Allyson Pishko MD MSCE Assistant Professor November 13 2021 Disclosures Research funding Sanofi Genzyme Outline Paroxysmal Nocturnal Hemoglobinura PNH How Why Diagnosis Signssymptoms of PNH ID: 909766
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Slide1
Understanding PNH
The Aplastic Anemia and MDS International Foundation
Allyson Pishko, MD MSCEAssistant Professor
November 13, 2021
Slide2Disclosures
Research funding: Sanofi Genzyme
Slide3Outline
Paroxysmal Nocturnal Hemoglobinura (PNH)How? Why
?DiagnosisSigns/symptoms of PNH
Hemolytic Anemia
Thrombosis
Treatment for PNH
Slide4Paroxysmal Nocturnal Hemoglobinuria
Slide5Paroxysmal
Nocturnal Hemoglobinuria
Sudden
onset of Symptoms
Slide6Paroxysmal
Nocturnal Hemoglobinuria
Increase
in Symptoms at Night
Slide7Paroxysmal Nocturnal
Hemoglobinuria
Blood
in
the Urine
Slide8PNH – HOW?
Slide9PNH- How?
Red Blood Cells are the “oxygen carrying cells” in the body
Red Blood cells develop from stem cells in bone marrow
Average person makes 2-3 million blood cells per second!!
Blood
(2021) 137 (10):
1304–1309
Slide10PNH- How?
Red Blood Cells have markers on their surface that tell the immune system they are “
self
” aka “
do
not
attack!
”
Slide11PNH-How?
Complement is part of immune systems defense
Complement should deposit on bacteria to tag for “destruction”
CD55 and CD59 on the red cell prevents complement from binding
Slide12PNH-How?
PIGA mutation
A mutation in the stem cells in the bone marrow causes red cells from that stem cell to lose CD55/CD59
NO CD55/CD59
Slide13PNH-How?
Without CD55/59 the complement deposits on red cells
This causes them to “burst” or “lyse”
Slide14PNH – Diagnosis
Slide15PNH- Diagnosis
% of cells with loss of CD55/CD59
Tests are used to measure the % of cells that have lost CD55/CD59
Slide16PNH- Diagnosis?
Flow cytometry measures the “clone size” or % missing these “protective markers” on the surface
Slide17PNH – Why?
Slide18PNH- Why
?
“Acquired” (not inherited) mutation in PIGA in the stem cell
No clear risk factors for developing
Closely associated with an “immune condition” aplastic anemia
Sometimes clones found incidentally in otherwise well individual
Lots of questions remain!
Slide19PNH – Signs/Symptoms
Slide20PNH- Signs/Symptoms
Hemolysis
LDH
Haptoglobin
Slide21PNH-Signs and Symptoms
Smooth Muscle Contraction
Slide22PNH-Signs and Symptoms
Clotting
Slide23PNH-Signs and Symptoms
Fatigue
Abdominal Pain
Slide24PNH – Treatment
Slide25PNH- Treatment
Complement inhibitors
EculizumabRavulizumab
Slide26PNH- Treatment
Complement inhibitors
EculizumabRavulizumabPegcetacoplan
Slide27PNH- Treatment
Risk for infectionsVaccination for meningitis
Antibiotics
Slide28PNH- Other Treatments
Anticoagulation (blood thinners) for thrombosis
If bone marrow failure (ex. severe aplastic anemia), bone marrow transplant may be considered
Slide29References/Acknowledgements
Images created with Biorender.com
Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood. 2021;137(10):1304-1309. doi:10.1182/blood.2019003812“PNH: When blood machinery goes wrong”. Nature Video. Feb 2020
Slide30Thank
you!
Questions?
@
PishkoMD