Hematology/Oncology Flashcards
compensatory mechanisms in anemia
increased CO
increased extraction ratio
RIGHT shift on Oxy-Hb dissociation curve (increased 2,3 BPG)
expansion of plasma volume
general indications for blood transfusion
- Hb < 7 g/dL
2. pt requires increased O2 carrying capacity - i.e. pt with CAD or cardiopulm dz
what is pseudoanemia?
decrease in Hb and Hct secondary to dilution (acute volume infusion or overload)
MCC of death due to anemia
myocardial ischemia
formula for converting Hb to Hct
Hb x 3 = Hct
how does 1 Unit of packed RBCs affect Hb and Hct levels?
increases Hb level by 1 point and Hct by 3 points
if pt has low Hb and Hct, what are the next tests to determine cause of anemia?
reticulocyte count
mean corpuscular volume
reticulocyte index > 2%
excessive RBC destruction and blood loss - the BM is responding to increased RBC requirements
reticulocyte index < 2%
inadequate RBC production by BM
how do you administer Packed RBCs?
mixed with Normal Saline and infuse 1 unit over 90-120 minutes; check CBCs once complete
what does fresh frozen plasma contain?
all of the clotting factors - no WBCs, RBCs or platelets
what is FFP given for ? (3)
- high PT/PTT
- coagulopathy
- deficiency of clotting factors
how do you assess response of FFP?
look at PT and PTT
what is cryoprecipitate and what is it used for?
- contains factor VIII and fibrinogen
- used for: hemophilia A, DIC and vWD
1 unit of platelets raises platelet count by how much?
10 000
what is the ONLY time you use whole blood?
massive blood loss
- in a ratio of 1:1:1 of platelets:FFP:PRBCs and warmed
a pt who recently received a blood transfusion suddenly develops fever, chills, NV, flank pain, chest pain and dyspnea - what should you be worried about?
intravascular hemolysis due to ABO-mismatched blood
management of acute hemolytic reaction due to ABO-mismatched blood
- stop transfusion
- aggressive fluid replacement to avoid shock/renal failure
- Epi. for anaphylaxis
- dopamine/NE to maintain BP
a pt who received a blood transfusion 2 weeks ago develops mild fever, jaundice and anemia - what should you consider?
delayed hemolytic transfusion reaction (Extravascular hemolysis) due to mismatched minor RBC antigens
what is the next step in assessing anemia if the reticulocyte index is < 2?
exam smear and RBC indices- ie. MCV
differential diagnosis of microcytic anemia (MCV < 80)
iron deficiency
anemia of chronic disease
thalassemias
ring sideroblastic anemias
differential diagnosis of macrocytic anemia (MCV > 80)
vit B12 /folate deficiency
liver disease
stimulated erythopoiesis
differential diagnosis of normocytic anemia (MCV 80-100)
aplastic anemia BM fibrosis tumor anemia of chronic disease renal failure
what do you need to R/O in elderly pt with iron deficiency anemia?
colon cancer
major causes of iron deficiency anemia
- chronic blood loss - menstrual or GI loss
- dietary deficiency
- increased requirements - i.e. growth, pregnancy, lactation
what is the most reliable test for diagnosing iron deficiency anemia?
decreased serum ferritin (below 10 ng/ml)
what lab findings are characteristic of iron deficiency anemia?
low serum ferritin
low serum iron
high TIBC and low TIBC saturation
high RDW
what can cause a falsely elevated serum ferritin
malignancy and inflammatory states - ferritin is also an acute phase reactant
what is the gold standard for dx. iron deficiency anemia?
bone marrow biopsy
- rarely performed unless no
first step in tx. of iron deficiency anemia?
oral iron replacement w/ ferrous sulfate
- give trial to menstruating woman but in everyone else, attempt to determine point of chronic blood loss
young patient is brought in with massive hepatosplenomegaly, expansion of marrow space, growth retardation and failure to thrive; CBC reveals microcytic anemia - dx?
B-thalessemia major (aka. Cooley’s anemia)
how do you dx. B-thalassemia major?
hemoglobin electrophoresis –> HbF and HbA2 are elevated
Tx. of B-thalessemia major?
frequent PRBCs transfusios with desferrioxamine to prevent iron overload
if you suspect iron deficiency anemia, but it does not respond to iron - what should you do next?
