Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and serious blood disorder characterized by the abnormal breakdown of red blood cells (hemolysis). This condition is caused by a genetic mutation in the PIG-A gene, which leads to the deficiency of certain proteins on the surface of blood cells, making them susceptible to destruction by the body’s immune system. Your immune system can mistakenly attack and break down red blood cells in your body because they lack specific protective proteins.

Paroxysmal nocturnal hemoglobinuria (PNH) is a condition that can affect individuals of any age. It’s not something you’re born with, but it can pose life-threatening risks. However, various treatments are available to improve symptoms and manage potential complications.

PNH manifests differently in each person. While some may experience only minor issues, others may face more severe symptoms. One of the significant risks associated with PNH is the occurrence of blood clots, which can affect up to 30% of individuals with this condition.

Causes of Paroxysmal Nocturnal Hemoglobinuria

PNH arises due to a genetic abnormality, but it isn’t inherited from parents nor can it be passed on to offspring.

A mutation in a specific gene leads to the production of abnormal red blood cells that lack the protective proteins, making them vulnerable to the immune system’s attacks. This process is known as “hemolysis.”

Some medical experts suggest a possible connection between PNH and weakened bone marrow. People with a certain form of anemia called aplastic anemia have a higher likelihood of developing PNH.

Conversely, individuals with PNH are at an increased risk of developing aplastic anemia, although not everyone with PNH will develop this condition. Aplastic anemia involves a decrease in the production of new blood cells by the bone marrow.

Prevalence

PNH is considered a rare disorder, with an estimated incidence of 1 to 1.5 cases per million individuals per year. However, its prevalence may be underestimated due to undiagnosed cases and the complexity of diagnosis.

Symptoms of Paroxysmal Nocturnal Hemoglobinuria

The name “paroxysmal nocturnal hemoglobinuria” stems from one of its distinctive signs: the presence of dark or bright red blood in urine during nighttime or morning hours. “Paroxysmal” denotes “sudden,” “nocturnal” refers to “at night,” and “hemoglobinuria” signifies “blood in the urine.” This occurrence is observed in up to half of individuals with PNH.

The symptoms of this condition are attributed to several factors:

1. Broken Red Blood Cells:
   • Fatigue and weakness
   • Headaches
   • Shortness of breath
   • Irregular heartbeat
   • Abdominal discomfort
   • Difficulty swallowing
   • Pale or yellowish skin
   • Easy bruising
   • Erectile dysfunction in men
2. Anemia (Too Few Red Blood Cells):
   • Tiredness and weakness
   • Headaches
   • Shortness of breath
   • Irregular heartbeat
   • Abdominal pain
   • Difficulty swallowing
   • Pale or yellowish skin
   • Easy bruising
   • Erectile dysfunction in men

The severity of symptoms can vary from person to person, usually correlating with the quantity of faulty blood cells present in the body.

Additionally, the symptoms of blood clots depend on their location:

Skin:

• Redness, pain, or swelling in the affected area

Arm or Leg:

• Soreness, warmth, and swelling in the limb

Stomach:

• Abdominal pain
• Ulcers and bleeding

Brain:

• Intense headache with or without vomiting
• Seizures
• Difficulty in movement, speech, or vision

Lungs:

• Difficulty breathing
• Sharp chest pain
• Coughing up blood
• Profuse sweating

Blood clots pose significant risks. If you suspect a blood clot, it’s crucial to contact your doctor promptly. In emergencies, such as experiencing difficulty breathing or movement, sudden headaches, chest pain, or seizures, dial 911 without delay.

Risk Factors

While PNH is primarily a genetic disorder, certain factors such as infections, inflammation, and pregnancy can exacerbate symptoms or trigger a worsening of the condition.

Diagnosis of Paroxysmal Nocturnal Hemoglobinuria

When you consult your doctor, they’ll inquire about your medical history and any noticeable symptoms. Additionally, they may ask you the following questions:

• Have you observed blood in your urine?
• What medications are you currently taking?
• Have you experienced any indications of blood clots?
• Have you encountered any stomach or digestive issues?
• Have you undergone testing for aplastic anemia or any bone marrow disorder?

Routine blood tests will be conducted, including a complete blood cell count to assess your blood cell levels. Furthermore, you’ll likely undergo additional examinations, such as flow cytometry. This test evaluates whether your red blood cells possess the necessary proteins for protection. Urine tests to identify hemoglobinuria, and bone marrow biopsy to assess the production of blood cells.

