Symptoms and Causes of Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease that develops when your blood cells are formed. It can lead to the abnormal destruction of blood cells, resulting in a wide range of symptoms.

People who have PNH can have either a few symptoms that come and go or severe symptoms that can have fatal complications.

This article will provide an overview of the symptoms that you can expect with PNH, as well as why the condition develops.

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Frequent Symptoms

Paroxysmal nocturnal hemoglobinuria (PNH) occurs when there is a problem with your stem cells, which are created in your bone marrow. The rare disorder causes your blood cells to develop incorrectly and malfunction. This dysfunction can lead to complications, including:

  • Hemolytic anemia (red blood cells are destroyed faster than they are made)
  • Intravascular hemolysis (blood cells burst)
  • Thrombosis (blood clots block veins and arteries)
  • Infections
  • Bone marrow failure (not making enough blood components)

These problems can affect the entire body, so the symptoms of PNH can vary.

Your blood cells do a lot of important work in your body, like carrying oxygen to your tissues, clotting blood, and fighting infections. PNH symptoms are the noticeable effects that occur when these blood cells are not working properly.

Some of the most common symptoms that people with PNH will experience include:

  • Anemia (lack of healthy red blood cells to carry oxygen to body tissues)
  • Fatigue
  • Weakness
  • Pale skin
  • Shortness of breath
  • Increased heart rate
  • Chest pain
  • Difficulty swallowing
  • Abdominal pain
  • Dark-colored urine, especially in the morning
  • Bruising
  • Tiny red spots on the skin (petechiae)
  • Difficulty controlling bleeding even from small wounds
  • Headache
  • Flu-like or cold symptoms

Hemoglobinuria

Hemoglobinuria is when hemoglobin is abnormally present in your urine. About 50% of people with PNH develop hemoglobinuria as a symptom of the condition.

Rare Symptoms

Most people with PNH experience mild symptoms that may continue for years, with periods of flare-ups (worsening of symptoms) and remission (relief of symptoms). In some cases, more severe symptoms can develop suddenly and cause life-threatening complications.

Rare or advanced symptoms of PNH include:

  • Blood clots
  • Kidney disease or failure
  • Jaundice (yellowing of the skin and whites of the eyes)
  • Sharp abdominal pain
  • Bloating
  • Confusion
  • Low blood cell counts (pancytopenia)
  • Low white cell counts (leukopenia)
  • Pregnancy complications
  • Erectile dysfunction

Common Causes

PNH is caused by a genetic mutation. Unlike other conditions that are caused by genetic mutations, PNH is not inherited. The gene mutation is acquired during your lifetime. It affects only 1 or 2 people per million.

Who Gets PNH?

One or 2 people per million will develop PNH. The condition affects men and women equally, and it usually develops between the ages of 35 and 40.

Some people may experience mild symptoms of PNH for decades. The mortality rates with PNH are typically 35% at 5 years and 50% at 10 years.

The gene mutation that causes PNH occurs in several steps. First, a mutation develops in the phosphatidylinositol glycan class A (PIGA) gene, which helps create proteins that protect blood cells from early destruction.

The mutation develops as blood cells are formed in bone marrow, but its effects do not become obvious until the cells begin to malfunction later.

It's not known what triggers the cells to stop working properly, but attacks on the immune system, illness, and stress, have all been linked to the appearance of PNH symptoms.

Roughly one-third of people with the condition were previously diagnosed with aplastic anemia—a condition in which the body does not produce enough new blood cells. However, it's not clear if the association is linked to aplastic anemia or to a combination of aplastic anemia and its treatment with medications that suppress the immune system.

Risk Factors

There are no known risk factors for PNH other than having aplastic anemia. The risk factors for aplastic anemia have not been directly linked to PNH, but they include:

Complications

In most cases, the complications of PNH are related to its symptoms. Anemias and other forms of low blood counts can lead to serious health consequences. For example, hemolytic anemias and blood clots can be fatal.

There are also other conditions that are associated with PNN that can increase your risk of complications, including:

  • Myelodysplastic syndrome (a group of diseases of the bone marrow)
  • Acquired aplastic anemia (when the body stops making certain types of blood cells)
  • Bone marrow failure (when the body no longer produces enough blood cells to meet its needs)
  • Leukemia (a type of cancer of the blood)
  • Budd-Chiari syndrome (when a blockage or narrowing occurs in the veins that supply the liver and blood builds up, causing the liver to get bigger)

When to Seek Medical Attention

The treatment for PNH depends on the severity of your symptoms. In the beginning, you may only feel occasional weakness and fatigue that you may think are due to other causes. However, as PNH becomes more severe, you will begin to notice signs and symptoms that will likely prompt you to seek medical care.

Schedule an appointment with your doctor if you have weakness or fatigue that does not go away with rest or that persists for a long time. You should also call your doctor for symptoms like:

  • Dark-colored urine (especially when you wake up in the morning)
  • Chronic flu-like symptoms
  • Recurring abdominal pain
  • Difficulty swallowing

Some symptoms of PNH come on suddenly instead of gradually building over time. These can be a sign of severe PNH or complications like blood clots. You should call 911 or see emergency care if you experience symptoms such as:

Summary

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition that develops when there is a problem with how your blood cells are formed. The condition can lead to low blood counts, fatigue and weakness, blood clots, and other serious complications.

The disorder is not inherited, and there is not much that you can do to prevent PNH. If you have signs or symptoms of PNH, it's important to tell your doctor. While PNH can be fatal within a decade if left untreated, many people do well if they get the right treatment.

A Word From Verywell

Paroxysmal nocturnal hemoglobinuria (PNH) can have different symptoms, some of which can be mistaken for other conditions. Common symptoms include weakness, fatigue, and bruising or bleeding.

PNH symptoms can be shared by a lot of other conditions, but early diagnosis and accurate treatment can help you avoid possibly fatal complications.

Frequently Asked Questions

  • What causes paroxysmal nocturnal hemoglobinuria?

    Paroxysmal nocturnal hemoglobinuria is caused by a genetic mutation that affects how blood cells are formed in bone marrow.

  • Is paroxysmal nocturnal hemoglobinuria inherited?

    No. PNH is an acquired genetic mutation, not an inherited one. There are other forms of anemia that can be inherited, but PHN is not one of them.

  • Is bloody urine a symptom of PNH?

    If hemoglobin is in the urine, it can make it appear reddish in color—but it does not mean that the urine is bloody. Also, not everyone with PNH has discolored urine as a symptom. Weakness and fatigue are more common.

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6 Sources
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