Hb electrophoresis to R/O thalassemias
what happens if you have deletion of 2 alpha globin loci?
mild, microcytic hypochromic anemia
common in African-Americans
usually asx. w/ no tx. needed
pt comes in with hemolytic anemia, splenomegaly, and significant microcytic hypochromic anemia; Hb electrophoresis shows Hb H - what should you consider?
Hb H disease - mutation/deletion of 3 alpha globlin loci
what is Hb H
tetrads of B-globin chains
what is Hb-Barts?
tetrads of Y-globin chains form when there is deletion or mutationof all four alpha-globin loci resulting in fatal hydrops fetalis
which alpha-thalassemia requires tx and what is the tx?
HbH disease - tx. w/ frequent PRBC transfusions w/ desferrioxamine
what are the iron studies findings in thalassemia pts?
normal/high serum ferritin
normal/high serum iron
normal TIBC
normal/high RDW
what are the iron studies findings in sideroblastic anemia pts?
increased serum iron and ferritin
normal/low TIBC
TIBC saturation is normal/high
what are some acquired causes of sideroblastic anemia?
drugs - chloramphenicol, alcohol, INH
lead exposure
collagen vascular disease
myelodysplastic syndromes
what are the hereditary causes of sideroblastic anemia?
defect in ALA synthase
abnormal vit B6 metabolism
what are the iron studies findings in anemia of chronic disease?
low serum Fe
low TIBC
low serum transferrin
high serum ferritin
characteristic finding in aplastic anemia
BM is empty with no precursor cells leading to pancytopenia (anemia, neutropenia and thrombocytopenia)
causes of aplastic anemia
idiopathic radiation exposure drugs - chloramphenicol, NSAIDs, alcohol, sulfonamides, gold, carbamazepine viral infection chemicals - benzene, insecticides
how do you definitively dx. aplastic anemia?
bone marrow biopsy
what is the definitive tx. of aplastic anemia?
bone marrow transplantation
what two reactions is vit B12 necessary for?
conversion of homocysteine to methionine
conversion of methylmalonyl CoA to succinyl CoA
what is the characteristic neuropathy in vit B12 deficiency?
demyelination of posterior columns, lateral corticospinal tracts and spinocerebellar tracts
what kind of cancer are pts with pernicious anemia at higher risk for?
intestinal type - gastric ca.
gastric carcinoid
- perform periodic stool testing for FOB
diagnostic findings in vit. B12 deficiency
- hypersegmented neutrophils
- serum vit B12 level < 100
- serum methylmalonic acid and homocysteine levels elevated
- ab’s against IF
what Schilling test result implies dietary deficiency of vit B12
after giving radioactive Vit B12, if urine levels are > 5%
what do you do if in the Schilling test, urine levels are below normal (<5%)?
give radioactive vit B12 w/ IF –> if they go up after, then you know you have IF deficiency; if they do not go up, it is due to malabsorption
tx. of vit B12 deficiency
cyanocobalamin IM once per month
serum methylmalonic acid levels are only increased in what deficiency?
vit B12
- this test allows you to tell it apart from folate deficiency
what general lab findings do you see in hemolytic anemia?
elevated reticulocyte count
elevated LDH and bilirubin
decreased haptoglobin
decreased Hb/Hct
what kind of cells can be seen on PB smear in thalasemia?
target cells
what kind of cells on smear are characteristic of TTP, DIC, prosthetic heart valves and hemolytic anemias?
schistocytes
helmet cells
what characteristic clinical features (in addition to those of anemia) can be seen in hemolytic anemias?
jaundice
dark urine - esp. IV processes
what kind of cells are seen on smear in intravascular hemolysis)
schistocytes
which cells suggest extravascular hemolysis?
spherocytes
helmet cells
what types of cells characterize G6PD deficiency?
heinz bodies
what vitamin should be supplemented in hemolytic anemia?
folate
sudden drops in Hct are usually due to..
parvovirus B19 infection
folate deficiency - acute aplasia
what should you suspect in a young blank male who presents to you with painless hematuria?
sickle cell trait
what is really the only clinical feature seen in sickle cell trait?
