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213 Cards in this Set
- Front
- Back
-Neutrophils 43-65%
-Basophils <1% -Eosinophils 0-3% |
granulocytes
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-Lymphocytes 24-44%
-Monocytes 4-8% |
agranulocytes
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Predominantly attack bacteria
Mature has 2-5 lobes- hence polymorphonuclear term also used Cytoplasm contains lysosomal enzymes First to arrive to site of injury Attack cells “marked” with antibodies or complement proteins Short lived 10 hrs or 30 min if attacking Can attack upto 1-2 dozen bacteria |
Neutrophils
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Red granules and bi-lobed
Attack objects covered with antibodies -phagocytic -attack bacteria, protozoa, cellular debris, FLUKES, AND PARASITES (Remember for later) Thru exocytosis release toxic compounds and nitric oxide (what does that do?) Can be elevated with allergies Try to reduce inflammation |
Eosinophils
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Stain with basic dyes
Rare in circulation Eat up damaged tissue Release granules that contain histamine and heparin |
Basophils
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Very large- twice as large as RBC
Nucleus oval shaped Travels thru circulation and enters tissue to become macrophage which are STRONG phagocytizers- can engulf objects larger than them EBV??? (Ebstein Bar Virus: lymphocytes were so large that they were mistaken for monocytes |
Monocytes
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Stain with lack of granules and thin halo of cytoplasm
Elevated in viral infections Three types -T cells -B cells -NK cells |
Lymphocytes
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Production stimulated by:
-Thrombopoietin: from kidneys -Interlukin 6 (inflammatory cytokine: PAY ATTENTION TO THIS) cytokines: instruct other cells -Multi-colony stimulating factor support |
Platelets
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Most abundant protein
Helps drive osmotic pressure Low levels can cause lower extremity edema or 3rd spacing of fluid -can be caused by cancer which steals albumin or underproduction (liver) Transports fatty acids, hormones, meds (hence- think pharmacology…what do you need to do about meds if _____ is low?) (low ______levels > med levels can build up and become toxic) (if _______ is low, Ca needs to be increased)(every 0.1 below normal, add 0.8 to Ca level) |
albumin
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T (Thymus dependent) Lymphs
B (Bone marrow dependent) Lymphs NK (Natural Killer) cells: -often have CD Markers (cluster of differentiation) -CD8: found on cytotoxic T cells and suppressor cells -CD4: found on helper T-cells |
lymphocytes
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Referred to as Humoral Immunity
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B Cell lymphocytes
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Mature B-cells release ________ which release antibodies/gammaglobulins
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plasma cells
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IgG: largest and most diverse
IgE: attaches to surface of basophils and mast cells IgD: helps with B-cells IgM: LARGE macromolecule, 5 antigen binding sites- why see rise first with infections IgA: found in mucous (nl to have in sinuses), tears, and saliva- circulate blood -ex: Henoch Schonlein Purpura Which goes up on first exposure? Which takes off on second exposure? |
types of antibodies
IgM goes up first on first exposure IgG takes off on second exposure |
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Small proteins that are released by macrophages and lymphocytes that have been infected by viruses
Binds onto membrane of normal cell and signals production of antiviral proteins These antiviral proteins interfere with viral replication inside cell Alpha, Beta, and Gamma (make people feel crappy! and can become anemic) |
Interferons
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11 proteins
Named so b/c it helps action of antibodies Work by: -destruction of target cell membranes -stimulation of inflammation -attraction of phagocytes -enhancement of phagocytosis -(punctures bacterial cell walls) |
Complement System
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WBC:
RBC: Platelets: |
WBC (NE, LYMPH, BASO, EOS, and MONO) 5-10,000
RBC (H and H) 4.5-6 x 106/µL men; 4-5.4 x106/µL for women Platelets 150-350,000 |
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HEMOGLOBIN AND HEMATOCRIT
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Men 14-18 g/dl 42-54%
Women 12-16 g/dl 36-48% |
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can be caused by sepsis, MDS, vasculitis, autoimmune ds (SLE)
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thrombocytopenia (low platelet count)
nl: 150,000 - 350,000 A plt level greater than 50k is not a problem 30-50k moderately increased risk of bleeding 10-30k severely increased risk of bleeding (don’t transfuse plt unless bleeding-but not common) <10k severely increased risk-transfuse 1 unit of plt |
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MCV
mean cell/corpuscular volume micro/macro |
80-100 fenoliters
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MCH
mean cell/corpuscular hemoglobin ave mass of Hgb/RBC decreased in microcytic anemia |
27-33 pg
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MCHC
mean cell/corpuscular Hgb concentration hypochromic: microcytic anemia normochromic: macrocytic anemia hyperchromic: spherocytosis |
31 -35%
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RDW
red cell distribution width used mainly to distinguish anemia of multiple cause from single cause |
12-15%
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increased in alcoholism, reticulocytes, pernicious anemia, vit B12 def
decreased in Fe def, thalasemia, chronic dz low w/ + stool guaiac = GI cancer |
MCV
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RBC of unequal sizes
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anisocytosis
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RBC of unequal shape
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poilocytosis
suggest defect in maturation of RBC |
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Target cells
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bull’s eye appearance suggesting thalasemia or liver disease (or severe Fe deficiency)
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Rouleau Formation
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Multiple Myeloma
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clusters of DNA remains in RBC
seen in hypo or asplenia, severe hemolytic anemia, megaloblastic anemia, hereditary spherocytosis, MDS |
Howell-Jolly bodies
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retic count range
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1 - 2%
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occurs when the EPO is produced from the kidneys stimulating the BM to get the stem cells to give rise to faster differentiation creating more erythrocytes (but remember- they are slightly immature)
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Reticulocytosis
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: BM puts out more retics to compensate for the anemia
-retic count elevated -can be normocytic or macrocytosis -and even RDW will change-remember anisocytosis corresponds with RDW b/c retics are larger than normal RBC’s) |
Hemolysis
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Reticulocytosis w/ anemia
If there is anemia with a retic count nl or slightly elevated |
Reticulocytosis w/ anemia -then hemolysis or blood loss is the most likely cause
If there is anemia with a retic count nl or slightly elevated it's suggestive of substrate problem (Fe Def, Vit B-12, etc) or maturation problem (MDS) |
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CLINICAL PEARL! How can you determine if anemia is being compensated?
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As a fast rule, if a patient is anemic, add the retic count and the Hgb. If they equal or come close to 15 then the anemia is compensated.
