anemia Flashcards
EPO is produced
by the kidney in response to adequacy of tissue oxygenation
role of EPO
enhances growth and differentiation of the erythroid progenitors into normoblasts
d. When a normoblast extrudes its nucleus to form a RBC it is called a
reticulocyte
Reticulocytes retain ribosomal network for about ____ and then
Reticulocytes retain ribosomal network for about 4 days (3 d in marrow, 1 d in blood) then lose RNA and become mature RBC
MCC of microcytic
i. IDA
ii. Thalassemia
MCC of normocytic
i. ACD (Anemia of chronic disease)
MCC of Macrocytic
i. B12/Folate deficiency
ii. With increased reticulocytes:
1. Hemolysis
sxs due to decreased oxygen or hypovolemia
Exertional dyspnea, dyspnea at rest, varying degrees of fatigue, bounding pulses, palpitations, “roaring” sound in the ears (can hear their heart beat in their ears)
e. Acute bleeding with severe volume depletion may lead to sxs of
fatigue, muscle cramps and can progress to postural dizziness, lethargy, syncope, hypotension, shock and death
mild anemia is more common with sxs associated with
exertion
as it progresses you will see fatigue and dyspnea at rest
PE and CM evidence for hemolysis
Splenomegaly
petechial rashes
jaundice abdominal pain = sign of hemolysis
evidence that the bone marrow is suppressed
Pancytopenia? Lack of retic count?
Recurrent infections
what do we want to start thinking of with iron deficiency
Why? lots of ETOH, dietary deficiency, underlying illness
NSAIDS and ASA
can cause bleeding and anemia
hydrourea
medication for sickle cell disease
worry about renal failure b/c
decreased EPO
LDA HSM and bonetenderness
can give you indication of underlying cancer or bone marrow probem
if your pt has anemia what would you expect from reticulocytes
high because if the bone marrow is healthy it should be pumping out more reticulocytes
if you have anemia the reticulocytes should NOT be 1% like it is normally
Iron studies/panel include
Iron, TIBC, transferrin saturation, ferritin
what to order if you suspect hemolytic anemia
LDH (elevated in certain types of CA and hemolytic anemia),
indirect bilirubin
haptoglobin (decreased in hemolytic)
why would you order EPO level or serum Cr
worried about anemia from renal damage
hypochromic microcytic anemia
IDA
Consider hemolysis in what type of anemia picture
normocytic
Leukopenia (low WBC) + anemia usually due to
bone marrow suppression, hypersplenism, vitamin B12 or folate deficiencies
Leukocytosis (increase WBC)+ anemia typically indicates
indicates infection, inflammation,
or hematologic malignancy (WBC over 60,000)
increase in neutriphils
iii. Inc neutrophils in infxn
; inc monocytes in
in myelodysplasia
inc eosinophils with
parasites or allergic disease
; dec neutrophils
s/p chemo
; dec lymphocytes
in HIV or steroid tx
Thrombocytopenia with anemia ddx
DDx includes
hypersplenism malignancy involving bone marrow autoimmune platelet destruction sepsis vitamin B12 or folate deficiency
Thrombocytosis with anemia ddx
DDx includes
myeloproliferative disease chronic iron deficiency inflammatory infectious or neoplastic disorders
Can provide information not otherwise available in a CBC with diff
Peripheral blood smear
MCC on anemia
IDA
GIB is THE MCC of th MC anemia
Iron is stored primarily as
ferritin first levels to decrease with IDA
Causes of Iron Deficiency
¢ Deficient diet
¢ Decreased GI absorption
¢ Increased iron requirements (Pregnancy & lactation)
Blood loss (GI, menstrual, blood donation)
¢ Hemoglobinuria
¢ Iron sequestration (Pulmonary hemosiderosis)
pica is a sx related to
IDA
skin changes in anemia
” Skin and mucosal changes: smooth tongue, brittle nails, cheilosis (dry cracked areas on corners of mouth which can bleed)
if you have a clear suspicion of IDA or GIB
might have stool positive for a occult blood
first indicator of IDA
Ferritin
then TIBC due to increase binding sites open as iron is
- Peripheral smear from a patient with iron deficiency shows
pale small red cells with just a scant rim of pink hemoglobin; occasional “pencil” shaped cells are also present. Normal red cells are similar in size to the nucleus of a small lymphocyte (arrow);
thus, many microcytic cells are present in this smear. Thalassemia can produce similar findings.