isosthenuria and increased rate of UTIs
what does the prognosis of sickle cell disease depend on?
the frequency of vaso-occlusive crises
MC clinical manifestation of sickle cell disease vasoocclusive crises
painful crises involving bone - multiple sites
what is usually the first manifestation of sickle cell disease?
hand-foot syndrome (dactylitis) - painful swelling of dorsa of hands and feet seen in infancy
splenic sequestration crises
in sickle cell dz, sudden pooling of blood into spleen results in rapid development of splenomegaly and hypovolemic shock; potentially fatal
what is priapism due to in sickle cell crises?
infarction of prostatic plexus of veins
tx. that can potentially prevent recurrence of priapism in sickle cell dz
hydralazine
nifedipine OR
antiandrogen (stilbestrol)
what types of infections are sickle cell pts susceptible to?
encapsulated bacterias - SHiNS
salmonella osteomyelitis
screening test for sickle cell trait/disease
sickle cell prep - blood smear with chemical added to remove O2 from hemoglobin - looks for sickled cells
diagnostic test for sickle cell dz
hemoglobin electrophoresis
what should sickle cell pts receive prophylactically until age 6?
penicillin
folic acid supplments in definitely
which drug is used to enhance HbF levels and reduce incidence of painful crises in sickle cell dz?
hydroxyurea
which conditions in sickle cell dz warrant consideration for blood transfusion?
acute chest syndrome
priapism unresponsive to other measures
cardiac decompensation
stroke
causes of spherocytosis
hereditary G6PD deficiency ABO incompatability hyperthermia autoimmune hemolytic anemia
diagnostic test for hereditary spherocytosis
osmotic fragility test - RBC burst in hypotonic saline
lab findings in hereditary spherocytosis
elevated reticulocyte count
elevated MCHC
direct Coombs test result is negative
what is the Tx. for hereditary spherocytosis?
splenectomy
- vaccinate against pneumo, H.flu and meningococcus several weeks before
what nationality of people are primarily affected by G6PD deficiency?
African-Americans - mild form
Mediterranean descent - severe form
precipitants of hemolytic episode in G6PD deficiency?
sulfonamides/sulfur containing drugs - TMP/SMX primaquine (antimalarials) nitrofurantoin dimercaprol fava beans infections (MCC)
CF of G6PD deficient pts
hemolytic episodes marked by jaundice and dark urine that is induced by either an infection or a drug
characteristic cells seen in G6PD pts
Heinz bodies - Hb precipitates
Bite cells
how do you diagnose G6PD deficiency?
measurement of G6PD levels - do not do this during a crises but rather when pt is asymptomatic
what is the “Warm” autoimmune hemolytic anemia?
IgG ab that binds to RBC mbs resulting in extravascular hemolysis in the spleen
what is “cold” autoimmune hemolytic anemia?
IgM ab binds to RBC mb at temp. between 0-5 C producing complement activation and intravascular hemolysis primarily in liver
which infections are associated with cold AIHA?
mycoplasma pneumonia
infectious mononucleosis
cold agglutinin disease
cyanosis of ears, nose, fingers and toes in cold temperatures
how do you diagnose autoimmune hemolytic anemia?
Direct Coomb’s test
Tx. of warm AIHA
steroids - prednisone in divided doses
- splenectomy if pt doesnt respond to steroids
Tx. of cold AIHA
avoid exposure to cold
RBC transfusion if absolutely necessary
what is the deficiency in paroxysmal nocturnal hemoglobinuria?
deficiency of anchor proteins that link complement inactivating proteins to RBC mbs resulting in unusual susceptibility to complement mediated lysis of RBCs, WBCs and platelets
in addition to anemia (pancytopenia) and hemolysis, what CF can be seen in paroxysmal nocturnal hemoglobinuria?
thrombosis of venous systems ex. Budd Chiari
most sensitive and specific test for PNH
flow cytometry of anchored cell surface proteins - CD55 and CD59 } DAF
Ham’s test
test for PNH - cells incubated in acidic serum, triggers alternative complement pathway resulting in lysis of PNH cells
sugar water test
test for PNH - PNH cells lyse in sucrose
Tx of PNH
glucocorticoids - prednisone (DOC)
- alternates: BM transplant, eculizumab
CF of idiopathic thrombocytopenic purpura
minimal cutaneous and mucosal bleeding
low platelet counts
generally healthy
what do you suspect in a young female whose CBC shows a platelet count of 15 000; she reports no symptoms.
idiopathic thrombocytopenic purpura
definite dx. of ITP
BM biopsy - shows increased megakaryocytes
first line tx. in ITP
steroids -prednisone
how can you tx. pts with ITP who have platelet count < 10 000 or develop a life threatening bleed?