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-cytic refers to
-chromic refers to |
cytic refers to MCV
chromic refers to MCHC (concentration of HgB in RBCs) |
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The 3 most common causes of normocytic, normochromic anemias are
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1. Mild Fe deficiency
2. Marrow damage or inflammation 3. Chronic disease or inadequate EPO stimulation; another cause: sideroblastic anemia |
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Anemia will often be mild
Red Cell Indices will be normocytic and normochromic (MCV 80-100; MCH 26-33) Serum Fe (slightly reduced or may not be if chronic kidney disease is the cause) TIBC (total iron binding capacity) should be low to nl- the irons there on the RBC’s Ferritin should be increased or normal-storage okay Problem: stored Fe (ferretin) not being used and not put into circulation |
The 3 most common causes of normocytic, normochromic anemias are
1. Mild Fe deficiency 2. Marrow damage or inflammation 3. Chronic disease or inadequate EPO stimulation; another cause: sideroblastic anemia With mild Fe def- normocytic, normochromic anemia with a slightly reduced serum Fe, low to nl TIBC, and nl or increased ferritin With anemia d/t chronic kidney disease- normocytic, normochromic, elevated BUN/cr, may be diabetic or hx of nephrectomy, or chronic HTN |
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MICROCYTIC ANEMIA
Causes include: |
1. Moderate to severe Fe def
2. Thalasemia 3. Anemia of chronic disease Microcytic anemias are usually the result of cytoplasmic maturation defects causing the RBC’s to be smaller than nl |
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Anemia is microcytic, hypochromic, with an elevated TIBC (more potential room for Fe to bind to), low serum Fe and ferretin (low ferretin is gold standard)
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IRON DEFICIENCY ANEMIA*
One thing that is extremely important: Fe def is a diagnosis of exclusion! Refer to above- blood loss is most common cause |
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Can get brittle nails, smooth tongue, or dysphagia as in Plummer-Vinson Syndrome (esophageal webs form)
Pica is the HALLMARK: eating ice chips, dirt, clay - foods not rich in Fe Peripheral smear usually nl at first then later stages show anisocytosis and poikilocytosis Really severe: target cells or even pencil shaped- you probably won’t see this What would the PLT count be? Think back! high, reactive phenomenon |
IRON DEFICIENCY ANEMIA*
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Hereditary disorders which are characterized by reduction in alpha and beta globin chain synthesis; common hemoglobinopathy
Hgb is made up of globin chains so a reduction in these chains causes a defect in hemoglobinization of RBC’s which in turn causes the microcytosis and hypochromia; in other words each RBC holds less Hgb Microcytosis: usually out of degree with anemia RBC count might be normal |
THALASEMIAS
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seen more in asians- SE Asia and China
-can have minor (2 ____ globin genes) or Hgb H disease (1 ____ globin genes) -____ minor –nl life expectancy with modest anemia(Hct 28-40%) -Hgb H disease –pallor and splenomegly -can go through hemolytic anemias (Hct 22-32%) when go thru stress or infection |
Alpha thalasemia
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usually affects greek and mediteranean decent
-shows up at 6 months of age b/c Hgb F gets replaced by Hgb A -severe anemia (Hct 10% or less), growth failure, pathological fractures, jaundice -often require frequent transfusions leading to Fe overload which is toxic to hrt, liver, joints, and endocrin system - modest anemia Hct 28-40% |
Beta Thalasemia
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Diagnosis by history, physical and by Hgb electrophoresis!
ALSO A TIP OFF: microcytosis with anemia (low H+H) but NORMAL RBC count Hgb Elect. will distinguish between hemoglobinopathies like thalasemia or sickle cell Usually no treatment required for Beta minor or alpha minor-need to identify b/c treat with folate BUT NOT WITH FE |
THALASEMIA
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Causes include:
1. Folate Deficiency 2. Vit B12 Deficiency 3. MDS 4. Hypothyroidism 5. Chronic ETOH abuse 6. Hemolytic Anemias (sometimes) |
MACROCYTIC ANEMIAS
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Body has enough bodily stores for 2-3 months
commonly found in fruits and green leafy veggies Inadequate diet: anorexics, alcoholics; overcooking veggies; drugs-sulfa drugs Macrocytosis (MCV when found is usually >100) Signs and symptoms include glossitis, vague GI complaints, along with all the s+s of anemia BUT NO neurological defecits |
folic acid deficiency
macrocytic anemia |
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found in all foods of animal origin
Enough stores in body for 2-3 years Rare except in strict vegans, alcoholics, and pts with PA, Crohn’s disease or hx of abd surgeries absorbed by binding to intrinsic factor IF, and being transported to terminal ileum to be absorbed. Pernicious Anemia (PA) is most common cause: lack of IF to absorb (IF made in stomach and absorbed in ileum) S+s –all that with anemia with glossitis, GI complaints, and neurological problems- parasthesias, problems with balance, and in severe cases cerebral dysfunction; loss of vibratory sense upon examination |
VIT B12 DEFICIENCY
macrocytic anemia |
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(s/s same as folic acid deficiency + neurologic problems)
MCV usually >110-140fl Labs: level <240pg/ml and methylmalonic acid >1000nmol/l See hypersegmented neutrophils on peripheral smear |
VIT B12 DEFICIENCY
macrocytic anemia |
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Group of d/o that have cytopenias, abnl RBC morphology, and possibly abnl cytogenetics
Usually from advanced age (weak bone marrow), exposure to chemicals, chemo or radiation (10 yrs after tx) Basically you get ineffective blood production |
MDS / myelodysplastic anemia
(macrocytic anemia) |
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Starts at age of 68 and above (about how long stem cells function for before they “give”)
Bone marrow biopsy- only way to diagnose MCV 100-110fl, with abnl RDW Risk for bleeding (low plts), fatigue (anemia) or infections (low wbc’s) This is a PRE –Leukemic condition! |
MDS / myelodysplastic anemia
(macrocytic anemia) |
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Prognosis is based on FAB Classification System: % increased blasts, # of cytopenias, and cytogenetics (abnl chromosomes) (if genetics is normal, MDS may be minor)
Cytogenic abnormalitties to look out for are: chromosome 5q- (more indolent and treated with Revlamid) or monosomy 7- more aggressive Stem cell transplant only cure but pts are often too weak and elderly |
MDS / myelodysplastic anemia
(macrocytic anemia) |
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The thought with drugs is to use drug that inhibits DNA methylation to induce expression of genes
Drugs include Vidaza, Revlamid, Dacogen Also try supportive care like transfusions and iron chelation from freq transf. Try to stimulate Bone marrow with procrit or leukine |
MDS / myelodysplastic anemia
(macrocytic anemia) |
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chronic ETOH abuse can lead to what type of anemia
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macrocytic anemia
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Group of d/o where the RBC survival is reduced
Normally the BM has the ability to increase RBC production 8 fold Hct can normally decrease 3% per week so a drop of Hct of 9% over 3 weeks does NOT indicate hemolysis However, if Hct is falling faster then hemolysis or blood loss is cause |
HEMOLYTIC ANEMIA
(can sometimes cause macrocytic anemia) |
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Often find specific lab abnl
-retic elevated (25% its not) -haptoglobin is low -bilirubin: indirect and total may rise to 4mg/dl -LDH will be high: indicates high cell turnover |
HEMOLYTIC ANEMIA
(can sometimes cause macrocytic anemia) |
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d/o of the RBC membrane where spectrin (protein to hold RBC together) is defected
Result- RBC not as flexible and it cannot pass thru capillaries –thus its gets destroyed- happens in spleen also causing SPLENOMEGLY Usually found in young adulthood PE- icteric and splenomegly In youth jaundice tends to wax and wane |
HEREDITARY SPHEROCYTOSIS
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Under microscope the RBC’s are spherical
Osmotic Fragility Test: checks to see of RBC’s are spherical vs elliptocytosis Coomb’s Test negative: what is this test? used to look for AI disease of RBCs Anemia is mild since BM can keep up with transient reticulocytosis Treat pt with Folic Acid 1mg qd Treatment of choice is Splenectomy: why? that's where most of RBCs are destroyed |
HEREDITARY SPHEROCYTOSIS
