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1/
@HawraAllawati (senior resident) here! Current fellow/MGH res alum @the_tjroberts & I found ourselves checking off an infamous task at 2 AM
[x]swing special slide
This inspired the following
! Follow along & we guarantee that you will have a BLAST 
! #MedTwitter
![1/ @HawraAllawati (senior resident) here! Current fellow/MGH res alum @the_tjroberts & I found ourselves checking off an infamous task at 2 AM[x]swing special slideThis inspired the following ! Follow along & we guarantee that you will have a BLAST ! #MedTwitter](https://pbs.twimg.com/media/EdDVyFKXkAEM5Vn.jpg "1/ @HawraAllawati (senior resident) here! Current fellow/MGH res alum @the_tjroberts & I found ourselves checking off an infamous task at 2 AM[x]swing special slideThis inspired the following ! Follow along & we guarantee that you will have a BLAST ! #MedTwitter")
@HawraAllawati (senior resident) here! Current fellow/MGH res alum @the_tjroberts & I found ourselves checking off an infamous task at 2 AM
[x]swing special slide
This inspired the following
! Follow along & we guarantee that you will have a BLAST ! #MedTwitter
2/
63 M presents w CC of SOB x3 weeks. ROS: easy bruising.
T 39.0, BP130/80, O2 99% on 2L NC.
WBC 23K (2% neutrophils, 60% blasts), Hgb 8, plt 20. K 4, Cr 1.2, INR 1.7, D-dimer >1K, fibrinogen 112.
You pause and astutely start worrying about... acute leukemia!
What now?!
63 M presents w CC of SOB x3 weeks. ROS: easy bruising.
T 39.0, BP130/80, O2 99% on 2L NC.
WBC 23K (2% neutrophils, 60% blasts), Hgb 8, plt 20. K 4, Cr 1.2, INR 1.7, D-dimer >1K, fibrinogen 112.
You pause and astutely start worrying about... acute leukemia!
What now?!
3/
1)take a deep breath!
2)never worry alone! This IS something to
your friendly onc fellow for (yes, even at 2 AM)! While you wait for a callback, you:
3)Look for & treat dangerous complications of acute leukemia:
Bleeding/DIC
TLS
Febrile Neutropenia
Leukostasis
1)take a deep breath!
2)never worry alone! This IS something to
your friendly onc fellow for (yes, even at 2 AM)! While you wait for a callback, you:3)Look for & treat dangerous complications of acute leukemia:
Bleeding/DICTLSFebrile Neutropenia Leukostasis
4/
You checked for complications, stabilized the pt & sent flow cytometry.
Now off to the lab!
There you see:
Many blasts (large nucleus, immature chromatin, scant cytoplasm)
Few promyelocytes (light blue cytoplasm & magenta-staining granules)
You checked for complications, stabilized the pt & sent flow cytometry.
Now off to the lab!There you see:
Many blasts (large nucleus, immature chromatin, scant cytoplasm) Few promyelocytes (light blue cytoplasm & magenta-staining granules)
5/
What do you -with the help of an onc fellow- do FIRST?
Flow= flow cytometry
ATRA= All trans-retinoic acid
BM= Bone marrow
What do you -with the help of an onc fellow- do FIRST?
Flow= flow cytometry
ATRA= All trans-retinoic acid
BM= Bone marrow
6/
Before we answer, let's review your suspected Dx, APL!
Epi: 8% of adult AML cases. Median age 47
can present w pancytopenia & associated sx (fatigue, SOB, bleed/bruise). Leukocytosis (like in this case) is a marker of high-risk disease https://www.ncbi.nlm.nih.gov/books/NBK459352/
Before we answer, let's review your suspected Dx, APL!
Epi: 8% of adult AML cases. Median age 47can present w pancytopenia & associated sx (fatigue, SOB, bleed/bruise). Leukocytosis (like in this case) is a marker of high-risk disease https://www.ncbi.nlm.nih.gov/books/NBK459352/
7/
Dx: t(15,17) translocation (that results in fusion of PML-RAR gene). You don't need 20% blasts if that's present
Pathophys: PML-RARA fusion protein blocks differentiation
cells are stuck in the promyelocyte stage
Dx: t(15,17) translocation (that results in fusion of PML-RAR gene). You don't need 20% blasts if that's presentPathophys: PML-RARA fusion protein blocks differentiation
cells are stuck in the promyelocyte stage
8/
Prognosis: w/o tx, short term survival is very poor! Median survival is <1 mo.
A major cause of this is hemorrhage! Up to 40% can have a fatal head bleed
That's why coagulopathy & APL = medical emergency!
But why are pts with APL so prone to bleeding?
Prognosis: w/o tx, short term survival is very poor! Median survival is <1 mo. A major cause of this is hemorrhage! Up to 40% can have a fatal head bleedThat's why coagulopathy & APL = medical emergency! But why are pts with APL so prone to bleeding?
9/
Simplified into 2 main mechanisms:
DIC
(unlike in sepsis there are higher levels of Protein C&S in APL hence
bleeding)
Hyperfibrinolysis
Annexin II (expressed on blasts) plasmin by tPA dependent mechanism 
fibrinolysis.
More on this: https://pubmed.ncbi.nlm.nih.gov/29703489/
Simplified into 2 main mechanisms:
DIC (unlike in sepsis there are higher levels of Protein C&S in APL hence
bleeding)HyperfibrinolysisAnnexin II (expressed on blasts)
plasmin by tPA dependent mechanism fibrinolysis.More on this: https://pubmed.ncbi.nlm.nih.gov/29703489/
10/
Therefore w acute leukemia (& esp if APL is suspected):
Do a neuro exam (head bleed in APL)
Check Plt, D-dimer, fibrinogen, INR & have a low transfusion threshold: Fibrinogen >150, plt >30-50,INR <1.5
ATRA as soon as you *SUSPECT* APL (don't need confirmed dx)
Therefore w acute leukemia (& esp if APL is suspected):
Do a neuro exam (head bleed in APL) Check Plt, D-dimer, fibrinogen, INR & have a low transfusion threshold: Fibrinogen >150, plt >30-50,INR <1.5ATRA as soon as you *SUSPECT* APL (don't need confirmed dx)
11/
ATRA promotes the terminal differentiation of malignant immature promyelocytes to mature neutrophils!
Despite high early mortality, with treatment, remission rates can be >90% !!
Back to the case:
You treated the pt w ATRA, transfused & later confirmed the dx of APL!
ATRA promotes the terminal differentiation of malignant immature promyelocytes to mature neutrophils! Despite high early mortality, with treatment, remission rates can be >90% !!Back to the case:
You treated the pt w ATRA, transfused & later confirmed the dx of APL!
12/
Take home points:
Acute leukemia? Look for DIC/bleeding, TLS, febrile neutropenia, leukostasis
Pts. with APL have high short term mortality & high risk of bleeding. Make sure you check coags & do a neuro exam
Start ATRA if you suspect APL!
Take home points:
Acute leukemia? Look for DIC/bleeding, TLS, febrile neutropenia, leukostasisPts. with APL have high short term mortality & high risk of bleeding. Make sure you check coags & do a neuro examStart ATRA if you suspect APL!
13/ Thank you for following along this #tweetorial Feedback is welcome!
*case details were changed to protect pt privacy*
S/o to chief @ArielleMedford for reviewing this with me!
*case details were changed to protect pt privacy*
S/o to chief @ArielleMedford for reviewing this with me!
