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:
Paraoxysmal Nocturnal Hemoglobinuria (PNH) cause?
Red cell membrane defect leading to intermittent dark urine and venous thrombosis and chornic form of hemolysis.
damaged PIG-A gene –? No GPI on the RBC membrane..if there is no PIG-A gene then CD55 (Decay Accelerating Factor) cant attach to the RBC membrane and protect the RBC –> without this complement are free to lyse the RBC.
For anemia - give RBCs
for Thrombosis give Warafrin!!
What are PNH patients at increased risk for?
PNH is a clonal stem cell disorder that can develop into Aplastic Anemia or Lukemia
What is the MCC of death for patients with PNH?
VENOUS thrombosis!
Hepatic vein thrombosis - Budd-Chiari Syndrome
PNH treatment?
Eclizumab blocks C5 and also lowers amount of venous thrombosis
What do you have to look out for before perscribing the following Monoclonal Antibodies (MABs)?
Etanercept
Eclizumab
Rituximab
Etanercept - make sure patient doesn’t have Tb
Eclizumab - vaccinate against Nisseria
Rituximab - look for hepb and hep c first
Whats the number one cause of G6PD related Hemolysis?
Infection.
G6PD patients are normal until they have some type of a stress. #1 cause is infection
Drugs often can cause the oxidative stress that slips G6PD patietns into hemolytic states “in question stem look for hemolysis after drug ingestion”
Fava beans
G6PD findings
IV hemolysis (everything you see in any IV hemolysis you see here)
High LDH (anytime cells break you have high LDH)
Bilirubin
Elevated retic count
Normal MCV
Low haptoglobin
Hemoglobinuria
Definitive test for G6PD deficiency? G6PD level (best if tested 1 week after event)
what is the Definitive test for G6PD deficiency?
G6PD level (best if tested 1 week after event)
How do you diagnose G6PD deficiency during an acute event?
Do a peripheral Smear with a Supravital stain (you can only see heinz bodies with a supravital stain!)
Heinz bodies - precipitated hemoglobin inclusions seen in RBCs
Bite Cells - Indicate removal of Heinz bodies
G6PD level to confirm disease is done at least 1 week later
Where else do you see heniz bodies?
Alpha thalassemias. thus to confirm that this is G6PD must do G6PD level one week later.
G6PD treatment?
No specific therapy beyond HYDRATION and TRANSFUSION if hemolysis is severe.
Main therapy is to avoid the trigger that led to the oxidant stress in the first place.
Aplastic anemia findings?
Failure of all 3 cell lines produced in bone marrow:
Anemia (RBCs)
Leukopenia
Thrombocytopenia
On CBC all 3 cell lines are low.
Bone Marrow will be empty (no precursors)
Thus MAT is Bone Marrow Biopsy
Causes of Aplastic anemia:
Radiation
Toxins (benzene) –> leads to myelodysplastic syndrome, lukemia/lymphoma
Drugs –> nasaids, chloramphenocol, alcohol
Infections –> hepatitis, HIV, CMV, EBV, ParvoB19
What are symptoms of aplastic anemia?
RBC deficency –> anemia –> fatigue
WBC deficency –> neutropenia –> infections
Thrombocyte deficency –> Bleeding
Must do Bone Marrow biopsy to confirm!!!
What is seen on bone marrow biopsy in Aplastic Anemia
CBC - pancytopenia
Bone marrow biopsy will show Hypoplastic marrow and fat filled, with NO abnormal cells seen.
Aplastic anemia treatment?
Mild disease:
growth factors- EPO / Darbepoetin; Filgastrim / sargramostim
Severe disease
BMT - for patients young and healthy (less than 40yo)
can cure up to 80-90%
If BMT not possible for patient then use immunospuppresive agents like:
antithymocyte globulin, cyclosporine, and prednisone
these therapies can lead to remission in 60-70% of pts.
What are the two types of WBC tumors?
Lukemia and Lymphomas
whats the diff?
Location. They are the same tumors in diff locations.
Lukemia - blood
Lymphoma - LN
How do you diagnose all Lymphomas and what are the 2 kinds?
How do you diagnose the two?
Biopsy the Lymph nodes… (lymphomas are WBC tumors in LNs.. biopsy it.)
