Anemia Flashcards
What is normal Hgb?
Women: 12-15 g/dL
Men: 13-17 g/dL
1-2 g/dL LOWER in women and AA men than white men
What is the prevalence of anemia?
~1 in 77 people
10-12% of people over 65
20% of people over 85
10% of nursing home residents
Common factor in chronic illness
What is the prevalence of symptoms in anemia?
MOST are asymptomatic
Acuity: may be rapid or chronic onset
Severity varies
Young vs. old patients
What are the symptoms of anemia?
- Dyspnea
- Chest pain
- Palpitations
- Dizziness/lightheadedness/syncope
- Fatigue/weakness/exercise intolerance
- Neuro changes (with profound anemia, you can see stroke-like symptoms…rare)
What are the signs of anemia?
Often NO signs
Vital sign changes:
Orthostasis/tachycardia after 30% blood volume loss
Hypovolemic shock after 40% blood volume loss
Conjunctival pallor
Scleral icterus (from hemolytic anemia, increased bili)
Angular chelitis (more with deficiencies)
Glossitis
Lymphadenopathy
Heart murmur, signs of HF
Splenomegaly
Peripheral neuropathy: abnormal vibration, proprioception
DOE with profound anemia because body senses decreased O2
What does the red cell size tell you about the pathology of anemia?
Microcytic anemia = MCV <80, indicating decreased production of RBCs (more older cells); is it a bone marrow issue or issue of not having the necessary ingredients?
Normocytic anemia = MCV 80-100
Macrocytic anemia = MCV >100, indicating majority of cells are immature, the problem is not related to the bone marrow
What are possibly pathogeneses of anemia?
Decreased production (by the bone marrow) Increased destruction Sequestration
What is the differential of microcytic anemia (MCV<80)?
- Iron deficiency (MOST COMMON)
- Anemia of chronic disease - body cannot access the Fe
- Thalassemia - genetic mutation on heme subunit so that cannot make normal Hgb for RBCs
- Sideroblastic anemia - bone marrow makes ringed sideroblasts rather than normal RBCs
What is the differential of normocytic anemia (MCV 80-100)?
- Anemia of chronic disease
- Anemia of renal failure
- Hemolysis
- Hypothyroidism
- Early blood loss
- Primary bone marrow disorder (myelodysplasia, bone marrow infiltration, myeloma, aplastic anemia)…if this goes on long enough, can turn microcytic
What is the differential of macrocytic anemia (MCV>100)?
Megaloblastic (most common):
- B12 deficiency
- Folate deficiency
Non-megaloblastic
- Liver disease
- Medications
- Myelodysplasia
- Reticulocytosis
- Alcohol
- Hypothyroidism
What does the peripheral smear look like in megaloblastic macrocytosis anemia?
- Large, oval RBCs
- Hypersegmented neutrophils that are packed with protein junk
What are elements of the HISTORY when evaluating possible anemia?
Possible sources of blood loss
-Menstrual history
-Hx/sx suggestive of GI bleeding (dark stool, emesis with blood)
-Urinary loss (hematuria)
-Pulmonary loss (hemoptysis)
PMH - chronic illnesses?
PSH - gastric bypass/bowel surgery like small bowel resection that decreases absorption?
Medications
-GI blood loss (NSAIDs)
-Hemolysis
-Bone marrow suppression
FH - anemia, thalassemia, sickle cell?
Diet - veggies/fruits? meats? access? alcohol? vegan?
Pregnancy - increases blood volume, so a relative low Hgb/Hct
What does the CBC tell you?
WBC Hgb/Hct PLT MCV RDW
What is RDW?
Normal: 11-15%
Indicates the variety of cells present
Will be increased when the bone marrow is acting correctly in response to microcytic anemia
Use this in addition to MCV to make determination of cause of anemia
What is transferrin?
- Made in the liver
- Glycoprotein that reversibly binds to Fe and transports Fe from the blood to BM, spleen, and liver
- High levels indicates possible IDA
- Low levels may indicate liver disease or hemolytic anemia
What is TIBC?
