Heme/onc

Front 1

-Neutrophils 43-65%
-Basophils <1%
-Eosinophils 0-3%

Back 1

granulocytes

Front 2

-Lymphocytes 24-44%
-Monocytes 4-8%

Back 2

agranulocytes

Front 3

 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

Back 3

Neutrophils

Front 4

 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

Back 4

Eosinophils

Front 5

 Stain with basic dyes
 Rare in circulation
 Eat up damaged tissue
 Release granules that contain histamine and heparin

Back 5

Basophils

Front 6

 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

Back 6

Monocytes

Front 7

 Stain with lack of granules and thin halo of cytoplasm
 Elevated in viral infections
 Three types
-T cells
-B cells
-NK cells

Back 7

Lymphocytes

Front 8

 Production stimulated by:
-Thrombopoietin: from kidneys
-Interlukin 6 (inflammatory cytokine: PAY ATTENTION TO THIS) cytokines: instruct other cells
-Multi-colony stimulating factor support

Back 8

Platelets

Front 9

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)

Back 9

albumin

Front 10

 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

Back 10

lymphocytes

Front 11

 Referred to as Humoral Immunity

Back 11

B Cell lymphocytes

Front 12

 Mature B-cells release ________ which release antibodies/gammaglobulins

Back 12

plasma cells

Front 13

 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?

Back 13

types of antibodies

IgM goes up first on first exposure
IgG takes off on second exposure

Front 14

 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)

Back 14

Interferons

Front 15

 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)

Back 15

Complement System

Front 16

WBC:
RBC:
Platelets:

Back 16

 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

Front 17

HEMOGLOBIN AND HEMATOCRIT

Back 17

 Men 14-18 g/dl 42-54%
 Women 12-16 g/dl 36-48%

Front 18

can be caused by sepsis, MDS, vasculitis, autoimmune ds (SLE)

Back 18

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

Front 19

MCV
mean cell/corpuscular volume

micro/macro

Back 19

80-100 fenoliters

Front 20

MCH
mean cell/corpuscular hemoglobin

ave mass of Hgb/RBC
decreased in microcytic anemia

Back 20

27-33 pg

Front 21

MCHC
mean cell/corpuscular Hgb concentration

hypochromic: microcytic anemia
normochromic: macrocytic anemia
hyperchromic: spherocytosis

Back 21

31 -35%

Front 22

RDW
red cell distribution width
used mainly to distinguish anemia of multiple cause from single cause

Back 22

12-15%

Front 23

increased in alcoholism, reticulocytes, pernicious anemia, vit B12 def
decreased in Fe def, thalasemia, chronic dz

low w/ + stool guaiac = GI cancer

Back 23

MCV

Front 24

RBC of unequal sizes

Back 24

anisocytosis

Front 25

RBC of unequal shape

Back 25

poilocytosis

suggest defect in maturation of RBC

Front 26

Target cells

Back 26

bull’s eye appearance suggesting thalasemia or liver disease (or severe Fe deficiency)

Front 27

Rouleau Formation

Back 27

Multiple Myeloma

Front 28

clusters of DNA remains in RBC
seen in hypo or asplenia, severe hemolytic anemia, megaloblastic anemia, hereditary spherocytosis, MDS

Back 28

Howell-Jolly bodies

Front 29

retic count range

Back 29

1 - 2%

Front 30

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)

Back 30

 Reticulocytosis

Front 31

: 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)

Back 31

 Hemolysis

Front 32

 Reticulocytosis w/ anemia

 If there is anemia with a retic count nl or slightly elevated

Back 32

 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)

Front 33

CLINICAL PEARL! How can you determine if anemia is being compensated?

Back 33

 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.