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caused by occlusion of the hepatic vein or inferior vena cava. Its presents with the classical triad of abdominal pain, ascites and hepatomegaly. Seen w/ paroxysmal nortunal hemoglobinuria
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Budd-Chiari syndrome
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Acquired clonal stem cell d/o resulting in abnl sensitivity to RBC memebrane to lysis by compliments- particularly CD55** and CD59**
Absence of CD55 and CD59 by flow cytometry lead to cell at risk for lysis Degree of hemolytic anemia can vary at increased risk of clotting and can cause weird clotting problems such as Budd-Chiari syndrome |
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
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Pt’s often notice urine is reddish brown in morning when pt has episodic hemoglobinuria- b/c urine is most concentrated in AM
Pt’s can become Fe deficient related to chronic Fe loss CHECK FLOW CYTOMETRY for CD55 and CD59 Treat w/ Fe replacement and even prednisone help vs hemolysis |
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
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x- linked d/o seen primarily in black men
Causes episodic hemolytic anemia usually during oxidative stress when get infections or exposed to certain drugs like sulfonamides, nitrofurantoin, quinine When experiencing anemia- reticulocytosis, and increased indirect bilirubin See “bite” cells and Heinz bodies on smear No tx required- avoid stressors |
G6PD
Glucose-6-Phosphate Dehydrogenase Deficiency |
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AUTOIMMUNE HEMOLYTIC ANEMIA
Acquired autoimmune process allowing IgG autoantibody to bind to RBC and lyse it Half cases are idiopathic Sometimes related to SLE, CLL, and lymphomas: these are diseases were immune system is “out of wack” dev antibodies towards own cells Coombs test positive Rapid onset of hemolytic anemia w/ reticulocytosis What is tx? |
Treat initially w/ prednisone 1-2mg/kg- NEED to KNOW DOSE ON THIS ONE*****
If steroids don’t work: splenectomy |
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Group of d/o involving intravascular destruction of RBC including HUS, TTP, valve hemolysis (hrt valve), metastatic adenocarcinoma, vasculitis, etc
HALLMARK- fragmented RBC’s on smear (shistocytes and helmet cells) |
MICROANGIOPATHIC HEMOLYTIC ANEMIAS
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One of 5 major hemoglobinopathies
On Beta chain in the 6th amino acid position there is a substitution of valine for glutamic acid RBC membrane stiffens, there is increase viscosity, and the dehydration of RBC d/t K leakage and calcium influx |
sickle cell anemia
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involve pain anywhere in body and may from hrs to weeks
NO TESTS DIAGNOSITIC FOR CRISIS- JUST Hx Repeated crisis of >3 hospitalizations correlate w/ poorer prognosis Worsened by repeated infections, exercise, anxiety, abrupt changes in temp, altitude hypoxia, fever, hypertonic dyes Repeated infarctions can destroy tissue having microvascular beds which in turn promotes sickling- Spleen frequently lost in first 18-36 months of age Splenectomy or infarction of spleen makes pts more susceptible to infections |
sickle cell anemia crisis
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Diagnose by:
-history- intermittent episodes of ischemic pain -PE- ulcers on legs, neurological deficits related to strokes, hemorrhage or retinal vessels, etc -Protein and Hgb Electrophoresis -RBC morphology on smear |
sickle cell anemia
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-comprise many different sub-types
-range from indolent to very aggressive lymphomas -painless lymphadenopathy -fever, nite sweats, or wt loss - B symptoms more diffuse lympadenopathy |
NHL
Non-Hodkin's lymphoma |
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S+S:
-nite sweats + fever- hypermetabolic -bulky lymphadenopathy -changes in bowels d/t increased size nodes -Cutaneous T-cell Lymphoma: patches on skin-OFTEN MISDX AS PSORIASIS -Burkitt’s Lymphoma: abd pain or fullness Labs: CBC may be abnl, LDH often elevated (cell turnover), Beta 2 microglobulin: elevated |
NHL
Non-Hodkin's lymphoma |
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presence of Reed-Steinberg cells
-bimodal age in 20’s and 50’s -painless lymphadenopathy -fever, wt loss, nite sweats, generalized pruritis |
Hodgkin's lymphoma
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Diagnosis
CT scans used to check for nodes PET/CT: checks for nodes and biological activity BMB: may show bone marrow involvement Lumbar Puncture: can have menningeal involvement- checks subtype (usually not required) Need to biopsy nodes to find out type of lymphoma (need to take entire lymphoma out) Histological type and grade determines course Skin biopsy for CTCL: think of it in someone who has a scaly rash thought to be psoriasis that doesn’t respond to steroids or vit d analogues |
NHL
Non-Hodkin's lymphoma |
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Peaks in 20’s and 50’s
Thought to be caused by EBV- Cluster outbreaks?? S+S: fever, nite sweats, wt loss, or painless lymphadenopathy -may only involve 1 node or nodal area -pain of nodes after ETOH Labs -CBC may be anl -EBV titer to r/o Mono or other ds in differential |
Hodgkin's lymphoma
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Pt’s are at increased risk for other malignancies:
-other lymphomas -leukemias -gastric CA -lung Ca Breast CA Breast CA especially seen in women who were tx’ before the age of 30-35 WHY???- ANYONE? breast is in treatment field |
Hodgkin's lymphoma
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Plasma cell d/o where plasma cells increase abnlly from a single clone
Cells expand and cause clinical manifestations Anemia (80%), bony pain (70%), and kidney disease (25%) **(MC lab finding) Clone of plasma cell proliferates |
MULTIPLE MYELOMA
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Median age 65; usually in 6th decade
Plasma cells secretes OAF’s: osteoclast activating factors that eat bone marrow causing cytopenias- Anemia and bony pain (70%) Prescence of Immunoglobulins produces cause hyperviscosity Specific light chains on immunoglobulins cause kidney damage: Myeloma kidney Plasma cells can form tumors: Plasmocytomas (spinal cord) |
MULTIPLE MYELOMA
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S+S:
-fatigue (anemic) -bony pain: back pain -frequent infections-WHY??-think back about immunoglobulins (immunocompromised; immune system shuts down because of presence of lots of antibodies) -frequent mucosal bleeding or alterations in mental status: hyperviscosity PE:-hepatosplenomegly may or may not -lymphadenopathy may or may not -retinal vein engorgement: hyperviscosity if the immunoglobulin gets too high but not too common -NO bony tenderness****** |
MULTIPLE MYELOMA
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CBC: anemia almost always (80%)**
-CMP: hypercalcemia, elevated KFT’s, and elevated total protein and globulin protein -Peripheral Smear: Rouleau formation but can be nl -SPE: M spike HALLMARK! (figure 98-2) serum plasma electrophoresis BONE SCANS USELESS! |
MULTIPLE MYELOMA
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Beta-2 Microglobulin: carries prognostic factor but debated (>3mg/L= worse prognosis)
-Bone Marrow Biopsy: 20-30% plasma cells in marrow * (must be done to confirm) -Rouleoux formation on peripheral smear -often have elevated protein on and low albumin- WHY?? protein production is taken over to make antibodies and albumin is compromised |
MULTIPLE MYELOMA
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To diagnose:
-SPE: monoclonal protein -IFE: reveals type -Skelatal survey: plain films of body to check for lytic lesions-how are they caused? (bone scan is of absolutely no use!!) -BMB: reveal >20-30% plasma cells (used to be 30% but recent data says 20% w/ other s+s) BMB: bone marrow biopsy Lytic Skull Lesion |
MULTIPLE MYELOMA
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Elevated immunoglobulin (IgG, IgA, or IgM) on SPE w NO lytic lesions, increase # plasma cells in marrow, or lights chains in urine)
****Approx 2% of pts go on to develop more severe disease like Myeloma, Amyloidosis, CLL, or lymphoma |
MGUS
Monoclonal gammopathy of undetermined significance (one immunoglobulin in elevated for unknown reason) |
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M Spike
IgM spike |
M spike: MM
IgM spike: Waldenstroms |
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D/o of B-cells containing both lymphocytic and plasma cell components
Arises from marrow but does not cause lytic lesions Proliferation of IgM- macromolecule- very large- Hyperviscosity S+S: weakness, fatigue, epistaxis (blood vessels get enlarged and engorged), dizziness, etc SPE: IgM spike-HALLMARK (phorese to get ride of IgMs) PE: hepatosplenomegly; retinal vein engorgment (sausage link) Treatment -emergent plasmapheresis! -chemotherapy-CHOP |
Waldenstroms Macroglobinemia
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what is it used for?