Total Iron Binding Capacity
Measures the blood’s capacity to bind iron with transferrin
Transferrin sat = Serum Fe/TIBC x 100
When transferrin sat is low, indicates IDA
What are reticulocytes and how do you measure them?
Reticulocytes = immature blood cells
Retic count = the % of retics in your blood, so not an accurate assessment of bone marrow activity when you’re anemic
Reticulocyte Index (RI) is a more accurate measure of the reticulocytes because it adjusts the number according to pt’s Hct, a good marker of bone marrow response to anemia
If RI > 1, it is responding appropriately
If RI is very low, it is a chronic process
What will the CBC look like in a patient with IDA?
Low iron
High TIBC
Low ferritin (Note: ferritin is an acute phase reactant, so if the pt is older with lots of conditions, this may be increased 2/2 inflammation)
Fe/TIBC < 18%
MCV/RBC > 13 (helps differentiate between thalassemia)
What will the CBC look like in a patient with anemia of chronic disease (AOCD)?
High ferritin (because it is an acute phase reactant)
Low iron (cannot get it out of stores, so low in blood)
Low TIBC
Fe/TIBC > 18%
How do you approach the differential diagnosis in microcytic anemia?
- Rule out IDA: look at ferritin, serum Fe, TIBC, transferrin sat (Fe/TIBC); MCV is usually 60s-70s
- Consider thalassemia: MCV usually <50
- Is there a cause for AOCD?
What is the diagnostic approach to normocytic anemia?
Step 1: Rule out nutritional anemias (Ferritin, B12, Folate)
Step 2: Rule out anemia of renal insufficiency
-GFR < 60 (lack of erythropoietin)
-Normal peripheral smear
-Inappropriately normal serum erythropoietin
Step 3: Look for hemolysis (likely other s/sx with this)
-Increased LDH (cell destruction)
-Increased indirect bilirubin (Hgb catabolism)
-Increased reticulocytosis
-Decreased haptoglobin (serum protein that clears Hgb)
Step 4: Consider AOCD or bone marrow disorder
What are the lab results in hemolysis?
- Increased LDH (cell destruction)
- Increased indirect bilirubin (Hgb catabolism)
- Increased reticulocytosis
- Decreased haptoglobin (serum protein that clears Hgb)
What is the diagnostic approach to macrocytic anemia?
Step 1: Rule out meds that cause macrocytosis (alcohol, hydroxyurea, methotrexate, trimethoprim, AZT, 5-FU, chemo)
Step 2: Rule out nutritional causes
-Check B12, Folate, MMA, Homocysteine
Step 3: Look for bone marrow disease
Why do you check Methylmalonic acid?
B12 helps convert MMA to Coenzyme A
Thus, increased MMA may indicate B12 deficiency
B12 levels may be normal, but checking MMA can indicate a deficiency
What is the prevalence of IDA?
Highest in women of childbearing age:
12% in women 12-49
9% in women 50-69
Ethnic differences amongst women:
10% in non-hispanic whites
19% in AAs
22% in Mexicans living in US!!!
Much rarer in men (2-3%) and requires an intense workup
What is the differential of IDA?
Blood loss -Menstrual -GI -Urinary, Pulmonary Decreased absorption -Malabsorption -Partial gastrectomy Increased requirements -Pregnancy/Lactation Decreased intake -Children/Vegans
What will a peripheral smear show in IDA?
Hypochromic RBCs
How do you evaluate a patient with IDA?
GI evaluation: colonoscopy/EGD in men, postmenopausal women, or premenopausal women with symptoms
Menstruating women without localizing GI symptoms can be treated empirically with iron
How do you treat IDA?
Oral iron: -Start daily and titrate to BID/TID -Treatment duration for 4 months Follow-up: -Re-check Hgb in 1 month (corrects in 6-8 weeks)
IV iron:
- Iron dextran, ferric gluconate, or iron sucrose (venofer)
- Used when pt unable to tolerate oral iron or malabsorption
- SE: anaphylaxis (iron dextran)
What are the SE of oral iron?
Constipation, abd pain, nausea, dark stools, interactions with other meds
Treat with stool softeners, take with food, titrate slowly
What’s the deal with Alpha Thalassemia?