IVIG
two new drugs approved for ITP in splenectomy-resistant pts?
romiplastim
eltrombopag
Type 1 HIT
heparin causes platelet aggregation within 48 hrs of starting heparin tx; no tx is needed
Type 2 HIT
heparin induces antibody-mediated injury to platelet; seen in 3-12 days after heparin tx; d/c heparin immediately
pt comes in with signs of hemolytic anemia, thrombocytopenia, a rising Creatinine level, fever and fluctuating neurologic signs - what should you consider?
TTP
How do you Tx. TTP?
plasmaphoresis (large volume)
decrease in platelet count by 50% after heparin suggests ?
HIT
main complication of HIT
venous thrombosis with DVT and PE
diagnostic tests for HIT
antiplatelet factor IV antibody
serotonin release assay
Tx. of HIT
stop heparin
disorder of platelet adhesion due to deficiency of platelet glycoprotein GP1b-IX
Bernard Soulier disease
disorder of platelet aggregation due to deficiency in platelet glycoprotein GPIIb/IIIa
Glanzmann’s thrombasthenia
what is the role of vWF?
- mediates adhesion of platelets to injured vessel wall (GP1b/IX and subendothelium)
- carrier of factor VIII in blood
MC inherited bleeding disorder
vW disease
how can you diagnose vW disease?
prolonged bleeding time but normal platelets
aPTT may be prolonged
decreased plasma vWF and factor VIII
reduced ristocetin-induced platelet aggregation
how can you tell vW dz apart from hemophilia A?
bleeding in vWD is much milder than in hemophilia, factor VIII levels are not reduced as much and spontaneous hemarthrosis do not occur
first line tx. for vWD
desmopressin (DDAVP) - induces endothelial cells to secrete vWF
what do you do if pt with vWD does not respond to DDAVP?
try factor VIII concentrates
- also given during major trauma or surgery
how much factor VIII do you need before signs of bleeding appear?
> 10% of normal factor VIII and patients are asymptomatic
lab findings in hemophilia A
prolonged PTT
low factor VIII levels
- everything else is normal
mixing study results in hemophilia A
if plasma from a hemophiliac pt is mixed with normal plasma, the PTT normalizes –> this is indicative of a factor deficiency
how can you prevent recurrent hemarthroses in hemophilia?
prophylactic factor VIII concentrates
synovectomy / radiosynovectomy
Tx of acute hemarthrosis in hemophilia
analgesia - codeine +/- acetaminophen (avoid NSAIDS and aspirin)
immobilization, ice packs etc
mainstay of therapy for hemophilia
factor VIII concentrate
- for acute bleeding episodes and before surgery/dental work
what drug may be helpful in mild hemophilia A?
DDAVP - can increase factor VIII level four-fold
what is the defect in hemophilia B?
factor IX
(1) normal PT
(2) normal PTT
(3) normal bleeding time
(1) 11-15 sec
(2) 25-40 sec
(3) 2-7 min
lab findings in DIC
Increased: - PT, PTT, bleeding time and thrombin time - high d-dimers Decreased: - fibrinogen level - platelet count
coagulopathy due to liver disease
PT and PTT are elevated
- all else is normal
coagulopathy due to vitamin K deficiency
PT is initially prolonged, PTT prolongation follows
how do you Tx. DIC?
must take care of underlying cause
- things like FFP, platelet transfusions and cryoprecipitate can buy you time
how can you confirm the diagnosis of vitamin K deficiency?
correction of PT/PTT after admin for vit. K
how do you correct vitamin K deficiency coagulopathy?
oral or parenteral vitamin K
FFP if severe bleeding is present
what type of bleeding is most common in coagulopathy due to liver disease?
GI bleeding - ex. varices
tx for coagulopathy due to liver disease if there is prolonged PT/PTT or bleeding..
