Heme/Onc Flashcards
(95 cards)
1
Q
Name triggers/associations for ITP (immune thrombocytopenic purpura)
A
- idiopathic
- triggered by medications
- associated with SLE, CLL, Lymphoma, HIV, HCV, H. pylori
2
Q
What characterizes PNH? Flow cytometry?
Treatment?
A
- Chronic Hemolytic Anemia (abdominal pain during times of increased hemolysis)
- Iron deficiency through urinary losses
- Venous thrombosis (**Budd Chiari syndrome)
- Pancytopenia
- CD55 and CD59
Tx: eculizumab (reduces intravascular hemolysis, hemoglobinuria, and need for transfusion) ALL must be on prophylactic anticoagulation and iron + folic acid
3
Q
What 3 conditions are acquired defects of hematopoietic stem cells? (present with pancytopenia)
A
- Aplastic anemia
- PNH
- MDS
clinic overlap, and all cause pancytopenia
4
Q
Treatment of Apastic Anemia
associated condition?
A
- withdraw any offending agents (meds, radiation, toxins, fix nutritional deficiencies)
- Immunosuppression, 1st line = Cyclosporine and antithymocyte globulin (70% get disease control)
- If <50yo t/c allogenic HSCT potentially curative
Associated w/ Thymoma (so is pure red cell aplasia, and myasthenia gravis)
5
Q
Etiology of pure red cell aplasia? What does Bone Marrow show? Treatment?
A
T cell autoimmunity = pregnancy, thymoma, malignancy
or
Direct toxicity to erythrocyte precursors = viral, drug tox
BM = erythroid hypoplasia, clonal CD57+ T cells = large granular lymphocytosis
Tx:
- transfusion, immunosuppression (prednisone, cyclosporine, antithymocyte globulin)
- IVIG for pt with AIDS and chronic parvo B19
- Methotrexate or cyclosporine for large granular lymphocytosis
- Thymectomy for thymoma
6
Q
Evaluation for Pancytopenia
A
- BM aspirate + biopsy (hypocellular with inc fat content)
- Cytogenic analysis to exclude other BM disorders (ie. MDS)
- PNH screening flow cytometry with cell surface markers CD55 and CD59 absent
- Vit B12 + folate, hepatitis, HIV
7
Q
Myelodysplatic Syndromes
- Describe BM
- Describe peripheral smear
- Which subtype has a specific treatment? what is that treatment?
A
- hypercellular marrow with dysplastic erythroid precursors
- cytopenias in at least 2 cell lines + morphological abnormalities of erythrocytes (macrocytosis with nucleated erythrocytes and tear drop cells)
- -5q syndrome > lenalidomide to treat (2/3rds will respond)
8
Q
Treatment of high or very high risk MDS (by IPSS-R criteria)? What are you trying to prevent?
A
- Preventing transformation to AML
- Fit + Young – allogenic HSCT
- not bm transplant candidate – azacytidine and decitabine
9
Q
CML
- clinical picture + CBC findings
- diagnosis
- Treatment + SE
A
- Asx, splenomegaly, leukocytosis with inc #granulocytic cells in all phases of maturation in peripheral blood smear, if blasts 10-20% = accelerated or if >20% = blast phase (to AML)
- molecular = philadelphia chormosome (t 9:22) + BCR-ABL gene in peripheral blood or bone marrow
- Tx:
- - Tyrosine Kinase Inhibitors (imitanib, dasitinib, nilotinib) –> SE QTc prolongation
- - Allogenic HSCT if have accelerated or blast crisis
- - Hydroxyurea - palliative to alleviate leukocytosis and splenomegaly
10
Q
Essential Thrombocythemia
- Sx
- mutation?
