Hemat. Approach to Anemic Patient Flashcards
Define Anemia
- Reduction in RBC mass or blood hemoglobin concentration
- more than 2 standard deviations below the mean for age/gender/population
6 factors affecting Hg levels
- age
- race
- gender
- sexual maturity
- genetics
- altitude
How do
age, race, gender, sexual maturity, genetics, altitude
affect Hg levels?
- Babies/ kids: small bodies mean small losses are a big deal
- African, Asian, Mediterranean at higher risk for anemia.
- Normal levels are based on Caucasians (go figure)
- Women need to make more blood for menstruation, but also have lower Hg than men
- Prepubescent lower than post
- if mom or dad have anemia, kid might
- Higher elevations make people produce more Hg so they can perfuse tissue with the lower oxygen levels…adaptive.
What’s the process erythropoiesis
- renal interstitial peritubular cells detect low O2 in blood
- They secrete EPO (erythropoietin) into blood
- EPO stimulates proliferation and differentiation of RBC progenitors into Reticulocytes and prevent apoptosis
- Retics differentiate increasing in number
why does anemia develop
- RBCs not being made efficiently (Production)
- Bleeding (Loss)
- Extravascular and Intravascular Destruction
Red Flags for Anemia History/Intake
- Neonatal jaundice in the 1st 24 hrs
- Diet low in Fe, B12, Folate, Pica.
- G6PD deficiency gene expression (x-linked)= destruction of RBC
- triggered by fava beans, moth balls, aspirin, sulfadrugs, NSAIDS, severe stress, infection, nitrofurintoin,
- Gallstones at early age (Hg stones)
- splenomegaly and fam hx of splenectomy
- hepatomegaly
- pre disposition populations
- dark urine
- jaundice, fatigue… etc.
Physical Signs on Exam secondary to Anemia
Glossitis (red swollen tongue)
angular cheilitis (B12 deficiency)
Fe deficiency: spooning nails
Icterus esp in lower scerla (under lower eye lid)
frontal bossing of forehead (bone marrow expansion): Rickets, congenital syphilis, beta thalassemia,
Hyperproliferative Anemias and Hypoproliferative anemias
hyper: associated with increased destruction: dark urine, jaundice, splenomegaly, anemia when destruction overwhelms production
hypo: lower production, etiology usually localizes in marrow, typical symptoms of anemia
Hb/Hgb
the concentration of hemoglobin: oxygen carrying proteins
2 beta and 2 alpha chains. each chain has associated heme group and each heme group has a central iron which binds oxygen.
HCT (%)
Hematocrit percent (should be 3x hemoglobin)
% of blood volume occupied by RBC
what does MCV mean?
mean cell corpuscular volume:
tells us the average volume of RBCs collected.
relates to RBC size to tell if micro=<80, normo=80-100, or macrocytic >100
neonates 110 normal, 70 at 1 year old
if larger, it’s newer cells (macrocytic)
MCH
Mean cell hemoglobin: average Hb concentration of the RBCs
(when cell size change,
what is MCHC?
Mean [Hg] per ONE Red blood cell
What does a Reticulocyte Count mean?
How do you evaluate for Anemia?
a direct reflection of rate of RBC production
indirect reflection of rate of RBC destruction (elevated in disorders with more destruction)
(reported as % and an absolute number “ARC”)
Use ARC and %retic x RBC to get the whole picture
if pt has retic of 1% (normal) that’s fine unless their Hg is low, then retic should be high and compensating.
two classifications and 3 sub classifications of anemia
PATHOPHYSIOLOGIC:
- decreased production
- blood loss
- increased destruction
MORPHOLOGIC
- Macrocytic
- Normocytic
- Microcytic
What are disorders of erythrocyte production?