tx of IDA
tx the cause and anemia
FeSO4 325mg PO TID = 1st line
Tana says she usually starts 1 time a day
also refer pts to dietician or council them on diet
don’t take iron with milk=bad absorption band constipation
MC SE of IDA tx
FeSO4 325mg PO TID
Causes nausea, constipation, dark stools in many pts
slow Fe or plant based iron less SE but —>less absorption
when would you use parenteral iron therapy for IDA
” Intolerance to oral iron, refractory IDA, GI disease, uncorrectable continued blood loss
when to recheck iron for IDA tx
3-6 mos after acheiving normal labs
should see return to H/H in 2 mos
want to check every 3 weeks or so until back to normal
then iron panel
want to keep checking periodically
CC of anemia of chronic disease
Chronic infection or inflammation (Sarcoidosis, RA)
Cancer
Liver disease
Chronic renal failure
pathophys of ACD
RBC survival is decreased
Bone marrow fails to compensate adequately for shorter RBC lifespan
o ↓ Serum ferritin o ↑ TIBC o ↓ Hgb/Hct o Microcytic, hypochromic cells o Anisocytosis & Poiklocytosis
Iron Deficiency Anemia (IDA)
ACD is what type of anemia
normocytic anemia
TX of ACD
” Treatment is not usually necessary
“ Purified recombinant erythropoietin is used in renal failure and some types of cancer or inflammatory diseases (eg: RA)
“ Hemodialysis is also used in patients with renal failure
“ Treat any coexistant iron or folate deficiency
Thalassemias anemia is caused by defective
defective hemoglobinization of RBC
hallmark of Thalassemias
Microcytosis out of proportion to the degree of anemia
o ↓ Hgb/Hct o ↓ Serum iron, TIBC o ↓ Serum EPO o Normocytic, normochromic cells o Normal retic count o ↑/Normal serum ferritin
ACD
specifically in renal failure you will see decrease in EPO
low serum iron due to iron sequestering
going to see low TIBC
high ferritin
Alpha-Thalassemia mainly effects
Affects primarily people from SE Asia and China
Alpha-Thalassemia
Hemoglobin H disease is
Hemoglobin H disease is a severe form with excess β-chains that form a β4 tetramer
type of thalassemia that is incompatible with life
Hydrops fetalis
3 Alpha-globin genes
Silent Carrier Normal 80-100
2 Alpha-globin genes
Thal. Minor 28-40% 60-75
these pts are completely fine with normal Hct and really marked MCV (60-72)
microcytsosis OUT OF PROPORTION
1 Alpha-globin genes
Hgb H dz 22-32% 60-70
α-thalassemia trait seen as what labs
how to dx
mild anemia
Hct 28-40%, very low MCV, normal RBC count
Reticulocyte count and iron studies normal
CBC of Hemoglobin H Dz
marked hemolytic anemia, Hct 22-32%, very low MCV
Reticulocyte count is elevated
Peripheral smear of α-thalassemia trait
microcytic, hypochromic RBC with
occasional target cells
how to dx subtypes of alpha thalassemia
GOLD STANDARD
Hemoglobin electrophoresis shows no significant abnormality
electrophoresis in Hemoglobin H Dz
Hemoglobin electrophoresis shows a fast migrating abnormal Hgb H as 10-40% of Hgb
Hemoglobin H Dz Peripheral smear
hypochromia, microcytosis, target cells, poikilocytosis
microcytosis out of proportion to anemia in italian or greek pt usually
Beta-Thalassemia
Beta-Thalassemia usually Results in a relative increase in the percentage
Hgb A2 and Hgb F compared to Hgb A
Beta-Thalassemia Major
Homozygous B
90-96% Hgb F
Beta-Thalassemia Minor
Hgb A: 80-95%
Hgb A2: 4-8%
Hgb F 1-5%
β-thalassemia minor (trait)
β-thalassemia minor (trait): clinically insignificant microcytic anemia
when do we see sxs of β-thalassemia major
children normal at birth, develop severe anemia at 6 mos when Hgb F switches to Hgb A
sxs of β-thalassemia major
- Growth failure, bony deformities, HSM, jaundice; requiring multiple transfusions
- If not treated properly, can develop cardiac failure, cirrhosis, endocrinopathies
Peripheral smear from a patient with beta thalassemia trait.