- Treatment (low vs. high risk)
A
- usu Asx, or vasomotor (erythromelalgia), livido reticularis, HA, vision sx, arterial/venous thrombosis, 50% splenomegaly
- JAK2 mutation (50%)
- Tx:
- low risk - ASA 81 (<60yo, no thrombosis, WBC<11)
- high risk (nonpreg) - ASA + Hydroxyurea
- high risk + TIA/CVA/MI/GIB = plateletpheresis
11
Q
Secondary causes of polycythemia
A
- Hypoxemia ** most common
- Volume contraction 2/2 diuretics
- Androgens
- Secretion of Erythropoietin 2/2 kidney or liver carcinoma
12
Q
How do diagnose Polycythemia Vera? Treatment?
A
- Hb >16 (female) or >16.5 (male) and low EPO – epo-indepenent prolif of erthrocytes
- therapeutic phlebot to keep hct<45%
- ASA 81mg for all unless c/i
- Hydroxyurea if high risk thrombosis (>60-yo, prev thrombosis, leukocytosis)
13
Q
Hypereosinophiic Syndrome
- Eo count?
- pathophys?
- Treatment
A
- Eo count >1500/mcl
- molec activ of PDGFR a or b (platelet derived growth factor receptor)
- Imitinib otherwsie use glucocorticoid
14
Q
AML
- CBC + peripheral smear
- how to dx?
- When to consider alternate dx?
A
- high WBC, low Hgb, LOW PLATELETS - bleeding/bruising/infection. Smear - blasts, auer rods
- BM with >20% myeloblasts
- if lymphadenopathy or hepatosplenomegaly b/c does not happen in AML
15
Q
APML translocation + clinical picture + treatment (SE? tx?)
A
- t (15;17) translocation- disturbs retinoic acid receptor
- significant bleeding 2/2 fibrinolysis + DIC (clotting)
- ATRA (all trans retinoic acid) - start ASAP b/c high mortality of APML
- SE ATRA - differentiation syndrome (fever/hypoxemia/pulm infiltrate/hyperleukocytosis) - treat w/ dexamethasone
16
Q
Name 4 plasma cell dyscrasias
A
- MM
- MGUS
- Waldenstrom macroglobulinemia
- AL amyloidosis (light-chain assoc amyloidosis)
17
Q
difference btwn MGUS vs. Smoldering MM vs. MM
Whats the interval of screening?
A
- MGUS - monoclonal protein <3g/dL, BM clonal plasma cells <10%, no end organ damage»_space; ANNUAL LABS + H&P
- Smoldering MM - monoclonal prot =/>3g/dL, BM =/>10% plasma cells, no end organ damage»_space; must first get whole body MRI to assess for lytic lesions (if skeletal survey negative)»_space; then Q3 MONTH LABS
- MM - above + end organ damage (CRAB)
18
Q
AL Amyloidosis
- how to diagnose?
A
** abdominal fat pad aspirate or BM bx ** showing apple green birefringence under polarized light with congo red staining
- kappa/lambda chain detection + typing
- serum or urine M protein OR clonal plasma cells in bone marrow
(AL amyloidosis found in 10% of pts with MM, but may be diagnosed in pts who lack other myeloma findings)
19
Q
Waldenstrom Macroglobulinemia
- What is it
- How to diagnose
- What concerning syndrome can pts get? Tx?
A
- Indolent B-cell lymphoma with clonal lymphoplasmacytic infiltration of the bone marrow that secretes IgM in the blood (IgM Spike)
- B symptoms (fever, sweats, wt loss) + anemia, HSM
- Dx by BM bx
- 1/3rd get Hyperviscosity Syndrome – Medical Emergency»_space; Plasmapheresis
20
Q
Name the 4 Myeloproliferative Disorders
A
CML
PCV
Essential Thrombocytosis
Myelofibrosis (MF)
21
Q
Smudge cells
A
CLL
22
Q
How do you urgently reverse Warfarin coagulopathy?
A
Four factor prothrombin complex concentrate (PCC) - contains factors II, VII, IX, and X as a lyophilized powder and can be administered quickly in a small reconstituted volume. It provides effective hemostasis 90% of the time.