2 types:
Hodgkins—> has Reed Sternberg cells
Non-Hodgkins –> does not…
After you figure out non-hodg vs hodg then you STAGE THE TUMOR!
How do you treat lymphomas?
Identify –> stage
Then treat with Chemo!
How do you diagnose lukemia?
CBC or Bone Marrow Biopsy (will see the abnormal WBCs here)
There is 2 types of lukemia
Acute –> more than 20% blasts in BM (must check BONE MARROW for acute)
Chornic- Mature cells –> must DO CBC check blood for chronic
what if you have acute lukemia with blasts below 20%
if you have blasts that are elevated but below 20% then its not acute lukemia!! its called myelodysplastic syndrome (precursor)
Acute Lukemia Definition and disease progression
Rapid onset of Bone Marrow Failure form derangement of pluripotent stem cells –> relentless destruction of normal production in entire BM – > blood cells lose ability to mature and function
Eventually Lukemic blast cells crowd out all normal cell lines in the bone marrow –> leading to pancytopenia
Anemia –> fatigue
Infections –> No productive WBCs
Bleeding —> thrombocytopenia
What disorder is ALL associated with?
down syndrome
what are symptoms associated with acute lukemias?
bone pain - crowding of BM with blasts causes bone pain.
Enlargement of liver / spleen
Enlargment of lymphnodes seen in ALL (Lymphoblasts going home to nodes)
High numbers of Lukemic cells can cause Leucostasis –> sludging of blood in vasculature –> Depending on which vessele the slugging is happening in you can get the following symptoms headaches, dyspnea, confusion, hemohrage.
For patients having these symptoms do Leukophoresis! this works quick.. you cant wait for chemo.. that will take to long.. these are acute symptoms.
What is seen in M3 (promeyelocytic lukemia)?
M3 is a subtype of AML!
M3 is associated with DIC
In M3 you see Auer Rods
What kind of symptoms do you get in M4 and M5?
M4 and M5 are subtypes AML
They “M”imic “Meningitis” like symptoms.
What is leucostasis? and what is treatment?
High numbers of Lukemic cells can cause Leucostasis –> sludging of blood in vasculature –> Depending on which vessele the slugging is happening in you can get the following symptoms headaches, dyspnea, confusion, hemohrage.
For patients having these symptoms do Leukophoresis! this works quick.. you cant wait for chemo.. that will take to long.. these are acute symptoms.
What are other disorders with pancytopenia and how do you differentiate from Acute Leukemia?
Pancytopenia seen in: Aplastic Anemia Bone Marrow Infections Metastatic cancer involving marrow B12 Deficiency SLE Hypersplenism Myelofibrosis
None of these will have BLASTS! On BMB. Must do BMB
IF you see high number of blasts (>20%) its acute leukemia not another cause.
How do you differentiate between AML and ALL?
Must do a Stain! cant tell just off seeing blasts in biopsy.
AML:
Auer rods / myeloperoxidase - M3
Esterase - M4 and M5
PAS+ = M6
ALL:
TdT (Terminal Deoxynucleotidyl Transferase) - this is diagnostic
You see blasts with TdT = ALL
also will see CALLA (common ALL antigen) AKA CD10 - Blasts with CALLA = ALL
ALL can be B cell or Tcell how do you differentiate?
CD <10 = T cell
CD ~ 20 (19-23) = B cell
T cell tumors are much more malignant. “T” stands for terrible.
MAT = Flow Cytometry. This can give you info on CD number and thus what kind of specific subtype it is.
What is the MAT to diagnose AML and ALL?
Flow cytometry
Acute Lukemia treatment
Chemo –> Goal is to get patient to remission
If there is relapse –> BMT
AML Treatment?
AraC (cytosine arabinoside)
+
Danorubicin or Idrarubicin
Both have cardiotoxicity!
Add Methotrexate if on spinal tap you see blasts - only scenario that you give methotrexate in AML.
If AML M3 (15:17) give the above + ATRA (all trans retinoic acid)
ALL treatment?
Danorubicin (cardio tox)
Vincristine (peripheral neuropathy)
Prednisone
Methotrexate - Give to all ALL patients!
