Receiving a diagnosis of a rare disease can be confusing, especially when you learn that minor details about the disease can have a significant impact on your experience and care. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder that affects your red blood cells. Each year, only about 400 to 500 people in the United States are diagnosed with PNH.

There are three main types of PNH — classic (hemolytic) PNH, subclinical PNH, and PNH with a primary bone marrow disorder.

In this article, we’ll cover the three types of PNH to help you understand their similarities and differences so you feel more confident managing this chronic condition.

1. Classic (Hemolytic) PNH

People with classic PNH often have signs of hemolysis, a process where red blood cells are broken down. Once broken down, red blood cells release hemoglobin (a protein in red blood cells that helps carry oxygen). However, they don’t have signs of any other bone marrow disease like aplastic anemia or myelodysplastic syndrome.

How Is Classic PNH Diagnosed?

It can be difficult to diagnose PNH because it’s a rare disease. Also, it may look like other conditions, and symptoms can vary from person to person. The gold standard test for diagnosing PNH is flow cytometry, which looks at the surface of your red blood cells and granulocytes (a type of white blood cell) to check for changes. All types of PNH can typically be diagnosed using flow cytometry.

Other exams may help narrow down the type of PNH you or a loved one has. Your healthcare team may check you for clinical signs and symptoms of classic PNH.

Signs of classic PNH that your doctor may look for include:

• Increased reticulocyte counts — More immature red blood cells that compensate for the destruction of red blood cells
• High levels of lactate dehydrogenase (LDH) — An enzyme or special type of protein that may increase with the breakdown of red blood cells
• Low levels of haptoglobin — A protein that helps clear away the debris from destroyed red blood cells
• Absence of signs of bone marrow disease, such as aplastic anemia

What Are the Symptoms of Classic PNH?

In general, symptoms of PNH can vary and overlap. Many people with classic PNH have symptoms like:

• Fatigue (extreme tiredness that doesn’t go away with rest)
• Dyspnea (shortness of breath)
• Episodic hemoglobinuria (occasional hemoglobin in the urine, causing dark-colored urine, especially noticeable in the morning)
• Thrombosis (blood clots)
• Pain
• Organ dysfunction — For example, renal insufficiency (kidneys aren’t working properly) or pulmonary hypertension (high blood pressure in the blood vessels of the lungs and the right side of the heart)

Classic PNH can cause a range of symptoms like fatigue, pain, and dark-colored urine.

People with classic PNH don’t have bone marrow disease, so their symptoms are more linked to hemolysis.

How Is Classic PNH Treated?

Classic PNH can be treated with complement inhibitor therapy, a type of medication that helps prevent your immune system from attacking your red blood cells and reduces hemolysis. New treatments can help improve quality of life, though some symptoms may continue.

2. Subclinical PNH

People with subclinical PNH don’t usually have any signs of hemolysis, but they have another condition that causes bone marrow dysfunction.

How Is Subclinical PNH Diagnosed?

Subclinical PNH can only be diagnosed using flow cytometry. In contrast to classic PNH, the size of the PNH clone (i.e., the number of abnormal cells) on flow cytometry is very small in subclinical PNH. Unlike other types of PNH, subclinical PNH isn’t likely to show signs in other tests, like a basic metabolic panel or complete blood count with differential.

What Are the Symptoms of Subclinical PNH?

Unlike other types of PNH, subclinical PNH doesn’t cause symptoms related to hemolysis. The main symptoms people with subclinical PNH may have are related to their bone marrow deficiency or failure. Such bone marrow conditions include aplastic anemia (AA) and myelodysplastic syndrome (MDS).

Unlike other types of PNH, subclinical PNH doesn’t cause symptoms related to hemolysis.

How Is Subclinical PNH Treated?

There are no specific treatment options for subclinical PNH, so your healthcare team may focus on treating your bone marrow disorder.

3. PNH With a Primary Bone Marrow Disorder

PNH with a primary bone marrow disorder is a type of PNH where there are signs of both hemolysis and a bone marrow disorder. Typically, the bone marrow disorders that occur are AA or MDS.

How Is PNH With a Primary Bone Marrow Disorder Diagnosed?

Diagnosis of PNH with a primary bone marrow disorder will depend on two factors:

• Signs of a bone marrow disorder, like AA or MDS
• PNH-related signs, like hemolysis

A diagnosis of PNH with a primary bone marrow disorder includes signs of both a bone marrow disorder and hemolysis.

Your doctor may order lab and blood tests similar to those used to diagnose classic PNH, including a flow cytometry test. However, the diagnosis of PNH with a primary bone marrow disorder is different from classic PNH. Unlike in classic PNH, your healthcare team will also look for signs of bone marrow disease, which often requires performing a bone marrow biopsy.

What Are the Symptoms of PNH With a Primary Bone Marrow Disorder?

The symptoms of PNH with a primary bone marrow disorder — and their severity — can vary from person to person. Those with PNH with a primary bone marrow disorder can experience both the symptoms of classic PNH and symptoms from their bone marrow disease, such as:

• Symptoms related to anemia (not enough red blood cells or hemoglobin)
• Thrombosis
• Pain
• Organ dysfunction
• Frequent infections, bruising, and bleeding

How Is PNH With a Primary Bone Marrow Disorder Treated?

Many people with PNH with a primary bone marrow disorder receive treatment focused on their bone marrow disease. Sometimes, treatment for PNH symptoms, like hemolysis or thrombosis, is needed.

How Is Classic PNH Different From Other Types of PNH?

Classic PNH is different from subclinical PNH in that classic PNH causes hemolysis and related symptoms, while subclinical PNH doesn’t show signs of hemolysis. Classic PNH is different from PNH with a primary bone marrow disorder in that it isn’t related to another bone marrow disorder like AA or MDS.

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