23
Q
Treatment of patient with hypogammaglobulinemia + recurrent infections
A
IVIG
ie. multiple myeloma with recurrent sinusitis
24
Q
Hereditary Spherocytosis
- Exam
- Dx
A
- 2nd and 3rd MCP osteophytes
- cirrhosis, cardiomyopathy, DM, skin pigmentation, fatigue, arthralgias, loss of libido
- transferrin sat >45% + high ferritin
- confirm with genetic testing for mutation in HFE gene
25
What type of transfusion/blood do you give in autoimmune hemolytic anemia?
ABO matched
Rh matched
but doesn't have to be cross-matched b/c may be impossible to find 2/2 DAT detecting IgG or complement coating that body forma autoantibodies against
26
Treatment of iron overload from chronic transfusion
Chelating agents
- PO deferasirox
- IV deferoxamine
27
Dabigitran reversal agent, when to use?
Idarucizumab -- give before emergent surgery! (elevated aPTT, dabigitran elimination half-life is 12-17hr with normal renal function)
"ida-dabigitran"
28
Pre-op Hb goal for sickle cell patient undergoing low to medium risk surgeries?
Hb 10 (by simple transfusion)
29
Patient starts Warfarin, they then get "retiform purpura" with areas of skin necrosis -- whats the diagnosis?
Protein C or S deficiency (+when warfarin is started has transient hypercoag state b/c reduces prot C activity by 50%) the rash shows up when heparin is discontinued
30
What are the PERC Criteria? (pulm embolism rule out criteria)
- <50yo
- HR <100
- SpO2 >95%
- No hemoptysis
- No estrogen use
- No previous DVT or PE
- No unilateral leg swelling
- No surgery or trauma requiring hospitalization in the last 4 weeks
31
Type of transfusion for low fibrinogen?
cryoprecipitate
32
How to distinguish DIC vs. Liver coagulopathy
both have low fibrinogen but in liver disease -- normal/increased Factor VII -- which is consumed/low in DIC
33
Alpha thal trait
- electropheresis
- Hb, MCV
- Treatment?
- normal electropheresis! normal Hb A2 and Hb F
- Hb 10, chronic microcytic anemia
- Can supplement Folic Acid (NOT iron b/c inc ability to absorb iron >> overload)
34
Beta Thal minor
- Hb, MCV
- elecropheresis
- chronic microcytic anemia
- electrophoresis -- excess alpha chains link with delta (HbA2) and lambda chains (HbF) to produces increased amounts of Hb A2 + Hb F
35
If patient has asymptomatic INR elevation, at what point do you have to treat?
INR 4.5 - 10 = watch
| INR >10 = PO Vit K 2.5mg
36
Describe electropheresis of Hemoglobin S B-thalassemia
- HbA 5-30% (inversely proportional to sx of pain crisis)
| - HbS ~60% (vs. sickle cell trait have HbS<<50% and more HbA vs. sickle cell disease HbS <90% and no HbA)
37
How do you diagnose presumptive TTP? Treatment?
Dx - blood smear with schistocytes in a patient with hemolytic anemia and thrombocytopenia, fever, change in mental status
Schistocytes = microangiopathic hemolytic anemia (MAHA)
Tx = emergent plasma exchange
38
pancytopenia with macrocytosis + peripheral blood smear with macrocytic erythrocytes and rare nucleated erythrocytes + 6-lobed neutrophils with negative Coombs test
B12 (cobalamin) deficiency, intermedullary hemolysis (with elevated LDH and bili)
**occurs with other autoimmune conditions (ie. hashimoto thyroiditis)
**B12<200, but if not can get MMA + homocystine levels which will be elevated in 98% of B12 deficiency
**B12 def can present with subacute combined degeneration of spinal colum (weakness, paresthesias, ataxia) without anemia or macrocytosis
39
what in an iron panel confers definite iron deficiency?