CML definition
Massive overproduction of Myeloid cells
All cells are being overproduced – but mostly Myeloid (WBCs)
WBC count will be so high that it often results in leukostasis –> do leukopheresis when symptoms present
CML caused by (9;22) translocation = Philadelphia chromosome
Philadelphia chormosome characteristics:
BCR; ABL translocation –> increased Tyrosine Kinase activity (always phosphorylating)
Treatment = Imantinib (blocks tyrosine kinase)
‘tinib’ = tyrosine kinase inhibitors.
Does Imantinib cure CML?
no. It stops Tyrosine Kinase, and thus the Tumor Cannot grow. But it doesnt shrink the tumor or anything.
CML presentation
Abdominal pain
splenomegally (spleen gets huge, same size as liver almost)
Leukostasis (dyspnea, priapism, blurry vision)
CML Diagnosis and treatment
B12 is often elevated in CML
Need to see the philadelphia chormosome to make diagnosis –> PCR or FISH for BCR-ABL is the most accurate test.
Elevated platelet count
Imatinib, Dasatinib, Nilotinib
These Tinibs are the best initial therapy.
If the tinibs dont work then do BMT (this is 2nd line.. always try tinibs first)
Chronic Lymphocytic Lukemia
Seen in OLDER PEOPLE (>50 for sure)
Massive overproduction of mature, but still leukemic, lymphocytes usually from the monoclonal production of B lymphocytes
Etiology is unknown
Asymptomatic elevation of WBCs - found on routine evaluation / during investigations for other problems –> mainly Lymphocytes
This is a lukemia.. but it may have 1 or 2 enlarged nodes also
CLL prognosis
Survival for stages 0 and 1
10-12 years even without treatment
Survival of stage 3 and 4
1-2 years
What dictates a higher stage?
when there is anemia - stage 3
when thre is thrombocytopenia - stage 4
stage 0- lymphocytosis alone stage 1- lymphadenopathy stage 2- splenomegaly stage 3 - anemia stage 4 - thrombocytopenia
CLL diagnosis
Elevated WBCs with Lymphocytic predominance (80-90%)
Strongly associated with CD19
Smudge cells seen on smear are characteristic of CLL
Diagnosis confirmation will be with Flow Cytometry finding B and T cells.
Will be positive for B-cell (CD19-23) AND T-cell (CD-5) = this is characteristic
CLL treatment
treat high stage only (anemia and thrombocytopenia) stage 3 and 4.
Treat with Fludarabine - DOC choice.. has greater efficacy then chlorambucil.
Also Give:
Prednisone - for patients with autoimmune hemolysis or thrombocytopenia (stage 4)
Rituximab - Patients with hemolytic anemia, ITP, Or those who express CD20
Chlorambucil only used when patient cant come to the office every week for chemo with fludarabine.
Hairy Cell Lukemia
Middle aged man with: pancytopenia splenomegaly monoctyopenia dry tap despite hypercellular bone marrow on Biopsy.
Hairy cell lukemia best initial test and most accurate test and treatment
BIT - Smear showing Hairy cells (must use TRAP stain)
MAT - Immunotyping by flow cytometry - and finding CD11c, CD103, or CD25
Treatment- cladaribine / pentostatin = adenosine deaminase inhibitors. they cause deoxyadenosine to accumulate in hairy cells.. this is toxic and kills the hairy cells.
Myelodysplastic syndrome findings and treatment
Precursor to lukemia Acute Lukemia (less than 20% blasts).
Most common defect is 5q deletion - if this is seen there is a special treatment.
elderly patient with pancytopenia, elevated MCV, fatigue, infections or bleeding.
Give periodic transfusions and control infections as they arise
Give EPO as needed
Disease specific therapy:
if 5q present - give Lenalidomide
If not present then treat with Azacitidine or Decitabine
only known cure - BMT
What is the MCC of death from Myelodysplastic syndrome?
Infections or bleeding.
they develop these far before developing AML
Myelodysplastic cells are megalsoblastic how do you differentiate from B12 / Folate deficency?
Screen for B12 / folate levels.
Also do a peripheral smear - you will see bi-lobed neutrophils (mature)
Also check the 5q deletion.
Polycythemia Vera pathophysiology
Normally when there is hypoxia the body triggers EPO production and you make more RBCs.