Front 34

-cytic refers to

-chromic refers to

Back 34

cytic refers to MCV

chromic refers to MCHC (concentration of HgB in RBCs)

Front 35

 The 3 most common causes of normocytic, normochromic anemias are

Back 35

1. Mild Fe deficiency
2. Marrow damage or inflammation
3. Chronic disease or inadequate EPO stimulation; another cause: sideroblastic anemia

Front 36

 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

Back 36

 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

Front 37

MICROCYTIC ANEMIA
 Causes include:

Back 37

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

Front 38

 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)

Back 38

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

Front 39

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

Back 39

IRON DEFICIENCY ANEMIA*

Front 40

 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

Back 40

THALASEMIAS

Front 41

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

Back 41

 Alpha thalasemia

Front 42

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%

Back 42

 Beta Thalasemia

Front 43

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

Back 43

THALASEMIA

Front 44

 Causes include:
1. Folate Deficiency
2. Vit B12 Deficiency
3. MDS
4. Hypothyroidism
5. Chronic ETOH abuse
6. Hemolytic Anemias (sometimes)

Back 44

MACROCYTIC ANEMIAS

Front 45

 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

Back 45

folic acid deficiency

macrocytic anemia

Front 46

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

Back 46

VIT B12 DEFICIENCY

macrocytic anemia

Front 47

(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

Back 47

VIT B12 DEFICIENCY

macrocytic anemia

Front 48

 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

Back 48

MDS / myelodysplastic anemia

(macrocytic anemia)

Front 49

 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!

Back 49

MDS / myelodysplastic anemia

(macrocytic anemia)

Front 50

 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

Back 50

MDS / myelodysplastic anemia

(macrocytic anemia)

Front 51

 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

Back 51

MDS / myelodysplastic anemia

(macrocytic anemia)

Front 52

chronic ETOH abuse can lead to what type of anemia

Back 52

macrocytic anemia

Front 53

 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

Back 53

HEMOLYTIC ANEMIA

(can sometimes cause macrocytic anemia)

Front 54

 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

Back 54

HEMOLYTIC ANEMIA

(can sometimes cause macrocytic anemia)

Front 55

 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

Back 55

HEREDITARY SPHEROCYTOSIS

Front 56

 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

Back 56

HEREDITARY SPHEROCYTOSIS

Front 57

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

Back 57

Budd-Chiari syndrome

Front 58

 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

Back 58

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Front 59

 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

Back 59

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Front 60

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

Back 60

G6PD
 Glucose-6-Phosphate Dehydrogenase Deficiency

Front 61

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?

Back 61

 Treat initially w/ prednisone 1-2mg/kg- NEED to KNOW DOSE ON THIS ONE*****
If steroids don’t work: splenectomy

Front 62

 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)

Back 62

MICROANGIOPATHIC HEMOLYTIC ANEMIAS

Front 63

 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

Back 63

sickle cell anemia

Front 64

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

Back 64

sickle cell anemia crisis

Front 65

 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

Back 65

sickle cell anemia

Front 66

-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

Back 66

NHL
Non-Hodkin's lymphoma

Front 67

 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

Back 67

NHL
Non-Hodkin's lymphoma

Front 68

presence of Reed-Steinberg cells
-bimodal age in 20’s and 50’s
-painless lymphadenopathy
-fever, wt loss, nite sweats, generalized pruritis

Back 68

Hodgkin's lymphoma

Front 69

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

Back 69

NHL
Non-Hodkin's lymphoma

Front 70

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

Back 70

Hodgkin's lymphoma

Front 71

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

Back 71

Hodgkin's lymphoma

Front 72

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

Back 72

MULTIPLE MYELOMA

Front 73

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)

Back 73

MULTIPLE MYELOMA

Front 74

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******

Back 74

MULTIPLE MYELOMA

Front 75

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!

Back 75

MULTIPLE MYELOMA

Front 76

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

Back 76

MULTIPLE MYELOMA

Front 77

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

Back 77

MULTIPLE MYELOMA

Front 78

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

Back 78

MGUS
 Monoclonal gammopathy of undetermined significance (one immunoglobulin in elevated for unknown reason)

Front 79

M Spike

IgM spike

Back 79

M spike: MM

IgM spike: Waldenstroms

Front 80

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

Back 80

Waldenstroms Macroglobinemia

Front 81

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

Back 81

NHL

Front 82

if allergies and parasitic ruled out, it may be this. these are the only things than can increase eosinophils

Back 82

Chronic Eosinophilic Leukemia/Hypereosinophilic Syndrome (CEL/HES)

Front 83

 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!

