Hemato-oncology Finals Flashcards
(188 cards)
1
Q
Side effect of Aspirin
A
- GI- peptic ulcers, Gastritis
- bleeding -1-3%
- Allergy bronchospasm
- Renal and hepatic toxicity at overdose.
- Tinnitus
2
Q
Which are the P2Y12 inhibitors
and what is the MOA?
A
Thioemopyridines
block irrevesibly the affect of ADP on PLT
TicoliPiDe
CloPiDogrel
Prasugrel
PD like ADP. and ptetzel
Ticagrelor- not DPI family, rether is reversbly inhibit P2Y12. can acuse Dyspnea
3
Q
Indication for DAPT
Aspirin + P2Y12 inhibitors
and indication for P2y12 inhibitors alone
A
- replacement of aspirin after- MI, storke, PAD
- combination- after BMS for 4 weeks / after DES for > 12 months
- CVA / high risk TIA- 3-4 weeks,only aspirin afterwards
4
Q
Side effect of P2Y12 inhinbitors
(ticolipide, prasugrel, clopidogrel)
A
- bleeding- stop 5-7 prior major surgery
- TTP (ADAM13 Ab) - most with Ticolipide
5
Q
When we will give prasugrel?
in which situations?
A
ACS who are going to PCI
6
Q
What is the main C/I for Prasugrel?
A
complete C/I
Hx for Cerebelovascular disease
relative C/I:
* Renal failure
* weight < 60 Kg
* Age > 75
7
Q
Indication for Ticagrelor?
A
Secondary prevention after ACS (better then clopidogrel in high risk pt)
mainly as DAPT for 3-4 weeks after ACS / CVA/ high risk TIA
8
Q
Main side effect of Ticagrelor?
A
Dyspnea (15% pt)
9
Q
What is the use of Dipyridamole and MOA?
2 main uses
A
MOA
PDE3 inhibitor = high cAMP levels= inhibit PLT + inhibit adenosis uptake by the cells = vasodilation
indications:
1. secondary prevention with Aspirin for Stroke/ TIA
2. Cardiac Chemical stress test- can cause coronary steal
Side effect- vasodilation = flushing, hypotension, headace
10
Q
all the following medication are class of:——–
Tirofiban
eptifibatide
Abciximiab
How they are administerd?
Side effects?
A
IIB/IIIA antagonists- Fab who bind the receptor
All IV
Side effect
Bleeding
Thrombocytopenia- must follow and monitor PLT count
Every medication has B and A in their name
11
Q
Whats the different between LWMH and UF heparin
and how its expressed in the MOA?
A
UF heparin- verabile sized of heparin polymers
LMWH- only small polymers
the meaning of that
UFH- activation of ATIII»_space; inactivation of all intinsic pathway including X + Thrombin
LMWH- only inhibit X
12
Q
What is the Antidote of UF heparin?
A
Protamine sulfate
13
Q
Pt under UF-heparin should be monitor and adjust doses by?
and when we will use
A
**PTT
**
use:
1. acute setting- DVT, PE, MI, stroke
2. PPx in hospital for DVT
14
Q
What is a major severe adverse affect of Heparin?
A
HIT (heparin induce thrombocytopenia)
complexes of PLT Factor IV + Heparin + IgG»_space; can activate PLT»_space; Thrombosis + Thrombocytopenia
IgG Ab against PF4- heparin complex is formed
less common in LMWH
15
Q
Dx of HIT
Tx for HIT
A
Dx:
timeline- 5-14 days after start heparin
Ab against Heparn- PF4
most specific test- Seratonin release essay
Tx
Stop heparin»_space; start direct Anti-thrombin inhibitors (Bivarlirudin / Lepirudin - IV/ SQ).
can give instead of direct thromin inhibitors DOACS (direct thrombin or factor Xa inhibitors- DTI
vein and artery thrombosis
Xa inhibitors- ApiXaban, RibaroXaban
DTI- irudin suffix (IV/ SQ), Dabigatran (PO)
16
Q
The dose given with LMWH should be adjust to
A
Kidney function
17
Q
iIn which 3 types of Pt we will monitor use of LMWH (EnoXaheparin)
and by which test
A
Monitor:
anti factor Xa test- flurosence
3 Pt that should be monitored
1. renal insuff.
2. obesity
3. pregnancy
18
Q
How to start give Warfarin
A
due to its delay affect- start with UFH / LMWH / Fondaparinux until effect of warfarin seen
19
Q
What is the Goal INR for mechanical valve under Warfarin?
A
most cases- 2-3
in mehanical valve- 2.5-3.5
20
Q
main adverse effect of Warfarin
A
- bleeding
- Skin necrosis- most prone are pt with protein C & S def.
בחסר של 2 החלבונים גם ככה יש יותר קרישיות וורפרין מוריד עוד יותר את הרמות שלהם וזה גורם בעצם לאפקט הפוך- להיות היפר-קרישיות ונקרוזיס של העור
21
Q
Antidotes for Warfarin
A
- Vitamin K
- FFP
- Protein C concentrate
22
Q
Should a pregnant women continue the use of warfarin?
