Anemias part 1 Flashcards
What does a CBC include
RBC count
Hgb/Hct (aka H&H)
Red cell indices
Reticulocytes (immature RBCs)
WBC count (with or without differential)
Platelets
what is Hgb
Hemoglobin - measure of total amount of hemoglobin in the peripheral blood
what is hemoglobin
oxygen carrying proteins
often a proxy for RBC amount/function
falsely reduced by dilution and vice versa
elevated in environments/conditions producing hypoxia (high altitudes, smokers, COPD,etc)
what is Hct
Hematocrit - measure of total blood volume made up of RBCs
expressed as a percentage
What is the RBC indices
look at specific properties of RBCs (size, shape, Hgb, ect)
what is included in the RBC indices
mean corpuscular volume (MCV)
mean corpuscular hemoglobin(MCH)
mean corpuscular hemoglobin concentration (MCHC)
Red cell distribution width (RDW) - how many different sizes are there? Range of sizes?
what are reticulocytes
total number of immature RBCs - used as a proxy for bone marrow function
RBC spit out their nucleus and RNA during maturation - reticulocytes haven’t spit out their RNA yet
what are the types of leukocytes
neutrophils
lymphocytes
monocytes
eosinophils
basophils
what are common causes of increased WBC
infection, trauma, malignancy, leukemias, tissue necrosis
WBC are an acute phase reactant
what is a CBC with diff used for
to identify underlying cause of leukocytosis
what are neutrophils
primarily for phagocytosis, indication of bacterial infections aka PMNs
what is the presence of immature neutrophils
“left shift”
gives indication that BM is pumping out WBCs before they are fully developed in response to some threat (real or perceived)
what are lymphocytes
T and B cells, responsible for antigenic immune response; chronic bacterial and viral infections
what are monocytes
similar function as PMNs, but are present longer in the blood
phagocytosis of bacterial infection
what are basophils and eosinophils
involved in allergic response (histamine) - also respond to parasitic infections
what is a platelet count sort of a proxy for
clotting function but sometimes even with normal number of platelets they can be dysfunctional
when can platelet levels be reduced
consumption (used up in clotting)
reduced production by BM
sequestration in the spleen
destruction (drugs, autoimmune, infections)
hemorrhage
dilution (blood replacement with platelet-poor fluids)
what is a normal absolute count of neutrophils
2500-8000
what is the normal absolute count of lymphocytes
1000 - 4000
what is the normal absolute count of monocytes
100-700
what is the normal absolute count of Eosinophils
50-500
what is the normal absolute count of basophils
20-100
what are signs of anemia
DOE (dyspnea on exertion)
Fatigue
bounding pulses
palpitations
muscle cramps
postural dizziness
syncope
headache
jaundice
what are history clues that may lead to anemia diagnosis
abdominal pain
melena - old/dark blood in stool
Pica - eating ice/dirt/cigarette butts
Menorrhagia - heavy period
NSAID/ASA use
pregnancy
hematochezia - bright red blood in stool
hematoemesis - blood in vomit
history of gastric bypass
+ FH of RBC disorder
history of ETOH abuse
dysphagia
malnutrition
how is anemia diagnosed
low number of circulating RBCs
low Hgb, low Hct or low absolute number of RBCs
what is the classification of anemia by Hgb status
mild: anything 10.0+
Moderate = 7.0-9.9
Severe = <7.0
how does elevated MCV present
RBCs larger than normal (aka macrocytic)
how does decreased MCV present
RBCs smaller than normal aka microcytiic
how does elevated MHC present
more Hgb per cell than normal (also hyperchromic) - darker
how does decreased/low MCH present
hypochromia (paler)
What is MCHC
mean corpuscular hemoglobin concentration
average Hgb concentration per RBC
percentage of RBC volume that is Hbg
what is the formula MCHC
MCHC = Hgb/Hct
what is anisocytosis
large variety of cell sizes; large, normal and smaller RBCs present
elevated RDW
what is Poikilocytosis
abnormally shaped RBCs
what is a peripheral smear
microscopic examination
tells us RBC color, shape, size, overall structure
how does a peripheral smear present with a B12 or folate deficiency
megaloblastic process
Macro-ovalocytes - ‘big’ and ‘oval’
what are schistocytes/helmet cells
fragmented RBCs
intravascular destruction (DIC, TTP, etc)
what is hyperchromia
loss of central pallor, spherocytes