Rituxan: first drug in > yrs to have extended survival- smart chemo -monoclonal antibody that targets CD20 receptors -specific lymphoma have more CD20 receptors so respond better -example: follicular >CD20; mantle cell or marginal cell < CD 20 |
NHL
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if allergies and parasitic ruled out, it may be this. these are the only things than can increase eosinophils
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Chronic Eosinophilic Leukemia/Hypereosinophilic Syndrome (CEL/HES)
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Group of d/o that have cytopenias, abnl RBC morphology, and possibly abnl cytogenetics
Usually from advanced age (weak bone marrow), exposure to chemicals, chemo or radiation (10 yrs after tx) Basically you get ineffective blood production Starts at age of 68 and above (about how long stem cells function for before they “give”) Bone marrow biopsy- only way to diagnose MCV 100-110fl, with abnl RDW Risk for bleeding (low plts), fatigue (anemia) or infections (low wbc’s) This is a PRE –Leukemic condition! |
MDS / MYELODYSPLASTIC SYNDROME
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Prognosis is based on FAB Classification System: % increased blasts, # of cytopenias, and cytogenetics (abnl chromosomes) (if genetics is normal, MDS may be minor)
Cytogenic abnormalitties to look out for are: chromosome 5q- (more indolent and treated with Revlamid) or monosomy 7- more aggressive Stem cell transplant only cure but pts are often too weak and elderly The thought with drugs is to use drug that inhibits DNA methylation to induce expression of genes Drugs include Vidaza, Revlamid, Dacogen |
MDS / MYELODYSPLASTIC SYNDROME
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Usually found by elevated H + H
Bone marrow biopsy preferred RBC mass can aid in diagnosis (>125% nl RBC mass is diagnostic but BMB is definitive telling whether primary to secondary) Also presence of JAK2 Mutation in >80% of PV Diagnosis made by BMB: hypercellular, panhyperplasia, and absent Fe stores Erythropoietin level will usually be low: BM cranking out RBC’s without influence of EPO |
POLYCYTHEMIA VERA
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S+S include: (hyperviscosity symptoms) H/A, dizziness, blurred vision, tinnitus, fatigue, splenomegly, generalized pruritis after shower or in hot weather-why? dilation, histamines go to surface
May also c/o nose bleeds or have evidence of GI bleeding-engorgement of vessels (i.e.- increased risk of PUD) Face will often be swelled up (plethora) |
POLYCYTHEMIA VERA
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complication: thrombosis**
What is the treatment of choice? drain the blood; phlebotomy Other treatment options include hydroyurea or anagrelide for elevated plts Slight elevation of plts- ASA Avoid oral iron- why? NEVER EVER TAKE IRON: like putting fuel on the fire |
POLYCYTHEMIA VERA
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Phlebs for PV (know these numbers)
Primary PV: Secondary PV: |
POLYCYTHEMIA VERA
Primary PV: keep Hct <45% or lower if the pt is symptomatic Secondary PV: keep Hct <50% |
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Elevated plt count found on CBC (as high as 2 million)
Must r/o Fe def especially if anemic, CA, inflammation, etc Plt count >600k carries a slightly reduced life expectancy Pt’s at risk for thrombosis and paradoxically bleeding (plt are increased in # but may not act nl) BMB is diagnostic showing megakaryocytes in high proliferation with little of no granulocyte or erythroid proliferation May also see JAK2 mutation (<50%) Hydroxyurea and anagrelide |
ESSENTIAL THROMBOCYTOSIS
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Extremely rare
BMB: hypercellular with Fibrosis of marrow Marked Anemia with Striking splenomegly (huge!), and occaisional hepatomegly Treatment by transfusions and ….? Fe chelation Can use procrit or aranesp Younger pts consider allogenic BM Transplant Often considered the burn out phase of PV |
MYELOFIBROSIS
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Overproduction of myeloid cells
CBC often shows striking elevated WBC (as high as 100-200k) Usually found in middle age ****PCR/bcr/abl: blood test that checks for philadelphia chromosome (translocation of chromosomes 9+22) |
CML
CHRONIC MYELOGENOUS LEUKEMIA |
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S+S include: fatigue, night sweats, and a low grade fever d/t hypermetabolic process
May c/o abd pain d/t organomegly Labs: increased WBC, reduced LAP score, presence of bcr/abl by PCR, and <5% blasts BMB not required |
CML
CHRONIC MYELOGENOUS LEUKEMIA |
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Disease used to hold a grave prognosis with the disease progressing after few years from the chronic phase to blast crisis (>30% blasts)
Treatment with Gleevec 400mg qd and similar drugs have extended the time in the chronic phase for 11-13 years! But costly (goal is to get bcr/abl to undetectable levels) Gleevec works by actually shutting down expression of philadelphia chromosome |
CML
CHRONIC MYELOGENOUS LEUKEMIA |
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eosinophils go up)
(CNL, HES/CEL, MCD, and MPD unclassifiable) Absence of BCR-ABL, dyrerythropoiesis, granulocytic dysplasia, or monocytosis Just know that HES/CEL involve increased number of eosinophils in which case you need to r/o PARASITIC INFECTION and CML which can involve increased eosino’s but neutrophil in CML elevated too |
NON-CLASSIC MPD
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Remember!
All the myeloproliferative d/o and MDS can transform into |
acute leukemia
In acute leukemia the progenitor cells loose the ability to differentiate Most causes of acute leukemia however arise from no clear cause If leukemia arises from MDS or MPD- worse prognosis- why? Chemicals such as benzene and cytotoxic agents like ones used for chemo can even cause leukemia (examples include melphelan, etoposide, etc) |
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most of time no specific cause
If chemo causes the leukemia, it usually developed from MDS into leukemia and involves abnormalities of chromosomes 5 and 7 (refer back to MDS) Treatment harder to get under control if it came from a myeloproliferative d/o |
ACUTE LEUKEMIA
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seen more in elderly
-median age 60 -presence of Auer rod Both have differences but let's focus on similarities first HALLMARK: pancytopenia with circulating blasts (immature cells) Pts will be ill Have bleeding (TCP-low plt) from nose, gingiva, etc; widespread bleeding not as common Infection d/t neutropenia- such as cellulitis, pneumonia, etc Gum hypertrophy, bone pain- long bones, joint pain Hyperleukocytosis- really high WBC (>200,000/UL)- sounds paradoxical- why still get infections? Hyperleukocytosis can cause impaired circulation, H/A,c onfusion- s+s of increased viscosity of blood S/t need to be treated by EMERGENT LEUKOPHORESIS!- which means….? |
Acute Myelogenous Leukemias (AML)
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80% seen in kids, 20% in adults
-peak incidence b/t 3-7 yrs of age Both have differences but let's focus on similarities first HALLMARK: pancytopenia with circulating blasts (immature cells) Pts will be ill Have bleeding (TCP-low plt) from nose, gingiva, etc; widespread bleeding not as common Infection d/t neutropenia- such as cellulitis, pneumonia, etc Gum hypertrophy, bone pain- long bones, joint pain Hyperleukocytosis- really high WBC (>200,000/UL)- sounds paradoxical- why still get infections? Hyperleukocytosis can cause impaired circulation, H/A,c onfusion- s+s of increased viscosity of blood S/t need to be treated by EMERGENT LEUKOPHORESIS!- which means….? |
Acute Lymphoblastic Leukemia
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HALLMARK- what? pancytopenia w/circulating blasts
Bone Marrow- Would the Bone marrow be hypo or hypercellular? with mostly blast- need >20% in BM to make diagnosis Peripheral smear >90% blasts |
Leukemias
Acute Myelogenous Leukemias (AML) -seen more in elderly -median age 60 -presence of Auer rod Acute Lymphoblastic Leukemia -80% seen in kids, 20% in adults -peak incidence b/t 3-7 yrs of age |
|
most common lymphoid leukemia
-usually found incidentally on CBC but pts can present with fatigue or lymphadenopathy (LAD) -CBC will show an elevated WBC with predominately lymphocytosis -up to 80% will have LAD and 50% with hepatosplenomegly -usually idolent unless have subtype prolymphocytic leukemia-characterized by larger and more immature cells |
CHRONIC LYMPHOCYTIC LEUKEMIA
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usually follow the disease- try to avoid treatment as long as possible unless the WBC increases to >70- 80000, the pt is symptomatic, or unless they progress into stage 2 or higher if severe enough
-one thing to look out for in about 5-10% cases may develop autoimmune hemolytic anemia (AIHA) or tcp- how treat? *12% of “out of the blue” ITP or AIHA later go on to develop CLL |
CHRONIC LYMPHOCYTIC LEUKEMIA
|
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D/t injury of BM or abnl expression of stem cell
Can be d/t drugs: chloramphenicol, gold salts; toxins: benzene, toluene; chemo/radiation; after hepatitis infection; SLE Report to office d/t bleeding, infection, weakness, etc PE: pallor, purpura, petechiae BUT NOT enlarged spleen, LAD, or bone tenderness Avg age of diagnosis- 25 yrs CBC: pancytopenias which is HALLMARK BMB: hypocellular marrow treat w/ cyclosporine; cyclophosphamide in refractatory cases- used for older pts >50; <50 yrs- allogenic BMT DON’T FORGET: symptomatic care- transfuse RBC’s, PLT’s, antibiotics Severe cases w/ Absolute Neutrophil Count ANC <500, plt count <20k, retics <1%, and BM w/ <20% cellularity- poorer prognosis |
APLASTIC ANEMIA
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Uncommon- presents middle age
More common in men Pts present w/ gradual fatigue or infections w/ enlarged spleen PE: splenomegly is almost always present w/ half of cases having hepatomegly CBC: pancytopenia w/ monocytopenia “Hairy cells” seen on peripheral smear BMB: dry tap Treatment of choice cladribine producing benefit in 95% of cases and CR in >80% cases Majority of pts live >10 yrs Really only diagnose w/ smear and BMB |
HAIRY CELL LEUKEM IA
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Measure of integrity of intrinsic and final common pathways of coag cascade
Represents time in seconds for patient’s plasma to clot after the addition of phospholipid, an intrinsic pathway activator- calcium (part of intrinsic pathway) |
PTT
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increased Hct does what to the PT/PTT?
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prolongs PT/PTT
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In a mixing study of prolonged PT/PTT, pt's plasma is mixed with normal plasma, if PT/PTT corrects it is due to what? If it is inhibited (still abnormal) it is due to what?
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PT/PTT corrects: clotting factor deficiency of intrinsic pathway, like VIII, IX, XI, XII
PT/PTT inhibited: there is an inhibitor and further testing is required: could be due to 1)drug: heparin, direct thrombin inhibitor 2) specific factor inhibitor (factor VIII or V4), 3)nonspecific inhibitor (lupus anticoagulant - antiphospholipid antibodies) |
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antibodies directed against protein phospholipid comlexes
Even though prolongs PTT paradoxically it places pt at increased risk of clots! Test for it by PTT or dilute Russel viper venom tests which contain phospholipids As a result, these should shorted clotting time (does not mean they have lupus, PTT prolonged but at risk for clots) |
Lupus anticoagulants (LAC)
|
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interfers with factors VII, IX, X and protein C and S
-PREGNANCY CATEGORY X!!!! three most common reasons to use: 1) A-Fib INR 2-3 2) DVT/PE INR 2-3 3) Hrt valve replacement: INR2.5-3.5 |
Coumadin / Warfarin
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inhibits factors IIa (thrombin) and Xa mainly
-large mlcle and not well absorbed subcutaneously -risk of Heparin Induced Thrombocytopenia (HIT) |
Heparin/ Unfractionated Heparin (UFH)-
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SAFE TO GIVE WITH PREGNANCY:
total dose = wt (mg/kg BID) |
LOVENOX
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Triad
stasis, recent trauma/surgery, and hypercoagulable state increased risk for venous thromboembolisms (VTE’s) Hypercoag states include specific blood abnormalities or even drugs or conditions such as cancer (Trouseau’s syndrome), pregnancy, smokiing, estrogen, etc (surgery > 60 min, also older than 40 >> increased risk of clots) |
VirchHow's triad
stasis, recent trauma/surgery, hypercoag state |
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Mutations reduce levels or decrease its functional capacity
20 fold increase risk of thrombosis General population prevelance 0.02% 1-3% of pts with VTE have this Can be low d/t liver disease, nephropathy, or heparin (in nephropathy, pts are losing proteins) |
Antithrombin III Deficiency
|
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Both are vitamin K dependent proteins
Both can be low in Nephrotic Syndrome- think what is spilled in the urine??? Both are affected by warfarin and medical conditions |
Protein C and S
Protein C: 10 fold increase risk of VTE 0.2-0.4% prev 3-5% of VTE pts have this Protein S: 10 fold increase risk of VTE 0.03-0.13% prev 1-5% pf VTE pt’s have this |
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(feedback is not effective)
Factor Va is essential cofactor to allow conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin clot This is inactivated by protein C Mutation Arg506Gln: single AA substituted allowing resistance to inactivation or activated protein C resistance so continues to clot b/c high levels of prothrombin thrombin (factor IIa) Heterozygous: 5 fold risk Homozygous: 80 fold! (much rarer) Higher in whites |
Factor V Leiden Mutation
factor V def: will bleed |
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Mutation of nucleotide substitution in 3’:untranslated region of prothrombin gene which results in greater function of prothrombin (factor II)
3 fold risk VTE (only need to know this) |
Prothrombin Gene G20210A Mutation
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Both are diseases where the body forms antibodies against phospholipids
Phospholipids are supposedly precursors of inflammatory processes in arteries and may contribute to plaque formation Thus breaking up plaques: clots |
LAC and Anticariolipin Antibody
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Approach to a Patient with a VTE
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Want to find out if they had risk factors (surgery, pregnancy, cancer)
Start UFH or LMWH first for a few days before starting coumadin (sounds paradoxical but coumadin initially will drop protein c and s levels placing pt at higher risk of VTE before actually taking effect to “thin” blood out) After a few days (~2-3) start coumadin If pt started on UFH, LMWH, or coumadin, recommended not to run hypercoag panel because some tests will be falsely low (see next table) Rec to wait until off coumadin for 3 weeks before running tests (increased risk: surgery > 60 min or an older pt) |
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VTE and Coumadin
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One VTE: no need for coumadin for life
One VTE and hypercoag: no need for coumadin for life Two VTE and Hypercoag: depends on how serious VTE was Three VTE and hypercaog: LIFE Different Hematologists argue a lot about the above- not true everywhere you go |
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Like injecting draino into area clotted off
Indicated in patients who are having severe extremity pain Often times not helpful in upper extremity DVT’s because of high risk of re-thrombosis |
Thrombolysis
|
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What can cause false abnl PT values?
Would a pt with nephrotic syndrome be at higher risk for a VTE? Pt with COPD and secondary erythrocytosis has prolonged PTT and PT. Why? How would you treat a 85 yr old with a history of DVT’s and history of falls differently than a younger pt with no comorbidities? |
What can cause false abnl PT values? meds, increase H&H
Would a pt with nephrotic syndrome be at higher risk for a VTE? Reason for your answer. spilling protein Pt with COPD and secondary erythrocytosis has prolonged PTT and PT. Why? citrate has more effect if plasma is small How would you treat a 85 yr old with a history of DVT’s and history of falls differently than a younger pt with no comorbidities? IVC filter and avoid coumadin |
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most testicular cancer are what kind of tumors
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germ cell (90-95%)
1. Nonseminoma (will have AFP and BHCG) -embryonal -tetromas -choriocarcinomas -mixed 2. Seminomas (will not see AFP) (better prognosis, radiation sensitive) |
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only risk factor for testicular CA and #1 S&S
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cryptorchism R>L
painless enlargement of teste |
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3 things that elevate alk phos
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liver dz
bones placenta |
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what is the Gleason score?