- Peripheral smear from a patient with beta thalassemia trait. The field shows numerous hypochromic and microcytic red cells (thin arrows), some of which are also target cells (blue arrows).
B-Thalassemia Major
tx with allogenic bone marrow transplant
Mild thalassemias do not usually require treatment
” Hemoglobin H tx
disease treated with folate supplements and regular transfusions; iron chelation therapy often used; splenectomy
Mild thalassemias do not usually require treatment
CBC of B-Thalassemia Major
severe anemia with very low Hct
CBC of
B-Thalassemia Minor
” CBC: mild anemia, Hct 28-40%, MCV low (55-75 fL
Folic acid (folate) deficiency and c yanocobalamin (vitamin B12) deficiency
are all
Megaloblastic Anemias
Megaloblastic Anemias are macrocytic anemia seen with what smear
- Peripheral blood smear showing a hypersegmented neutrophil (7 lobes) and macro-ovalocytes, a pattern that can be seen with cobalamin or folate deficiency.
with MCV elevation
check B12 AND foalte
causes of B12 deficiencies
i. Decreased production of intrinsic factor
Pernicious anemia; gastrectomy
Helicobacter pylori infection
Competition for vitamin B12 in the gut
iv. Pancreatic insufficiency
v. Decreased ileal absorption of vitamin B12
Surgical resection; Crohn’s disease
Dietary and transcobalamin II deficiencies are rare causes
tx for B12 deficiency
Pernicious anemia: 100mcg IM daily x 1 week then weekly x 1 month then monthly for life
1000mcg IM monthly (no PA)
” 1000mcg po qd continued indefinitely
macrocytic anemia with neurologic findings
B12!!!!
AFTER B12 tx when should pt return to normal
- Hypokalemia may occur at onset of treatment
- Hematologic findings normalize in 2 months
sxs of B12 macrocytic anemia
Changes in mucosal cells leading to glossitis; vague GI complaints including anorexia, diarrhea
Peripheral nerves affected leading to paresthesias, dysequilibrium, dementia and other neuropsychiatric changes
Reversible if treated within 6 months
Pale, mildly icteric; decreased position or vibration sense on PE
dx studies for b12 deficient anemia
” Anemia of variable severity
“ MCV elevated to 110-140 fL
“ Peripheral smear with macro-ovalocytes, hypersegmented neutrophils; poikilocytosis and anisocytosis
“ Decreased reticulocyte count
“ WBC count and platelets may be decreased; pancytopenia may be present
“ Abnormally low serum vitamin B12 level
Clinical Presentation of folic acid anemia
” Mucosal changes similar to vitamin B12 deficiency and megaloblastic anemia
“ No neurologic abnormalities
“ Symptoms of anemia
“ Fatigability, tachycardia, palpitations, DOE
dx studies for folic acid anemia
” Anemia of variable severity
“ MCV elevated to 110-140 fL
“ Peripheral smear with macro-ovalocytes, hypersegmented neutrophils; poikilocytosis and anisocytosis
“ Decreased reticulocyte count
“ Decreased RBC folate or serum folate level
“ Normal serum B12 level
causes of folic acid anemia
i. Dietary deficiency (lack of absorption)
1. Alcoholics, anorexia, malnutrition, overcook foods
ii. Decreased absorption
1. Tropical sprue; drugs (phenytoin, sulfasalazine)
iii. Increased requirement in –
1. Chronic hemolytic anemia; pregnancy; exfoliative skin disorders
iv. Loss of folic acid through dialysis
v. Inhibition of reduction to active form
1. Methotrexate
general category for a decrease in RBC survival
XVI. Hemolytic Anemias
Intrinsic RBC defects leading to hemolytic anemia
o Enzyme deficiencies
o Hemoglobinopathies
o Membrane defects
Intravascular destruction of RBC leading to hemolytic anemia
o Microangiopathy
o Transfusion reactions
o Infections
o Paroxysmal hemoglobinuria
Extrinsic RBC defects leading to hemolytic anemia
