In clinical terms, paroxysmal nocturnal hemoglobinuria (PNH) is synonymous
with glycosylphosphatidylinositol (GPI) deﬁciency, and is an acquired
clonal disorder associated with somatic mutations of the X-linked PIGA
gene in hematopoietic stem cells. 5
PNH is a rare disease with an estimated annual incidence of 4 per million.
1 The condition is a progressive and debilitating hematopoietic stem cell
disorder characterized by chronic hemolysis. Periods of hemolysis could
be initiated by infection, surgery, whole blood transfusion, injection
of contrast dyes or even severe exercise. 2 Early identiﬁcation of PNH
in patients may contribute to improved long-term outcomes with this serious
disease; however, PNH can be a life threatening condition with 35 percent
of patients dying within 5 years of diagnosis.
Thrombosis is the leading cause of death in PNH. Pulmonary embolism and
deep vein thrombosis are among the most commonly reported thrombotic events.
4 The risk of these adverse events exist in PNH regardless of clone size,
lack of transfusion history, severity of anemia, anticoagulant therapy
or level of hemolysis. 6
The disease may undergo partial remissions and exacerbations. In over half
of patients, both the proportion of abnormal cells and the clinical severity
decrease with time. In approximately 3-5 percent of PNH patients, the
disease progresses to acute leukemia. 2
Several complement defense proteins are decreased or absent in PNH:
● DAF, CD55 (decay accelerating factor),
● MIRL, CD59 (membrane inhibitor of reactive lysis),
● C8-binding protein (homologous restriction factor).
Other proteins that are deﬁcient in PNH include:
● CD58 (leukocyte function antigen 3),
● CD14 (endotoxin-binding protein receptor),
● CD24, and CD16a (Fcγ receptor). 2
The pioneering use of the therapeutic monoclonal antibody eculizumab, which
binds to and prevents the activation of the complement protein C5, represents
a signiﬁcant advance in treatment for patients with PNH and is the standard
therapy for hemolytic PNH. The only curative procedure for PNH is bone
marrow transplantation although for the majority of patients the associated
risks are too great to justify transplantation.
The availability of a diagnostic ﬂow cytometry assay means that a deﬁnitive
diagnosis of PNH can be established rapidly in most cases, resulting in
improved patient management and prognosis. 3
1. Johnson RJ, Hillmen P: Paroxysmal nocturnal haemoglobinuria: Nature’s
gene therapy? Mol Pathol 2002; 55:145-152.
2. McPherson & Pincus: Henry’s Clinical Diagnosis and Management
by Laboratory Methods, 21st ed. Copyright©2006W. B. Saunders Company. p. 216.
3. Richards SJ, Barnett D. The role of ﬂow cytometry in the diagnosis
of paroxysmal nocturnal hemoglobinuria in the clinical laboratory. Clin
Lab Med. 2007 Sep;27(3):577-90, vii.
4. Hillmen P, et al. Eﬀect of the complement inhibitor eculizumab on thromboembolism
in patients with paroxysmal nocturnal hemoglobinuria. Blood, 2007;110:4123-4128.
5. Richards SJ. Recent advances in the diagnosis, monitoring, and management
of patients with paroxysmal nocturnal hemoglobinuria. Cytometry B Clin
Cytom 2007; 72(5): 291-8
6. Hill A, Richards SJ, Hillmen P. Recent developments in the understanding
and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol.
2007 May;137(3):181-92. Review.