A
No- Teratogenic
should use UF heparin during pregnancy
לא עובר בחלב אם
23
Q
What should be done in the following situations:
1. a-symptomatic with INR 3.5-10
2. a-symptomatic with INR > 10
3. Severe bleeding
A
1.** a-symptomatic with INR 3.5-10**- stop comadin until INR reach 2-3
2. a-symptomatic with INR > 10- vitamin K po (2.5-5 mg) + halt warfarin
3. **Severe bleeding **- vitmain K IV 5-10 mg, give PCC (2, 7, 9, 10)
before high risk procedures- stop 5 days earlier warfarin
PCC- prothrombin concentrate complex
24
Q
When is the only situation we will give warfarin with out Heparin before?
A
propylaxis for Afib
25
Doac vs Warfarin
* Major bleeding sites risk?
* efficacy in prevention of stoke in Afib pt?
* clearance site?
* Major bleeding sites risk?
**Warfarin- brain**
**DOAC- GI**
* efficacy in prevention of stoke in Afib pt?
**SAME**
* clearance site?
**Warfarin- liver**
**DOAC- kidneys (C/I CrCl < 15**
26
all of the following are belong to the group of ------
Dabigatran
RivaroXaban
ApiXaban
**DOAC**
27
Indication for DOACs
1.** Stroke ppx in Afib** (no mechanical valve or reumathic fever- warfarin)
2. **VTE Treatment **- theres not resude in doses if renal failure exist (in contrast to ppx Afib)
3. **2nd ppx after VTE**
4. **after hip / knee surgery**
5. **2nd ppx coronary disease / PAD**
| Not given as a Tx for **APLA**
Not for pregnent of breasfeeding mom
## Footnote
VTE = venous thromboembolism
28
Antidote for the following DOACS
Dabigatran
Factor Xa inhibitors ( RivaroXaban + EpiXaban)
* **Da**bigatran- I**da**rucizumab
* Factor Xa inhibitors ( Rivaro**Xa**ban + Epi**Xa**ban)- Ade**Xa**net
29
Which Anti-coagulent have the same efficacy with less bleeding event as Enoxaheparin in Tx of **STEMI**
Fondaparinux
inhibit only Xa and not thrombin (like LMWH)
30
Which type of hemolysis will lead to Hemoglobinurea?
**Intravascular**
31
Which Major complication can be cause by G6PD ?
AKI
32
Whate are the main medications that can cause G6PD Hemolysis ?
* **Dapsones**
* ** Sulfadrugs**
* **Primaquine **+ quinidine - Anti-malerian
* Isoniazid- TB
* **Nitropronetoin**
* **Rasburicase** (TLS- hyperuricemia)
* **Methylene blue**
* Sedoral **(Phenazopyramdine**)
| Definite risk in **bold**
33
**Heredatiry Spherocytosis**
whats the problem?
Extravascular / intra-vascular hemolysis
Mutation in **Sp**ectrin / Ankyrin- RBC cytoskeleton
**mainly extravascular**
| נושאים חמצן סבבה אבל הממברנה קשיחה
34
In Heraditery Spherocytosis:
what will elevate or decrease:
RDW
MCHC
MCV
* RDW- high
* MCHC- high (same volume smaller RBC)
* MCV- normal or a bit low
35
Warm AIHA:
Ab? Degree?
Extravascular / intravascular
**IgG in 37 degree**
**Extravascular-**by macrohages in spleen
36
Warm AIHA Etiologies?
1. SLE
2. infections- HIV, HCV, EBV
3. CLL
4. Methyl DOPA (HTN) pregnancy
37
Warm AIHA + Autoimmune Thrombocytopenia
we will think of
Evan's syndrome
autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), with or without immune neutropenia
38
How we diagnose warm AIHA and what is the Tx?
Dx- **Direct coombs- IgG **
Tx:
**Blood transfusion ** for acute presentation
first line- prednisone + RTX
if refactory- Splenectomy
## Footnote
Direct- test for Ab **bound to RBC**
indirect- serum Ab against RBC
39
Cold AIHA
Ab? Dagree?
IgM , low temparture < 30
**Intra + extravascular hemolysis**
40
how we diagnose cold AIHA?
What are the etiologies?
**Dx**
Direct coombs test- C3 bound
**Etiologies**
Mycoplasma
EBV
CMV
## Footnote
mechanism- cold Tm >> IgM bind to RBC >> C3 also bind >> elevate TM >> IgM dissolve but **C3 still bound**
41
Tx for cold AIHA
1. prevent exposue to cold
2. RTX
no effectivness for prednisone / splenectomy
42
What are the 3 Disease we will see MAHA (microangiopathic hemolytic anemia)
1. HUS
2. PTT
3. DIC
**the only situations we will see schiystocytes**
| also malignant HTN
43
Which 2 types or parasites can cause normocytic anemia
Maleria
Babesia
44
PNH?
what is the mutation?
how it can affect blood cells?
aqueird mut. in GPI anchor >> can't present CD55-CD59 (Complement inhibitory protiens) >> cause destruction by the complement and MAC complex
**can cause pancytopenia**
45
Which type of cancer can develop on the basis of PNH?
AML
46
reccurent abdominal pain, Budd-chiari , and pancytopenia with hemoglobiurea can raise suspicion for-----------?
PNH
47
PNH
Dx?
Tx?
Dx:
Flow cytometry- CD55-59
Tx:
Eculizumab- bind C5 and inhibit MAC comlex formation.
**does not improve the extra-vasuclar hemolysis, C3 will still be bound to RBC**
## Footnote
Definitve- BM transplent- only if severe PH/ aplastic anemia
Anti-coagulation- only after VTE/ other thrombopylic
48
How to rull out psuado Thrmbocytopenia?
Take another sample in a tube with Sodium-citrate or heprain
cause by clampin of PLT in EDTA tube (blood smear = clamping of PLT)
49
most common cause of thrombocytopenia?
Drug induce
50
Wet purpura and Retinal bleeding in Thrombocytopenia can indicate of
high risk for life-thrething bleeding
51
**ITP**
pathophysiology
Tx- for low risk / high risk and when we will treat?
**pathophysiology**
Anti- GPIIb/IIIa Ab >> digest by spleen
**אבחנה שבשלילה**
**Tx < 30 K PLT**
prednisone / Dexamethasone/ AntiD (only in D+), IVIG
**low risk pt-** in community wth 1 medication
**High risk pt-** hospitelization + few medications
| Hirg risk- bleeding, PLT < 5K, sighs of dangrous bleeding
## Footnote
other options for Tx: Splenectomy, RTX, TPO agonists (Eltrombopag)
52
Which medication can be given in Refactory ITP?
how much % of remmision is obtained?
**RTX**
30% remission
53
Which disease are Thrombotic thrombocutopenic Microangiopathies?
* TTP
* HUS
DIC
54
What is the classic Triad of HUS and the pentade of TTP
**Triad of HUS**
1. Renal insuff.
2. MAHA
3. Thrombocytopenia
**Petnade of TTP**
HUS + Fever + neurologic symptoms
55
What is the pathophysioligical condition in TTP
Ab against ADAMS13
| **Congenital TTP (apsho-shulman)**- congenital deff. in ADAMS13
## Footnote
**ADAMS13-** the enzyme who cleaves wVF polymerse and prevent blood vessel occlusions >> activate of PLT >> thrombosis + MAHA
56
How we diagnose TTP?
**ADAMS13 < 10%**
57
Tx for TTP
**daily plasmaphersis-** until PLT are normelizeid and no hemolysis for 2 days.
**steroid are usally added**
58
which medication can shorten the lengh of TTP episodes and reduce reccurence?
**RTX**
59
Which medication for TTP is made against vWF and **reduce mortality**?
Caplacizumab
(risk for reccurence- 40%)
60
Etiology for HUS?
and Tx
Etiology- E.coli 0157:H7 infection, pneumoccoc
Tx:
supportive, 40% will need dialysis
61
Whats the different between HUS and aHUS?
aHUS theres not diarrhea before HUS
Tx- aHUS **Eculizumab - C5 inhibitor**
## Footnote
Eculizumab- also given in PNH, block formation of MAC complex
62
which Anti-coagulant component are fiven in:
FFP
PCC
cryoparcipitate
FFP- everything
PCC- 2,7,9,10, proteins C+S
cryoparcipitate- fibrinogen, 8, vWF
63
Hemophilia A + B
what is the inheritence?
which is more common?
X-linked
A (VIII) more common
64
if a pt have hemophilia A and theres no avaliable factor 8, what other **Best** option can the doctor give?
**Cryoparcipitate**
(Factor 8, vWf, fibrinogen)
65
How Desmopressin can help a pt with hemophilia A
Desmopressin helps realse factor 8 + vWF fromt the Whady pallady bodies >> more factor avaliable
## Footnote
desmopressin- bed-wetting, central DI
66
Which medication can be given in hemophilia a thet is skipping factor 8 and do not need it
**Emicizumab**
bringfactor IX to X (does not need factor 8)
## Footnote
עמיקיזומאב מחבר בין שני צידי העמק
67
How can we diagnose in Hemophilia that **Ab are create to the given factor and acts as an inhibitors?**
**Mixing study** does not improve after adding normal plasma
68
Hemophilia C
Which factor is missing
which decendent is common?
Tx?
missing of factor XI (prolong PTT solely)
**יהודים אשכנזים ועיראקים**
**Tx**
in severe disease before big procedure- F.XI concentreate or FFP. **can add hexacepron** in mild bleeding **not urogenital bleeding**
## Footnote
bleeding are muco-cutaneous- similiar to low PLT but here the bleeding time is normal and PTT prolong
69
DIC
mortality rates
30%-8080%
70
What are the most common cuases for DIC
* Bacterial sepsis
* Trauma
* Obs. compications
* Adenocarcinoma (prostate, pancrea..)
* APL (acute promyolacyte leukemia)
71
What is the most sensetive test in DIC?
D-dimer
72
What the Different between DIC and chronic DIC?
**Chronic DIC**
PT/PTT + fibrongens are normal
## Footnote
גידולי מתסתטיים, המנגיומה ענקית ותסמונת העובר המת, דימומים קלים המוגבלים לעור ולמקוזות
73
Tx for DIC
**most important- treat the underlying cause**
1. **for hemmoragic symptoms- **PLT infusions when < 20K
2. **For fingrinogen levels > 150**cryopacipitate (8,13,vWF, fibrinogen) or fibginogen
3. **PT < 3 below to ULV**- FFT, vitamin K, if bleed hexacapron
4. **Thrombotic syndromes**- low dose heparin only. **not when severe DIC or active Bleeding**
74
Which factors are depent in vitamin K?
2,7,9,10, protein C + S
75
what is the erlieast finding in vitamin K def? and why
PT prolongation >> factor VII has the shortest half life.
76
Which coagulation factor is use as indicator for liver failure as the reason for a coagulapthy?
**Factor V**
does not depent on vitamin K.
77
Tx for coagulaphtis secondary to liver failure?
1. Vitamin K IV
2. 4F-PCC prefer on FFP (less vol.)
3. PLT infusion- PLT < 10-20K in active bleeding or < 50K before surgery
4. cryoparcipitate- fibrinogen < 100-150 unless pt is bleeding
78
f **Ab development against clotting factors**
which type of population are more prone?
which factor is most prone
Factor VIII- **aquicerd Hemophilia A**
Pt:
pregnancy/ post-partum.
mainly age > 60
79
What is bethesda assay use?
indentify the specific clotting cator and levels of Ab against it
80
How can we eridicate the Ab against Clotting factor?
first line- steroids , cyclophospamid
second lie- IVIG, anti-CD20
81
the present of Celiac can lead to which type of anemia?
Microcytic hypochromic anemia- Iron Deff. anemia
82
What is the Tx for anemia of elderly?
symptomatic and irreversible
EPO
Blood transfusion- only for certain pt with Hb > 7-8
83
What is Pernicious anemia
Ab against perital cells in the gut >> no IF is produce >> can't bind B12 >>Megaloblastic anemia
84
In which place B12 is detach from IF and reabsorb in the body?
Terminal ilium - thats why chron pt might present with megalobalstic anemia (terminal ilitis)
85
Severe cases of B12 def. can present with
| related to blood cells
pancytopenia
neurological deficiet- peripheral neuropathy , ataxia, dementia, depression
86
Tx for B12 for irreversible reasons and what should we watch for
**B12 IM injections for life**
can cause **hypokalemia**
but does not required Tx most of the time
87
MTX can cause a deff. in which vitamin?
B9- Folate
88
What are the resons for microcytic anemia
TAILS
* Thalasemmia
* Anemia of chronic disease
* Iron deff.
* Lead poisonnig
* Sideroblast
89
What is Mentzer index?
how to calculate
MCV/RBC
**help differantiate btw talashemia and iron def.**
MCV/ RBC < 13 = thalasemmia
MCV/ RBC > 13 = Iron deff.
90
MDS can cause pancytopenia hypo or hypercellularity of BM?
Hypocellularity or Hypercellularity
91
Etiologys for Pancytopenia hyper-cellularity of BM?
MDS
PNH
Myelofibrosis
sys.diseases- SLE, B12, folate, HIV, TB...
92
What is the first step when pancytopenia is present?
**Emeregent blood smear- ** acute leukemia
**BM biopsy-**if unexplained pancytopenia >> mainly hypoproliferative
93
Aplastic anemia def. ?
PAncytopenia + hypocellularity of BM
| a lot of Fat with hypocellularity- this is the Dx in BM biopsy
94
What is the Tx options for Aplastic anemia
**BM transplent-** 1st line for youngs with match sibiling
**Immunosuppresive Tx**- for older pt / pt with no match on BM transplent
**ATG (antithymocyte globulin) + Cyclosporin**- 1st line
| עוד תרופות שמגרות מח עצם כמו
TPO
GM-CSF
לחשוב על כל מה שיכול לגרות BM
## Footnote
ההנחה שהתהליך מתווך מע' חיסון ולכן אנטי-טימוציט גלובין יכול לעזור
95
What is the benefit in using **Eltrombopag (TPO)** in aplastic anemia?
יכול לאושש את השורות במקרים רפקטורים, ומשפר תגובה ל-ATG
כשניתן ביחד
96
What is Fanconi anemia?
Heraditery Aplastic anemia
**> 50% with physical deformations**
| mutation in DNA repair anzyme >> Mainly crosslink
## Footnote
wierd thumbs, caffe olea, short sature
97
When I say Pure red cell aplasia
you say
**Thymoma**
98
Pure red cell aplasia
how we diagnose?
Reticolocytopenia < 1%
if unexplain demend BM exmination
## Footnote
in kids- if heraditery = **Diamond Blackfan-** weird fingers, Black BM, high HbF
99
Which secondary conditions can cause Pure red cell aplasia
1. Thymoma (remember M.G)
2. Lymp. malignancies (CLL)
3. Parvo B19- Sickle cells, thalasemia , shperocytosis
100
How to diagnose Multiple Myloma?
1. **> 10% plasma cells in BM or Plasmocytomas **( masses in bones or soft tissue of plasma cells)
2. **one of the following- Organ demege:**
* C- hypcercalcemia > 11
* R- renal failure - Cr > 2 or CrcL < 40
* A- anemia- below 10 or >2 below Low limit
* B- bones lesions- lytic
**Markers thet can repalce criteria 2:**
* > 60% plasma cells in BM
* light chain ratio > 100
* Focal lesion in MRI (step before lytic lesions) - at least 2 in size > 5 mm
| **SLiM CARB**
S- sixty precent
Li- light cheins
M- MRI
101
Defintion of MGUS?
when we dont need to check BM
monoclonl Ab < 10% in BM **or** less then 3 gram in serum
+
no SLiM- CARB
no BM biopsy- monoclonal IgG < 1.5 (low ) light chain ratio - 0.125-8 **no need to check for diagnosis follow up is enough**
| דורש מעקב ולא טיפול, סיכוי של 1% בשנה להתקדמות
102
Defintion of Smoldering MM?
monoclonal Ab in serum > 3 gr/dL **or** 10-60% plasma cells in BM
no SLiM- CARB
| דורש מעקב ולא טיפול, סיכוי של 10% בשנה להתקדמות
103
Which test are benefical and not beneficial for Bone test in MM
1. ALKP- not elevated = no osteoblast activity
2. מיפוי עצמות- לא מתאים
good test- CT/ MRI / PET-CT
| Bone reabsoprion = hypercalcemia
104
Most common reason for renal falilure in MM?
**Hypercalcemia **- due to iadequate ability to concentrate the urine >> polyurea >> low GFR...
105
What is the **earliest** menefistation of Light chain tubular damage in MM?
Fanconi syndrome
| Metabolic acidosis with normal AG + hypokalemia + hypophosphatemia
106
MM + nephrotic syndrome will raise a suspicion of
Amiloydosis
107
Which 2 parameters asses the dagree risk of MM?
the **International Staging Systme- SSI**
and what is the Strognest single prognostic factor
**Albumin
B2-microglobulin**
if low albumin + high B2-Mg >> **high risk**
| **B2-microglobulin- Strongest solely prognostic factor**
108
Which medication include in the **induction therapy** at MM?
and what in **Maintanence therapy**
1. Lenalidomine- rq aspirin or Anti-coagulation
2. Brotezonib- proteosome inhibitor
3. Dexa/ prednisone
4. DaratuMuMab- anti-CD 38
**Maintanance:**
1 medication from above at low dose
109
Tx of choice in Hyper-viscosity synd?
Plasma-phersis
| IgM Ab- Waldenstrom macroglobulinemia
110
What are the the distinct features of Waldenstorm macroglobulinemia VS MM
**WM**
1. IgM (in MM rare)
2. CD20+
3. mut. in MYD88 (90% in WM)
4. no lytic lesions
111
Which type of anemia can happen in hyper IgM (Waldenstrom macroglulinemia)
AIHA- cold type. (positive coombs- C3)
## Footnote
warm type - IgG
112
how we Dx Waldenstrom macroglulinemia
**BM biopsy** > 10% Lymp + lots of Mast cells
**MYD88 mutation** > 90% of pt
113
Tx in Waldenstrom macroglulinemia when:
1. mild disease (like MGUS)
2. phenomenon related to abundane IgM
3. severe disease with hyperviscosity
4. Hyperviscosity menefistations
1. **mild disease (like MGUS)**- followup
2. **phenomenon related to abundane IgM** RTX (anti-CD20)
3. **severe disease with hyperviscosity**- R&B protocol (Bendamustin + RTX )
4. **Hyperviscosity menefistations**- plasmaphersis (remember visual diturbance)
## Footnote
R&B protocol- also in follicular lymphoma
114
**Acute leukemia **
what is the hallmark
| ALL, AML,T-ALL,AMPL
**hallmark-** leukocytosis
**Blasts - acute**
one of the progenitors (precursors)
RBC- PV
Granolocytes - CML
PLT- ET
## Footnote
mature - chronic
115
what are the 3 main cheracteristics of AML
1. BM depresson
2. Extra-medullary - gums, skin, CNS
3. Leukemic blast sequel- DIC, luekostasis, TLS
## Footnote
DIC- more common in AMPL (higher auer rods)
116
**TLS**
Electrolyte disbalance?
Dgx?
Tx?
**Electrolyte**
Hypercalcemia
Hyperurecemia
hyperphosphatemia
hypocalcemia
**Dgx:**
**labs + 1 of the 3:**
1. renal insuff.
2. arrythmias/ Cardiac arrest
3. sezuires
**Tx:**
hydration + alopurinoll (in high risk pt)
**Rasburicase-** if TLS occure, reduce uric acid. **C/I in G6PD**
## Footnote
בדיקת רמת חומצהאורית תחת ראזבוקריאז- מבחנה שטופה עם הפרין. על קרח
117
Dgx criteria for Acute leukemia?
