Paroxysmal nocturnal hemoglobinuria (PNH) definition and facts
- PNH is a rare, chronic disease that
causes rapid breakdown of red blood cells and can result in reddish or
cola-colored urine, often seen in the early morning after urination. PNH is due
to a spontaneous mutation in gene material.
- Signs and symptoms of paroxysmal nocturnal hemoglobinuria include one
or more the following:
- PNH is not inherited. It is genetic,
but is due to a spontaneous mutation that individuals do not pass on to their
- Diagnosis of paroxysmal nocturnal hemoglobinuria is sometimes difficult
since many symptoms are nonspecific but the patient's history, physical exam and
urine tests such as flow cytometry, light sensitivity tests, sugar water or
sucrose tests, and others demonstrate red blood cells break up easily. Radiologists can use MRI and/or ultrasound
to demonstrate blood clots that might compromise a person's blood flow with PNH.
- Although transplantation of stem cells
can treat people with paroxysmal nocturnal hemoglobinuria, such treatment is reserved for the most severe cases
because of transplant-associated high risk morbidity and mortality. However, the
drug Soliris (eculizumab) can increase the quality of life and lifespan of most
people with PNH.
- The prognosis for people with PNH that
is diagnosed and treated appropriately ranges from good to fair, depending upon
the individual's response to treatments. People who have PNH, but are not
treated for the disease, have a prognosis of
fair to poor due to a reduced lifespan.
What is paroxysmal nocturnal hemoglobinuria (PNH)?
Paroxysmal nocturnal hemoglobinuria or PNH is a rare and chronic disease that
results in an abnormal breakdown of red blood cells. PNH is due to a
spontaneous genetic mutation that causes red blood cells to be deficient in a
protein, leaving them fragile. Because the kidneys help to filter out waste
products from red cell breakdown, when urine is concentrated overnight as a
person with PNH sleeps, the morning urine may be reddish to a darker, cola color. This
led to term the problem as "nocturnal." One of the red blood cell products that
the kidneys metabolize into the urine is hemoglobin (hence, "hemoglobinuria").
Because urine discoloration occurs irregularly due to physiological changes, the
disease was thought to occur irregularly and so was termed "paroxysmal."
What Causes a Genetic Disease?
A genetic disease is any disease that is caused by an abnormality in a
person's entire genetic makeup (genome). The abnormality can range from minuscule to major -- from a discrete mutation in
a person's DNA or a gross chromosome abnormality. Some genetic disorders are inherited from the parents, while other genetic diseases are
not. There are a number of different types of genetic inheritance, such as a
- single gene inheritance (for example, cystic fibrosis and Marfan
- multifactorial inheritance (for example, breast cancer, heart disease,
diabetes, and arthritis),
- chromosome abnormalities (for example, Down and Turner syndromse), and
- mitochondrial inheritance (for example, MELAS, a form of dementia).
What are the signs and symptoms of paroxysmal nocturnal hemoglobinuria (PNH)?
People with PNH usually complain of feeling weak and noticing a change in the
coloration of the urine when they urinate in the morning. Consequently, signs
and symptoms of PNH are:
What is the prevalence of paroxysmal nocturnal hemoglobinuria (PNH)?
The prevalence or occurrence of PNH is very uncommon and there are very few
statistics about this disease. However, experts estimate that the disease occurs
about 5 to 10 times less frequently than
aplastic anemia (also an uncommon
disease). PNH can occur in males and females at any age. It is most frequently
found in adults with the median age of diagnosis being 45 years old.
How is paroxysmal nocturnal hemoglobinuria (PNH) inherited?
PNH is not inherited. It is due to a spontaneous genetic mutation that occurs
in the PIGA gene. The mutation makes stem cells that are deficient in a protein.