Ferritin <14 ng/mL
40
Other than alcohol, name 3 other drugs that cause macrocytic anemia
zidovudine
hydroxyurea
methotrexate
41
Sphreocytes (name 2 conditions)
Autoimmune hemolytic anemia
| Hereditary sphreocytosis
42
Target Cells (name 3 conditions)
thalassemia
liver disease
"other hemoglobinopathy"
43
Bite Cells
G6PD (eccentrically located Hb confined to one side of cell)
44
What causes cold agglutinin hemolysis? What do you see on peripheral smear? Treatment?
**smear with erythrocyte agglutination**
Myocplasma
CLL
lymphoproliferative disease
Tx: cold avoidance or rituximab if persitent sx (steroids and splenectomy ineffective)
45
Whats the test for autoimmune hemolytic anemia?
DAT (coombs test)
46
Indications for exchange transfusion in sickle cell
Acute CVA
Fat embolism
ACS requiring ICU/intubation
prophylactic - with history of ischemic CVA
47
Betal thal major treatment
transfusion
iron chelation (if Ferritin >1000)
splenectomy
HSCT (severe)
48
Prolonged PT
| Normal aPTT
Factor VII deficiency or inhib
Vit K def
Warfarin ingestion
DIC Liver disease
49
Normal PT
| Prolonged aPTT
Factor VIII, IX, XI, or XII
vWD (if severe and VIII low)
Heparin exposure
50
Prolonged PT
| Prolonged aPTT
Deficiency of II, V, X
severe liver dx, DIC, Vit K def, Warfarin tox
Heparin overdose
51
what can you give mild hemophilia A patients for acute bleeding or prior to minimally invasive procedure?
Desmopressin
**also 1/3rd pt can have F VIII inhibitor which you can measure with bethesda assay, if low <5 units can overcome with factor replacement
52
What can you give to prevent new skeletal-related events + improve survival in MM pts requiring therapy?
IV bisphosphonate -- Zolendronic Acid or Pamindronate (indefinite)
53
Heparin resistance, as evidenced by normal aPTT despite heparin administration. Causes?
Antithrombin Deficiency**
increase acute phase reactant protein (ie. Factor VIII) which will bind and neutralize heparin, others increase clearance of heparin,
54
Cause of prolonged aPTT that does not fully correct with mixing study? Dx + Tx
presence of inhibitor
Usually think of autoantibody to factor VIII aka acquired hemophilia A (women>men)
Treatment - recombinant Factor VII
55
Treating ITP in pregnancy
- when
- how
Plt <30,000
| IVIG
56
Tx of small cell lung CA with large centrally located tumors and no mets
Chemo + Radiation (cure 20-30%)
57
Tx of high risk prostate CA? what makes them high risk?
- GNRH agonist + radiation
| - PSA >20, or Gleason score 8-10, or extraprostatic extension
58
Tx of locally advanced head and neck CA
Cisplastin or Cetuximab + radiation
| Cisplatin is c/i in kidney disease
59
Treatment of early stage hormone receptor positive breast cancer in premenopausal woman
10yr of Tamoxifen (even if goes into post menopausal)
if already post menopausal then use aromatase inhibitors (lestrozole, anastrozole)
60
Tx for classic Hodgkin Lymphoma
Chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine)
61
Name 4 classic and 1 non-classic type of Hodgkin Lymphoma
1. nodular sclerosing
2. mixed cellularity
3. lymphocyte predominant
4. lymphocyte depleted
non-classic = nodular lymphocyte-predominant subtype with CD20 cell surface Ag
62
Treatment of advanced ovarian CA with germline BRCA1 and BRCA2 mutations previously treated with 3 or more lines of chemo
Olaparib - oral poly ADP polymerase inhibitor (PARP)
63
Newly diagnosed metastatic nonsquamous, non-small cell, lung cancer -- what should you first evaluate for before tx? why?
Activating Mutations
- if EGFR mutation --> tx with erlotinib
- if ALK and ROS1 mutations --> crizotinib
can start chemotherapy while awaiting results, but obtain tests b4 starting chemo
64
What do you have to monitor while on aromatase inhibitors?