o Liver disease o Hypersplenism o Infections o Oxidant agents o Microangiopathy o Autoimmune o Leukemia o Burns
most important tests for hemolysis
Decreased serum haptoglobin (won’t see this in other types of anemia)
Increased indirect bilirubin in the blood
also
Elevated serum LDH levels in microangiopathic hemolysis and others
Hemoglobinuria and positive urine hemosiderin with intravascular hemolysis
Autosomal recessive hemoglobinopathy
Sickle Cell Anemia
Affecting 8% African Americans
Factors that influence RBC sickling:
Concentration of Hgb S in the RBC –>the more Hgb S you have, the more likely you are to have sickling
RBC dehydration Other types of Hgb in the cell (Hgb F) Anything that leads to deoxyhemoglobin state 1. Acidosis, hypoexmia
Sickle cell anemia c sickle cell trait
AS genotype in trait
40% Hgb S
SS in sickle cell
86-98% Hgb S
Sickle cell crisis
Sickle cell crisis
“ Acute painful episodes due to acute vaso-occlusion; associated low-grade fevers
“ Clusters of sickled cells occlude the microvasculature of the organ(s) involved
“ Bones and chest most often affected
“ Last hours to days
“ Occur spontaneously or due to infection, dehydration, hypoxia
Clinical presentation of sickle cell anemia
Chronic hemolytic anemia produces jaundice, pigment gallstones, hepatosplenomegaly
Poorly healing ulcers over the lower tibia, heart failure, retinopathy
Severe hemolytic or aplastic crises may occur when bone marrow decompensates or in splenic sequestration of sickled RBC
Chronically ill patients; poor growth and development
Life expectancy between 40-50 years of age
Sickle cell diagnostic studies
Diagnostic Studies
“ Chronic hemolytic anemia with Hct 20-30%
“ Peripheral blood smear with sickled cells (5-50%), nucleated RBC, target cells, and Howell-Jolly bodies indicating hyposplenism
“ Reticulocytosis 10-25%
“ WBC count elevated 12-15K; thrombocytosis may occur
“ Increased indirect bilirubin b/c of hemolysis
GOLD STANDARD
Diagnosis confirmed by Hgb electrophoresis
tx of sickle cell
No specific treatment is available for the primary disease of sickle cell anemia
Maintenance with folic acid supplements
Blood transfusions for aplastic or hemolytic crises
Acute crisis treated with oxygen, fluids, blood transfusion, and treatment of any underlying infection if present
Hydroxyurea (500-750mg/d orally) to reduce frequency of pain crises
Allogenic bone marrow transplant for young patients may be curative
Pneumococcal vaccination recommended to reduce infections, particularly post-splenectomy
Very low MCV order
ii. Very low MCV order Hgb electrophoresis for thalassemias, SSD
Normocytic usually
should order..
Usually ACD
order iron studies b/c these pts can have coexistent iron deficiency, CMP
Consider hemolysis, may need haptoglobin
RBC Transfusion indications
10/30 Rule = Hgb < 10g/dL or Hct<30%
Estimated blood volume loss (>30%)
Symptomatic anemia (dizzy, SOB, fatigue)
Effect of blood on H/H
Each unit of packed RBC (300mL volume has 200mL of RBC) will raise Hct 3-4% and Hgb 1g/dL if no continued bleeding
Bone Marrow Biopsy indications
i. Unexplained anemia, leukopenia, thrombocytopenia, or pancytopenia
ii. Diagnosis/staging of lymphoma or solid tumors
iii. Diagnosis of plasma cell disorders and leukemia
iv. Evaluation of iron metabolism and stores
v. Evaluation of storage and deposition diseases
vi. Evaluation of FUO; suspected unusual infections
vii. Unexplained splenomegaly
viii. Evaluation of suspected chromosomal abnormality
When to Refer
There appears to be more than one type or cause of anemia
A more complicated or unusual type of anemia is present
Anemia does not improve with treatment