hereditary spherocytosis
(circular and darker in color)
what is hypochromia
not enough hemoglobin, thalassemia, iron deficiency, sideroblastic
what are target cells
relative ‘membrane excess’; abnormal surface-to-volume ratio
liver disease, thalassemias
what are spiculated cells
liver disease, uremia
disorganization in cell membrane (lipids, proteins)
AKA echinocytes: Spiny
what are Burr cells assicated with
uremia
what is acanthocytes associated with
liver disease
what are Howell - Jolly Bodies
nuclear remnants
asplenia or hyposplenia (sickle cell)
seen on wright -giemsa stain
what are Heinz Bodies
denatured hemoglobin
‘inclusion bodies seen with crystal violet dye)
what are basophilic stippling
percipitation of ribosomes
*lead/heavy metal poisioning, thalaseemias, ETOH abuse
What are the Microcytic anemias
TIC
Thalassemias
Iron deficiency
Chronic disease
Siderobloastic
What are thalassemias
group of hereditary anemias (autosomal recessive) - one of the most common autosomal recessive in the world
absent or defective synthesis of adult hemoglobin (alpha and beta chains)
results in RBC destruction in bone marrow or intravascular hemolysis due to damaged red cell membranes
Where are thalassemias often seen/attributed with
historically regional: sub-saharan africa, mediterranean, middle east, india, southeast asia/china, central asia
conferred protection from malaria
What is Hemoglobin H
4 beta chains
error in alpha chains - clumping of beta chains
what is hemoglobin Barts
4 gamma chains
error in alpha chains early in life means more gamma chains ; not compatible with life
what is Hemoglobin S
sickle; 2 alpha, 2 mutated beta
what is Hemoglobin C
2 alpha, 2 differently mutated beta
What are the different types of Thalassemias
Alpha (major and minor)
Beta (major and minor)
Hgb Barts
what are alpha thalassemias
more common in AA, southeast asians or Chinese descent
most likely dx in pts <6months of age
gene deletion or mutation
what is the presentation of alpha thalassemias
often found on incidental screening:
- maternal/paternal screening
- newborn screenings
-part of adult physical screening
when and who do we see beta thalaseemia in
more common in AA and mediterranean pts
most likely diagnosed about 6+ months of age
-fetal Hgb (HbF) being replaced by adult Hgb
what is the presentation of beta thalassemia
asymptomatic (beta thalassemia minor)
beta thalassemia intermedia - mildly symptomatic, mild anemia, occasional transfusions
beta thalassemia major - severe anemia, transfusion
what are the clinical symptoms of thalassemia
fatigue
dizziness
dyspnea
tachycardia
HA
Leg cramps
difficult concerntration
pallor/jaundice
ulcerations
arrhythmias
heart failure
splenomegaly
immunocompromise
cholelithiasis
cirrosis or chronic liver failure
slow growth rate
delayed puberty
what are the clinical bone presentation of thalassemias
bone expansion
bone fragility and pathologic fractures
iron in the joints - arthropathies
what are shown on thalassemia labs
modest reduction in HCT - mild anemia
significantly reduced MCV - small RBC (microcytic)
normal RBC #
normal RDW
Normal iron studies
peripheral smear results: hypochromia, microcytosis, target cells, acanthocytes (spur cells)
what is the definitive diagnosis test for thalassemia
hemoglobin analysis (electrophoresis, genotypic, HPLC)
what is the treatment for mild thalassemia
asymptomatic do not need treatment
do not give iron - it can be damaging
what are the treatment options for thalassemia
folic acid supplementation
avoid oxidative drugs
TRANSFUSIONS
IRON CHELATION THERAPY
+/- splenectomy
BMT in severe cases
What is the number one cause of anemia worldwide
iron deficiency anemia
what are the main causes of iron deficiency anemia
blood loss (most common): GI bleeding (usually occult), NSAID induced, menorrhagia, malabsorption
Inadequate dietary intake: more likely in peds and females
what is the spectrum of iron deficiency
iron depletion (no stored iron)
iron deficient erythropoiesis (no storage and transport and functional iron being used)
iron deficiency anemia (no storage and transport and functional iron being used)
what are the general anemia complaints
Pica, brittle nails, spoon shaped nails, cheilosis, smooth tongue, esophageal webs
how does iron deficiency anemia present on peripheral smear
hypochromia, microcytic cells, target cells, nucleated red cells
what iron studies confirm iron deficiency anemia
serum ferritin
serum iron
serum transferrin aka total iron binding capacity (TIBC)
transferrin saturation (Tsat)
what is the treatment for menstruating females with AUB with iron deficiency anemia
emperic treatment
What needs to be done prior to beginning treatment for iron deficiency anemia
search for the source of the anemia (usually source of bleeding)
what are the treatment options for iron deficiency anemia
empiric iron treatment OR no evidence of non-dietary cause
120-200mg ELEMENTAL iron per day over 2-3 doses
typically ferrous sulfate 325mg PO TID, titrate up
what are the Adverse effects of Ferrous sulfate
constipation, black stools, GI upset
what should the result of iron deficiency anemia treatment be
Hgb increases 1mg/dL over 1 month
continue for minimum of 3 months
most sources recommend continuing for 6-12 months
will take several months for labs to normalize and stores to replenish
what are dietary iron sources
heme iron comes from animal food source - beef, lamb, pork, poultry, eggs, fish
non-heme iron comes from plant based foods - fruits, nuts, vegetables, grains, legumes
cast iron cookware increases dietary iron
what vitamin improves the absorption of iron
vitamin C
what is another name for anemia of chronic disease
anemia of inflammation
what is anemia of chronic disease
many etiologies - dependent on underling disease state
chronic inflammation - iron use ineffective, iron absorption impaired, decreased responsiveness to erythropoietin (Epo)
organ failure - decreased EPO production
any active malignancy
older adults - reduced sensitivity to EPO, reduced EPO production, chronic inflam
impaired marrow function
what is often co-occurring with anemia of chronic disease
iron or folate deficiency - worsens anemia
blood loss of hemolysis - also worsens anemia
what is EPO
erythropoietin
what is the lab presentation of anemia of chronic disease
variable
often mild-moderate anemia (Hgb >8)
normochronic, normocytic OR hypochromic, microcytic
normal or increased iron stores
normal or decreased TIBC, serum iron
peripheral smear is normal
what is the treatment of anemia of chronic disease
treat underlying cause/disease process
correct complicating factors (blood loss, folate deficiency, iron deficiency)
IV iron supplementation if warranted
EPO administration = must be Hgb <10, attempt to avoid transfusion
Transfusion - failure of other treatment - ongoing blood loss
what is the etiology of aplastic anemia
aka ‘bone marrow failure’ - anemia PLUS reduction in all other cell lines (pancytopenia)
more prevalent in asian and middle eastern populations
peak incidence: bimodal (15-25 and 65-69)
what are the causes of aplastic anemia
idiopathic
SLE
Chemotherapy
Radiation
Toxins
Drug induced
Hereditary
what is the presentation of aplastic anemia
often symptoms/consequences in reduction of other cell lines
increase incidence of infections
purpura/petechiae and abnormal bruising
abnormal bleeding
anemia symptoms: weakness, fatigue, pallor
what is diagnostic of aplastic anemia
pancytopenia
- low hemoglobin
- low absolute reticulocyte
- low neutrophil count
- low platelet counts
what does a biopsy show for aplastic anemia
hypocellular marrow with fatty infiltration
+/- abnormal or malignant cells or fibrosis
what are the treatment options for aplastic anemia
d/c any potential inciting agents
if mild = supportive care
- RBC and platelet transfusions
- treatment of infections
if severe and younger than 40 with compatible sibling donor - BMT from sibling donor
if sever and >40 OR <40 with no compatible sibling donor - immunosuppression
what is the prognosis of aplastic anemia
in severe: median survival of 3 month without treatment - 20% survive 1 year
in young adults (<20) with related BMT - 80-90% complete response rate
with pharmacologic treatment about 90% get partial response
patients treated without BMT are at increased risk for other marrow disorders
what is sideroblastic anemia
rare in practice
impaired heme synthesis - iron accumulation
what causes sideroblastic anemia
myelodysplasia
chronic alcoholism
hereditary
copper/B6 deficiencies
drug induced
LEAD POISONING UNTIL PROVEN OTHERWISE
what are the labs for sideroblastic anemia
normal or hypochromic cells on peripheral smear