DEXA q2 years, if T score < - 2.5 start bisphosphonate
(anastrozole, letrozole, exmestane) - postmenopausal breast cancer adjuvant treatment
**aromatase inhibitors are c/i in premenopausal women
65
When do you use adjuvant chemo in breast cancer?
triple negative (hormone receptor neg), HER2-positive, high grade, extensive lymphovascular invasion, and, positive nodes
66
When is trastuzumab used? what screening do you have to get before starting?
Monoclonal antibody used for HER-2 positive breast cancer -- used as adjuvant to chemotherapy
get eval of LV function (echo) before starting and monitor during
67
Key treatment differences in SCLC vs. NSCLC
SCLC - usually systemic. For both get CT c/a/p + PET to stage.
SCLC - adding radiation to chemo only when limited stage disease. If extensive - offer chemo b/c can increase survival.
NSCLC - radiation in Stage I-III in addition to cisplastin or platinum based chemo. If stage IV (mets beyond contralat mediastinal LN) -- chemo + immunotherapy with antiPDI checkpoint inhibitor. Offer chemo only if good performance status, otherwise no.
68
What is a sister Mary Joseph node? Virchow Node?
```
SMJN = periumbilical node
VN = left supraclavicular node
```
both can be found in gastric cancer
69
Treatment of
- colon cancer
- rectal cancer
COLON
- surgery -- if single metastatic lesion to single organ, remove primary and mets lesion. Also of course if confined to colon (Stage I) or local invasion (Stage II)
- resection + chemo -- mets to regional LN (stage III)
- chemo -- distant mets (Stage IV)
adjuvant chemo == FOLFOX or CAPOX
for metastatic = FOLFOX and FOLFIRI -- addition of bevacizumb mab against VEGF, increases efficacy of chemo, anti-EGFR monoclonal ab cetuximab or panitumumab (alone or in combo with chemo) - but cant use if have k-ras and n-ras mutation
RECTAL
- stage II-III preoperative radiation+chemo and postoperative chemo
70
Treatment of anal cancer
Radiation + mitomycin + 5-FU
| avoid surgery
71
Treatment for advanced ovarian cancer
IV and intraperitoneal chemo (after debulking) - cisplatin and paclitaxel
16mo improvement in medial overall survival in stage III ovarian cancer if no residual mass >1cm after debulking surgery
72
Neuroendocrine tumors
Pancreatic vs. Gastrointestinal NET (carcinoid)
- Treatment differences
- How to eval for somatostatin receptor?
- appear same, treated different
- Pancreatic NET - can tx with chemo, sunitinib (anti-VEGF ), everolimus (mTOR inhib)
- GI NET - usu asx, just follow CT 3-6mo. no chemo.
- surgery if symptomatic local tumors
- can use Idium 111 pentetreotide scan to evaluate for somatostatin receptor and can treat with analogs (octreotide or lanreotide)
73
Prostate Cancer Treatment
- local vs. hormonal
- castration sensitive vs. castration resistant in metastatic disease
Early stage gleeson <10 - active surveillance if life expectancy >5yr and not many commodities
Local = external beam radiotherapy/brachytherapy/radical prostatectomy
If high risk disease, need adjuvant ADT (androgen deprivation therapy) for 2-3 yrs (GNRH agonist - luprolide, goserelin)
Metastatic disease
(1) Castration sensitive disease
- --- docetaxel + ADT
(2) Castration resistant (progresses despite ADT)
- -- 1st line chemo= docetaxel + prednisone
- -- ketoconazole, megesterol, glucocritcoids, estrogens
- -- new anti-androgens - abiraterone & enzalutamide
74
What does elevated AFP in testicular cancer indicate?
