Paroxysmal Nocturnal Hemoglobinuria (PNH)
A rare acquired disorder that destroys red blood cells
Quick Facts
- Type: Rare acquired blood disorder
- Hallmark: Red blood cell breakdown (hemolysis)
- Classic sign: Dark urine, especially in the morning
- Serious risk: Blood clots (thrombosis)
Overview
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder in which red blood cells lack certain protective proteins on their surface. Without this protection, part of the immune system called the complement system attacks and destroys the red cells, a process known as hemolysis. The released hemoglobin can color the urine dark, classically noticed in the first morning urine, which gives the condition its name.
PNH is acquired during life rather than inherited. It arises from a change (mutation) in a gene called PIGA within blood-forming stem cells of the bone marrow. The disorder ranges from mild to serious and is closely linked with bone marrow failure conditions such as aplastic anemia. Modern treatments have greatly improved the outlook.
Symptoms
Symptoms vary widely depending on how much red cell destruction is occurring. Common features include:
- Dark or cola-colored urine, often most noticeable in the morning
- Fatigue, weakness, and shortness of breath from anemia
- Pale skin
- Abdominal pain or difficulty swallowing
- Episodes of feeling unwell that come and go
A particularly dangerous feature of PNH is an increased tendency to form blood clots, which can occur in unusual locations such as veins of the abdomen or brain. Sudden severe headache, leg swelling and pain, abdominal pain, or shortness of breath may signal a clot and require urgent medical attention.
Causes
PNH is caused by an acquired mutation in the PIGA gene in a bone marrow stem cell. This mutation prevents cells from anchoring certain protective proteins to their surface. As that abnormal stem cell multiplies, it produces blood cells vulnerable to attack by the complement system.
The disorder is not passed from parent to child and is not contagious. It often occurs alongside bone marrow failure, and some people develop PNH after, or together with, aplastic anemia.
Risk Factors
- A history of aplastic anemia or other bone marrow failure disorders
- Adulthood, as PNH most often appears in young to middle-aged adults
- There are no known lifestyle, dietary, or environmental causes
Because PNH is acquired and uncommon, most people have no family history and no identifiable risk factor before diagnosis.
Diagnosis
PNH is confirmed with a specialized blood test called flow cytometry, which detects red and white blood cells missing the protective surface proteins. Doctors may suspect PNH in someone with unexplained hemolytic anemia, dark urine, blood clots in unusual sites, or bone marrow failure.
Additional tests often include a complete blood count, markers of red cell breakdown (such as elevated LDH), and a bone marrow examination to assess for aplastic anemia or related conditions.
Treatment
Treatment is tailored to the severity of the disease. Options include:
- Complement-blocking medications: Targeted drugs that block the complement system can dramatically reduce red cell destruction, ease symptoms, lower transfusion needs, and reduce clotting risk.
- Supportive care: Blood transfusions for anemia, plus folic acid and sometimes iron supplements.
- Clot prevention and treatment: Blood thinners may be used to prevent or treat thrombosis.
- Bone marrow (stem cell) transplant: The only potential cure, generally reserved for severe disease or significant bone marrow failure because it carries substantial risks.
- Vaccination: People on complement-blocking therapy need vaccines against certain bacteria, especially meningococcus, because the treatment raises infection risk.
When to See a Doctor
See a doctor for unexplained fatigue, recurring dark urine, or signs of anemia. If PNH has been diagnosed, stay in regular contact with a hematologist (blood specialist).
Seek emergency care for symptoms that may indicate a blood clot, including sudden severe headache, sudden shortness of breath, chest pain, severe abdominal pain, or a swollen, painful leg. People on complement-blocking therapy should seek urgent care for fever, because it could signal a serious infection.
Frequently Asked Questions
Why is the urine dark in PNH?
When red blood cells break apart, they release hemoglobin into the blood, which is filtered into the urine and turns it dark or cola-colored. It is often most noticeable in the first morning urine because hemolysis can build up overnight.
Is PNH inherited?
No. PNH is acquired during life from a mutation in a bone marrow stem cell. It is not passed from parent to child and cannot be caught from another person.
What is the most dangerous complication of PNH?
Blood clots (thrombosis) are the most serious complication and can occur in unusual locations such as veins in the abdomen or brain. Sudden severe headache, abdominal pain, leg swelling, or shortness of breath are warning signs that need emergency care.
Can PNH be cured?
A bone marrow (stem cell) transplant is the only potential cure, but it carries significant risks and is usually reserved for severe cases. For most people, complement-blocking medications control the disease effectively.
Why do people on PNH treatment need vaccines?
Complement-blocking medications increase the risk of infection from certain bacteria, especially meningococcus. Vaccination before starting treatment helps protect against these serious infections.
References
- MedlinePlus, U.S. National Library of Medicine. Paroxysmal nocturnal hemoglobinuria.
- National Organization for Rare Disorders (NORD). Paroxysmal Nocturnal Hemoglobinuria.
- National Heart, Lung, and Blood Institute (NHLBI).
- Aplastic Anemia and MDS International Foundation.