In cases where symptoms of a blood clot are present, further tests will be administered to detect their presence.

Treatment of Paroxysmal Nocturnal Hemoglobinuria

The primary objective of treating PNH is to alleviate symptoms and prevent complications. The treatment plan will be tailored based on the severity of your symptoms and the progression of the disease.

For individuals experiencing mild symptoms of anemia, treatment may involve:

• Folic acid supplements to support the bone marrow in producing more normal blood cells.
• Iron supplements to stimulate the production of red blood cells.
• Eculizumab (Soliris), a medication that inhibits the breakdown of red blood cells. This can enhance anemia, reduce or eliminate the need for blood transfusions, and lower the risk of blood clots. However, it may increase susceptibility to meningitis infection, necessitating vaccination against meningitis.
• Ravulizumab (Ultomiris), a drug similar to eculizumab but with a longer duration of action. Instead of biweekly infusions, patients typically require only six or seven infusions annually.
• Pegcetacoplan (Empaveli), a targeted therapy option for individuals new to treatment or transitioning from eculizumab or ravulizumab.

Other treatment modalities include:

• Blood transfusions to address anemia, which is the most common issue associated with PNH.
• Blood thinners to reduce the likelihood of blood clot formation.

Bone Marrow Stem Cell Transplant: This procedure stands as the sole curative option for PNH. It involves replacing the patient’s bone marrow stem cells with healthy ones obtained from a suitable donor, typically a sibling. Notably, these stem cells are not derived from embryos.

Bone marrow transplants are generally reserved for young individuals with severe PNH due to the associated health risks. If deemed suitable by your healthcare provider, it’s essential to discuss the potential risks and benefits before proceeding with this treatment option.

Clinical Trials: If standard treatments prove ineffective for your PNH, participating in a clinical trial might be a viable option. These trials explore novel treatment approaches before they are widely available. Before considering participation, consult with your doctor to understand the trial’s requirements and weigh the potential benefits and risks.

Home Care Tips

Maintaining good self-care practices is crucial for managing PNH and ensuring your overall well-being.

1. Follow a Healthy Diet: Consume a nutritious diet rich in iron and vitamin C, as vitamin C enhances iron absorption. Opt for combinations like iron-fortified cereal paired with strawberries or a spinach salad complemented with orange slices.

2. Stay Active: Regular exercise is essential, but tailor your workouts to your individual condition. Consult your doctor to determine the most suitable exercise regimen. If your red blood cell count is low, avoid activities that strain your heart, chest, or breathing.

3. Prioritize Protection: Minimize your risk of infections by practicing proper hygiene, such as frequent handwashing, and avoiding crowded places and sick individuals. Notify your doctor promptly if you experience a fever or unusual fatigue. Ensure your vaccinations are up to date.

4. Seek Support: Connect with others who understand your journey by joining a local or online PNH support group. Discuss options for support with your doctor.

5. Pregnancy Planning: If you’re considering pregnancy, consult your doctor beforehand, as PNH may pose risks for both you and your baby. Your healthcare team will closely monitor your health and the baby’s well-being throughout pregnancy if you decide to proceed.

6. Address Emotional Well-being: Acknowledge and address your emotional needs, as they are integral to your overall health. It’s normal to experience emotions like anger, sadness, or stress post-diagnosis. Consider speaking with a counselor for support, especially if these emotions begin to impact your daily life.

7. Utilize Support Networks: Engage with friends and family, keeping them informed about your condition and how they can assist you. Open communication ensures they can provide the support you need.

Prevention

Since PNH is a genetic disorder, it cannot be prevented. However, genetic counseling may be helpful for individuals with a family history of the condition to understand their risk and make informed decisions about family planning.

When to See a Doctor:

If you experience symptoms such as unexplained fatigue, dark urine, or abdominal pain, it is important to consult a healthcare professional for evaluation and diagnosis. Early detection and management of PNH can help prevent complications and improve outcomes.

Outlook/Prognosis

The prognosis for individuals with PNH varies depending on the severity of the condition and the presence of complications. With appropriate treatment and management, many people with PNH can lead productive lives, although long-term monitoring and support may be necessary.

Sources

• National Organization for Rare Disorders (NORD)
• American Society of Hematology (ASH)
• National Institutes of Health (NIH)
• European Society for Blood and Marrow Transplantation (EBMT)
• Academy of Nutrition and Dietetics: “Healthy Eating for Women.”
• Aplastic Anemia and MDS International Foundation
• Johns Hopkins Medicine