FFP
what is the role of protein C
inhibitor of factors V and VIII
- deficiency leads to unregulated fibrin synthesis
what is the role of protein S
protein S is a cofactor for protein C - so a deficiency leads to decreased protein C activity
factor V leiden mutation
activated protein C resistance - protein C can no longer inactivate factor V
MOA of heparin
potentiates antithrombin III to inhibit clotting factors IIa and Xa; prolongs PTT (intrinsic pathway)
adverse effects of heparin
bleeding transient alopecia osteoporosis HIT rebound hypercoagulability
C/I to heparin
previous HIT active bleeding recent surgery on eyes, spine or brain hemophilia/thrombocytopenia severe HTN
how can you reverse the effects of heparin?
standard hep has short half life, so its effects stop w/in like 4 hours; but if you need to you can give PROTAMINE SULFATE
benefits of LMWH
given subcutaneously (not IV)
no monitoring needed
less side effects
- better for outpatient use
MOA of LMWH
inhibit factor Xa (less IIa and platelet inhibition)
what is the therapeutic INR you want on warfarin?
2-3
adverse effects of warfarin
hemorrhage
skin necrosis
teratogenic
should not give to alcoholics or pts prone to falls (risk of IC bleed)
mechanism of warfarin skin necrosis
inhibits protein C and S first, leading to hypercoagulable state with thrombus formation in first few days of admin; MC in pts with congenital protein C and S deficiency to start
what do you do if your INR is too high while pt is on warfarin?
lower/omit dose; if very high, give vitamin K
- if severe bleeding, give pt FFP
MOA of clopidogrel
blocks binding of ADP to platelet receptor P2Y12; reduces platelet activation and aggregation
indications for use of clopidogrel
pretreatment for pts before PCI (600 mg)
after PCI w/ stend placement for 12 mths (75 mg)
peripheral artery disease
acute coronary syndromes
if a patient is taking clopidogrel, which other drugs should you avoid?
PPIs
what should you do in any women over age 30 presenting with a breast mass?
biopsy - conservative approach
a young woman presents with a round, moveable breast mass which changes in size over course of menstrual cycle - what is this most likely?
fibroadenoma
a woman presents with bilateral breast pain that cycles with hormonal changes…
fibrocystic changes
what should you always order before beginning tamoxifen therapy for breast cancer?
echocardiogram - high risk of cardiotoxicity (esp. if EF < 55%)
diagnostic criteria of MGUS
IgG spike < 3 g/dL
< 10% plasma cells in BM
Bence-Jones proteinuria < 1 g/24 hrs
no end organ damage
a pt presents with low Hb, high calcium, high serum protein and poor renal function - what should you suspect?
multiple myeloma
CRAB mnemonic for multiple myeloma
hyperCalcemia
Renal failure
Anemia
lytic Bone lesions
diagnostic criteria for mutliple myeloma
- > 10% plasma cells in BM
- one of the following:
- M protein in serum or urine
- lytic bone lesions
what does a peripheral smear look like in someone with multiple myeloma?
RBCs in rouleaux formation
lab findings in multiple myeloma
hypercalcemia elevated total protein, but lower albumin elevated ESR elevated BUN/Cr pancytopenia may be present
Tx. of choice for mutliple myeloma
autologous hematopoietic stem cell transplantation
how do you tx. multiple myeloma pts who are not transplant candidates?
systemic chemotx with alkylating agents: melphalon, prednisone, thalidomide
a pt comes in fatigue, weight loss, LAD, splenomegaly, anemia; lab tests show IgM > 5 g/dL and Bence Jones proteinuria - dx?
Waldenstrom’s macroglobulinemia
Tx. of hyperviscosity syndromes
plasmaphoresis
chemotherapy
pt presents with painless LAD of the cervical LNs along with fever, night sweats and recent weight loss; he also notes pruritus - dx to consider?
Hodgkin’s lymphoma
how do you diagnose Hodgkin’s lymphoma?
LN biopsy showing Reed-Sternberg cells surrounded by inflammatory cells
what tests do you do to determine staging in HL?