* Blasts > 20% in blood smear / BM
* Genetic changes (leukemia-defing)
* Extra medullary disease
| **one of the follows**
118
What is the most importent prognostic factor in Acute leukemia?
Cytogenetic of tumor cells (translocation and ect)
119
which leukemia and what the prognosis?
t(15:17)
AMPL- good prognosis
PML-RARA (fusion)
| The t(15:17)- what causes AML to become APL (AMPL)
120
Tx for APL (AMPL)
ATRA = A retinoic acid in combination with ATO ( Arsenic Acid)
| if pt. first present with DIC - add vitamin A to the DIC therapy ASAP
121
AML Tx:
induction
consolidation
BM transplent
**induction: intensive or non intensive:**
* intensive (age < 65, low co-morbidites) - **3+7 = 7 days cytarabine + 3 daunorubucin**
* non-intensive- semi-paliatve tx
**Consolidation**
* Chemothrapy - for good prognosis like t(15:17), t(8:21)
* BM transplent- bad prognosis (young pt < 75, FLT3-LTD)
**BM transplent- allogeniec (other person)**
1. no full remission - 20% chance of healing
2. after full remission
122
What are the biological Tx in AML?
1. TKI against FLT3
2. monoclonal Ab- Gemtuzumab (cd33)
3. CPX-351
4. Ventoclax
123
Why we should not give to APL pt the chemothrapy given in AML (Cysterabin + Antracyclin 7+3)?
**can cause Severe DIC**
124
What is APL differentioation syndrome?
secondary to ATRA Tx
התאים הממאירים נצמדים לאנדותל כלי דם ריאתיים- דיספניאה, אגירת נוזלים, כאבים בחזה וכדומה
**Tx:**
Steroids
in severe cases- temporary stop ATRA
125
What mutation we will see it all of the following:
PV
ET
myelofibrosis
**JAK2 mutation** (Chromosome 9 >> Tyrosine kinase)
in 95% of pt
| הפעלה ביתר של רצפטור EPO
126
which MPD are presented with:
1. red and puffy skin
2. Aquagenic pruritus
3. DVT- mainly budd-chiari
**Polycytemia vera**
Thrombosis- atrieal / veins
hyperviscosity- neurologic symptoms
127
Complications of PV?
1. progress to myelofibrosis ~ 15%
2. Leukemia- AML
3. Gout- due to high turnover = hyperurecmia
## Footnote
Hyperurecimia- Treat with alloperinol only if symptomatic/ under chemo
pruritus- Anti-histamins / anti-depressant
128
What is the influence of Polycetemia vera on
1. EPO levels
2. Blood vol
3. RBC mass
1. EPO levels- low
2. Blood vol- high
3. RBC mass- high
129
Major cause of death in PV?
Thrombocytosis >> mainly a/w arytrhocytosis
130
Tx for PV
**phlabetomy**- הקזות דם
goal- HB < 14, HCT < 45%- 42% (M-F)
**Hydroxyurea-** inhibit DNA synthsis (try to prevent as much as can)
131
Erythromealgia is a/w which of the following?
PV, ET, myelofibrosis
and how we treat
**PV**
Tx- Aspirin
| Erythema and burning pain in lower extremites
132
What are the clinical featurs of extra-medullary hematopoasis?
* Splenomegaly
* Tear-drops RBC (dacrocytes)
* immature meyaloids
* anemia (normo-normo) + Thrombocytopenia
* Hyperuricemia
| im primary myelofibrosis- also B symptoms = high metabolism
133
Tx for Primary myelofibrosis
**BM transplent-** only curative Tx
**PEG-INF-a-** reduce fibrosis in early stages, in late can worsen the BM failure
**Ruxolitinib- ** inhibit JAK2. can improve splenomegaly and symptoms. also survival (not curative). S.E- anemia + low PLT.
**Steroids-** can improbe anemia and Thrombocytopenia
**C/I for splenectomy**
134
Essiential Thrombocytosis
major risk factor for thrombosis?
what are the 2 major adverse affect?
**Major risk-** smoking
2 makor adverse affect:
1. thrombosis
2. bleeding
## Footnote
also erythromelaglia
135
What we must do in order to establish a diagnosis of ET?
**Rule out Reactive Thrombocytosis**
* Iron def.
* Hemmorage/ Hemolysis
* Infection
* Cancer
which means we also need to take Acute phase reactent
136
When we decide to treat ET?
and what is the Tx?
Based on the symptoms and not the PLT number
1. Aspirin- CVA/TIA/ Ertyhromelalgia
2. Anagrelide, PEG-INF-alpha , hysroxyurea- lower PLT count
3. vWF disease (PLT > 1M)- Hexacapron as necessery and avoid aspirin
137
What is the main factor to consider to detrmine prognosis and therapy selection in MDS?