NONseminomatous tumor or tumor component --> must treat at such
(hCG can be elevated in seminomatous or nonseminomatous)
75
Treatment for seminoma (testicular cancer)
- stage I (low risk)
- Stage II-III
- PET scan positive residual masses
in general cisplatin-based chemo recommended over radiation
- observation, if need tx give 1-2 doses of carboplatin chemo
- II=III = cisplatin based chemo for intermediate, advanced, and nonpulmonary visceral mets
- Residual masses PET scan positive should be resected
76
Treatment for nonseminoma testicular CA
- Stage I
- Stage II-III
- Bulky RP LN
- Elevated Tumor markers but negative imaing
- active surveillance, 1 cycle of cisplatin chemo, or retroperitoneal LN dissection
- All the rest === cisplatin chemo
77
Name 4 paraneoplastic syndromes related to Renal Cell Carcinoma
erythrocytosis
AA amyloidosis
polymyalgia rheumatica
hepatic dysfunction (unrelated to mets)
78
Treatment for RCC
- surgical
- targeted
- early/local - partial or radical nephrectomy
- mets - debulking nephrectomy
Targeted
(1) VEGF inhib (bevacizuab) or VEGF tyr kinase inhib (sunitinib, sorafenib, pazopanib, axitinib)
(2) mTOR inhib (everolimus, temsirolimus)
(3) Immunotherapy w/ PD1 inhib (pembrolizumab, nivolumab)
79
MEN 1
MEN 2A
MEN 2B
MEN 1 - pituitary, parathyroid, pancreatic NET
MEN 2 -- Medullary thyroid CA (high calcitonin) + pheochromocytoma
2A - parathyroid
2B - mucosal neuromas (marfinoid too)
80
What gene mutation should you test for in FNAB of thyroid nodule? why?
BRAF gene mutation - papillary carcinoma = more aggressive forms of cancer
81
What germ line mutation is associated with medullary thyroid cancer? so what?
RET proto-oncogene
| screen family mem bers for disease if positive
82
Most common thyroid cancers? treatment?
```
PFMA
papillary (85%)
follicular (10%)
medullary (3%)
anaplastic (1%)
```
- papillary and follicular = total thyroidectomy followed by radioiodine therapy
- medullary = total thyroidectomy and neck dissection (no radioiodine b/c not taken up by c-cells)
83
When to stop antibiotics for febrile neutropenia?
when ANC =/>500
84
Neutropenia + RLQ abdominal pain -- whats your concern?
Typhlitis (necrotizing enterocolitis) --> get CT abdomen
85
When to start antifungal therapy in febrile neutropenia?
persistent fever despite 4-7 day of empiric broad spectrum antibiotics
86
Treatment of Hairy Cell Leukemia
Cladribine (nucleoside analog, other is pentostatin)-- complete and durable remission
("dry tap" 2/2 marrow cell fibrosis + pancytopenia + progressive splenomegaly with NO lymphadenopathy
87
What is Idelalisib?
P13K kinase inhibitor - oral agent for treatment of relapsed follicular lympohoma (once transformation is excluded)
88
When to start breast cancer screening for patients who've had chest wall radiation?
If had chest wall radiation before the age of 30 years -- screen @ 25yo or 8 yrs post radiation (whichever is latest)
89
How do you treat high-grade or recurrent low-grade cancer?
1. TURBT ..followed by..
2. Intravesical chemo with BCG or mitomycin and periodic cystoscopies
If mets/muscle invasion - then cisplastin chemo
90
How to treat metastatic recurrent breast cancer with E/P positive her HER2 negative? (previous adjuvant aromatase inhibitor tx)
Letrozole + palbociclib ( oral CDK4 and CDK6 inhib) synergistic
91
You've diagnosed metastatic NSCLC, what do you now have to test for?
PD-L1 expression
| b.c Pembrolizumab (MAD vs. PDL1) is superior to chemotherapy
92
Steps to diagnose testicular cancer
1. US to determine testicular mass
2. bhCG and AFP levels
3. orchiectomy to get tissue diagnosis
93
BRAF
melanoma
94
HER2
breast cancer
| upper GI tumors
95
RAS
colorectal cancer (EGFR monoclonal antibodies)