Normally - when HcT is High then EPO is turned off.
In PCV you will see HIGH HcT and LOW EPO!!
Over expression of JAK2 Kinase
Essential Thorombosthenia signs and symptoms and treatment.
Same pathophys as PCV –> over-expression of JAK2
Will see either thrombosis or bleeding
Platelet count can be above 1 million sometimes.
Treatment - Hydroxyurea - reduce cell count
Use Anagrelide when hydroxyurea supresses RBCs too much.. this will suppress RBCs less.. but its second line.. use hydroxyurea first!
PCV signs and symptoms
RBCs produced in excessive amounts in absence of hypoxia or increased EPO levels
Patients present with:
eleveated hematocrit
splenomegaly
sometimes elevated Platlets and WBCs (myeloproliferative - can do other cell lines too)
Thrombosis
Plethora, Redness / fullness of face
Itching after warm bath (use antihistamine)
Confirm diagnosis by viewing high levels of JAK2 = MAT
PCV Treatment
phlebotomy and aspirin - thrombosis prevention
Hydroxyurea - lowers cell count
Allopurinol / Raburicase - protects agains uric acid rise
Antihistamines
Ruxolitinib - Jak2 inhibitor. Second line for patients not responsding to hydroxyurea or not on it.
Multiple Myeloma Overview
Clonal Abnormality of Plasma cells (B cells).
Unknown etiology
Over production of functionless immunoglobulins
Disease of Bone Marrow! –> over production results in replacement of BM
Bone Pain:
Punched out lesions in bone (most common clinical manifestation is bone pain in MM)
Bone pain most common in back and ribs, secondary to pathologic fracture
Renal Failure:
Caused by Bence Jones Proteins
high cell turn over can also lead to elevated uric acid.
Hypercalcemia:
Polyuria, Polydipsia, AMS, Short QT interval on EKG
What is the MCC of death in multiple myeloma?
infections - all the immunoglobulins are useless
Vaccinate these patients against encapsulated organisms. Problem is vaccine wont be super effective since they cant make the right immunoglobulins.. however theyll be able to make some.. so it is still worth doing.
First test done with bone pain in MM?
X- ray to see lytic lesions
NOT BONE SCAN!
Multiple Myeloma Diagnosis
- x-ray of affected bone –> punched out lesions
- Protein Electropheresis –> Markedly elevated monoclonal immunoglobulin (gamma) spike. This can be stated as “elevated total protein with normal albumin”
Everyone has a spike at Albumin.. these patients will have a second spike at the Gamma range (IgG or IgA)
- Beta2 Microblobulin is elevated in 75% of patients and corresponds to severity of disease
- Hypercalcemia (bone destruction)
- Elevated BUN / Cr - damage to kidneys from bence jones and hypercalcemia
- BMB - greater than 10% plasma cells confirms the diagnosis
Multiple myeloma treatment
Best initial therapy = Combination of Dexamethasone + Lenalidomide, Bortezomb or both.
Lenalidomide (proteasome inhibitor) only used in two diseases:
- Multiple Myeloma
- Myelodysplastic syndrome with 5q deletion
Mephlan + Prednisone is used in older patients
*very important (board question) - if youre going to do a BMT on a patient, then DO NOT use mephalan
Autologus BMT for younger healthy patients (will improve survival but not cure cancer) - candidates for transplant should get thalidomide (or lenalidomide) and Dexamethasone
Autologus vs Allogenic BMT
Autologus = your own marrow being put back into you
Allogenic = someone elses marrow being put into you
Autologus will prolong survival in some diseases like MM.. because it will take the tumor a while to grow again in the new area.
Allogenic will cure the disease.. but you also have to find the perfect match so the recipient does not reject the marrow.
Monoclonal Gammopathy of Unknown Significance (MGUS)
Overproduction of a particular immunoglobulin by plasma cells without anything else seen in Multiple myeloma.. so patients will NOT have:
- Bone lesions
- Renal failure
- Hypercalcemia
- Anemia
- nomral beta2 microglobulin levels
- Bone marrow has less than 2% plasma cells
No “M” spike.
This can eventually become Multiple Myeloma down the road.
