Paroxysmal Nocturnal Hemoglobinuria: What It Is and How It Is Treated

Written by Medicover Team and Medically Reviewed by Dr Nilesh Wasekar , Hematologists

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1. Causes 2. Find a Doctor 3. Diagnosis 4. Treatment 5. FAQs

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired blood disorder characterized by the destruction of red blood cells, an increased risk of blood clots, and, in some patients, impaired bone marrow function. These problems can lead to anemia, fatigue, abdominal pain, dark urine, and other complications.

PNH develops when acquired changes in blood-forming stem cells cause red blood cells to become vulnerable to destruction by the immune system. Early diagnosis and appropriate treatment can reduce hemolysis, lower the risk of blood clots, and improve quality of life.

What are the Types of Paroxysmal Nocturnal Hemoglobinuria?

PNH can be described according to its main clinical features and its relationship with bone marrow disorders.

Classic PNH: Characterized mainly by complement-mediated destruction of red blood cells, leading to hemolysis and symptoms such as anemia and dark urine.
PNH with Bone Marrow Failure: PNH occurs alongside conditions such as aplastic anemia or myelodysplastic syndromes, which can reduce the production of blood cells.
Subclinical PNH: A small population of PNH blood cells may be detected during testing without significant symptoms or clinically important hemolysis.

What are the Symptoms of Paroxysmal Nocturnal Hemoglobinuria?

Symptoms of PNH vary depending on the degree of red blood cell destruction, blood clot formation, and bone marrow involvement.

Hemolysis and Hemoglobinuria

Destruction of red blood cells releases hemoglobin into the bloodstream. The kidneys can filter this hemoglobin into the urine, causing dark or reddish urine that may be more noticeable in the morning.

Anemia and Fatigue

Ongoing red blood cell destruction can cause anemia, resulting in fatigue, weakness, pale skin, dizziness, and shortness of breath.

Blood Clots

People with PNH have an increased risk of blood clots (thrombosis). Clots may develop in unusual locations, including the abdominal veins or blood vessels of the brain.

Abdominal Pain and Difficulty Swallowing

Abdominal pain may occur because of blood clots or smooth muscle spasms associated with hemolysis. Some people may also experience difficulty swallowing.

Bone Marrow Failure Symptoms

When PNH is associated with bone marrow failure, symptoms may include easy bruising, bleeding, recurrent infections, and low blood cell counts.

Other Symptoms

Headaches
Chest pain
Shortness of breath
Difficulty concentrating
Erectile dysfunction in some men

What are the Causes of Paroxysmal Nocturnal Hemoglobinuria?

PNH is caused by an acquired mutation in the PIGA gene in a blood-forming stem cell. Unlike many inherited genetic disorders, PNH is generally not passed from parents to children.

Genetic Mutation

The PIGA gene is involved in producing glycosylphosphatidylinositol (GPI) anchors, which attach certain protective proteins to the surface of blood cells. A mutation in this gene prevents affected cells from producing these anchors properly.

Complement-Mediated Hemolysis

Without protective GPI-anchored proteins such as CD55 and CD59, red blood cells become vulnerable to destruction by the complement system. This causes intravascular hemolysis, which is a major feature of PNH.

When to See a Doctor?

Consult a Haematologist if you develop persistent symptoms of anaemia, unexplained dark urine, or other unusual blood-related symptoms. Early evaluation can help identify PNH and prevent serious complications.

Persistent fatigue, weakness, dizziness, or pale skin
Dark or reddish urine, particularly in the morning
Shortness of breath, headaches, or unexplained abdominal pain
Easy bruising or unusual bleeding
Recurrent infections

Get medical help immediately if:

Severe chest pain or difficulty breathing
Sudden severe abdominal pain
Sudden weakness, confusion, severe headache, or other possible signs of a blood clot
Severe bleeding or rapidly worsening weakness

These symptoms may indicate serious complications of PNH, including thrombosis or severe anemia, and require urgent medical evaluation.

