Heme/Onco Flashcards
causes of non megaloblastic macrocytic anemia
liver disease - cirrhosis
alcohol
drugs - 5-FU, Ara C, zidovidine
lesch nylan
folate
3-6wk supply, green leafy veggies
pt with tea and toast diet
decreased methymalonic acid and increased homocysteine
mcv >100
b12
3-10 years, animal products
tingling, numbness - DCMLS affected - 2pt discrimination, proprioception, numbness
strict uneducated vegan or compromised absorption
b12 absorption causes
pernicious anemia - IgA attacks parietal cells –> no intrinsic factor
crohns dz - terminal ileum predilection
gastric bypass - bypass parietal cells absorption of b12
dx of b12 def
increased methylmalonic acid
increased homocysteine
increased MCV
tx of b12 def
PO - nutritionally def pts
IM - impaired absorption pts
schilling test interpretation
po b12 given after b12 receptors saturated –>
urine b12 (+) = nutritional issue urine b12 (-) = malabsorption
types of microcytic anemia
iron def
anemia of chronic dz
sideroblastic
thalassemias
ferritin =
TIBC =
ferritin = stored iron
TIBC = potential storage
sideroblastic anemia basics
increased Iron
ringed sideroblast on biopsy - iron gets stuck in mitochondria
reversible causes of sideroblastic anemia
drugs
etoh
lead poisoning
irreversible causes of sideroblastic anemia
b6 def
myelodysplastic syndrome
iron def anemia pt presentation
old guy colon cancer +fecal occult blood test
young women with menometrorrhagia
dx of iron def anemia
decreased Fe
decreased Ferritin
increased TIBC
bone marrow biopsy = gold standard
tx of iron def anemia
iron 324mg TID + stool softeners for constipation side effects
anemia of chronic inflammatory disease
RA pts
Lupus pts
asymptomatic anemia
dx and tx of anemia of chronic inflammatory disease
increased ferritin
decreased Fe
decreased TIBC
tx - nothing - EPO if severe - better to tx underyling dz
thalassemias
problem with globin
minor thal - asymptomatic - no tx
major thal - transfusion dependent - tx = transfusions - with deforaxamine for iron overload
dx of thalassemias
nml Fe, nml ferritin, nml TIBC
hemoglobin electrophoresis
alpha 1 - asymptomatic, alpha 2 - mild anemia, alpha 3 - severe anemia, alpha 4- hydrops
beta 1 mild and beta 2 severe
next step after finding anemia that is normocytic
LDH
Haptoglobin
Bilirubin
Smear
normocytic anemia with
increased LDH
decreased haptoglobin
increased bilirubin
hemolysis
- sickle cell
- g6pd def
- hereditary spherocytosis
- PNH
normocytic anemia with + smear
cancer
- myelodysplastic
- leukemia
sickle cell dz
cells sickle - HgbSS - AR
vasocclusive crisis –> pain
- acidosis, hypoxemia, dehydration
Acute chest, acute brain, priaprism
dx and tx sickle cell
dx - hgb electrophoresis - smear - sickle cells = crisis
tx - hydroxyurea - increased Hgb F, IVF, O2, pain control
exchange transfusion for acute crisis
iron overload - deforaxamine
G6PD def
blacks and oxidative crisis with meds:
- dapsone
- TMP -SMX
- Nitrofurantoin
dx of G6PD
smear - heinz bodies, bite cells,
during crisis G6PD level nml - check 6-8wks later
tx - remove stressor
hereditary spherocytosis
RBC membrane protein problems - ankrin, spectrin, pallidum
dx - smear - best test - osmotic fragility
tx - splenectomy - folate and iron
autoimmune hemolytic anemia
+ coombs test
–> IgM - cold myeloplasma, mono –> tx - avoid cold
–> IgG - warm - autoimmune (spherocytes) dz, cancer –> tx –> steroids, rituximab, splenectomy
PNH
def of PIGA gene - easier complement formation
shallow breathing at night -> acidotic state -> easier complement formation
PNH dx and tx
dx - flow cytometry CD55
tx - supportive if severe Eculizumab
AML basics
67 y/o
exposure hx - benzene, radiation, CML hx
acute presentation - infection, fever, weight loss, bone pain, anemia, etc
AML dx and tx
dx - smear - blasts - BM biopsy > 20% blasts
- (+) myeloperoxidase and auer rods
tx - M3 - all trans retinoic acid (vit A)
- not M3 = chemo
ALL basics
acute presentation
kids - 7 y/o
dx and tx of ALL
dx - smear - blasts BM >20% blasts
- (+) tdt and (+) cALLa
tx - chemo and prophylaxis CNS ARA-c (+/- radiation)
CML basics
asymptomatic
high high WBC >60,000
middle age 47 y/o
dx of CML
BM biopsy - > philadelphia chromosome, t(9:22) BCR-ABL fusion protein, tyrosine kinase
tx of CML
imatinib and complication can be ALL crisis
CLL basics
asymptomatic
87 y/o
BM biopsy showing lymphocytes
tx of CLL
old > 65 + no symptoms –> do nothing
old > 65 + symptoms (hyperviscosity syndrome - HA) –> chemotherapy
young + donor –> stem cell transplant
hodgkin lymphoma
reed sternberg cells
night sweats, fever, weight loss
dx = 2a or better
tumor burden = local
hodgkin lymphoma - odd presentations and tx
pel epstein fevers (cyclical)
etoh –> painful LN
tx - ABVD or BEACOPP (if severe)
non hodgkin lymphoma
(-) B symptoms
2b or worse at dx
spreads hematogenously –> everywhere
burkitt lymphoma - starry sky, extra nodal dz
tx - rutiximab - CHOP
staging of lymphoma
I - 1 LN - same side as diaphragm
II - >1 LN - same side as diaphragm
III - >1 LN - opposite side as diaphragm
IV - metastatic disease
presentation of non tender lymphadenopathy –> next step =
excisional biopsy
vincristine
vinblastine
ADR
Peripheral neuropathy
bleomycin ADR
pulmonary fibrosis
cyclophosphamide ADR
hemorrhagic cystitis
adriamycin
doxorubicin
danurubicin
ADR
cardiomyopathy
cisplatin ADR
ototoxicity
nephrotoxicity
Multiple myeloma
path
produce incomplete IgG –> M spike
make osteoclast stimulating factor –> osteolytic lesions
make bence jones proteins –> AKI
infections and protein gap
MM presentation
older 70 y/o hypercalcemia renal failure anemia bone pain
dx of MM
M spike
spep +
skeletal survey +
upep +
tx of MM
> 70 + no donor = chemo - melphagon + steroids + either thalidimide or bortezumub
< 70 + donor = stem cell transplant
MGUS
early myeloma (2% convert to MM) asymptomatic, old pts >85 y/o
spep + but (-) upep and (-) skeletal survey –> BM <10% plasma cells
monitor no tx
waldenstroms
secretes IgM –> M spike
hyperviscosity syndrome
fever night sweats weight loss
dx and tx of waldenstroms
spep + but (-) upep and skeletal survey (-) BM biopsy –> (>10% lymphoma)
tx - Rituximab based chemo
hyperviscosity tx = plasmaphoresis
primary hemostasis
endothelial injry -> vWF attaches to glycoprotein on platelet -> adhesion -> activation –> release of TXA2 and ADP -> platelets aggregate –> fibrinogen mesh -> platelet plug
secondary hemostasis
Ip Ep
10
5
2
1 --> 1a (fibrinogen) found on platelet plug --> fibrin clot ---> dimers (via plasmin)
plasminogen –> plasmin (via TPA)
signs/symptoms of bleeding
superficial, vaginal, skin - petechiae
workup –> CBC (platelet count) –>
low –> thrombocytopenia –> destruction, production sequestration
nml –> platelet dysfunction –> NSAIDs, aspirin, clopridogrel, Von Willebrands dz, bernard dz, glanzman dz
thrombocytopenia destruction causes
ITP
TTP
DIC
HIT
thrombocytopenia production causes
aplastic anemia
myelodysplastic syndrome
Von Willebrands Dz
decreased vWF
decreased factor 8
nml plt count
dx - vWF assay
tx - DDAVP, factor 8 infusion
bernard soulier dz
glanzman dz
bernand - def of glycoprotein 1b
glanzman - def of glycoprotein IIb/IIIa
signs/symptoms of bleeding
deep bleeding, hematoma, arthrosis
workup –> PT/PTT –>
mixing study –> if no correction –> inhibition
--> if corrects ----> factor def - hemophilia A/B - vit K def - warfarin - von willebrands dz - DIC
TTP path
hylaine clot def of ADAMS T13
presentation of TTP
F - fever A - anemia - MAH T - Thrombocytopenia R - renal failure N - neuro symptoms
dx and tx of TTP
dx - cbc - low plts –> smear - schisocytes - nml PT/PTT - nml fibrinogen - nml d-dimer
tx - exchange transfusion
DIC
fibrin clot - basically use up all clotting factors and bleed
sick as shit - sepsis, icu, shock –> bleed
dx and tx of DIC
dx - cbc - low plts -> smear - schistocytes - high PT/PTT
- low fibrinogen - high d-dimer
tx - supportive - fix underlying problem
HIT
path and dx
antibodies to plts
7-14 days on heparin –> plts drop
dx - HIT abs
tx of HIT
stop heparin
start argatroban bridge to warfarin
ITP
abs to plts
women with autoimmune disorder with low plts
dx of exclusion
tx - steroids, if critically low IV Ig –> splenectomy –> if that fails then rituximab
APS
antiphospholipid antibody syndrome
lupus pt or pt with multiple miscarriages
arterial and venous clots
dx - russel viper venom assay
tx - warfarin 2-3 INR if not working 4-5 range
fresh frozen plasma contents
contains all the clotting factors
contains RBCs/WBCs/ Platelets
use for - coagulopathy, def of factors,
cant be given if pt vit K def
cryoprecipitate
contains factor VIII and fibrinogen
for hemophilia A - DIC - and VWDz
reticulocyte index
> 2%
< 2%
> 2% = excessive RBCs destruction or blood loss and bone marrow is responding
< 2% = inadequate RBC production by bone marrow
MCC of thalessemia
beta thalessemia minor
patho phys of anemia of chronic disease
the release of inflammatory cytokines has a suppressive effect on erythopoisesis
causes of aplastic anemia
idiopathic
radiation exposure
meds - chloramphenicol, sulfonamidses, gold carmbazepine
chemicals - benzene
presentation of aplastic aneia
pancytopenia
anemia
petechia
increased incidence of infection due to neutropenia
other cause of b12 def
diphyllobthrium atum infection
other causes of folate def
MTX
phenytoin
causes of warm AIHA
lymphomas - CLL leukemias SLE Collagen vascular disease alpha methyldopa
causes of cold AIHA
mycoplasma pneumonia
infectious mononucleosis
HIT
type 1
type 2
type 1 - <48hrs - heparin causes direct platelet aggregation
type 2 - 3-12 days - heparin induced antibody mediated injury to platelets
signs of thrombocytopenia
petechia
mucosal bleding
epistaxis
ecchymosis at sites of minor trauma
itnracranial hemorrhagen and heavy GI bleeding can occur <5,000
TTP basics
HUS
Fevere
AMS
HUS basics
MAE
Thrombocytopenia
Renal failure
main complications of HIT
venous thrombosis
DVT
function of vWF
enhances platelet aggregation and adhesion
dx of vWD
increased bleeding time
nml plts
nml PT/PTT
decreased plasma vWF
decreased factor VIII activity
first line tx of vWD
desmopressin
if no response then give factor VIII
therapeutic range for
heparin
warfarin
heparin PTT 60-90
Warfarin INR 2-3 (if mechanical dz - INR 2.5-3.5)
DIC tx
cryoprecipitates - replace clotting factors and fibrinogen
FFP replaces all clotting factors
give platelets if <30,000
vit K basics
II VII IX X
Protein C and S
Post translational modification - gamma carboxylation
Factor VII
shortest half life of all clotting factors so a prolonged PT is what you will see first
pts with antithrombin III deficiency
do not respond to heparin
heparin MOA
potentiates the action of AT to primarily inhibit clotting factors IIa and Xa
prolong PTT
cholestatsis and affects vit K
leads to decreased Vit K absoprtion –> vitamin K deficiency
contraindications for heparin use
previous HIT
active bleeding - GI bleed, intracranial bleed
hemophilia, thrombocytopenia
severe HTN
recent surgery on eyes, spine or brain
antidote for heparin
protamine sulfate
ADR of warfarin
skin necrosis - cause by rapid decrease in protein C
teratogenic
clopidogrel MOA
blocks the binding of ADP to P2Y12 receptor which reduces platelet activation and aggregation
increases the bleeding time
risk factors for breast cancer
prior hx of cancer
pts age
family hx
female
unopposed estrogen (early menarche, late menopause, nulliparity)
thoracic radiation
smoking, alcohol consumption
Multiple myeloma basics
low Hgb
high Ca
poor renal function
walden macroglobulinemia
hyperviscosity syndrome
can lead to retinal dilation with hemorrhaging and possible blindness
M spike
MM tx
hematopoietic stem cell transplantation if pt is:
young
asymptomatic
has NOT had chemo before
HL with worse prognosis
lymphocyte depleted hodgkin lymphoma
Rituximab MOA
monoclonal antibody against CD20
risk factors for NHL
HIV/AIDs
immunosuppression
EBV, HTLV-1
H pylori
follicular lymphoma basics
most common form of NHL
t(14;18)
55 y/o
painless peripheral lymphadenopathy
diffuse large cell B lymphoma
locally invasive
presents as large extranodal mass
85% cured with CHOP therapy
burkitt lymphoma basics
B cell lymphoma
african link with jaw and EBV infection
t(8;14)
starry sky night
lymphocytic lymphoma
t cell lymphoma
may progress to T-ALL
aggressive with rapid dissemination
mycosis fungoides
t cell lymphoma of skin
eczemoid skin lesions
cribriform shape of lymphocytes
if hematogenous - sezary syndrome
CHOP therapy for lymphomas
C - cyclophosphamide
H - hydroxydanomycin
O - Oncovin (vincristine)
P - Prednisone
Auer rods =
AML
tumor lysis syndrome
chemo complication rapid cell death with release of intracellular contents causes: hyperkalemia hyperphosphatemia hyperuricemia
polcythemia vera
Jak2 kinase mutation
severe pruritus after hot bath or shower
hyperviscosity syndrome - HA, dizzy, weak
thrombotic bleeding
dx criteria of polycthemia vera
major
- elevated RBCs: Men >36, Women > 32
- O2 sat > 92
- splenomegaly
Minor
- thrombolysis
- leukocytosis
- LAP > 100
- B12 > 900
tx of polcythemia vera
repeated phlebotomy to lower HCT