Mutated stem cells that are not malignant (cancerous) can still increase in numbers by
normal clonal expansion to produce red blood cells that are not normal. If the
mutated stem cells increase in numbers, then PNH symptoms can develop. There may
be other factors that are not well understood that encourage the proliferation
of the mutated stem cells. Experts suggest the factors causing bone marrow
failure may play a role in PNH development since there is a close association
between PNH cells and the development of aplastic anemia and myelodysplastic
syndrome. Because PNH is not inherited, individuals do not pass the spontaneously
mutated gene to their children.
Which specialties of health-care professionals treat paroxysmal nocturnal
Individuals that are diagnosed with PNH can be monitored by their primary care
physicians. However, specialists such as hematologists, internists, transfusion
specialists, immunologists, radiologists, and dietitians (to ensure adequate
vitamin and iron intake) are often consulted to help diagnose and care for the
patient with paroxysmal nocturnal hemoglobinuria.
How is paroxysmal nocturnal hemoglobinuria (PNH) diagnosed?
Because symptoms of PNH can mimic other common diseases, it can be somewhat
difficult to diagnose initially. However, health-care professionals may suspect PNH
from the patient's history and from screening exams such as white blood cell count that shows
anemia and discolored urine that is not infected.
Tests for PNH include
- flow cytometry,
- complement lysis sensitivity test,
- acidified serum lysis test with
the Ham test, and
- a sugar water or sucrose lysis test.
All of the specialized
tests show that the patients' red blood cells are abnormal and fragile.
In addition, other tests may suggest PNH because they can demonstrate
intravascular hemolysis (for example, an elevated reticulocyte count, elevated
serum lactate, low or absent serum haptoglobin, and others).
Radiologists can use MRI and/or ultrasound to demonstrate a blood clot
(thrombus) that may be compromising the blood flow in a person with PNH, for example, to
the liver or other organs.
These tests can help distinguish PNH from other problems such as typical and
atypical hemolytic - uremic syndromes and other kidney - related diseases that
cause blood or hemoglobin to be in the urine.
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What is the treatment for paroxysmal nocturnal hemoglobinuria (PNH)?
Although the ideal treatment for PNH is to replace mutated stem cells,
transplantation of stem cells is reserved for the most severe cases because of
difficulty of matching histocompatibility antigens from the donors to the
patient and because stem cell transplantation is associated with fairly high
morbidity and mortality. Fortunately, in 2007, the drug Soliris (eculizumab) was
approved by the US FDA to treat the hemolysis associated with PNH. Although the
drug doesn't treat the underlying cause (genetic), it can improve the quality of
life and lifespan of the person with the disease. However, experts recommend that
vaccinated against serogroup B Neisseria meningitidis before receiving the drug.
Some experts recommend giving prophylactic antibiotics daily.
Bone marrow hyperplasia that occurs with PNH can be treated with anti-thymocyte
globulin (ATG) while anemia can be treated with various types of transfusion
products. Corticosteroids have been used to reduce the effect of complement –
mediated red blood cell breakage.
Leading cause of death in patients with PNH is blood clotting
(thromboembolism). Some experts recommend that the patients that have had
previous thrombosis be placed on anticoagulation medications.
Treatment protocols are designed for each patient, patients are urged to
discuss their treatment protocols with their doctors and to keep all follow-up
appointments. Although extremely rare, a few patients may spontaneously resolve
PNH. But for most patients, treatments are needed for the rest of their lives.
What is the prognosis for a person with paroxysmal nocturnal hemoglobinuria
The prognosis or outcome for a person with PNH that is diagnosed and
treated, especially if treated with eculizumab, ranges from good to fair,
depending upon the person's response to treatments. Individuals with PNH that are untreated
have a prognosis of fair to poor due to a reduced lifespan (about 10 years after
diagnosis), frequently ended by a devastating thrombotic (blood clot) event.
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REFERENCE: Besa, E. C., MD. "Paroxysmal Nocturnal Hemoglobinuria Treatment & Management." Medscape. Updated Jun 29, 2016.