**Karyotype**
138
Bad and Good prognosis factors in MDS
1, **negetive-** lots of blasts, genetic mutation on chromosome 7 (not q5/q20)
2. **positvie-** q5del (related to thrombocytosis) good respond to lenalidomide
139
AA amyloidosis is the most common seen in which reumatologic disease?
**RA-** 40 %
**FMF**
Demage to kidneys.
140
ATTR amyloidosis
which systems are mainly involve?
Heart-Restrictive cardiomyopathy (most senstive by MRI)
peripheral nerves
| Diastolic HF
141
Which amyloidosis is seen in dialysis pt?
| and what are the 2 main clinical features
beta-2 microglobulin (is not removed in dialysis)
**main features:**
Carpal tunnel syndrome
pain in shoulders (also joints)
142
Which Anti-coagulation factor is related to Raccoon eye phenomenon in amyloidosis?
**Factor X**- פגיעה פבעילות שלו, אכימוזות בעיקר סביב העיניים
143
Macroglossia is pathognemonic for which type of Amyloidosis?
**Light chain**
144
Which kidney involvment is seen in amyloidosis?
Nephrotic syndrome with hypoalbuminemia
145
How we Dgx Amyloidosis (systemic)?
1. Abdomial fat pad biopsy >> if negetive we will biopse from damage organ
2. Congo red
## Footnote
if ATTR suspect >> DPD מיפוי
146
Restrictive cardiomyopathy due to amyloidosis is C/I to use which kind of Heart drugs?
CCB, BB, digoxin
147
Which organ is most prone to Damage in AL amyloidosys?
| and 2nd most common
1. Kidneys- 70% of pt
2. heart- **number 1 reason of death**
148
Tx for AL amyloidosis?
**like Active MM**
1. Lenalidomine- rq aspirin or Anti-coagulation
2. Brotezonib- proteosome inhibitor
3. Dexa/ prednisone
4. DaratuMuMab- anti-CD 38
**Maintanance:**
1 medication from above at low dose
149
Which translocation define CML?
| and whats the survival rates for 10 years?
t(9:22) philadelphia chromosome
BCR-ABL - tyrosine kinase
| 86% survive in 10 years
150
What is the Tx for CML?
TKI - Imatinib
BM transplent- only for those who resistance to TKI
Interferon- only for pregnant women
| אימת הטירוזין קינאז
## Footnote
Tinib suffix for TKI
151
How can we rule out Leukomoid reaction vs CML
**LAP score**
Low- CML
High- Luekomoid reaction
## Footnote
LAP- leukocyte alakaline phosphetase- CML is low
152
Whats the only different between SLL to CLL?
number of lympocytes.
SLL < 5K
CLL > 5K
153
how to Dgx and Tx CLL?
**Dgx:**
* **Smudge cells**- blood smear
* Flow Cytometry- CD5 , CD20
* monoclonal B cells > 5000
**Tx**
most of the time only followup
154
Which 2 menefistation are affect in CLL staging to ctage III/IV?
Lymphadenpathy / Heptosplenomegaly / cytopenia secondary to BM involvment
| Autommune phenomenas does not effect staging
155
What are the main complications of CLL
Pure red cell aplasia (also in tymoma)
BM insuff. - reticulocytopenia < 1%
infectios- leading cause of death
warm AIHA (IgG), ITP - RTX, Steroids, IVIG
**Transformation to DLBCL**- RCHOP or EPOCH-R
## Footnote
הטיפול הוא סימפטומתי בסיבוכים עצמם וגם נוכחות סיבוכים לא בהכרח מחייבת טיפול
156
Which medication (only if decided) is the Tx of choice in CLL?
BCL2 inhibitors with or w/o RTX:
1. **Ibrtinib**- B for BCL and tinib for TKinhibtor. a lot of side effect with risk of bleeding, HTN, Afib
2. **Acalabrutinib-** same with less side effect
3. **Venetoclax-** BCL2 inhibitor = more apoptosis
157
Which symptomatic Tx can help in CLL with Hypogamaglubalinemia + reccurent severe infections
**IVIG**
158
What is the test of choice in order to classift the lymphoma type?
**Excisional biopsy**
| FNA cannot diagnose lymphoma
159
Which test should always be done prior to Tx with antracyclins?
* Echocardiograpy- asses LVEF
* fertility
160
How we stage Lymphoma
By the involvment of LN:
Stage 1- only 1 site involve
Stage 2- 2 or more sites in same side
stage 3- sites from both sides of diapragm
stage 4- extranodular sites involvment
161
Which type of NHL is the most common?
and whats the Tx?
DLBCL
Tx:
1st line- R-CHOP (RTX, Cyclophospamid, Doxorubicin, vincristin, presnisone) ~ 60% curable.
## Footnote
if CHF - no antracyclins
162
Which medication from the R-CHOP is the only one to show increase in survival rates in DLBCL
RTX
163
When we will consider Allogenic BM tansplantation in DLBCL?
A disease which refacrtory to all lines:
1. R-CHOP
2. ICE protocol (rescue protocol) + autologous Transplent
3. CART-T
4. Bi-specific Ab
164
Whice type of indolent lymphoma is the most common?
