Heme/Onc Flashcards
What is the goal INR for a patient with a mechanical heart valve?
2.5-3.5
What initiates the intrinsic pathway? extrinsic pathway?
Intrinsic = collagen exposure following vascular trauma Extrinsic = endothelium produced TF
What causes the paradoxical hypercoagulability when taking warfarin?
This occurs at first b/c warfarin inhibits Protein C and S BEFORE it inhibits factors 2,7,9,10.
What is found in cryoprecipitate?
Factor VIII, fibrinogen mainly (this is why you choose cryo over FFP)
some factor XIII, vWF and fibronectin,
What is the tx for hemophilia?
Cryoprecipitate
DDAVP can also be used in mild hemophilia (helps the body produce more factor VIII)
What is the most common inherited bleeding disorder?
vWF deficiency. It is much milder than hemophilia and results from lack of VIII.
What drug worsens VWF disease? Why don’t you see petechiae with this disease?
ASA will worsen the bleeding. No petechiae b/c the platelet dysfunction is not that bad.
What will labs for VWD look like? Dx? Tx?
prolonged aPTT, prolonged bleeding time
Normal PT and platelet count
Dx = Ristocetin cofactor assay Tx = DDAVP
What is the MOA of clopidogrel and ticlopidine?
They block the ADP receptor, needed for platelet aggregation
What is the most common hereditary thrombotic disease? MOA?
factor V Leiden - a polymorphism that makes it resistant to inactivity by activated protein C (factor V is stuck in the “on-position” and makes a ton of activated thrombin (more clots.)
How long do you tx w warfarin for first thrombotic event? After doing heparin of course.
3-6 months
6-12 months for second event
lifelong for everything else
What is the difference in terms of labs between severe liver disease and DIC?
In DIC, the factor VIII is depressed.
What 5 characteristics/signs of TTP?
Low plts microangiopathic hemolytic anemia neuro changes (delirium, seizure, stroke) impaired renal function fever
What differentiates HUS from TTP?
HUS will have high Cr levels
HUS, TTP, and DIC are the only causes of microangiopathic hemolytic anemia
What tx is contraindicated in TTP? what tx should you use?
platelet transfustion - this will worsen the condition due to platelet aggregation and microvascular thrombosis.
Tx: steroids to bust the microthrombi, and plasma replacement/plasmapheresis
What are the labs in DIC and TTP?
DIC = low clotting factors, plts, fibrinogen. High PT, PTT, d-dimer, and fibrin split products
TTP: everything is normal except low plts.
What is the Tx for HUS?
Supportive. No Abx as this could delay toxin expulsion
What is the Tx for ITP?
Dont really have to treat acute/childhood forms as these remit spontaneously.
For Chronic form, use corticosteroids, IVIG, and splenectomy (last resort if CTSDs don’t work after 6 months.
What is a high retic count? What does it indicate?
> 2.5% is high, this indicates hemolysis/hemorrhage is occuring and BM is responding by making more RBCs
What are the 4 causes of microcytic anemia?
TICS
Thalassemia
Iron Def
Chronic Disease
Sideroblastic anemia
What Heme test is HIGHLY SPECIFIC for iron deficiency anemia?
Elevated RDW
What is the serious side effect that could occur with IV iron dextran administration?
Anaphylaxis
What are the lab differences between iron def anemia and anemia of chronic disease?
Fe Def = low serum iron and ferritin, high TIBC (transferrin) and transferrin R
CD = low serum iron and TIBC (transferrin), high ferritin, normal transferrin R
Both: low serum iron, normal TIBC (transferrin, ferritin, and transferrin R
Which class of drugs can cause megaloblastic anemia?
Chemotherapeutic drugs
What organism can cause an infection which causes B12 def anemia?
Diphyllobothrium Latum. its a tapeworm. It can cause neuro issues as well (b12 you know.)
How will MMA and homocysteine levels look like in B12 and folate def anemia?
B12 = hi MMA, low homo Folate = normal MMA, hi homo
What do sperocytes look like? What do they indicate?
