epidemiology & diagnosis
The median age of onset
35 - 40
the triad of symptoms that characterize PNH
hemolytic anemia, pancytopenia, thrombosis
explain why vasoconstriction may occur in this disease process
scavenging on NO by free Hb --> smooth muscle contraction
In addition to complement this system also destroys RBCs
Reticuloendothelial system (Mononuclear phagocytic system)
expected CBC findings
anemia, thrombocytopenia, and/or pancytopenia
usually ↑ reticulocytes
equal
Expected findings on general exam
pallor, fatigue, weakness
location of hematopoetic stem cells
bone marrow
The hemolysis in PNH is __
both intravascular and extravascular
*but mostly intravascular
expected hemolysis work up results
↓ haptoglobin, hemosiderinuria, hemoglobinuria
400 - 500
ROS/exam findings that may occur due to vasoconstriction
Headache, abdominal pain, dysphagia, erectile dysfunction
This usually protects RBCs against complement-mediated hemolysis
Glycosylphosphatidylinositol* (GPI) anchor
*a glycolipid that anchors cell-surface proteins on the plasma membrane of hematopoietic cells
Expected direct Coombs test results
negative
Define paroxysmal nocturnal hemoglobinuria using the meaning of each word
sudden/irregular episodes of hemoglobin in the urine that occur at night or early in the morning
*note that many people w/ PNH do not actually have dark colored urine
We would expect to see increased infection risk due to ___
pancytopenia
The two GPI anchor protiens affected in PNH
CD55/DAF (Decay-accelerating factor)
CD59/MIRL (Membrane inhibitor of reactive lysis)
Expected flow cytometry results
CD55/59 deficient RBCs
PNH is an __ mutation on the __ gene
acquired, PIGA
First line treatment for significant clinical manifestations
Anti-C5 antibody (e.g., eculizumab, ravulizumab)
*Patients w/out symptoms or w/ mild symptoms: watchful waiting