You may not get a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) right away. PNH has symptoms that can resemble other health conditions, which means your doctor may need to rule out other diseases before confirming a diagnosis of PNH. This process is known as a differential diagnosis, and it may require multiple tests over time.

Read on to learn more about which health conditions doctors may need to rule out before diagnosing PNH and recommending treatment options.

PNH Symptoms and Diagnosis

PNH is a rare disease in which the immune system attacks red blood cells and breaks them apart, a process known as hemolysis. Hemolysis results in anemia (a low red blood cell count).

PNH is one of several diseases that can lead to bone marrow failure, in which the bone marrow doesn’t produce enough blood cells. Bone marrow failure develops when the immune system mistakenly attacks bone marrow cells. In the United States, around 400 to 500 cases of PNH are diagnosed each year.

PNH is one of several diseases that can lead to bone marrow failure, when the bone marrow doesn’t produce enough blood cells.

PNH can cause a wide range of symptoms, some of which can resemble symptoms of other diseases. Many of these symptoms are directly related to anemia. Symptoms of PNH can include:

• Fatigue
• Pallor (paleness)
• Back and stomach pain
• Throat spasms and difficulty swallowing
• Shortness of breath
• Problems with erections
• Kidney disease
• Blood clots
• Dark-colored urine, especially in the morning
• Abdominal pain

Tests Used To Diagnose PNH

The main test used to diagnose PNH is flow cytometry, a laboratory test that can identify abnormal red cells in PNH. Diagnosis of PNH can also involve blood tests to measure:

• Blood cells (complete blood cell count)
• Hemoglobin, a protein that carries oxygen
• Reticulocytes, or immature red blood cells
• Haptoglobin, a protein released by damaged red blood cells
• Bilirubin, a substance released from the breakdown of hemoglobin
• Lactate dehydrogenase (LDH), an enzyme released by damaged red blood cells

If your doctor suspects bone marrow failure, they may order a bone marrow biopsy, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans to learn more.

Other tests may be necessary for a differential diagnosis of another disease.

Conditions Similar to PNH

Here are some similar health conditions your doctor might need to rule out during a differential diagnosis.

1. Aplastic Anemia

Aplastic anemia is an autoimmune condition that’s closely related to PNH. Most researchers believe aplastic anemia is often a cause of bone marrow failure, which then leads to PNH. Many people have both aplastic anemia and PNH, so these conditions may be confirmed rather than ruled out during testing.

Many people have both aplastic anemia and PNH, which are closely related.

Symptoms of aplastic anemia are very similar to PNH. Blood tests and a bone marrow biopsy may be necessary in order to diagnose aplastic anemia.

2. Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a group of blood cancers in which the bone marrow produces damaged blood cells that don’t function properly. MDS can also cause bone marrow failure. Many symptoms of MDS can look like PNH.

People over 60 years old are most likely to develop myelodysplastic syndrome. Chemotherapy, radiation therapy, and exposure to some toxic chemicals also increase the risk of developing this disease. Blood tests, bone marrow biopsy, and genetic tests are used to diagnose MDS.

3. Autoimmune Hemolytic Anemia

Like PNH, autoimmune hemolytic anemia (AIHA) is a condition in which the immune system mistakenly attacks red blood cells. AIHA affects approximately 1 to 2 people out of 100,000. It most commonly affects females over 40, according to Cleveland Clinic, but it can occur in anyone. It can also be linked to other autoimmune conditions or be triggered by a viral infection.

AIHA causes symptoms of anemia that can resemble PNH. There are two types of AIHA — warm AIHA, which is more common, and cold AIHA, which occurs in cooler temperatures. Cold AIHA has some symptoms that distinguish it from warm AIHA and PNH, including:

• Cold hands and feet that may turn blue or discolored
• Pain in the back of the legs
• Heart murmur or heart failure

Like PNH, AIHA is an autoimmune condition that causes anemia. The two diseases cause many similar symptoms.

Some of the diagnostic tests for AIHA are also used for PNH. However, in people with AIHA, the immune system produces proteins called antibodies that attack red blood cells. These proteins can be identified using a Coombs test. A cold agglutinin titer test can determine if antibodies are produced in cold temperatures in order to diagnose cold AIHA.

4. Paroxysmal Cold Hemoglobinuria

Paroxysmal cold hemoglobinuria (PCH) is another type of AIHA that mostly affects children. Symptoms of anemia can be similar to those of PNH and AIHA. Some symptoms are more similar to cold AIHA, such as cold hands and feet that turn blue or grayish. Discolored or itchy skin can also occur in cold temperatures.

Doctors use the Donath-Landsteiner test to detect abnormalities present in PCH.

5. Primary Myelofibrosis

Primary myelofibrosis (MF) is another type of blood cancer called a myeloproliferative neoplasm (MPN). In people with primary MF, the bone marrow produces abnormal blood cells. These abnormal cells are fast-growing and cause scarring and inflammation in the bone marrow. Primary MF occurs mostly in people over the age of 60.

Many symptoms of primary MF can resemble PNH. An enlarged spleen, bone pain, joint pain, and gout are more distinctive symptoms of primary MF. Blood tests, imaging scans, and bone marrow biopsy are used to diagnose primary MF, as well as genetic testing of bone marrow cells.

6. Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is a rare disorder that causes blood clotting, damage to organs, and severe bleeding. DIC may be a serious complication of other conditions, such as cancer, liver disease, sepsis, and pancreatitis. It can also occur as a complication due to surgery, serious tissue injury, pregnancy, blood transfusion, or organ transplant.

Symptoms can appear similar to those of PNH. Blood clots are present in both PNH and DIC. In order to diagnose DIC, a partial thromboplastin time test and prothrombin time test can be used to measure how long it takes your blood to clot. A fibrinogen test and a d-dimer test can measure protein levels linked to blood clotting disorders.

Report All of Your Symptoms to Your Doctor

If you experience any new or changing symptoms, talk to your health care team. Diagnosing PNH as early as possible — along with any other condition you may have — can help ensure prompt, potentially life-saving treatment and improve your quality of life.

If you are in the process of getting diagnosed, attend all follow-up medical exams and tests. It’s important to be patient while your doctor works with you to accurately diagnose your condition.

Talk With Others Who Understand

On myPNHteam, people with paroxysmal nocturnal hemoglobinuria and their loved ones come together to ask questions, give advice, and share their stories with others who understand life with PNH.

Were you initially diagnosed with another condition before receiving a PNH diagnosis? Do you have any related conditions at the same time, like aplastic anemia? Share your experience in the comments below, or start a conversation by posting on your Activities page.