Back 83

MDS / MYELODYSPLASTIC SYNDROME

Front 84

 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

Back 84

MDS / MYELODYSPLASTIC SYNDROME

Front 85

 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

Back 85

POLYCYTHEMIA VERA

Front 86

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)

Back 86

POLYCYTHEMIA VERA

Front 87

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

Back 87

POLYCYTHEMIA VERA

Front 88

Phlebs for PV (know these numbers)
Primary PV:
Secondary PV:

Back 88

POLYCYTHEMIA VERA
Primary PV: keep Hct <45% or lower if the pt is symptomatic
Secondary PV: keep Hct <50%

Front 89

 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

Back 89

ESSENTIAL THROMBOCYTOSIS

Front 90

 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

Back 90

MYELOFIBROSIS

Front 91

 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)

Back 91

CML

CHRONIC MYELOGENOUS LEUKEMIA

Front 92

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

Back 92

CML

CHRONIC MYELOGENOUS LEUKEMIA

Front 93

 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

Back 93

CML

CHRONIC MYELOGENOUS LEUKEMIA

Front 94

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

Back 94

NON-CLASSIC MPD

Front 95

Remember!
 All the myeloproliferative d/o and MDS can transform into

Back 95

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)

Front 96

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

Back 96

ACUTE LEUKEMIA

Front 97

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….?

Back 97

 Acute Myelogenous Leukemias (AML)

Front 98

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….?

Back 98

 Acute Lymphoblastic Leukemia

Front 99

 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

Back 99

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

Front 100

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

Back 100

CHRONIC LYMPHOCYTIC LEUKEMIA

Front 101

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

Back 101

CHRONIC LYMPHOCYTIC LEUKEMIA

Front 102

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

Back 102

APLASTIC ANEMIA

Front 103

 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

Back 103

HAIRY CELL LEUKEM IA

Front 104

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)

Back 104

PTT

Front 105

increased Hct does what to the PT/PTT?

Back 105

prolongs PT/PTT

Front 106

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?

Back 106

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)

Front 107

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)

Back 107

Lupus anticoagulants (LAC)

Front 108

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

Back 108

Coumadin / Warfarin

Front 109

inhibits factors IIa (thrombin) and Xa mainly
-large mlcle and not well absorbed subcutaneously
-risk of Heparin Induced Thrombocytopenia (HIT)

Back 109

Heparin/ Unfractionated Heparin (UFH)-

Front 110

SAFE TO GIVE WITH PREGNANCY:
total dose = wt (mg/kg BID)

Back 110

LOVENOX

Front 111

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)

Back 111

VirchHow's triad
stasis, recent trauma/surgery, hypercoag state

Front 112

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)

Back 112

Antithrombin III Deficiency

Front 113

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

Back 113

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

Front 114

(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

Back 114

Factor V Leiden Mutation

factor V def: will bleed

Front 115

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)

Back 115

Prothrombin Gene G20210A Mutation

Front 116

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

Back 116

LAC and Anticariolipin Antibody

Front 117

Approach to a Patient with a VTE

Back 117

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)

Front 118

VTE and Coumadin

Back 118

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

Front 119

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

Back 119

Thrombolysis

Front 120

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?

Back 120

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

Front 121

most testicular cancer are what kind of tumors

Back 121

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)

Front 122

only risk factor for testicular CA and #1 S&S

Back 122

cryptorchism R>L

painless enlargement of teste

Front 123

3 things that elevate alk phos

Back 123

liver dz
bones
placenta

Front 124

what is the Gleason score?

Back 124

prostate Ca

most 5-7
range: 2-10

Front 125

what is the drug of choice for prostate ca

Back 125

lupron
GnRH agonist
decreases pit stim of LH/FSH
SE: fatigue, loss of libido, gynocomastia, bone pain, wt gain, syncope, ocular se

also: casodex

Front 126

smoking is only real documented risk factor

(also f hx)

Back 126

kidney ca

renal cell is most common

Front 127

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

Back 127

kidney ca

Front 128

kidney ca dx

Back 128

CT scan most valuable (shows vascularity)
then US (see if mass is cystic or solid)

Front 129

•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

Back 129

bladder ca

Front 130

where is most bladder cancer located

Back 130

• 90% occur w/ in bladder; 10% outside
• (superficial bladder = localized = inside bladder)

Front 131

•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)

Back 131

BCC

Front 132

•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

Back 132

SCC

Front 133

BCG tx

Back 133

bladder CA tx: chemo directly into bladder

Front 134

•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

Back 134

malignant melanoma

Front 135

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!)