**Follicular lymphoma**
| B- cell
## Footnote
uncurable , survival 15-20 yrs
165
Which translocation is seen in 85% of follicular lymphoma?
t(14:18)
BCL2- anti apoptosis protein
## Footnote
b2- microglobulin- a prognostic marker in indolent lymphoma
166
when we will decide to treat follicular lymphoma
| and what is the Tx?
עומס מחלה משמעותי - עם מחלה סימפטומתית / פגיעה באברי מטרה
**R&B- Bndamustin & RTX**
| like DLBCL- always use RTX (improve survival rate)
## Footnote
Also Tx for Waldarstom macroglubelinemia
167
# folliuclar lymphoma to DLBCL
What is the year rate for transformation?
how many pt will tranform?
how we Dgx?
year rate- 3%
pt will trnasform- 40%
dgx- LN biopsy
168
A pt with follicular lymphoma present with lymphadenopathy, night sweat, wight loss and increase LDH
we should suspect?
and how we treat?
**DLBCL**
tx:
not seen antracyclin >> R-CHOP
seen antracyclin >> rescue (ICE) + autologus BM transplant
169
**Burkkit lymphoma**
virus associated?
histological apperance
translocation?
Tx?
**EBV**
Starry skies
t(8:14)
Tx- EPOCH-R (same as all aggresive lymphomas)
| 70-80% curable
170
What is the characteristics of the lymphadenopathy in **hodgkin lymphoma**
* mainly in upper part of the body
* below diaphargm in older pt
171
Which electrolyte disbalance is common in hodgkin and what type of rush
hyperclacemia
arythema nodosum
172
most stong predictble prognosis factor in hodgkin?
**Staging = PET-CT**
* favourable- less LN involve, normal ESR,
* unfavorable- all the other
* early disease- unilateral (one side of dihaprgm)
* late disease- lateral
173
What is the Tx in hodgkin lymphoma
**standart protocol- ABVD + radiotherapy**
troughout the tx we do some more PET-CT scans and then deciding about the therapy.
**Brentuxomab-** anti-CD30 Ab (the B in ABVD)
| brentu like brend new RTX
174
Which 2 types of lung cancers are most related to smoking
SCC + SCLC
175
# lung cancer
Which type of tumors are mainly a peripharal finding and which are central?
peripharal- ACA, LCC (can be both)
Central- SCC, SCLC
176
which 3 main paran-neoplastic syndroms can be seen wth SCLC?
**the 3 A's**
* **ACTH-** excess cortisol >> cushing >> hyperglycemia
* **ADH-** SIADH , hyponathremia (confusion)
* **Anti-bodies- **anti pre-synaptic C-channel >> no Ach is realse = lambert eaton (like Mystenia gravis),
177
Which para-neoplastic syndrome is related to SCC?
**PTHrP **
hypercalcemia = Bones, Stones, Groans and psychatric tones
178
Which test will be made for confirmation of lung cancer (in any type)
Sampling of the tissue
179
What are the main reasons for False negetive for metastatic disease in SCLC under PET-CT
1.DM
2.nodules < 8 mm
3.slow growing tumors (AdenoCarcinoma, Broncoalve.Ca)
180
What are the main reasons for False positive for metastatic disease in SCLC under PET-CT
1. infections
2. granulomatotic disease
181
What is the imgaing reccomndation for SCLC?
* PET-CT
* Brain MRI
182
Tx for Non-SCLC
**Surgery**
* in every stage if the biology allow it- add biologic therapy, options:
* **E**GFR inhibitor - **E**rlotinib
* ALK inhibitors- Crizotinib (לאלק הירוק יש קריזות)
183
Non- SCLC
when the tumor is operatable and when it is not?
**Operatble tumor:**
* solitary tumor that allow imputation
* with or w/o involve **LN only if inside ipsilateral chest to the tumor**
**not operatable**
* involve critical structures in the chest- large vessels, voice cord, phrenic nerve, < 2 cm from carina
* Stage III- chemo (platimum) + radiotherapy >> immunotherapy with Durvalmab
* Stage IV- base on the pt (Chemo/ radio/biology/immuno)
184
What is the prefferd Tx in SCLC?
Chemo (platinum) + radiation - combination
185
# new noudle in CT
what is the approch in high risk cancer lung tumor?
removing the lesion with VATS (frozen section) >> if malignant >> lobectomy
## Footnote
high risk pt- smoker, > 60, large noudles > 1.5 cm, border are not smooth
186
What is the approch for mild risk for lung cancer in a new nodule found on CT?
**continue work-up**
1. PET if nodule >=1 cm
2. **Contrast CT**
3. peripheral nodule- FNA
4. air bronchous sign positive (direct bronchous to the lesion) - Bronchoscopia
## Footnote
if low risk < 10% for cancer>>High reso CT after- 3,6,9,12,18,24 (like baby clothes)
187
what is histocytes?
Connective tissue macrophage
188
What are the congenital disease with risk for **venous thrombosis (only)**
1. homozygous for Factor V lieden
2. pro-thrombin mutation / loss of prothrombin
3. def. in protein C + S
