Hematology Flashcards
What is the only indication for RBC transfusion with normal Hb?
Tissue Hypoxia
Confusion (brain)
Angina (heart)
Even if Hb or Hct are normal
How do you calculate Hct?
3x Hb
if Hb is 8
then Hct is 24
WHat if Hb is below 8?
RBC transfusion
What is the first tests you always do in any anemia?
CBC and Peripheral Smear
What is Anemia Defined as?
HCT:
<41% in men
<36% in women
or
Hb
<13.5 in men
<12 in women
Note this is anemia.. but does not warrant RBC transfusion
Microcytic MCV <80 Causes
- iron deficiency
- Thalassemia
- Sideroblastosis
- Lead poisoning (part of sideroblastosis)
- Anemia of chronic disease
Whats the next step when CBC shows microcytic anemia?
Iron studies
If iron studies are normal then you do Electorpheresis (to rule out thalassemia)
or
Bone marrow biopsy
Macrocytic Anemias >100 Causes
B12 / folate deficiency Alcohol Liver Disease Methotrexate Zidovudine / phenytoin
what is the next step after CBC shows macrocytic anemia?
Peripheral smear
IF you see hypersegmented neutrophils –> B12 deficency
If you see normal PMNs (3-5 segments) then its either alcohol liver disease methotrexate Zidovudine / phenytoin
Normocytic Anemia causes (80-100 MCV)
Hemolysis
Hemhorrage
Bone Marrow disorder
next step –> get the reticulocyte count
if retic count is low then its a bone marrow issue –> do BM biopsy
If reticulocyte count is high –> this is a sign of hemohrrage or hemolysis
Anemia symptoms
fatigue, tiredness, poor exercise tolerance.
DISEASE PROGRESSION :
dyspnea on exertion, light-headedness
systolic ejection murmur (flow murmur)
confusion, AMS
AMS (RBC transfusion!)
What does Red Cell Distribution Width tell you?
Measures Anisocytosis - the variation amongst the cells.
will help differentiate between IDA and Thalassemia
What is Coombs test for?
to differentiate Auto Immune Hemolytic Anemia vs Herditary Spherocytosis
What is Bone Marrow Biopsy useful for?
Normocytic anemia with low retic count
When you give 1 unit of RBCs how much should Hb and Hct go?
Hb - 1 point
Hct - 3 points
Hct Ranges?
For nomral young healthy people - can go as low as 20% (no lower)
For older patients with CAD - keep it above 30%
RBC appearance in IDA
in a normal RBC 1/3 of the rbc center should be pale
in IDA the RBC is microcytic and the 90% of it is pale in the center.
IDA has a very increased RDW (increased anisocytosis)
IDA in a young patient differential?
in women - heavy menstrual flow
in men - PUD
IDA in an older patient (over 50)
Do COLONOSCOPY!!
IDA in a 2 year old?
get a meckles scan!!
meckles diverticulum MCC
Pregnant woman with IDA?
caused by increased demand,
give her Iron and Folate (all pregnant women should be on iron and folate!)
what should you do for someone with IDA caused by poor oral intake or malabsorption?
you need Acid to absorb Iron. Give this patient vitamin C.. make their GI acidic.
if that doesnt work you have to to IV
IDA presentation
brittle nails
spoon shaped nails (poikilocytosis)
glossitis
pica
none of these are diagnostic. History helps - but you have to do iron studies to confirm diagnosis
IDA iron studies
Serum Iron - decreased Serum Ferritin - Decreased TIBC (transferrin)- increased RDW - increased Reticulocytes - Decreased
If Serum Ferritin is low (storage form) - then its automatically IDA
Remember Ferritin and Transferin are always opposite.
in IDA Ferritin is low! so transferin (TIBC) must be high
MAT for IDA?
Bone Marrow Biopsy (stainable iron stores)
rarely done.. not needed
Only do this if the patient has IDA and an inflammatory disease at the same time. This will cause ferritin to look high (anemia of chronic disease)
Treatment for IDA
Oral therapy - Ferrous Sulfate
If patients cant absorb it?
give IV
If patients are constipated
give IV
if patients have advanced kidney disease
give IV
What is anemia of chronic disease?
Defect in ability to sue iron sequestered in reticuloendothelial system
can be microcytic or normocytic
Anemia of chronic disease and hepcidin
Inflammatory mediators cause liver to release Hepcidin –>
Hepcidin blocks ferroportin –> thus cant absorb iron from GI tract or from Storage from in Macrophages
what kind of problem is anemia of chronic disease?
Iron Re-utilization problem!
Anemia of Chornic disease iron studies
remember always do iron panel as next step when you see microcytosis!