|
prostate Ca
most 5-7 range: 2-10 |
|
what is the drug of choice for prostate ca
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lupron
GnRH agonist decreases pit stim of LH/FSH SE: fatigue, loss of libido, gynocomastia, bone pain, wt gain, syncope, ocular se also: casodex |
|
smoking is only real documented risk factor
(also f hx) |
kidney ca
renal cell is most common |
|
S/S: gross and microscopic hematuria (60%)
occ flank pain or abd mass -wt loss -advanced disease: flank pain,abd mass, and hematuria -1/5th to 1/3rd: cough or bone pain- mets -(adenopathy. Renal cell commonly recurs. Pts often anemic; kidney produces erythro), normocytic normochromic. Hypercalcemia: bad prognostic sign) • Labs -CBC: anemia -CMP: hypercalcemia -UA: blood in urine |
kidney ca
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kidney ca dx
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CT scan most valuable (shows vascularity)
then US (see if mass is cystic or solid) |
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•Arises from Transition Cells thus
•Smoking, exposure to dyes, and exposure to XRT (radiation) •Higher incidence in men •15% present w/ mets •S+S: hematuria: intermittent -gross or micrscopic -irritative voiding sx’s -(may have to lean forward to void |
bladder ca
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where is most bladder cancer located
|
• 90% occur w/ in bladder; 10% outside
• (superficial bladder = localized = inside bladder) |
|
•Most common skin CA
•Sun exposed areas in fair skin •Appearance: papule or nodule w/ central scab; waxy and pearly appearance w/ telangectasias •Can ulcerate if ignored too long: RAT BITE appearence •Diagnose by shave or punch biopsy unless lesion is very large and irregular: excisional biopsy Treatment •Excision •Curettage and Electrodesiccation •Radiation therapy: cosmetic (face lesions) •Mohs Surgery: best cure rates 98% (microscopically controlled surgery) •(mainly freezing) |
BCC
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•Sun exposed areas in fair skin
•Can arise from an aktinic ketatosis •Red small hard nodules that can ulcerate (in middle)(rough borders w/central ulcer) •Low chance of mets 3-7% •Must r/o other skin lesions like keratoacanthoma (grow faster than sq cell) •Shave or bunch biopsy unless very large and irregular: excisional biopsy Treatment •Excision •Curettage and Electrodesiccation •Mohs surgery •Need to watch more closely •Radiation: cosmetic |
SCC
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BCG tx
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bladder CA tx: chemo directly into bladder
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•Leading cause of death d/t skin CA
•MOST important prognosis: Depth •Breslou’s Thickness + Clark’s Levels •Presence of nodal involvement-5 yr survival <30% •Distant met: <10% •Lentigo Melanoma: sun exposed areas •Superficial Spreading Melanoma: most common •Nodular Melanoma •Acral Lentiginous Melanoma: palms, soles, and nail beds •Melanoma: from mucous membranes |
malignant melanoma
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blue and congenital nevi
If spreads, prognosis is very bad!) Asymmetry Border: irrgeular Color Diameter Enlarging •Appear dark •Irregular borders and shapes •Pigmented streaks on nails •Often >6mm (>6mm : remove!) |
malignant melanoma
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•Treat by excision w/ AT LEAST 1-3 cm clean margins
•CHECK LYMPH NODES on exam. Don't miss this! •Sentinel node biopsy- medium risk •Intron chemo x 48 weeks for high risk (causes prolonged low grade fever) (don't respond well to radiation) •Vaccine trials: not widely used |
malignant melanoma
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Three Stages of Hemostasis
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1. Vascular Spasm
2. Platelet Plug Formation 3. Coagulation |
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Plt’s clump together through plt adhesion
Plt adhere to collagen and plt release ADP and thromboxanes to activate more plts Bind to fibrinogen: plt aggregate connected by fibrinogen Referred to as: |
primary hemostasis
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Comprised of Extrinsic and Intrinsic Pathways
Protein C, Protein S, and Antithrombin 3 help regulate the clot to prevent TOO much clotting. Thus a deficiency in any of these proteins makes a pt more likely to clot or hypercoagulable |
coagulation cascade = secondary hemostasis
|
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1)associated w/ bleeding time and plt count
bleeding is immediate and superficial w/ prolonged bleeding and normal plt count : plt function abnormalitie |
primary
|
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In secondary hemostasis, what is abnl if V, VII, X are affected.
What is sensitive to all except VII and XIII? |
PT
PTT |
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•(functional problem. PT and PTT should be normal)
•(pulls platelets to the wall) •(difficult to dx. Can fluctuate in times of stress) •Autosomal dominant d/o of the plt •Most common inherited bleeding d/o occurring in 1/100-500 pts •factor serves two main functions: -facilitates plt adhesion by linking plt membrane to vascular subendothelium -serves as a plasma carrier for Factor VIII: antihemopheliac factor ***Thus if there is a low level of ___ or a defect, one can see why bleeding is a result •Bleeding is highly variable ranging from minor bleeding to more severe bleeding •Affected greatly by taking ASA |
Von Willebrand’s Disease
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labs: normal
PE: mucosal bleeding, worse w/ ASA TX: vasopressin |
Von Willebrand’s Disease
type I is MC (80%) |
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•Autoimmune d/o where IgG autoantibodies are formed and bind to plt
•Destruction takes place in spleen •Occurs in childhood often after viral infection and is self limited •In adulthood it’s a chronic disease b/t 20-50 yrs of age; 2 female/ 1male •Pts c/o mucosal bleeding •Splenomegly should not be present •Labs: HALLMARK is low plt count- Go Figure •Positive platelet antibody •Peripheral smear: would plt be nl, large, or small •Coagulation studies like PT/INR + PTT should be nl Need to r/o other causes |
Idiopathic Thrombocytopenic Purpura ITP
tx: prednisone 1-2mg/kg |
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Idiopathic Thrombocytopenic Purpura (ITP) tx:
|
prednisone 1-2mg/kg
|
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how to differentiate TTP and HUS
thrombotic thrombocytopenia purpura vs hemolytic uremic syndrome |
TTP has neuro deficits
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•Uncommon syndrome w/ TCP, microangipathic hemolytic anemia, and increased LDH
•Seen in young adults.Brought on by drugs or infections (estrogen, quinine, clopidine, HIV infection) •Low level of ADAMTS 13 •Pts present w/ fevers, fluctuating levels of consciousness, renal failure, and focal neurological deficits •Severity measured by anemia, TCP, and LDH •PT, PTT, fibrinogen are usually nl or slightly abnl •Reticulocytosis •More at risk for clotting d/t hyaline thrombi •On smear: see shistocytes and fragmented cells •Lab tests reveal renal insufficiency (elevated BUN and proteinuria) •Can wax and wane for weeks to months •80-90% pt now recover w/ neuro abnl resolved |
Thrombotic Thrombocytopenic Purpura
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•Uncommon d/o consisting of microangipathic hemolytic anemia, TCP, and renal failure
•Like TTP w/ d/o primarily involved in kidney vasculature •Hyaline thrombi present in kidneys only causing renal failure •Anemia, TCP, and renal failure •Peripheral smear: fragmented RBC’s •Coag test should be normal •Differentiate this from TTP by absence of neuro deficits •Usually brought on after diarrheal illness like w/ Shigella, E-coli O157:H7, and Salmonella •In kids: manage renal failure •In adults: manage renal failure w/ plasmapheresis and FFP •NEED to treat renal failure early! |
Hemolytic Uremic Syndrome
no neuro deficit |
|
extrinsic pathway
-see abnl if factors V, VII, and X affected |
prothrombin time
|
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intrinsic pathway
-sensitive to all factors except VII and XIII |
partial thromboplastin time
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•Hereditary d/o w/ deficiency of Factor VIII
X-linked recessive: who will be affected? •Most common severe bleeding d/o •1/10,000 males affected (PTT is affected, not PT) •Bleeding time, PT, and fibrinogen levels should be nl •Pt report bleeding into joints and muscles •SPONTANEOUS HEMARTHROSES- virtually diagnostic (bleeding into jts and muscles) •Treat w/ Factor VIII concentrate Avoid Asprin |
Hemophilia A
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•X-linked recessive bleeding d/o d/t deficiency of Factor IX
•One seventh < common than Hem A •Tx: w/ Factor IX concentrate •Unfortunately F IX concetrate contains other proteins which can activate clotting factors so thrombosis risk is increased •No DDAVP •Avoid Asprin |
Hemophilia B
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depletes body of platelets and coag factors (paradox > clots)
clotting first, then bleeding bleeding from all site prolonged PT 3 main tests: D-dimer, PT, TCP |
DIC
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•Acts as cofactor of factors II, VII, IX, + X
green leafy veggies •Get from poor diet, chronic alcohol, malabsorption, and broad spectrum Axbx - killing gut flora •Bleeding or bruising •PT prolonged; not so much PTT |
Vitamin K Deficiency
|
|
low platelets
bleeding into mucous membranes |
ITP
|
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spontaneous hemarthrosis
|
hemophilia A
|
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pt w/Von Willibrand's dz will have abnl PT and PTT?
T or F |
false
|
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In TTP and HUS, what would you expect to see in peripheral smear?
|
shistocytes and fragmented cells
|
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primary or secondary:
TPP and vWF |
primary
|
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thrombocytopenia is seen in
|
ITP or TTP
|
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in mixing study
if both PT and PTT are prolonged it is probably: two options in mixing study: both prolonged or PTT prolonged and PT normal |
warfarin
|
|
factor v def:
factor v mutation: |
v def: will bleed
v mutation: higher propensity to clot |
|
splenectomy is most definitive tx but then immunocompromised
prednisone most definitive med tx, start high then taper don't transfuse pts!! |
ITP
|
|
2nd leading cause of death d/t malignancy in US second to lung
|
colorectal ca
primarily adenocarcinoma |
|
Risk Factors
Age: risk increases after 45 yrs of age w/ 90% after 50 yr (risk increases, esp after age 50) FHx: present in 20% of pt Inflammatory Bowel Disease (major risk factor, commonly misdx as IBS) -after ~7-10 yr w/ IBD, risks increases -cumulative risk rises to 20% after 30yrs (1 in 3 w/ cumulative vs 25% of general population) -MUST CONSIDER SCOPING PT 6-8 years after Dx of IBD!!! Diet and Drugs -high fats and red meat; low fruits/veggies/fiber -vit A, C, and E show no benefit -(exercise is beneficial) -NSAIDS and ASA: 30-50% decrease; COX2’s: Vioxx -new data says HIGH DOSES OF ASA (20 tabs/d) needed to reduce risk- NOT RECOMMENDED) Race blacks>whites: Genetics of Socioeconomic factors |
colorectal cancer
|
|
What is the best most cost effective screening test used to detect CRC? (recommended: give stool cards and do on 3 seperate days)
Most definitive? colonoscopy L or R? sided colon cancers: anemia, weakness, fatigue; rarely obstruction d/t large lumen L or R? sided colon cancers: lumen is smaller so can have obstructive sx w/ bowel changes; colicky ab pain |
fecal occult
R sided colon cancers: anemia, weakness, fatigue; rarely obstruction d/t large lumen L sided colon cancers: lumen is smaller so can have obstructive sx w/ bowel changes; colicky ab pain |
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at every stage in CRC screening, survival drops by what %
|
10%
|
|
which CA
chemo and rad after surgery only if below pelvic reflection - because it is always moving |
CRC
|
|
colon and rectal
which is whic resect > tx chemo > resect |
colon: resect > tx
rectal: chemo > resect |
|
Familial Adenomatous Polyposis
FAP: autosomal dominant syndrome affecting 1/10,000, numerous polyps (tumor suppressing gene) Mutation of adenomatous polyposis coli (APC) gene on chromosome _____ leading to premature stop codons during transciption This in turn leads to absence of tumor supressor genes |
5q21
|
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Hereditary Nonpolyposis Colorectal Cancer (HNPCC) also known as: _________
-increases risk of developing multiple CA like ovarian, renal, endometrial, gastric in addition to developing CRC -often involves ASCENDING COLON also causes colon cancer to occur at an earlier age than it might in the general population. |
Lynch Syndrome
|
|
FOBT: what is done next if positive
avoid beets, Vit C, fish, ASA/NSAIDS |
colonoscopy
|
|
RECOMMENDATIONS FOR COLORECTAL CANCER SCREENING
Ave-risk individuals greater than or equal to 50 years old |
Ave-risk individuals greater than or equal to 50 years old
Annual FOBT Flex sig every 5 years Annual FOBT and flex sig every 5 years Colonoscopy every 10 years Barium enema every 5-10 years |
|
RECOMMENDATIONS FOR COLORECTAL CANCER SCREENING
Ind w/fhx of a first-degree member w/colorectal neoplasia |
Single first-degree relative w/colorectal cancer dx at age 60
Begin screening at 40. Screening guidelines same as average risk, colonoscopy preferred Single first-degree relative w/colorectal cancer dx at less than 60 or multiple first-degree relatives: Begin screening at 40 or at age 10 yrs younger than age at diagnosis of youngest affected relative, whichever is first. Recommended screening: colonoscopy every 3 - 5 years |
|
Develops b/t age 50-70 yrs of age w/ 3 men/ 1 woman
Most pt present w/ advanced disease. Why? >90% have dysphagia of solid foods Sometimes odynophagia Wt loss common Can have tumor extension into tracheobronchial tree resulting in fistula: cough w/ swallowing Chest or back pain: mediastinal expansion May have supraclav or cervical nodes on PE |
ESOPHAGEAL CA
|
|
Look for hepatomegly on PE
(Advanced dz: flimsy, it spreads outward and up/down. Wt loss: very common! ) (Fistula w/ trachea: Upper: smoking, alcohol. Lower: ademona based) Adeno is becoming more common Squamous Cell -more common in blacks: not exposed to ETOH as long -chronic ETOC and tobacco use: higher risk -more in proximal 3rd of esophagus Adenomacarcinoma -more distal 3rd -develop as complication of Barrett’s GERD -increasing incidence now: increase in GERD |
ESOPHAGEAL CA
|
|
Lab tests: anemic on CBC, elevated liver functions or alk phos on CMP suggesting liver mets and bony mets
First test used to eval dysphagia- what? swallowing study, barium swallow > endoscopy CXR: widened mediatinum, nodes, pneumonias related to fistulas EGD: look and biopsy, differentiates b/t peptic strictures or other obstructive prob; biopsy tells histology CT scans or PET/CT’s Bronch is fistulas present |
ESOPHAGEAL CA
|
|
Uncommon <40 yrs of age
2 men/ 1 women Higher incidence in Latinos, Blacks, and Asian Americans Most tumor arise where? MALT What is a BIG risk factor? Most are Adenocarcinoma |
gastric Ca
|
|
gastric ca shows what kind of anemai
|
microcystic
|
|
this test is used in gastric Ca and looks for H pylori (it's also called the campylobacter test)
|
CLO test
|
|
where do pancreatic cancer occur:
head vs body/tail |
head: 75%
body & tail: 25% |
|
pancreatic cancer:
what is biggest risk factor? what is most common risk factor? |
Tumor results in death in 98% of pts
AGE in BIGGEST RISK FACTOR (>50 yr) Smoking in most common risk factor Other risk factors: DM, Chronic pancreatitis, obesity |
|
Most frequent s+s*****
-abd pain: becomes severe, can even radiate to L side and back; back greater in tumors in body and tail b/c often get real big before detection-WHY GET PAIN?? -wt loss (75%) -jaundice: tumors at head obstructing biliary tree (80%) Less frequent*** -glucose intolerance unresponsive to meds- can develop w/ in 2 yrs of dx -palpable gallbladder: (50%) Courvoiser’s sign (MC: Abd pain, wt loss, jaundice!!!!!!!!) (pain: celiac nerve right below pancreas) (wt loss is tremendous: can’t absorb food) (incidence = mortality)(Ca in head causes jaundice very quickly) |
pancreatic ca
|
|
what is Courvoiser's sign
|
palpable gallbladder in pancreatic CA
|
|
used in tx
CA 19-9 (not too specific or senstive to dx but used in follow-up) ERCP (more invasive) MRCP |
pancreatic CA
|
|
Gemzar: what are the 5 uses
|
pancreatic CA
lung bladder breast esophagus |
|
most common causes of liver CA
|
cirrhosis and ETOH
Hepatocellular CA -arise from parenchymal cells -associated w/ cirrhosis (80%) and Hep C -most common risk factors- Hep C and ETOH cirrhosis -also associated w/ Hemachromatosis- what is this? Cholangiocarcinomas -arise from ductular cells -less common |
|
S+S: cachexia, weakness, and wt loss
PE: ascities, hepatomegly, and occasional palpable mass, easy bruising (why?) clotting factors Labs -CBC: leukocytosis/ not leukopenia seen in chronic liver disease -anemia: related to chronic liver disease (normo/normo) -elevated AFP**** (70%) (also seen in testicular Ca) -CMP: elevated alk phos, LFT’s |
liver ca
|
|
accounts for 90% of lung ca
which is more aggressive |
NSCLC
small cell is more aggressive |
|
anorexia, wt loss, and asthenia (55-88%) [asthenia: physical weakness and loss of strength]
-new cough or change in chronic cough -hemoptysis: usually lesions around BRONCHUS -pain: if bony mets -pneumonia: if CA obstructs -pleural effusion -change in voice: where is location? central recurrent laryngeal nerve -SVC -Horner’s Syndrome: Pancoast Tumor presses on nerves Whenever first s+s listed above is present pt is @ least Stage IIIA!** |
lung ca
|
|
this is elevated in colorectal, gastric, pancreatic, lung and breast cancer
|
CEA
|
|
PET/CT are only used in which lung cancer type?