Back 135

malignant melanoma

Front 136

•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

Back 136

malignant melanoma

Front 137

Three Stages of Hemostasis

Back 137

1. Vascular Spasm
2. Platelet Plug Formation
3. Coagulation

Front 138

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:

Back 138

primary hemostasis

Front 139

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

Back 139

coagulation cascade = secondary hemostasis

Front 140

1)associated w/ bleeding time and plt count

bleeding is immediate and superficial

w/ prolonged bleeding and normal plt count : plt function abnormalitie

Back 140

primary

Front 141

In secondary hemostasis, what is abnl if V, VII, X are affected.

What is sensitive to all except VII and XIII?

Back 141

PT

PTT

Front 142

•(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

Back 142

Von Willebrand’s Disease

Front 143

labs: normal
PE: mucosal bleeding, worse w/ ASA
TX: vasopressin

Back 143

Von Willebrand’s Disease

type I is MC (80%)

Front 144

•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

Back 144

Idiopathic Thrombocytopenic Purpura ITP

tx: prednisone 1-2mg/kg

Front 145

Idiopathic Thrombocytopenic Purpura (ITP) tx:

Back 145

prednisone 1-2mg/kg

Front 146

how to differentiate TTP and HUS

thrombotic thrombocytopenia purpura vs hemolytic uremic syndrome

Back 146

TTP has neuro deficits

Front 147

•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

Back 147

Thrombotic Thrombocytopenic Purpura

Front 148

•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!

Back 148

Hemolytic Uremic Syndrome

no neuro deficit

Front 149

extrinsic pathway
-see abnl if factors V, VII, and X affected

Back 149

prothrombin time

Front 150

intrinsic pathway
-sensitive to all factors except VII and XIII

Back 150

partial thromboplastin time

Front 151

•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

Back 151

Hemophilia A

Front 152

•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

Back 152

Hemophilia B

Front 153

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

Back 153

DIC

Front 154

•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

Back 154

Vitamin K Deficiency

Front 155

low platelets
bleeding into mucous membranes

Back 155

ITP

Front 156

spontaneous hemarthrosis

Back 156

hemophilia A

Front 157

pt w/Von Willibrand's dz will have abnl PT and PTT?

T or F

Back 157

false

Front 158

In TTP and HUS, what would you expect to see in peripheral smear?

Back 158

shistocytes and fragmented cells

Front 159

primary or secondary:

TPP and vWF

Back 159

primary

Front 160

thrombocytopenia is seen in

Back 160

ITP or TTP

Front 161

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

Back 161

warfarin

Front 162

factor v def:
factor v mutation:

Back 162

v def: will bleed
v mutation: higher propensity to clot

Front 163

splenectomy is most definitive tx but then immunocompromised
prednisone most definitive med tx, start high then taper
don't transfuse pts!!

Back 163

ITP

Front 164

2nd leading cause of death d/t malignancy in US second to lung

Back 164

colorectal ca

primarily adenocarcinoma

Front 165

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

Back 165

colorectal cancer

Front 166

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

Back 166

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

Front 167

at every stage in CRC screening, survival drops by what %

Back 167

10%

Front 168

which CA

chemo and rad after surgery only if below pelvic reflection - because it is always moving

Back 168

CRC

Front 169

colon and rectal
which is whic

resect > tx
chemo > resect

Back 169

colon: resect > tx

rectal: chemo > resect

Front 170

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

Back 170

5q21

Front 171

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.