ACD iron panel: Serum Iron - low Serum Ferritin - starts normal then HIGH TIBC- low Reticulocytes- low
How do you treat anemia of chornic disease?
treat the underlying disease
this will cause decrease in inflammatory markers –> decreased hepcidin –> Iron released through ferroportin channels in GI and macrophages
Hereditary hemochromatosis
Absent HFE gene –> cant make Hepcidin.. Ferroportin channels stay open.. and Iron rushes into the body unchecked
Iron deposition in tissues
What happens if you give EPO or Iron supplements in Anemia of chronic disease?
in ACD you cant absorb or release iron.. giving more iron will cause hemochromatosis – dont do it
giving EPO will cause more RBCs to be made.. except they wont have iron.. no Heme.. dont do it
only time you do this is when ACD is due to:
Renal disease - Need EPO then
or
Chemo / radiation!
What causes Sideroblastic Anemia?
Hereditary Forms:
Defect in ALA synthase
Abnormality in B6 metabolism
Acquired Forms: B6 deficency (INH will cause B6 deficency)
Lead poisoning –> blocks ALA dehydrogenase and Ferrochelatase
Alcohol – Poisons Mitochondria.. cant make Hb
What characterizes siderbloastic anemia?
ringed siderolbast (this is diagnostic)
The ring is Iron trapped in the mitochondria of Nucleated RBCs
To diagnose Sideroblastic Anemia you must do a BONE MARROW BIOPSY!! with Prussian Blue stain and find ringed sideroblasts (most specific test)
Sideroblastic anemia iron studies
Always do Iron study first for microcytosis!
Serum Iron - Increased
Serum Ferritin - Increased
TIBC (transferrin)- Decreased
What does basophilic stippling of RBCs show on peripheral blood smear?
basophilic stippling
blue dots around the RBC
Sideroblastic Anemia Treatment
Remove offending drug
Treat Lead poisoning (for kids use succimer, for adults use IV drugs (EDTA, Dimercaperol)
Give Pyridoxine (2-4mg/day)
Thalassemia definition
Underproduction of either alpha or beta globin chains of Hb molecule
Hypochormic, microcytic anemia
Thalaseemia types
Alpha thalassemia
One gene deletion (normal patient)
CBC,Hb, MCV all normal
two gene deletion Mild anemia (HCT 30-40%, very low MCV)
three gene deletion (Hemogobin H) profound anemia (HCT 22-33), very low MCV
Four Gene deletion
Dead baby die inutero (Barts)
Thalassemia diagnosis?
Always start with Iron panel for microcytosis!
Thalassemia will have a normal iron panel. Next step is Hb Electrophoresis.. this will tell you which Thalassemia they have.
Beta thal Minor:
Heterozygous for mutation of Beta Hb Gene
Mild anemia with marked microcytosis
Electrophoresis will be abnormal –> low HbA and High HbA2 and HbF
How can you tell alpha thal minor and beta thal minor apart?
they both look the exact same.. Must do Hb electrophoresis to differentiate.
Alpha thal minor - normal electrophoresis
all HbA
In Beta thal minor - abnormal electrophoresis
low HbA, High HbA2, and High HbF
no treatment needed for thalassemia minors
Beta Thalassemia major presentation
Homozygous for mutations of both genes coding for beta hemoglobin gene
severly symptomatic starts at 6 months: growth failure jaundice hepatosplenomegaly bony deformities secondary to extramedulary hematopoesis (chipmunk facies)
Treatment for Beta Thal Major?
Life long blood transfusions (once or twice per month)
these patients will die from Hemochromatosis –> cirrhosis, CHF etc.
Give Folic acid supplementation
Give oral deferasirox or Deferiprone for hemochormatosis. easier to give then deferoxamine which requires a sub cutaneous pump
For severe - do splenectomy - spleen is the major area of hemolysis. this will reduce that
Allogenic stem cell transplantation is the only cure
What Red Cell finding will all thalassemias have?
Target cells!
if you see microcytic + target cells = Thalassemia
What is RDW for thal vs IDA?
IDA - very high RDW (anisocytosis)
Thalassemia - normal RDW (cells are all small.. but the same size as each-other)
What is the only cure for thalassemia
allogenic stem cell transplant
treatment of choice for beta-thall major
Macrocytic anemia - B12 Deficency Causes
MCC is Pernicious anemia
vegetarian diet
Malabsorption - celiac sprue, regional enteritis, Pancreatic insufficiency (need pancreatic enzymes to absorb B12)
Tape worm (dipholorbium latum)
Patient will present with macrocytosis, neuro issues
Pernicious anemia etiology
MCC of B12 deficiency
Type 2 hypersensitivity reaction
Autoimmune disorder involving gastric parietal cell antibodies –> results in decreased intrinsic factor –> cant absorb B12 in small intestine
Note: gastrectomy and atrophic gastritis can also cause decreased intrinsic factor production and thus B12 deficiency
B12 deficiency peripheral smear and CBC
Oval Macrocytes!!