No treatment for MGUS - just watch it. If it becomes MM then we treat.
Hodgkin disease: Definition
Neoplastic transformation of lymphocytes particularly in lymph nodes.
CHaracterized by presence of Reed-Sternberg cells
Reed-Sternberg cells spread in orderly, centripetal fashion to contiguous areas of lymph nodes.
What virus is associated with hodgkins lymphoma?
EBV found in 30%
Hodgkins presentation
Hallmark - enlarged, painless, rubbery non-erythematous, non-tender lymphnodes.
B Symptoms:
Drenching night sweats
10% weight loss
Fevers
Hurts more with alcohol use.
Lymphoma Staging
Stage1 = 1 node involved
Stage 2 = 2 or more lymph nodes on same side of diaphragm
Stage 3 = 2 or more lymphnodes on both sides of diaphragm
Stage 4 - Distant metastasis to organs / nodes / tissues
Lymphoma workup
1st Step = Excisional lymph node biopsy to confirm RS cells or other cells.
2nd Step = stage the cancer via CT or PET scan
3rd Step - Do BMB (to make sure that it didnt spread to BM).. if it did spread to BM then its automatically stage 4! MUST CHECK BM!!
In Non-Hodgkins Lymphoma – Brain is frequently involved.. so in this you will ADD an LP
Hodgkin Disease Treatment
All patients get Chemo with ABVD: Adriamycin (Doxorubicin) - cardiotoxic Bleomycin - pulmonary firborsis Vinblastine (Bone Marrow tox) Dacarbazine
Non-Hodgkins Lymphomas and associations
HIV and EBV - Burkits Lymphoma
HTLV-1 = Adult T-Cell lymphoma
H.Pylori = Maltoma
Hep C = Splenic Marginal Zone lymphoma
Non Hodgkin Lymphoma presentation
Same B symptoms as Hodgkins:
drenching night sweats, 10% weight loss, fevers
Same Hallmark symptoms - painless enlarged rubbery non-tender lymph-nodes.
However in this the lymph nodes dont hurt more with alcohol usage.
NHL treatment
Radiation + Chemo
Chemo = CHOP
Cyclophosphamide (hemorrhagic cystitis - treat with MESNA)
Hydroxy-Adriamycin (same as doxorubicin - cardiotox)
Oncovin (vincristine) - peripheral neruopathy
Prednisone
If it is CD20+ - then first do serology to make sure there is no HEP B or C and then add Rituximab (CD 20 antibody)
Bleeding disorders:
Platelet vs Coagulation disorders
Platelet disorders - present with Superficial bleeding Skin: Petechia Ecchymosis Purpura Bruising Mucus Membranes: Nosebleeds Menses GI/GU
Coagulation disorders - present with Deep Bleeding: Joints: Hemarthrosis Tissue: Hematoma Circumcision - heavy bleeding teeth loss - heavy bleeding
How do you work up platelet disorders?
- platelet count
2. PFA (platelet function assay)
How do you work up coagulation disorders?
Coag studies - PT / PTT (these two measure everything except factor 13)
Factor Assay - looking at D-dimers (Fibrin split product)
Mixing studies
ITP Cause
Thrombocytopenia of uknown origin
Idopathic production of paltelet anitbodies
Phagocytosis of platelet-antibody complexes by macrophages in spleen.
Sleenectomy will help in these patients (but not first line)
First line = Steroids!
IF its severe and uncontrolled with steroids –> spleenectomy
Presentation of ITP
Bleeding form superficial areas
skin, nasal, oral mucosa, GI tract, heavy periods
Petechiae, purpura, and ecchymoses are often found on exam
NO SPLEENOMEGALY
“healthy woman, comes in with excess bleeding.. all you find is low platlets” - ITP until proven otherwise
Normal peripheral smear and creatnine
Diagnosis of ITP
Antiplatlet antibodies - high sensitivity and low specificity
Next - must do BMB to prove its not a production issue. When you do BMB In these patients you will see normal amount of megakaryocytes.. thus the issue is with platelet desctruction not production.
This is a diagnosis of exclusion - Must rule out the other platlet destruction problems:
HUS - Renal problems (cant be this.. ITP is healthy patients)
TTP- CNS problems (cant be this.. ITP is healthy patients)
DIC - bleeding everywhere - Cant be this..