Back 171

Lynch Syndrome

Front 172

FOBT: what is done next if positive

avoid beets, Vit C, fish, ASA/NSAIDS

Back 172

colonoscopy

Front 173

RECOMMENDATIONS FOR COLORECTAL CANCER SCREENING
Ave-risk individuals greater than or equal to 50 years old

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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

Front 174

RECOMMENDATIONS FOR COLORECTAL CANCER SCREENING
Ind w/fhx of a first-degree member w/colorectal neoplasia

Back 174

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

Front 175

 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

Back 175

ESOPHAGEAL CA

Front 176

 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

Back 176

ESOPHAGEAL CA

Front 177

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

Back 177

ESOPHAGEAL CA

Front 178

 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

Back 178

gastric Ca

Front 179

gastric ca shows what kind of anemai

Back 179

microcystic

Front 180

this test is used in gastric Ca and looks for H pylori (it's also called the campylobacter test)

Back 180

CLO test

Front 181

where do pancreatic cancer occur:

head vs body/tail

Back 181

head: 75%
body & tail: 25%

Front 182

pancreatic cancer:
what is biggest risk factor?
what is most common risk factor?

Back 182

 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

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 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)

Back 183

pancreatic ca

Front 184

what is Courvoiser's sign

Back 184

palpable gallbladder in pancreatic CA

Front 185

used in tx
CA 19-9 (not too specific or senstive to dx but used in follow-up)
ERCP (more invasive)
MRCP

Back 185

pancreatic CA

Front 186

Gemzar: what are the 5 uses

Back 186

pancreatic CA
lung
bladder
breast
esophagus

Front 187

most common causes of liver CA

Back 187

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

Front 188

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

Back 188

liver ca

Front 189

accounts for 90% of lung ca

which is more aggressive

Back 189

NSCLC

small cell is more aggressive

Front 190

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!**

Back 190

lung ca

Front 191

this is elevated in colorectal, gastric, pancreatic, lung and breast cancer

Back 191

CEA

Front 192

PET/CT are only used in which lung cancer type?

Back 192

NSCLC

Front 193

surgery is rarely beneficial in which lung ca?

Back 193

SCLC
cenral location and may have met

Front 194

•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)

Back 194

mesothelioma

Front 195

• 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

Back 195

solitary lung nodule

Front 196

• 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

Back 196

BREAST CANCER

Front 197

• 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)

Back 197

BRCA 1+2

Front 198

what is BIRADS used for

Back 198

breast Ca
0: incomplete 4: suspicious, need bx
3: iffy
breast imaging reporting and data system

Front 199

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

Back 199

BREAST CANCER

Front 200

what is the CA 27.29 test used for

Back 200

breast ca
<38 nl

so-so test

Front 201

which breast ca type is most common

Back 201

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)

Front 202

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)****

Back 202

DCIS

Front 203

which is one sided and which is one both sides

DCIS and LCIS

Back 203

LCIS is on both sides

DCIS is on one side

Front 204

breast ca:
•ANY TUMOR >___cm, have to be suspicious of nodal involvement d/t large size-NEED to check nodes

Back 204

•ANY TUMOR >2cm, have to be suspicious of nodal involvement d/t large size-NEED to check nodes

Front 205

•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

Back 205

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)

Front 206

breast radiation is indicated when?

Back 206

-w/ any # of nodes or
-any # of nodes w/ extranodal extension
-following lumpectomy
-palliative for met lesions causing pain or obstruction

Front 207

chemotherapy for breast is indicated when?

Back 207

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

Front 208

tamoxifen use in breast ca

Back 208

• Tamoxifen
-not used for pt w/ clotting d/o
-pre or post menopausal
-HOT Flashes!
-> 5 yrs : increase in clots and endomet ca

Front 209

aromatase inhibitor use in breast ca:

Back 209

• Aromatase Inhibitors
-Arimidex, Femera, and Aromasin
-superior to tamoxifen alone
-Hot flashes
-osteopenia or osteoperosis

Front 210

breast ca follow-up:

Back 210

•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

Front 211

•HPV (16,18,31, 45, and 51-53) major risk factor
-HPV: binds + inactivates tumor suppressor gene
•Occurs at the squamocolumnar junction

Back 211

Cervical CA

Front 212

•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

Back 212

Endometrial Cancer

Front 213

S+S:
-abnl bleeding (80%)
-pus and lower abd pain
testing
-PAPS: not as effective
-endocervical and endometrial sampling
-hysteroscopy
-pelvic ultrasound: thickness

Back 213

Endometrial Cancer