(ROUND macrocytes are seen in other diseases like hemolysis, liver disease, myelodysplasia)
Retic count is decreased - Marrow is hypercellular
Vitamin B12 deficiency diagnosis
Most specific and first test = low B12
However this doesn’t tell you if the issue is folate or b12.
Next test you MUST do after this is Methylmalonic acid
Methylmalonic acid is only elevated in B12 deficiency not in folate deficiency
Once B12 deficiency is confirmed check for antibodies to intrinsic factor and parietal cells to confirm etiology.
How does schilling test work? (we dont actually do this in real life.. but its tested on USMLE as a thought experiment)
give radioactive b12. If this is found in the urine, then this means ur body was able to absorb the b12 and then you excreted it.. so that means you have normal absorption of b12, but just had a b12 deficiency (correct by IM b12)
If you give radioactive b12 and its not in the urine, then you can either have a disorder of parietal cells or lack of intrinsic factor. If you give b12 + intrinsic factor and now the B12 shows up in the urine then the issue as intrinsic factor (issue is pernicious anemia)
If you give radioactive b12 and intrinsic factor and it still doesn’t show up in the urine. Then give pancreatic enzymes. When you give pancreatic enzymes and its hows up in the urine now.. then you know the issue is a lack of pancreatic secretions.
If B12, pancreatic enzyme and intrinsic factor dont result in b12 in the urine.. then give Antibiotics! bacterial overgrowth can block absorption. If the antibiotics fix the problem then the issue was bacterial overgrowth.
If B12, Pancreatic enzymes, intrinsic factor and ABX dont fix it. then the issue is in the terminal illeum itself. Look for chrons / UC (backwash illeitis) etc.
B12 deficiency treatment
Life long IM B12 replacement
Folic acid replacement can correct the hematologic abnormalities but not the neurologic abnormalities.
Giving folate in b12 deficiency will make the neuro symptoms worse, thats why its important to confirm the diagnosis first
Make sure you give potassium to patients when giving B12 –> Rapid creation of RBCs will lead to hypokalemia.. need to suplement potassium
What must you give in addition to B12?
Potassium
Folic Acid Deficiency causes
folic acid is in green leafy veggies
Alcoholics - dont eat green leafy veggies
Pregnancy (increased requirement for folic acid)
Eczema (losing skin cells - lose folate)
Dialysis - lose folate during dialysis
Phenytoin - decreased folate in these patients
Folic acid deficiency diagnosis?
FOLIC ACID LEVEL!
they will ask you if its red cell folic acid level or plasma folic acid level - answer is RED CELL FOLIC ACID LEVEL
treatment - replace folic acid - orally.
Intravascular vs extravascular hemolysis
Both will have jaundice / elevated bilirubin (breaking RBCs)
intravascular - destruction within blood cells Decreased haptoglobin (this is specific to intravascular) In intravascular you will see hemoglobinuria and hemosidurinuria (neither of these are seen in extravascular)
Extravascular - Splenomegally
Chronic vs Acute Hemolytic Anemias
Chronic:
Sickle cell
PNH
Heredictary spherocytosis
Acute:
Drug Induced
Autoimmune (comes and goes)
G6PD Deficiency
Hemolytic anemia CBC
Elevated Retic count (trying to make more)
Normal MCV
LDH (any time a cell dies LDH goes up) and Indirect bilirubin are elevated
bilirubin above 4 is unusual in hemolytic anemia - start thinking bile duct obstruction at that point
Hemolytic anemia diagnosis
Haptoglobin low (only in intravascular)
No urinary bilirubin - (indirect bilirubin is bound to albumin)
Hemolytic anemia treatment
Transfusion - needed in all forms of anemia when the hematocrit becomes low
Hydration - to protect kidneys
Specific therapy to the cause of the anemia
sickle cell inheritance pattern and issue
autsomal recessive
replacement of valine instead of the normal glutamic acid in 6th position of beta globin chain
patient with sickle cell has sudden drop in Hb and low Retic - what is it?
When there is hemolysis of RBCs normally in all patients (including sickle cell) the bone marrow should make more (elevated retic)
However if a sickle patient has hemolyis and low Retic (HCT) that means there is a aplastic issue. Must do a bone marrow biopsy to confirm the diagnosis:
Parvo B19 infection or Folate deficency can cause this
Sickle cell chronic manifestations
Isosthenuria (concentrating defects) Hematuria SHINs infections (autosplenectomy) --> make sure to vaccinate these patients for H influenza and Pneumococcus
Growth retardations / skin ulcerations/ bilirubin gallstones / aseptic necorsis of femoral head / ostemoyelitis (salmonella) / retinopathy
What are the causes of death in sickle cell?
1 cause is sepsis - infection from encapsulated organisms
How do you treat acute painful crisis and acute chest syndrome in sickle cell?