ITP Treatment
No bleeding and platlets > 30,000 = no treatment mild bleeding or platelets <30,000 = steroids severe bleeding (GI / CNS) or platelets <10,000 = IVIG / Anti-Rho + Platelet transfusion
Recurrent episodes, steroids fail = spleenectomy or rituximab
spleenectomy or steroids not effective?
Romiplostim or eltrombopag
VWD disease
Autosomal dominant
Most common cause of congenital disorder of hemostasis
Decreased amount of vWF
Decreased ability of platlets to adhere to endothelial lining due to no VWF
Aggregation is NORMAL
ADHERENCE is ABNORMAL
Ristocetin is the ability of platelets to adhere. THis is only abnormal in 2 diseases:
- Von willebrand disease
- Bernard souiler syndrome (missing 1B)
vWD presentation
platlet type bleeding - similar to ITP: mucosal and skin bleeding: periods epistaxis petechiae bruising Excess bleeding after aspirin use
In VwD –> platelet count and production are normal.. but there is still bleeding.. so it must be a quality problem.
labs:
Normal platelet count
elevated bleeding time
Platelet function assay - will show abnormal ristocetin
vWD diagnosis and confirmation
Normal platelet count
elevated bleeding time
Platelet function assay - will show abnormal ristocetin
- vWF ag decreased
- ristocetin is abnormal
- Factor 8 is normal to low. If Factor 8 is low then the PTT will be elevated.
Von willebrand disease treatment?
Give DESMOPRESSIN!
desmopressin causes vonwillebrand factor and factor 8 release from ENDOTHELIAL cells.
Since desmopressin also releases factor 8 from endothelial cells... what other disease can it be used for? Hemophilia A (deficient factor 8)
If Desmopressin isnt working then you have to give the patient HUMAN factor 8 (not recombinant). Because Human Factor 8 has vonwillebrand factor in it. Recombinant factor 8 does not.
Human factor 8 = Humate P.
Hemophilia A and B: definition
Hemophilia A = deficiency of factor 8
Hemophilia B = deficiency of factor 9
This is x- linked –> moms will pass it to the sons.
Discovered by age 2 in most patients.
Symptoms - typical of coagulation disorders: Hemarthrosis Hematomas GI bleeding Urinary bleeding Bruising CNS bleeding
Hemophilia A and B - diagnosis
It will be a male with Increased PTT!
PT is normal
Bleeding time is normal
Platelet count is normal.
1st step - do a mixing study:
Mix patients blood with normal blood –> PTT becomes normal. thats a positive Hemophilia test.
This will only tell you that a factor deficiency is present.. will not tell you which factor!
If PTT does not correct with mixing then antibody inhibitor of factor is suspected.
So if mixing study is positive.. then to find out which specific hemophilia it is you have to check the Factor 8 and Factor 9 levels.. this will give you the definitive diagnosis.
What are the only diseases which increase only PTT?
Factor 8 deficiency - hemophilia a
Factor 9 deficiency - hemophila b
Factor 11 deficiency - Hemophilia c (very uncommon)
Factor 12 deficiency - but this one doesn’t bleed so its not in the differential.
8, 9, 11
Hemophilia A and B treatment
Hemophilia A = Desmopression ( will cause release of factor 8 from endothelial cells)
If desmopressin doesn’t fix it then give recombinant factor 8
Hemophilia B = give recombinant factor 9
In hemophilias you can give recombinant factors 8 and 9 because you dont need the vWF. In vWF disease you have to give HUMAN factor 8 because only that has vWF with it.
Vitamin K deficency
results in decreased production of factors:
2,7,9,10
this results in increased PT and PTT
Factor 7 usually runs out first –> thus PT is elevated first.
Caused by - dietary deficiency, malabsorption, use of antibiotics that kill vitamin K producing bacteria in the colon.
Warfarin overdose causes vita k deficency
Clinical presentation - bleeding that mimics hemophilia
May occur at sites of venapuncture.
Vita K deficiency diagnosis and treatment
Give vita K –> if this corrects PT and PTT then the diagnosis is confirmed.
Treatment:
For active bleeding - Fresh Forzen Plasma.
give vitamin K at the same time to correct the underlying production defect.
Coagulopathy of liver disease
Coagulopathy caused by decreased production of clotting factors by the liver.
The liver produces ALL clotting factors EXCEPT factor 8 and vWF - these are produced in the endothelial cells of blood vessels.
Any severe liver disease or cirrhosis will cause this
Elevation of both PT and PTT
PT elevates first (because factor 7 runs out first)
CLinically indistinguishable form Vitamin K deficency
How do you distinguish coagulopathy of liver disease from vitamin K deficency?
Give vitamin k.
If PT and PTT correct.. then its vita k deficency. If it doesnt.. then its coagulopathy of liver disease.
Treatment of coagulopathy of liver disease?
FOr acute bleeding - fresh frozen plasma
long term managment is based on nature of liver disease – liver transplant.
DIC
consumptive coagulopathy. use up all the plattlets to make clots. And then they lyse and you bleed to death.
causes are:
Delivery (amniotic fluid embolisim, abruptio placentae)
Infections - all infections but espcially nisseria
Cancers ( adenocarcinomas / M3 (promyelocytic lukemia)
M3 is a classic association with DIC.
DIC Labs
Decreased platlet count Elevated both PT and PTT Low fibrinogen level (Factor 1) Elevated D-dimer level (fibrin split products) Schistocytes on peripheral smear
Confirmatory test = elevated D-dimer
DIC treatment
FFP - Fresh frozen plasma and sometimes platelet transfusions to correct severe bleeding
Heparin - rarely used except when presenting with predominantly thrombosis
Correct the underlying cause!!!!
Heparin induced thrombocytopenia
Look at HISTORY! must have recieved Heparin.. one week later platelet count drops by 50%
Caused by antibodies against heparin - platelet factor 4 complexes.
Diagnosis of HIT
You can do an ELISA to see the antibodies that are activating the platelets
CHeck serotonin levels –> this will show that the platelets have been activated
Once patient gets HIT.. they can never get heparin again for the rest of their lives.
Treatement of HIT
- stop heparin
- and start Argatroban or Bivalirudin (direct thrombin inhibitors)
- Then start Coumadin!
Acute Hemolytic Transfusion reaction
Fever, Flank Pain, Hemoglobinuria, Renali failure and DIC within 1 hour of transfusion!
Positive coombs test *Antiboidy mediated
Caused by ABO incompatibility
Febirile non-hemolytic anemia (most common reaction from transfusion)
Fever and Chills ONLY
occurs within 1-6 hours of transfusion
Caused by cytokine accumulation durring blood storage. can be prevented by reducing WBCs in stored blood.
Delayed Hemolytic transfusion reaction
Mild fever and hemolytic anemia
occurs within 2-10 days after transfusion.
Positive direct coombs and positive new antibodiy screen
Caused by amanestic antibody response
Anaphylactic reaction to transfusion
Rapid onset of shock! –> angioedema / urtricaria and respiratory distress.
Within seconds to minutes of a transfusion.
Caused by recipient anti-IgA antibodies
Utricarial / Allergic transfusion reaction
Utricaria, flushing, angioedema, and pruritis
Within 2-3 hours of transfusion
Caused by recipient IgE antibodies and mast cell activation
Seminoma
and
Mixed Germ-cell tumors
Seminoma :
Elevated B-HCG with NORMAL AFP
Mixed Germcell tumors:
Elevated B-HCG and AFP
What is the preffered antigocagulation therapy in ESRD?
Warfarin - cant ever start warfarin alone because it inhibits 2,7,9,10 and anticoagulant proteins C and S
Inhibition of C and S causes a prothromobhotic state initially and thus needs to be bridged with heparin.
Start patients with unfractioned heparin (IV) and then on warfarin (same day.. typically that evening) until the INR is theraputic (usually 4-5 days).. then the patient can be DCd on warfarin.
What two anticogaulants can you not give in ESRD?
LMWH and Rivaroxaban (direct 10a inhibitor) are metabolized by the kidney, and are thus CONTRAINDICATED in ESRD
Wiskott - aldrich syndrome
X-linked recessive defect in WAS protein gene –> impaired cytoskeleton changes in leukocytes and platelets.
The impaired cytoskeleton leads to immunce dysfunction due to impaired cellular migration and immune synapse formation.
Clinical features:
exczema
microthrombocytopenia (small platelets, low count)
Reccurent infecitons
Treatment - stem cell transplant
Ataxia Telangiectasia
T-cell deficiency associated with a defect in DNA repair.
Causes immune dysfunction, cerebellar degeneration and a high risk for cancer.
Chornic Granulomatous Disease
Results from an inability of phagocytes to produce hydrogen peroxide in their lysosomes.
Abscesses due to fungi or catalase positive bacteria (s.aureus) are characteristic
SCID
Severe T-cell deficiency.
Interleukin-7-driven maturation of Tcells in the thymus is inhibited. Patients with SCID have virtually no T cells.
THe lack of T cells inevitably causes B cell dysfunction also.
When is dronabinol useful?
Preventing cachexia in advanced HIV!
Not useful in cancer related cachexia
Treating cancer related cachexia
Progesterone analogues (Megestrol Acetate and Medroxyprogesterone Acetate) and Corticosteroids are the treatments of choice in cancer related cachexia treatment.
SSRIs and cachexia
SSRIs can treat anoreixa related to depression. But if the patient has no underlying depression then SSRIs are not useful
GVHD pathophysciology
Caused by recognition of host major and minor HLA antigens by DONOR T-Cells (seen in up to 50% of patients with transplant from matched siblings)
Attacks the following:
skin - maculopapular rash on palms, soles, and face
Intestine - bloody diarhea
Liver - abnormal liver function tests and jaundice
Warfarin induced skin necrosis
Occurs in patients with protein C deficiency. Manifests as a edemeatous / purpuric rash that appears within the first few days of warfarin therapy.
Stop wafrarin! ang give Protein C concentrate
What is the MCC of pediatric stroke?
Sickle cell disease
Storke;; Focal neuro deficits Hemiparesis aphasia seizures AMS
Diagnose with Hemoglobin Electrophoresis
If you are concerned about the stroke must perfomr an MRI to confirm the diagnosis.
How does Heparin Work?
Heparin activates Antithrombin 3. Which in turn inactivates factor 2a (thrombin),9a and 10a.
Which factor is thrombin?
2a
How does clopidogrel work?
Clopidogrel is an anti-platelet which prevetns platelet activation by blocking ADENOSINE DIPHOSPHATE receptors on the surface of platelets
How does aspirin work?
it in hibits cox-1, therby inhibiting synthesis of Thromboxane A2
What will be elevated with either B12 or Folate Deficency?
Homocysteine.
Both FOlate and Cobalimin are involved in the conversion of Homocysteine to Methionine. If either are missing then Methionine levels drop and Homocysteine levels Rise!
How do you distinguish between folate and b12 deficency
check levels.
but you can look at Methylmalonic acid concentrations. Cobalimin (unlike folic acid) is involved in the conversion of Methylmalonyl-CoA to Succinyl-CoA.
A deficecny in cobalimin –> high levels of Methylmalonic acid.
How long does it take to develop B12 or folate deficiency from a lack of nutrition?
B12 - comes from meats. would take 5+ years to deplete body stores and become deficient.
folate - green leafy veggies. would take 5-10 weeks to develop nutritional deficiency.
Number of RBCs in IDA vs Thalassemia
What kind of RBCs wil you see on peripheral smear in thalassemia?
In IDA # of RBCs is decreased (normal = 3.7-6MM)
In Thalassemia - # of RBCs is NORMAL
Peripheral smear of Thalassemia = TARGET CELLS
How do you diagnose MM?
Screening tests of choice is Serum or urine protein electrophoresis or free light chain analysis.
Confirmation of diagnosis is done with BMB
For patients with sickle cell disease on Hydroxyurea.. how many of their cells will be HbF?
Sickle cell disease NOT on on hydroxy urea = 80-95% will be sickle cells and 10-15% will be HbF.
Patients on Hydroxyurea will have ABOVE 15% HbF!!
Parathesias post transfusion cause?
WHole blood and PRBCs are stored with Citrate (as a preservative).
Citrate chelates both Calcium and Magnesium. leading to decreased plasma levels in the recipient.
THis leads to parsthesias.