- Fe deficiency
- Lead poisoning
- Inflammation
- bone marrow failure syndromes
What are disorders with destruction probs
Hemoglobinopathies
RBC Membrane defects
enzyme deficiencies
What is RBC chromicity
clues on [Hg] : color or RBC
central palor: normal
MCH, MCHC can give clues, but Peripheral blood smear is more important
hyperchromic, normochromic, hypochromic, or polychromasia
What diseases are connected with these shapes, and what are these RBC shapes:
Target cells,
echinocyte
Acanthocyte
Spherocyte
Target cells: looks like a target: liver disease, HbC, HbD, HbE, Thalassemia
echinocyte: spiney like a sea urchin: Uremia, hypokalemia, artifact
Acanthocyte: irregularly shaped RBC with thorny projection: liver disease, PK deficiency
Spherocyte: sphere shaped, no central palor: HS Immune hemolytic anemia
Microcytic Anemia causes
Fe deficiency anemia
thalassemias (alpha & beta)
Chronic disease/ inflammation
Pb toxicicty
Most common anemia
Fe deficiency with 3% of young children in US
8-10% have Fe deficiency with out anemia
(pregnant women, adolescents, elderly)
(if Fe deficient and small bodied, a small blood loss could push them over the edge to become anemic)
Etiology of Fe deficiency
- Increased demand to make blood (infancy, adolescents, pregnant, making more rbcs)
- malnutrition (vegetarians, vegans, junk food diets)
- decreased absorption (gastrectomy, H. pylori, IBD, drugs)
- GI bleeds benign or malignant, GU bleeding heavy periods, blood donors
- drugs: NSAIDS, steroids
- chronic kidney disease, IBD, heart failure, obesity
Stages of Fe depletion, what labs would you order and why
1) Depleted iron stores (marrow iron/serum ferratin) 2-3+
2) Iron deficient erythropoiesis: Serum Fe <100ug/dl and %saturation is <30
3) Iron Deficient Anemia: HCT<40, RBC become microcytic and hypochromic
*don’t stop treatment too early, gotta build up stores! Serum Fe increases in one meal, Serum ferratin slower to build
What does low Fe look like with labs?
Low: Hg, MCV, MCH, MCHC, RBC count
Low uncompensated retic count
Increased TIBC/transferin (nothing to bind them)
Low ferritin (deficiency: <10-12ng/L, depletion: 12-20ng/L
normal is 20-300ng/L
Inflammation can falsely elevate Ferratin even if you don’t have iron stores
Problems with Fe Tx
Ferous sulfate tastes horrible.
Side effects include dyspepsia, constipation, nausea, abd pain,
Helps to take with food… decreases absorption, but some is better than not taking it at all.
Polysaccharide preparations sweeter
Foods with high Fe
Liver, red meat
beans/ greens
iron-fortified cereals/ grains
heme: meat, non-heme: vegetarian
therapeutic response to Fe treatment of deficiency
Tx works within 3 days.
see less hypochromia, increased RDW
increased reticulocytes in 2-3 days,
Hg & MCV goes up in a week
Serum iron 1-2 hrs
TIBC goes down: 2-3 weeks
Serum Ferritin goes up: 1-2 weeks, 3-4 to normal
Why are they having Fe loss in the first place?
What would you look for?
GI Blood loss: guaiac (occult stool), if positive endoscopy
Urea breath test
Test Antibodies for H. pylori, anti-transglutaminase (celiac sprue if fails to respond to oral iron)
C-reactive protein: inflammation? neoplasm? especially in elderly
Metro/menorrhagia: evaluate for bleeding disorder
Normal Treatment for Fe deficiency
Iron Salts 100-200mg elemental Fe in 2 doses
Ferrous Sulfate, Ferrous Gluconate Taken on empty stomach for best absorption, avoid coffee, tea, take with Vit C (acid helps absorption) Kids: 2-6mg/2 doses, NO MILK
**continue Tx 3mths to replenish serum ferritin***
when oral Fe is contraindicated, or another method is indicated
IV iron therapy : for those who can’t take orally (gastrectomy, duodenal bypass, H. pylori, celiac, IBD, genetic IRIDA, or if needs to be immediate recovery (severe anemia in 2nd-3rd trimester, chronic renal disease, substitution for blood transfusion (religious reasons), chemo anemia (from ESA)
contraindicated: 1st trimester of pregnancy, iron allergy (hypersensitivity rx)
What is anemia of Chronic Disease
Anemia from a chronic state of inflammation
(like cancer, chronic infection, lupus, RA, and other autoimmune disease, obesity, aging)
that causes impaired production of RBCs
What’s the pathophysiology Anemia of Chronic Disease that has to do with iron levels?