CT scan, CXR and BM biopsy
tx. of stage 1, 2 and 3A Hodgkin’s lymphoma
radiation therapy only
tx. of stage 3B and 4 Hodgkin lymphoma
chemotherapy = ABVD
- adriamycin, bleomycin, vincristine, dacarbazine
what lab test can sometimes correspond with disease activity in Hodgkin’s lymphoma?
elevated ESR
increased LDH = adverse prognosis
RFs for NHL
HIV/AIDs immunosuppression viral infections - EBV, HTLV1, HCV h.pylori gastritis autoimmune disease
what type of NHL presents are peripheral LAD and a t(14:18) translocation
follicular NHL
what infection and what translocation are associated with Burkitt’s lymphoma?
African variety = EBV infection
t(8:14)
pt presents with eczematoid skin lesions that progress to generalize erythroderma; his lymphocytes are cribiform shape
mycosis fungoides (T cell lymphoma of skin)
Sezary syndrome
disseminated form of mycosis fungoides
what are indirect indicators of tumor burden in NHL?
serum LDH and B2-microglobulin
chemotherapy used in NHL
CHOP - multiple courses
- cyclophosphamide
- hydroxydaunomycin (doxorubicin)
- oncovin (vincristine)
- prednisone
RFs for AML
radiation exposure
myeloproliferative syndromes
Down’s syndrome
chemotherapy - alkylating agents
poor prognostic indicators in ALL
age 9
WBC count > 100 000/mm3
CNS involvement
testicular involvement is common in what hematologic malignancy?
ALL
which leukemia presents with an anterior mediastinal mass?
T cell ALL
pt recently tx with chemotherapy for acute leukemia presents with hyperkalemia, hyperphosphatemia and hyperuricemia - dx?
tumor lysis syndrome - rapid cell death with release of intracellular contents
what study is needed for diagnosis of leukemia?
BM biopsy
chemotx. for AML
cystosine arabinoside AND either daunorubicin or idarubicin
chemotx. for ALL
vincristine
predniosone
daunorubicin
in which leukemia should you give prophylaxis for CNS involvement?
ALL - give MTX intrathecally
when does BMT come into play in tx. of acute leukemia?
any pt who relapses after chemotherapy
what disease is characterized by monoclonal proliferation of lymphocytes that are morphologically mature but functionally defective?
CLL
- usually in pts > 60
an elderly man comes in complaining he frequently gets respiratory and skin infections that are long lasting and difficult to tx. On exam you notice, painless LAD - what test should you do?
CBC - to diagnose CLL
lab findings in CLL
WBC 50,000-200,000 (80-90% lymphocytes)
smudge smells on PB smear
may have pancytopenia
what test is used to confirm CLL?
flow cytometry of peripheral blood - shows clonal population of B cells (CD19)
how do you tx. CLL?
usually observe patients until they become symptomatic (may take years)
Chemo = RFC (rituximab, fludarabine, cyclophosphamide)
standard of care for CML
imatinib
- tyrosine kinase inhibitors (also: dasatinib, nilotinib)
Lab findings in CML
WBCs 50,000-200,000 (left shift toward granulocytes)
eosinophilia/basophilia
leukemic cells in peripheral blood
decreased leukocyte ALP
pt comes in complaining of severe pruritus after a hot bath or shower - what should you consider?
polycythemia vera
CF of polycythemia vera
hyperviscosity sx
thrombotic phenomena
bleeding
splenomegaly/hepatomegaly
lab findings in polycythemia vera
elevated RBC count, hemoglobin/Hct > 50
reduced serum EPO levels
elevated vit B12 levels
thrombocytosis/ leukocytosis
Tx. of polycythemia
repeated phlebotomy
major criteria for dx. polycythemia vera
- elevated RBC mass (men > 36, women > 32)
- arterial O2 sat > 92%
- splenomegaly
minor criteria for dx. polycythemia vera
- thrombocytosis (plts > 400,000)
- leukocytosis (WBC > 120,000)
- leukocyte ALP > 100
- serum vit B12 > 900
essential thrombocythemia
Platelets > 600,000/mm3 with findings of splenomegaly, pseudohyperkalemia, elevated bleeding time and erythromelalgia
BM biopsy finding in essential thrombocytemia
increased number of megakaryocytes
Tx. of essential thrombocytemia
antiplatelet agents - anagrelide, aspirin
hydroxyurea if severe
