About PNH
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolysis, thrombosis, and bone marrow failure
PNH is a rare, acquired clonal disorder of hematopoietic stem cells caused by a somatic mutation in the PIG-A gene, leading to the production of red blood cells with absent or decreased expression of GPI-anchored proteins, including CD55 and CD591-3
In the absence of CD55 and CD59, RBCs become susceptible to complement mediated-hemolysis2
Hemolysis can be intravascular or extravascular. IVH occurs inside the blood vessels, while EVH occurs in the liver and spleen2
IVH occurs when PNH RBCs are destroyed by the membrane attack complex (MAC) in the terminal complement pathway2,4
EVH occurs when C3 fragments get deposited on PNH RBCs, tagging them for removal and destruction by macrophages in the liver or spleen in the proximal pathway of the complement system2,4
Patients with PNH can struggle with the effects of uncontrolled or poorly controlled hemolysis
A cross-sectional US survey of adults with self-reported diagnoses of PNH (N=122) evaluated the relationship between exposure to terminal complement inhibitors (eculizumab: n=35; ravulizumab: n=87) and clinical parameters, PNH symptoms, quality-of-life outcomes, and FACIT-Fatigue scores. Most patients (96.7%; eculizumab: n=35; ravulizumab: n=83) were on a C5i for ≥3 months.2
History of aplastic anemia was reported in 33.6% (41/122) of patients
Other comorbidities, such as myelodysplastic syndrome and other bone marrow disorders, were reported by <6% (n=7/122) of patients
Potential study limitations include:
The sample size for this survey is small, given PNH is a rare disease
The survey could be subject to selection bias, where dissatisfied patients are more motivated to participate
Subjectivity of patient-reported outcomes
PNH can have a substantial impact on patients' day-to-day experiences
For undiagnosed patients, your diagnosis of PNH can make a difference
PNH is a rare, acquired clonal disorder characterized by hemolysis, thrombosis, and bone marrow failure (BMF).1,9
The estimated global prevalence of PNH is 10 to 20 cases per million1
PNH can affect both males and females equally, with a median age of 36 years at disease onset1,10
Those living with PNH can struggle with the effects of uncontrolled or poorly controlled hemolysis1
Patients with PNH face IVH and may develop EVH.
IVH occurs inside the blood vessels when PNH RBCs are destroyed by the membrane attack complex (MAC) in the terminal complement pathway4,11,12
EVH occurs in the liver and spleen, and it can emerge in a proportion of patients treated with terminal complement inhibitors due to unchecked C3 opsonization2,4,11,13-17,*
*Based on preliminary studies in patients treated with eculizumab suggesting terminal complement inhibition induces C3 fragment deposition on PNH RBCs. The C3 fragments trigger destruction of the RBCs by macrophages, making EVH a potential consequence of terminal complement inhibition. Additional studies are needed to further understand the impact of terminal complement inhibition on EVH.2,4,11,13-17
Variable clinical presentation of PNH may contribute to diagnostic delays9,18
Patients living with undiagnosed PNH may face RBC transfusions, thrombosis, and other major vascular events.10,18
Your diagnosis is essential because similar symptoms can require vastly different treatments9,20,21
PNH symptoms often overlap with those of aplastic anemia (AA) and myelodysplastic syndrome (MDS), as these diseases can be associated with each other
PNH is not mutually exclusive to BMF disorders
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Could there be patients in your practice with undiagnosed PNH? Learn more from the Diagnostic Tool.