basophilic stippling is likely lead poisoning
how is sideroblastic anemia definitively diagnosed
bone marrow eval - “ringed sideroblasts on Prussian blue staining”
what is the treatment of sideroblastic anemia
treat underlying cause
transfusion PRN, ban be lead to iron overload
What are the normocytic anemias
ABCD
Acute blood loss
Bone marrow failure
Chronic disease
Destruction (hemolysis)
acute blood loss anemia
pts will be bleeding
obvious of occult
GI tract most common site of occult bleeds - if you have a pt >50 yo with unexplained or new anemia YOU MUST RULE OUT COLON CANCER
what is the treatment of acute blood loss anemia
stop the bleeding
replace the blood
what is hemolytic anemias
episodic or continuous RBC destruction
classified by intrinsic or extrinsic cuases
characterized by elevated reticulocyte count with stable or falling Hgb/Hct
what are intrinsic causes
problem is with the RBC
what are extrinsic causes
problem outside of the RBC (often autoimmune)
what are the lab values for hemolytic anemias
peripheral smear consistent with compensation for increased RBC loss. - blasts, nucleated red vells, various morphologic changes
elevated unconjugated bilirubin
+/- serum LDH
Low Haptoglobin
Coombs test - checking for agglutination
what does a + Coombs test mean
autoimmune hemolytic anemia
What is hereditary spherocytosis
most common genetic hemolytic disease
autosomal dominant
also likely many undiagnosed
RBC membrane defect with results in RBC shape changing from concave to spherical - less malleable, get stuck more often, decreased survival
what is the presentation of hereditary spherocytosis
most patients asymptomatic
may or may not be associated with anemia
peripheral smear: microcytosis, spherocytes - loss of central pallor
what is the treatment of hereditary spherocytosis
blood transfusions
chronic folic acid supplementation to sustain erythropoesis
treatment of choice = splenectomy
what is the etiology of G6PD deficiency
glucose - 6 - phosphate dehydrogenase deficiency
herediatary, x-linked recessive disorder (M>F)
primarily a single amino acid substitution
more common in AA, mediterranean and ashkenazi jewish pts (aka Favism)
what is G6PD deficiency
related to deficiency in the G6P enzyme
important in glulconeogenesis/glycolysis
also acts as natural antioxidant
deficiency results in episodic hemolytic anemia
stress caused by: infection, certain foods (fava beans) certain medications
what is the presentation of G6PD
most are asymptomatic
episodic symptoms related to triggers:
-pallor
-jaundice
-bilirubinuria
- fever
-weakness, dizziness, confusion
-fatigue
-dyspnea
-splenomegaly and/or hepatomegaly
-tachycardia, heart murmur
what is the lab presentation of G6PD
denatured hgb precipitates out - heinz bodies
also see ‘bite’ cells and ‘blister cells’
what is the definitive diagnosis of G6PD
enzyme assay - reduced levels of G6PD
what is the treatment of G6PD
avoid certain foods, meds, environmental exposures
Hemolytic episodes self limited with production of new RBCs
what is the etiology of sickle cell anemia
inherited anemia - autosomal recessive
RBCs with Hgb S SICKLE UNDER STRESS
most common in AA pts
symptoms start around 6 months of age - Hgb F levels declining
what is the presentation of sickle cell anemia
vascular occlusions - painful crises (organ swelling, dysfunction, infractions)
delayed growth/puberty
splenic sequestration
what are pts with sickle cell anemia at risk for
cholelithiasis
splenomegaly
leg ulcers
infections with encapsulated organisms
stroke
AVN
Priapism
retinopathy - blindness
osteomyelitis
hematuria, poorly concentrated urine (renal infarcts)
how is sickle cell anemia diagnosed
low Hgb, normal MCV
elevated reticulocyte count, elevated LDH, elevated indirect bilirubin
coombs test negative
sickles cells on peripheral smear
nucleated RBCs/Howell-Jolly bodies +/- target cells
Hgb electrophoresis >50% Hgb S
what is the treatment of sickle cell anemia
pain: analgesics, fluids, O2, rest
Prevention of crisis: hydroxyurea (increases Hgb F production)
prevention of complications: low dose PCN from dx until 6 years old, pneumococcal vaccine with booster every 10 years, chronic folate supplementations, PFTs screening, transcranial doppler screening
possible BMT transplant in kids PRIOR to organ damage
genetic counseling/prenatal testing