They are RBCs that lack central pallor (all 1 color)
They indicate autoimmune hemolysis or hereditary spherocytosis
EBV can cause autoimmune RBC destruction
So can mycoplasmal infection, CLL, RA, or meds
Reticulocytes will be elevated in hemolytic anemias
Will also have high LDH.
A + Coombs test will diagnose an autoimmune hemolysis
Anemic person has a pancytopenia, some cafe au lait spots, short stature, and radial/thumb hypoplasia. Dx? What will the bone marrow bx show?
Fanconi’s Anemia. = hereditary destruction of bone marrow cells
Bone marrow bx shows hypocellularity, and space occupied fat
Where is the issue in the RBCs in sicklers? Why is this an issue?
They have a B-chain malformation (glu –> val) This causes shorter RBC life which can lead to vaso-occlusion
What is the most common cause of osteo in sicklers?
S.A. but they also get salmonella! Watch out for the question being asked!
What is the tx for sickle cell?
Hydroxyurea, it stimulates the fetal hemoglobin production
What health maintenance should sicklers
PEN BID till age 5
Which drug increases the PTT? Which increases the PT?
PTT (intrinsic pathway) = Heparin
PT (extrinsic pathway) = Warfarin
What does the hemoglobin electrophoresis evaluation look like in a-thalassemia?
It looks normal! Although this is usually the way to Dx a thalassemia
What do pts with 0/2 B chains look like compared to 1/2 B chains?
0/2 chains = severe microcytic anemia and will need chronic transfusions/marrow transplant to survive!
1/2 chains = asymptomatic, but cells are microcytic and hypochromic on peripheral smear.
What do pts with 0/4 - 3/4 a chain thalassemia look like?
0/4 chains = pts die in utero
1/4 chains = hi reticulocyte count and skeletal changes due to expanded erythropoiesis
2/4 and 3/4 chains = usually asymptomati
What is the mutation that causes polycythemia vera? Tx?
JAK2 mutation causing clonal proliferation of a pluripotent marrow stem cell. All marrow lines will be increased! RBCs significantly affected.
Tx: hydroxyurea and ASA
What is the cause of a nonhemoltytic febrile transfusion reaction?
cytokines formed during storage of blood cause fever, chills, rigors, and malaise
Signs and symptoms of porpheria? Triggers? Tx for acute attacks?
photodermatitis, neuropsychiatric complaints, colicky abdominal pain, PINK or BROWN URINE the day after drinking/benzo use
Triggers = alcohol, barbs, OCPs
Tx = glucose (will stop the heme synthesis by providing negative feedback to heme synthetic pathway.)
What is the most common childhood malignancy? signs?
what will you find on bone marrow bx/aspiration?
ALL
kids will present with bone pain, TCP, and anemia
swollen bleeding gums, hepatosplenomegaly
bone bx will show blasts (myelo or lympho)
What would a pt with a very high WBC count in a pt with an acute leukemia be at risk for?
leukostasis (blasts occluding the microcirculation) which can cause pulmonary edema, ischemic injury, or DIC.
Remember, these WBCs are not very functional
You see cells that are MUCH larger than RBCs w/ round/kidney shaped nuclei and Auer rods on blood smear and myeloperoxidase…
Tx for APL type?
AML (type M3 APL to be exact.)
APL subtype is treated with all-trans-retinoic acid (ATRA) therapy. translocation between c15-17
You see cells that are about the same size as an RBC w/ large nuc:cytoplasmic ratio and visible clefts in their nuclei and NO myeloperoxidase…
ALL
Tumor lysis syndrome? How can this be avoided? Tx?
Renal insufficiency resulting from blast lysis during chemo. (can happen during CLL or NHL)
also - hyperkalemia, phosphatemia, uricemia, and hypocalcemia
This can be avoided by checking WBC count before chemo sessions, if it is high then start allopurinol to prevent hyperuricemia
If this is not treated before hand, use hydroxyurea in the setting of leukostasis to decrease WBC rapidly.
What will flow cytometry show for a pt with CLL?
smear?
Tx:
CD20 and CD21 (B cell markers, which would be expected in a B cell proliferative dz) but also CD5 (normally found on T cells)
smear will show a TON of small lymphocytes and SMUDGE CELLS and hypogammaglobulinemia
Tx: Tx is withheld until pts are symptomatic (recurrent infections, splenomegaly, anemia) and then the tx is PALLIATIVE.
Its ok, this happens in really old people
Most common translocation with CML?
Tx?
t(9,22) BCL-abl phili chromo
Tx: imatinib (blocks the tyrosine kinase of BCL-abl)
71 yo man with lethargy, constipation, dull back pain that is worsening. Normal labs except for hi Cr. Why?
He has Multiple Myeloma
His bad RF is due to urinary immunoglobulins (Bence Jones proteins) that form casts and cause nephropathy
What infection do you predict a pt with Hairy Cell Leukemia will present with?
Mycobacterium Avium Intracellulare (atypical)
What will the CBC in HCL show?
Tx?
it will show leukopenia (confusing!) and hairy cells on TRAP stain
Tx: nucleoside analogs (cladribine) or a combo of splenectomy and IFN-a
What viruses can cause non hodgkin’s lymphoma?
What is the most common translocation in NHL?
EBV (although more association with HL), HTLV-1, HCV
translocation = t(14-18)
Most NHL’s are of B cell origin, and NHL’s are MUCH more common than hodgkins lymphoma
What are the symptoms of Hodgkins lymphoma?
Dx?
systemic B symptoms (NS, fever, WL), pruritis, big spleen, Pel-Ebstein fevers (waxing.waning fevers!)
Dx = excisional bx - look for reed sternberg cells
What preventative measures are needed in a pt being treated for HL?
mammograph. chemo and radiation can lead to 2* neoplasms like AML, NHL, breast cancer, thyroid cancer
What are the 3 criteria for Dx of multiple myeloma?
tx?
> 10% plasma cells in bone marrow / plasma cell infiltration
M protein in serum or urine
lytic bone lesion
just M proteins is NOT dx for MM, it can be MGUS or waldenstroms macroglobulinemia at this stage
Also, bone scan may be NEGATIVE b/c this assesses osteoblast function, and MM is an osteoclastic process
Tx: Melphalen (alk agent), prednisone
What can hi levels of IgM do to you>
hyperviscosity, coagulation issues, reynauds, cold agglutinin disease (autoimmune hemolytic anemia) and amyloidosis
What will labs of MM look like?
marrow?
labs = elevated LDH, ESR, uric acid, alk phos
marrow = PAS+ IgM deposits around the nucleus
What amyloids are present in 1* and 2* amyloidosis? where do they deposit?
1* = AL (light chains) associated with MM and waldenstroms -tx = chemo
2* = AA (acute phase reactant amyloid) associated with chronic inflammatory diseases (RA) or infections -tx = transplantation or tx underlying inflammation!
Both tend to deposit in the heart, kidneys, and liver
What kind of amyloid is present in dialysis?
Dialysis related amyloid deposits B2 microglobulin
How do you calculate the absolute neutrophil count (ANC)
tx of neutropenia?
WBC * (%bands + %segs)
An ANC
Hematuria with eosinophilia, what is the infection?
schistosomiasis
WHAT IS the cutoff for an acute transplant rejection? MOA?
Tx?
5 days - 3 months
MOA for acute is T-cell mediated. hyperacute (minutes) is preformed Abs and GVHD is due to minor histocompatibility Ags.
Tx: CTSDs, OKT3, tacrolimus
What malignancy are you concerned for:
- Girl with facial angiofibromas, seizures, mental retardation
- atrophic glossitis, esoph webs, and anemia
- pagets disease of bone
- acanthosis nigrans
- This is tuberous sclerosis, be concerned for astrocytoma and cardiac rhabdomyoma
- this is plummer viston, be concerned for SZqCC of esoph
- 2* osteosarcoma or fibrosarcoma
- Visceral malignancy (stomach, lung, breast, uterus)