Hepsiden ( regulatory hormone made in liver, excreted to urine) tells Macrophages to keep iron inside cells, and not let it into circulation, and tells duodenal and intestinal cells not to absorb more Fe. This is because it thinks it is being invaded, and Fe makes bacterial infections stronger.
We expect higher hepsiden in Fe overload, and infection
lab findings in Anemia of Chronic Disease
mild-moderate anemia
MCV: normal to low
RDW: normal
Retic Count: low
Ferritin: normal to high (even if Fe is low)
treatment Anemia of Chronic Disease
- eradicate underlying disease
- if impossible,
- transfusions
- IV iron
- Erythropoesis Stimulating Agents
- New experimental approaches targeting IL-6 activity
What is macrocytic Anemia? what’s it caused by
Larger RBCs
Caused by B12 or Folate deficiency (DNA synthesis: mismatch between how much cytoplasm to put in cell and membrane so cells larger)
Non-Megaloblastic causes: Phentoin, Bactrim, ART, Chemo, hypothyroid, liver disease, alcoholics, myelodysplasia, bone marrow failure, reticulocytosis
What labs do we order if we suspect Macrocytic Anemia?
CBC with peripheral blood smear (hyper-segmented neutrophils/neutropenia)
reticulocyte count (to see if MCV 110-140 is bigger because more retics, also to see if production or destruction prob)
serum cobalamin, folate, and TSH
liver function test (alcoholics)
measure folate/cobalamin (needed for DNA synthesis including for RBCs)
Signs and symptoms of macrocytic anemia
Both for B12 and Folate deficiency, see glossitis-smooth tongue, and dyspnea with exercise, pallor, etc.
For B12, neuropathies, ataxia, seizures, psychiatric probs, decreased sensations
what causes B12 deficiency
pernicious anemia: (autoimmune) disease where autoantibodies destroy gastric parietal cells which produce intrinsic factor
malabsorption: IBS, chrons disease, celiac, bowel resection
Hemolytic anemia, excess blood loss
pregnancy: when more need is happening
Lab results for Macrocytic Anemia from B12 deficiency
moderate -severe anemia
elevated MCV 110-140
low reticulocyte (not compensated)
hypersegmented neutrophils and macroovalecytes on smear
mild thrombocytopenia and/or neutropenia
low serum B12, <170 (when normal or 170-210, confirm with elevated methylmalonic acid or homocystine)
Diagnosis for Pernicious Anemia
Anti-intrinsic factor antibodies (100%specific, but only 70% sensitive= false neg)
Anti-parietal cell antibodies (more sensitive, but less specific=false positive)
Shilling test (board answer)
Tx for B12 deficiency
IM or subcutaneous injection of 100mcg B12
daily x 1 wk, then weekly x 1 month, then monthly for life
OR
sublingual 1mg/day for EVER
(folic acid also recommended for first few mths of B12 tx)
Response to B12 Tx for Macrocytic Anemia
well-being in 1-2 days,
brisk retic increase in 3-4 days, and Hg in 10 days
***Hypokalemia can occur during early response because increased K+ use for RBC production*** monitor
neuropathies improve totally by 6 mths
Labs for Folate Deficiency
Mod-severe anemia
elevated MCV
low retic
hypersegmented neutrophils/macro-ovalcytes on peripheral smear
mild thrombocytopenia/neutrophils
RBC folic acid levels (better than serum folate b/c reflects body stores <150 is deficient)
also measure B12.
Tx of folate deficiency
daily oral folic acid 1 mg
Response is rapid wellbeing
retics in 5-7 days
total correction of hematologic abnormals in 2 mths
Non-megaloblastic anemia causes and Tx
anti-retroviral drugs, antiseizure meds, chemo, bactrim
hypothyroidism
non-alcoholic liver disease
chronic alcohol use: stop alcohol use, blood returns rapidly
Differential for Normocytic Anemia
+++Reticulocytes
hemolytic anemia
Post-hemorrhagic anemia
—Reticulocytes
acute hemorrhage
anemia of inflammation
renal/liver disease
marrow infiltration
myelodysplastic syndrome