Acute Painful Crisis:
O2 + IVF + Morphine
if there is signs of infection
then add ABX (3rd gen ceph - ceftriaxone) covers encapsulated organisms
If there is…
Acute CHest Syndrome / Priapism / Eye infarcts or CNS infracts (confusion / focal signs) then you must do a:
RED CELL EXCHANGE TRANSFUSION
Sickle Cell Diagnosis
first test = peripheral smear - will show sickled cells
if it doesnt and you are suspecting sickle cell anemia then do the Sickle prep (scikledex) - quick screening test used to diagnose sickle cell trait (cannot distinguish between trait and homozygous disease)
GOLD Standard and MAT = Hemoglobin electrophoresis (thiis will distinguish between trait and disease)
Chronic sickle cell management
(not painful crisis / acute chest syndrome)
Chronic:
Folic acid replacement
vaccinations - pneumo and h.influ
Hydroxyurea (to decrease frequency of vasoocclusive painful crisis) - preventative measure. Increases HbF. Start Hydroxyurea if patient is having 4 or more crisis per year
BMT
Acquired Hemolytic anemia types (3 types)
autoimmune - IgG mediated
cold agglutinin disease - IgM mediated –> C3. destroys Complex destroys RBC in liver
Drug - induced
How to differentiate between Autoimmune homolytic anemia and Cold Agglutinin?
Do a Direct Coombs test!
If direct cooms shows IgG = Warm Auto Immune Hemolytic Anemia
If Direct Coombs shows C3 = Cold Agglutinin
Acquired Hemolytic Anemia Smear
Spherocytes - ROUND RBCs with NO central Palor!!
Both AIHA and Hereditary spherocytosis have:
- spherocytes
- splenomegaly
- Increased MCHC
- Increased Osmotic Fragility
BUT ONLY AIHA will have a positive coombs test.
how do you know difference between autoimmune and hereditary spherocytosis?
Do Direct Coombs:
if its positive (shows IgG or C3) then its autoimmune
If its negative - then its hereditary spherocytosis
How do you treat acquired hemolytic anemia?
causes:
autoimmune (warm), cold agglutinin and drug induced
treatments:
drug induced - stop drug.
warm (auto Immune)
Mild disease - no treatment
Severe disease - STEROIDS!
Splenectomy - Done for patients not responsive to steroids
Cold agglutinin
Avoid cold
Rituximab (Anti-CD20 antibody) - found in B cells
Cant use steroids here (not antibody mediated, caused by C3.. also Spleenectomy wont work here since cells are destroyed in liver not spleen)
* Must check for HepB and HepC before starting Rituximab!@!@
Cold Agglutinin disease etiology
IgM antibody against RBCs in association with:
Malignancies - Lymphoma , waldenstroms Macroglobulinemia
Infections - Mono, mycoplasma
Ulcerative colitis
50% of patients will have no underlying disorder
Cold agglutinin presentaion
cyanosis of ears, nose, fingers, toes
weakness, pallor, jaundice, dark urine
Cold Agglutinin - C3 destroys RBCs in liver
Treatment with steroids wont work here (thats for antibodies)
Splenectomy wont work (cells are destroyed in liver not spleen)
Hereditary Spherocytosis
Chronic mild hemolysis with spherocytes, jaundice, splenomegally
Autosomal dominant
Loss of spectrin in RBC membrane caused by a mutation in one of 3 genes: spectrin ankyrin protein 4.2
Hemolysis occurs because spheres are not able to pass through the narrow passages of the spleen
Hereditary spherocytosis presentation
Chronic disorder with mild to moderate anemia
splenomegaly and jaundice –> bilirubin stones often occur, leading to cholecystitis, often at a young age.
Severe anemia occurs when co-infection with Folate deficiency or Parvo B19 infection
Hereditary spherocytosis Labs.. what are the following?
MCV MCHC LDH Indirect Bili Retic count Coombs test result
Elevated LDH (hemolysis.. anytime cells are lysing of any kind.. there is elevated LDH)
Normal to slightly decreased MCV
Elevated MCHC!! concentration of hemoglobin / volume is increased
Elevated indirect bilirubin and Retic count (just like any hemolysis)
Negative COOMBs!! helps differentiate from autoimmune or cold agluttinin
Cells have increased sensitivity to lysis in hypotonic solutions (osmotic fragility test)
Treatment:
folate replacement frequently
splenectomy (symptoms will resolve but spherocytes remain)
Confirmatory test, and treatment for PNH
Flow Cytometry to see ABSENCE of DAF (decay accelerating factor) = Gold standard
absence of CD55 and CD59
Flayer assay is flow cytometry for GPI. THis is actually the most accurate test, but most hospitals cant do it yet. So if this is on the test then this is the answer.
Treatment:
