Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease affecting hematopoietic stem cells (HSCs), which are created in the bone marrow. These HSCs develop into different blood cells (red blood cells, white blood cells, and platelets), and when defective, they differentiate into defective blood cells.1 

Paroxysmal nocturnal hemoglobinuria is caused by an acquired mutation in the PIGA gene of the HSCs. The PIGA gene is located on the X chromosome and encodes a protein with a pivotal role in the production of glycosylphosphatidylinositol (GPI). GPI works as an anchor for membrane proteins, and therefore, mutations in the PIGA gene lead to red blood cells losing GPI-anchored proteins, such as CD59. The loss of proteins renders the blood cells susceptible to destruction by complement activation. PNH is consequently characterized by intravascular hemolysis and hemoglobinuria.2

Having a dedicated medical team can help improve medical care for patients with PNH. Organizations like the Aplastic Anemic and MDS International Foundation offer resources for patients with PNH, such as online tools that can guide a search for local specialists.3,4

The care provided to a patient with PNH can involve different specialists and may vary by PNH type and symptoms. A patient’s first clinical visit often aligns with their initial signs and symptoms. Besides primary care providers (PCPs), other care takers may include hematologists, neurologists, gastroenterologists, nephrologists, cardiologists, gynecologists, and pediatricians. Although PNH specifically involves hematology, it is a multisystemic disease, so its clinical management must take a multidisciplinary approach.5,6

Primary Care Providers

Primary care providers are medical professionals that see patients with new and ongoing health issues. These doctors can practice in general medicine, pediatrics, or other areas such as internal medicine. They help patients with their overall health status but also refer patients to different specialists to help coordinate their medical care.3

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A hematologist is a specialist in the diagnosis, treatment, and management of diseases that affect the blood and bone marrow.3 This specialist will help in the diagnosis and management of PNH, requesting blood tests and discussing different treatment options with the PCP, which may involve treatments to manage symptoms or bone marrow transplantation.5

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The underlying cause of the defective HSCs in PNH is a mutation in the PIGA gene.1 A geneticist can therefore be involved in the diagnosis, management, and counseling of patients with PNH, as these doctors are specialized in diseases caused by genetic changes. A genetic counselor can also discuss the patient’s family history, options available for genetic testing, and the results of those tests.3

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Other Specialists

Depending on the patient’s symptoms or the need for additional evaluations or treatments, other specialists may be involved in the care team of a patient with PNH. A patient’s needs may also change over the course of their disease.3 

Because patients with PNH can suffer from gastrointestinal, neurological, nephrological, and cardiovascular symptoms, the care of these specialists is often required. When working in a coordinated effort, a care team can help manage disease and limit the damage to affected tissues.

Pregnancy can result in an exacerbation of PNH with breakthrough hemolysis and thromboembolic events, leading to increased neonatal and maternal morbidity and mortality.7 A gynecologist and obstetrician should therefore be involved in the care team before, during and after a patient’s pregnancy.5 Pediatricians should also be involved and should coordinate care with the hematologist if children are affected.5

Social workers may be involved in the care team when patients need to reduce the financial cost of treatment.5 Psychological support may also be provided through mental health professionals to help patients cope with the emotional burden of a chronic, lifelong disease.8

Read more about PNH complications

Preparing for a Doctor’s Visit

It is not uncommon for patients to leave the doctor’s office with questions. Keeping track of all medical records and health information and documenting symptoms, previous consultations, and treatments can help patients prepare for their medical appointments.9 Writing down questions before an appointment and choosing priorities for the discussion order can also help patients make the most of their time spent in the doctor’s office.3

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1. Paroxysmal nocturnal hemoglobinuria. National Organization for Rare Disorders (NORD). Accessed November 24, 2022.

2. Braunstein EM. Paroxysmal nocturnal hemoglobinuria (PNH). MSD Manual Professional Version. Updated September 2022. Accessed November 24, 2022.

3. Paroxysmal nocturnal hemoglobinuria: diagnosis & treatment. Genetic and Rare Diseases Information Center (GARD). Updated November 8, 2021. Accessed November 24, 2022.

4. Find a specialist. The Aplastic Anemia and MDS International Foundation. Accessed November 24, 2022.

5. Shah N, Bhatt H. Paroxysmal nocturnal hemoglobinuria. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated August 1, 2022. Accessed November 24, 2022.

6. Sahin F, Ozkan MC, Mete NG, et al. Multidisciplinary clinical management of paroxysmal nocturnal hemoglobinuria. Am J Blood Res. 2015;5(1):1-9. 

7. Fassett MJ, Hernandez Lopez AL. Treatment of paroxysmal nocturnal hemoglobinuria in pregnancy with eculizumab: a case report. Case Rep Womens Health. 2021;30:e00294. doi:10.1016/j.crwh.2021.e00294

8. Emotional health. The Aplastic Anemia and MDS International Foundation. Accessed November 24, 2022.

9. Take control of your care. The Aplastic Anemia and MDS International Foundation. Accessed November 24, 2022.

Reviewed by Hasan Avcu, MD, on 11/23/2022.