (ACD):
Desired outcomes?
- increased oxygen carrying capacity of blood
- decrease signs and symptoms of anemia
- improve QOL
- decrease need for blood transfusions
Anemia of Chronic Disease (ACD):
Treatment?
1) Iron supplementation
- Required by most patients receiving ESAs due to increased iron demand resulting from stimulation in RBC production
2) Erythropoiesis Stimulating Agents (ESAs)
- Consider when Hgb between 90-100 g/L
- And in non-dialysis patients when rate of Hgb decline indicates likelihood of requiring a RBC transfusion, goal of avoiding transfusions due to risk of alloimmunization or other RBC-transfusion-related risks
3) Vitamin B12 and folate supplementation
- Vitamins B, C and folic acid (water-soluble vitamins) often depleted with renal diet and hemodialysis therapy (replavite/jamplavite)
If on ESA, need to be on _____ as well
iron
What are some ESAs?
1) Epoetin alfa (Eprex)
- Given SC or IV 1-3 times per week
- 25% increase dose for IV vs SC
2) Darbopoetin alfa (Aranesp)
- SC or IV q1-2 weeks (can be extended up to every 3-4 weeks)
3) ESA dosage adjustments
- Usually 25% dosage increments (round to nearest prefilled syringes)
What contributes to ESA resistance ?
- Iron deficiency/folic acid or B12 deficiency
- Underlying infection, inflammatory condition or malignancy temporarily impair activity of ESA
- Blood loss; hemolysis
- Underlying hematologic disease
- Aluminum toxicity
- Hyperparathyroidism
- Catheter insertion
- Malnutrition
- Pure Red Cell Aplasia - very rare
What are high targets of ESAs associated with ? (>120 g/L)
- strokes
- thromboembolic events
- CV events
- possible increased risk of cancer (if Hx of cancer)
When should iron be started in relation to ESA for CKD anemia?
All CKD patients on ESAs should have adequate iron stores before initiation/increasing dose of ESA
Avoid giving IV iron to patients with active systemic _____
infections
*bacteria need iron to grow so you may worsen the infection if you give iron supplements during an acute infection