|
NSCLC
|
|
surgery is rarely beneficial in which lung ca?
|
SCLC
cenral location and may have met |
|
•Asbestosis exposure (8% risk)
•Arise from pleura (80%) or peritoneum (20%) •Asbestos in milling, brake linings, shipyard work, roofing, mining •60-80% pts report exposure •S+S similar to lung ca •Median survival from time of diagnosis: 5 months to 16 months •Surgery, Radiation, and chemo usually Ineffective •Chemo: Alimta FDA approved •(forms around pleaur > can't remove pleura. More likely to get pleural effusion; blocks lymphatics) |
mesothelioma
|
|
• Found on CXR: 1-6mm w/ good margins can be followed or worked up
• 1/3rd are malignant • Hx: check for smoking or exposure • If >6mm order PET/CT: if lites up consider biopsy • If follow- 2 yrs of stability suggests BENIGN- follow w/ CT’s q 3-6 months • BTW: please don’t ever order an MRI of the chest |
solitary lung nodule
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• Most common CA in women besides skin
• 2nd to Lung CA as cause of death • CA risk increases as age • Median age ~60 • 1/8 women develop CA • Incidence increasing (longer life expect) w/ less mortality (earlier detection, better understanding and tx) • 3-4 fold increase risk w/ FHx BUT…3/4th of time no FHx • 10% d/t mutation BRCA 1+2 |
BREAST CANCER
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• These are anti-suppressor genes
• Mutations have increased risk of developing Breast CA • Seek genetic counselor • Mutations can be readily sequenced • 85% lifetime risk w/ BRCA1 mutation • Women are typically younger pts with Breast CA • (BRCA mutation: almost always younger. Tumor suppressing genes. w/BRCA also at risk for ovarian ca) |
BRCA 1+2
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what is BIRADS used for
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breast Ca
0: incomplete 4: suspicious, need bx 3: iffy breast imaging reporting and data system |
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S+S:
-MOST common complaint is painless palpable lump -mastalgia, nipple discharge, erosion, retractions, hardness, shrinking of breast are < common -advanced: swelling of arm from mets to Node -jaundice or bony pain: mets-RARE -Most found in axillary tail (60%); Refer to Figure 16-1 |
BREAST CANCER
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what is the CA 27.29 test used for
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breast ca
<38 nl so-so test |
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which breast ca type is most common
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Invasive Ductal CA- most common
-arises from large or intermediate ducts -a lot of subtypes -Ductal CA in situ: precancerous lesion w/ no invasion into extraductal tissue 2. Infiltrating Lobular CA 3. Paget’s (1%): ductal ca w/ nipple ducts involved, itching and burning of nipple 4. Inflammatory (<3%): most malignant -mass grows w/ erythema of overlying skin -often mistook for infection -(suspect if unresponsive to abx) |
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breast ca:
considered premalignant -CA: if left untreated -behaves like early CA -tx w/ mastectomy w/ or w/o Radiation -then tamoxifen for 5 yrs -(usually one sided)***** •LCIS (lobular Ca in-situ) : premalignant -can develop breast can in either breast equally not just side found on -watch and wait BUT most pt want bilat total mastectomy -(equal in both breasts)**** |
DCIS
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which is one sided and which is one both sides
DCIS and LCIS |
LCIS is on both sides
DCIS is on one side |
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breast ca:
•ANY TUMOR >___cm, have to be suspicious of nodal involvement d/t large size-NEED to check nodes |
•ANY TUMOR >2cm, have to be suspicious of nodal involvement d/t large size-NEED to check nodes
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•After breast removed need to look at cytology:
1. Hormone Receptor +/- -Neg: can’t use Tamoxifen -Pos: use Tamoxifen or AI’s 2. HER2/neu overexpressed +/- which has better prognosis: neg or pos |
2. HER2/neu overexpressed +/-
-neg: better prognosis -pos: worse; means has extra HER receptors on cells when triggered start replication -w/ replication : CA grows faster and uglier -Herceptin used if HER2 positive: works extracellularly (herceptin protects ca everywhere except brain) -Tykerb: works intracellularly (goes into cells and blocks pathways downstream) |
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breast radiation is indicated when?
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-w/ any # of nodes or
-any # of nodes w/ extranodal extension -following lumpectomy -palliative for met lesions causing pain or obstruction |
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chemotherapy for breast is indicated when?
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indicated for node +
-may give if S/P mastectomy w/ node neg BUT Hormone Receptor (HR) neg (up for discussion b/t pt and clinician) or if HER2 overexpressed -metastatic site -often try to avoid in elder pts w/ poor performance status |
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tamoxifen use in breast ca
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• Tamoxifen
-not used for pt w/ clotting d/o -pre or post menopausal -HOT Flashes! -> 5 yrs : increase in clots and endomet ca |
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aromatase inhibitor use in breast ca:
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• Aromatase Inhibitors
-Arimidex, Femera, and Aromasin -superior to tamoxifen alone -Hot flashes -osteopenia or osteoperosis |
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breast ca follow-up:
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•1st yr: q3 months; 6mo Mammo
•2nd yr: q4 months; 6 or 12mo Mammo •3rd-5th yr: q6 months; yrly Mammo •5+ yrs: follow up yrly with yrly Mammo •Continue women’s health check up especially if on Tamoxifen-Why? endometrial ca, clotting, stroke |
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•HPV (16,18,31, 45, and 51-53) major risk factor
-HPV: binds + inactivates tumor suppressor gene •Occurs at the squamocolumnar junction |
Cervical CA
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•Most common female pelvic CA; 2nd overall to what?
•Most are curable when found (3/4th ) b/c confined to uterus •Postmenopausal women 50-70 yrs •Risk Factors: -unopposed estrogen or prolonged tamoxifen -obesity -nulliparous -DM -polycystic ovaries w/ prolonged anovulation |
Endometrial Cancer
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S+S:
-abnl bleeding (80%) -pus and lower abd pain testing -PAPS: not as effective -endocervical and endometrial sampling -hysteroscopy -pelvic ultrasound: thickness |
Endometrial Cancer
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