15% trait in AA and very common in SE Asian
Genotype and phenotype: aa/aa = normal -a/aa = silent carrier -a/-a or --/aa = trait --/-a = HbH disease --/-- = hydrops fetalis
What’s the deal with Beta Thalassemia
More common in Mediterranean, Greek, Italian, North African ethnicities
Genotype and phenotype:
B/B = normal
-/B = trait
-/- = homozygous
How do you learn about the alpha and beta subunits in thalassemias?
Hemoglobin electrophoresis
What will a peripheral smear in thalassemia look like?
Often will see target cells because of misfolded proteins
How do you diagnose thalassemia?
Beta thalassemia is diagnosed with Hgb electrophoresis and will show increased HgbA2
Alpha thalassemia is diagnosed with genetic testing, it is severe and often diagnosed at childhood
What is the treatment plan for thalassemia?
No treatment for thalassemia TRAIT
Genetic counseling provided if contemplating pregnancy
Do not supplement with iron
What is involved in the differential diagnosis of B12 deficiency anemia?
Decreased intake
-Vegan, alcohol (decreases intrinsic factor levels), elderly
Malabsorption
- PPI/H2 blockers that inhibit binding between B12 and intrinsic factor (cannot absorb B12)
- Lack of intrinsic factor/parietal cells (pernicious anemia, atrophic gastritis, gastrectomy)
- Other GI causes (sprue/celiac, ileal disease)
- Biological competition (bacterial overgrowth, tapeworm)
How do you evaluate a patient for B12 deficiency?
- B12 level
- Methylmalonic acid level (will be increased)
- Homocysteine (will be increased)
- Pernicious anemia (autoimmune issue where you cannot absorb B12): parietal cell antibody and intrinsic factor antibody levels
What is the dosing schedule for B12 treatment?
Oral
- Initial dose of 1,000-2,000 mcg/day for 1-2 weeks
- Maintenance: 1,000 mcg/day for life
IM
- Initial dose: 100-1,000 mcg/day for 1 week; then weekly for 1 month
- Maintenance: 100-1,000 mcg every 1-3 months
What are (red cell) intrinsic causes of hemolytic anemias?
Membranopathies - hereditary spherocytosis
Enzymopathies - G6PD deficiency
Hemoglobinopathies - Sickle cell disease
What are (red cell) extrinsic causes of hemolytic anemias?
Immune-mediated: autoimmune or alloiummune (transfusion reaction)
Microangiopathic: TTP (Thrombotic Thrombocytopenic Purpura), HUS (Hemolytic-Uremic Syndrome), DIC (Disseminated Intravascular Coagulation), HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet count)
Infection associated
What is involved in the diagnosis of hemolytic anemia?
Hemolysis Labs:
- Increased retic
- Increased LDH
- Increased unconjugated bilirubin
- Decreased haptoglobin
Peripheral smear:
- Schistocytes
- Spherocytes
- Sickle cells
What is the “Rule of Thirds” in older adults?
1/3 nutritional deficiency
1/3 anemia of chronic disease
1/3 unexplained anemia
When should you refer an anemic patient?
- Etiology is unclear
- Need for bone marrow biopsy
- Hemolytic anemias
- Need for transfusion (symptomatic anemia or not responding to oral therapy)
What is Rouleaux on a peripheral smear?
Shows stacks or aggregations of red blood cells
Present in multiple myeloma, macroglobulinemia, or artifact
What is the significance of schistocytes in a peripheral smear?
Schistocytes = RBC fragments resulting from membrane damage when they pass through vessels; sometimes called “bite cells”
Occur in:
Microangiopathic Hemolytic Anemias (MAHA) (e.g., DIC, HUS, TTP)
Severe burns, uremia
Hemolytic anemia
What is the significance of sickle cells on peripheral smear?
Crescent shaped cells that occur when sickle cell patients experience stressors like dehydration, infection, or low O2 supply
What is the significance of target cells on peripheral smear?
Seen in: Sickle cell (HbC) Thalassemia Liver disease Post-splenectomy Severe IDA