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How Is Paroxysmal Nocturnal Hemoglobinuria Diagnosed?

PNH is diagnosed using blood tests that identify the abnormal blood cells and assess the extent of hemolysis. Doctors may also evaluate bone marrow function and look for associated blood disorders.

Laboratory Tests

Flow cytometry: The primary test used to identify PNH cells by detecting the absence or reduced expression of GPI-anchored proteins on blood cells.
Complete blood count (CBC): Helps identify anemia and abnormalities in white blood cells or platelets.
Lactate dehydrogenase (LDH): Elevated levels can indicate active red blood cell destruction.
Haptoglobin: Low haptoglobin levels can support the presence of intravascular hemolysis.
Reticulocyte count and bilirubin: These tests help assess red blood cell production and destruction.
Urine tests: May detect hemoglobin released during hemolysis.

Bone Marrow Examination

A bone marrow examination may be recommended when blood counts are low or when doctors suspect an associated bone marrow disorder such as aplastic anemia or myelodysplastic syndrome.

What are the Treatment Options for Paroxysmal Nocturnal Hemoglobinuria?

Treatment for PNH depends on the severity of hemolysis, symptoms, blood clot risk, and whether bone marrow failure is present. The main goals are to control hemolysis, prevent complications, and support healthy blood cell production.

Complement Inhibitors

Medicines that block the complement system can reduce red blood cell destruction and the risk of PNH-related complications. Eculizumab and ravulizumab are examples of complement inhibitors used in appropriate patients.

Bone Marrow or Stem Cell Transplantation

Allogeneic stem cell transplantation can potentially cure PNH by replacing the affected blood-forming stem cells. Because transplantation carries significant risks, it is generally considered for selected patients, particularly those with severe bone marrow failure or other indications.

Supportive Care

Blood transfusions: May be required to manage severe or symptomatic anemia.
Anticoagulants: May be prescribed to prevent or treat blood clots when clinically indicated.
Iron supplementation: May be recommended when iron deficiency is confirmed.
Folic acid: May be used to support red blood cell production in patients with ongoing hemolysis.
Treatment of bone marrow failure: Additional therapies may be needed when PNH occurs with aplastic anemia or another bone marrow disorder.

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What are the Complications of Paroxysmal Nocturnal Hemoglobinuria?

PNH can cause serious complications if hemolysis and blood clot formation are not adequately controlled.

Thrombosis: Blood clots can occur in veins in unusual parts of the body and may become life-threatening.
Severe anemia: Ongoing red blood cell destruction can significantly reduce oxygen delivery to tissues.
Kidney problems: Repeated exposure to free hemoglobin can damage the kidneys over time.
Bone marrow failure: Some patients develop reduced production of red blood cells, white blood cells, and platelets.
Bleeding and infections: Low platelet and white blood cell counts associated with bone marrow failure can increase these risks.

PNH and Bone Marrow Failure

PNH can occur alongside bone marrow failure disorders, particularly aplastic anemia and myelodysplastic syndromes. Management may therefore require treatment of both PNH-related hemolysis and the underlying bone marrow disorder.

Aplastic Anemia

Aplastic anemia occurs when the bone marrow does not produce enough blood cells. Patients with PNH and aplastic anemia may require specialized hematology care and treatment directed at bone marrow failure.

Myelodysplastic Syndromes

Myelodysplastic syndromes can also coexist with PNH and cause abnormal blood cell production. Careful evaluation is required to determine the appropriate treatment strategy.

What Is the Long-Term Outlook for Paroxysmal Nocturnal Hemoglobinuria?

Advances in complement-inhibitor therapy have significantly improved outcomes for many people with PNH. Prognosis varies depending on disease severity, response to treatment, the presence of thrombosis, and associated bone marrow failure.

Regular follow-up with a hematologist is important to monitor blood counts, hemolysis, kidney function, treatment response, and potential complications. With appropriate management, many patients can achieve substantially better symptom control and quality of life.