PNH Symptoms
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The symptoms of the rare, acquired blood disease paroxysmal nocturnal hemoglobinuria (PNH) are paroxysmal, meaning they usually occur in sudden attacks. These PNH attacks may be triggered by factors that put stress on the body, such as infections or physical exertion.
PNH is characterized by abnormal blood cells, and particularly by the early death of red blood cells. This leads to PNH symptoms such as:
- blood in the urine
- low blood cell counts
- fatigue
- shortness of breath
- bone marrow problems
- blood clotting problems
- trouble swallowing
- abdominal pain
- erectile dysfunction.
Blood in the urine
Typically, blood in the urine is the main sign of PNH.
PNH is caused by the breakdown of red blood cells, which are responsible for transporting oxygen through the bloodstream. When red blood cells break — a process referred to as hemolysis — they release their contents into the blood. This includes large quantities of hemoglobin, the iron-rich protein that is responsible for giving blood its red, rusty color.
Excessive amounts of hemoglobin in the bloodstream can get filtered through the kidneys and end up in the urine. As a result, urine can exhibit a darker or blood-like color. This change in color is usually most prominent in the morning, as urine becomes more concentrated overnight while a person sleeps.
Difference between hemoglobinuria and hematuria
Hemoglobinuria refers to high levels of the protein hemoglobin in urine. This is what commonly occurs in PNH. By contrast, hematuria refers to red blood cells being detected in urine.
Because red blood cells are basically tiny sacks full of hemoglobin, hemoglobinuria and hematuria can both cause a similar discoloration in urine, and it is not possible to tell them apart with the naked eye. Differentiating between the two typically involves laboratory testing to check for the presence of red blood cells.
There also are medications, dietary changes, and other health conditions that can affect the color of urine. It is generally recommended that people who notice unexplained changes in the coloration of their urine should consult with a medical professional.
Low blood cell counts and bone marrow problems
Anemia, referring to low numbers of red blood cells, is another characteristic sign of PNH. Anemia can cause symptoms such as:
- fatigue
- shortness of breath
- weakness
- pale or yellowish skin
- headaches
- dizziness or lightheadedness
- irregular heartbeats or increased heart rate.
PNH also can cause the breakdown of white blood cells, which normally are responsible for protecting the body against infectious invaders. As a result of low white blood cell counts, people with PNH may be more prone to develop infections.
In PNH, mutations in the PIGA gene impair the function of hemopoietic stem cells, which reside in the bone marrow. Bone marrow-related health problems are common in PNH patients, and can include:
- aplastic anemia, where not enough new blood cells are being made, which occurs in about 40% of cases of PNH
- myelodysplastic syndrome, a type of cancer caused by abnormal blood-forming cells in the bone marrow that lead to low numbers of certain types of blood cells; these cancers are estimated to occur in 2% to 6% of PNH patients.
Clotting problems
As many as 40% of people with PNH experience thrombosis, or abnormal clots that form in the body’s blood vessels, interfering with blood flow.
Thrombosis is the main cause of significant morbidity and the most common cause of death among people with PNH. However, the prognosis for PNH has improved in recent decades — with modern treatment, life expectancy in PNH is close to that for the general population.
In people with PNH, thrombosis most commonly affects large veins in the abdomen, which can result in symptoms such as abdominal pain, swelling, and jaundice (yellowed skin due to liver dysfunction). Clots in brain blood vessels also are common, which may result in symptoms like headache, blurred vision, fainting, and seizures.
Clotting problems are reportedly more common among PNH patients in the U.S. and Europe — occurring in 30% to 40% of cases — compared with Asia, where rates are estimated to be less than 10%. In the U.S., rates of thrombosis in PNH vary by ethnicity: the condition affects about 73% of Black people with PNH, 50% of Latin American patients, and 36% of white or Asian patients. The reasons for these variations are poorly understood.
Less commonly than thrombosis, some people with PNH will experience impaired clotting, which can lead to excessive bleeding or hemorrhages.
Trouble swallowing, abdominal pain, and erectile dysfunction
When blood cells are destroyed in PNH, the body’s cleanup response is activated, but it quickly becomes overburdened. This results in free hemoglobin in the vascular system, and in the depletion of a signaling molecule called nitric oxide, or NO.
Nitric oxide plays many important roles in the body. Among them, it is important for controlling the activity of the smooth muscles that line the digestive tract and help to push food down the esophagus and through the intestines. In people with PNH, low levels of nitric oxide can lead to involuntary contractions of these muscles. This can result in symptoms such as:
- difficulty swallowing (dysphagia)
- spasms in throat muscles
- abdominal pain.
NO also is important for prompting blood vessels to relax and widen, a process know as vasodilation. Low levels of this signaling molecule can result in erectile dysfunction in people with PNH because vessels in the penis are unable to fill with blood.
Other symptoms
PNH also can result in other symptoms, to include severe tiredness, persistent fatigue, shortness of breath, kidney problems, difficulty swallowing, and stomach pains.
The kidneys, which are responsible for filtering out waste from the blood, can become overburdened and damaged in PNH patients. It is estimated that people with the disorder are at six times greater risk of developing chronic kidney disease compared with the general population.
People with PNH also may experience abnormally high blood pressure in the lungs, known as pulmonary hypertension, or right heart dysfunction, though these are not considered common.
Menorrhagia — an abnormal amount of blood loss during menstruation — can occur in people with PNH.
PNH also may increase the risk of complications during pregnancy. Rates of miscarriage and preterm birth are generally higher among PNH patients compared with the general population.
Who does PNH affect?
PNH is rare, estimated to affect fewer than 16 of every 1 million people worldwide. It can develop anytime between childhood and the latter decades of life, but most people are first affected by the disease between ages 30 and 40. PNH is slightly more common among women than men.
People with other underlying bone marrow disorders, such as aplastic anemia or myelodysplastic syndromes, seem to be at increased risk of developing PNH.
PNH News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about PNH symptoms
People with paroxysmal nocturnal hemoglobinuria (PNH) commonly experience attacks when symptoms suddenly worsen, which can be brought on by stressors like infection and trauma. Outside of these attacks, symptoms tend to ease. Modern therapies can help to ease PNH symptoms. In very rare cases, the symptoms of the disease resolve on their own, a phenomenon known as spontaneous remission.
Symptoms of paroxysmal nocturnal hemoglobinuria (PNH) may get worse over time, as ongoing blood cell damage puts continual stress on bodily systems. However, there is a lot of variation in how PNH symptoms change over time, and some patients may have stable disease for years, especially with modern therapy. People with PNH also may experience attacks when symptoms suddenly worsen, which can occur in response to triggers like physical exertion, infections, or stress.
There is wide variation in the rate of progression for symptoms of paroxysmal nocturnal hemoglobinuria (PNH). Some people with the disease may have relatively mild symptoms that are stable for many years, whereas in others the disease can rapidly progress to cause life-threatening symptoms.
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by blood cells breaking apart. Common symptoms include reddish or brown urine, low blood cell counts, fatigue and weakness, shortness of breath, difficulty swallowing, abdominal pain, and blood clotting problems.
Paroxysmal nocturnal hemoglobinuria (PNH) can develop anytime between early childhood and later in life, but symptoms of the disease most commonly appear between ages of 30 and 40.
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