PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A RARE BLOOD DISORDER

A rare and serious blood condition that affects the red blood cells is called Paroxysmal Nocturnal Hemoglobinuria (PNH). It is a form of hemolytic anemia in which the body breaks down red blood cells more quickly than they can be produced.^[1]The symptoms are the reason why it is called paroxysmal nocturnal hemoglobinuria:

• "Paroxysmal" refers to the sudden and recurring episodes of symptoms.
• "Nocturnal" indicates that these episodes often occur at night.
• "Hemoglobinuria" describes the presence of hemoglobin in the urine, which is a characteristic feature of PNH.

The prevalence of PNH is estimated to be around 1 to 16 cases per million individuals worldwide. PNH can affect anyone at any age, but middle-aged individuals and women are more commonly diagnosed.The exact prevalence may vary across different populations due to differences in genetic predisposition and diagnostic criteria. Cases appear highest in the US and Europe and lowest in Asia. Nonetheless, PNH remains a relatively rare condition.

In this blog, we will explore the causes, symptoms, and diagnosis of PNH, as well as take a look at some of the best treatment options and what to do if diagnosed with PNH when pregnant. Tips to manage and cope with PNH are also provided.

Paroxysmal Nocturnal Hemoglobinuria Symptoms

PNH symptoms can vary from person to person, and they may also change over time. Some people may experience mild symptoms, while others may have more severe symptoms. The most common symptoms of PNH include:

• Dark urine caused by the presence of hemoglobin from destroyed red blood cells
• Fatigue and weakness
• Shortness of breath
• Pale skin
• Headaches
• Difficulty swallowing (Dysphagia)
• Abdominal pain
• Blood clots
• Enlarged spleen
• Easy bruising and bleeding

A shortage of healthy red blood cells in the body as a result of the red blood cells being destroyed more quickly than they can be replenished, causes these symptoms.

The great impersonator. Paroxysmal Nocturnal Hemoglobinuria is sometimes referred to as the "great impersonator" because its symptoms can mimic those of other conditions, making it difficult to diagnose.^[2] It can be mistaken for other conditions such as anemia, kidney disease, or liver disease. Therefore, it is important for healthcare providers to consider PNH as a possible cause when evaluating patients with these symptoms. Improving prognosis for people with PNH requires early diagnosis and effective treatment.

PNH Complications

Complications of Paroxysmal Nocturnal Hemoglobinuria can occur due to the underlying immune system dysfunction and the destruction of red blood cells. Some of the complications associated with PNH include:

• Thrombosis: PNH increases the risk of blood clot formation (thrombosis) in veins and arteries. This may result in life-threatening side effects like stroke, pulmonary embolism, deep vein thrombosis, or heart attack.
• Kidney Problems: PNH can lead to kidney damage and dysfunction. Hemoglobin released during the breakdown of red blood cells can build up and harm the kidneys.
• Pulmonary Hypertension: Pulmonary hypertension, or elevated blood pressure in the arteries supplying the lungs, is a possible side effect of PNH. This may result in exhaustion, chest discomfort, and difficulty in breathing.
• Infections: PNH weakens the immune system, making individuals more susceptible to infections. Bacterial infections, particularly in the bloodstream, can be a serious complication of PNH.
• Bone Marrow Failure: PNH can lead to bone marrow failure due to constant destruction and turnover of red blood cells.

It is important for individuals with PNH to receive appropriate management and treatment to prevent and manage these complications. For those with PNH, routine medical monitoring and management can help improve outcomes and quality of life.

PNH Causes

Paroxysmal Nocturnal Hemoglobinuria is caused by a specific mutation that occurs in the PIG-A gene in bone marrow stem cells. The PIG-A gene plays a crucial role in the production of glycosylphosphatidylinositol (GPI)-anchored proteins.^[3]

These proteins anchor other proteins to the cell membrane of red blood cells. Some of these membrane proteins regulate the complement system of the immune system, which is responsible for identifying foreign antigens or allergens. When missing, the complement system does not recognize the blood cells, and the immune system proceeds to destroy them.

In those with PNH, stem cells carrying the mutation go on to form blood cells that are deficient or completely lack these proteins, leaving them susceptible to an immune attack.

PIG-A mutations may also impact platelets, raising the possibility of blood clots or thrombosis, yet more research is required to confirm whether this is the case or not.^[4]

When left untreated, hemoglobin, the main protein in red blood cells, begins to build up in the blood vessels and overwhelms the body's ability to clear it from the system. The body compensates by using nitric oxide to bind to excess hemoglobin, which can result in nitric oxide deficiency.

Nitric oxide is required for blood vessel dilation and immune function. This is why those with PNH can develop complications such as severe hypertension, thrombosis, and infections. It is also why they often have swallowing difficulties and abdominal pain. Hemoglobin and free iron can also deposit in other organs, such as the kidney, leading to scarring and damage.

Although extensive research has been conducted, the exact underlying cause of this genetic mutation in PNH still remains unclear. Most cases are not hereditary, meaning that they do not occur due to genetic defects that arise during fertilization. Instead, they appear spontaneously in red blood stem cells without any known external triggers. In rare instances, PNH can be inherited from a parent who already carries the mutated gene, yet this often results in embryonic abortion.

The severity of PNH symptoms can vary among individuals and may depend on the extent of deficiency or absence of GPI-anchored proteins.

How Is PNH Diagnosed?

PNH is a rare disorder, and its symptoms can be similar to other blood disorders, making it challenging to diagnose. However, there are specific tests that can help confirm a Paroxysmal Nocturnal Hemoglobinuria diagnosis.

A complete blood count (CBC), which measures the blood levels of platelets, red blood cells, and white blood cells is the initial step in diagnosing PNH. The CBC may reveal low amounts of platelets and red blood cells and high levels of white blood cells in patients with PNH.

The next step is a flow cytometry test^[5], which looks for the presence of a protein called CD55 on the surface of red blood cells. In people with PNH, this protein is deficient or absent, confirming a PNH diagnosis.

In some cases, a bone marrow biopsy may also be performed to confirm the diagnosis and determine the severity of the condition.

Paroxysmal Nocturnal Hemoglobinuria Treatment

There is currently no cure for PNH, but there are treatments available to manage the symptoms and improve the quality of life for people with this disorder. PNH treatment depends on the severity of the condition and the individual's specific symptoms.

Blood Transfusions

For people with severe anemia, blood transfusions may be necessary to replace the damaged red blood cells and improve symptoms such as fatigue and weakness.

Medications

Medications can be used to manage the symptoms of PNH and prevent complications. These may include:

• Blood thinners to prevent blood clots
• Iron supplements to treat anemia
• Immunosuppressants to reduce the destruction of red blood cells by the immune system
• Eculizumab^[6], a medication that blocks the immune system's attack on red blood cells

Bone Marrow Transplant

In severe cases of PNH, a bone marrow transplant may be recommended. This involves replacing the damaged bone marrow with healthy bone marrow from a donor. However, this procedure is risky and may not be suitable for everyone.

PNH Prognosis

The prognosis of Paroxysmal Nocturnal Hemoglobinuria can vary depending on the individual. Without treatment, the disease can be life-threatening, and patients are expected to live for 10-22 years on average. However, with proper management and treatment (especially with Eculizumab), the prognosis can be improved by as much as 75%, and patients are able to lead lives almost as long as someone unaffected.

Medications, lifestyle modifications, and routine monitoring can help manage symptoms and prevent complications. An improved prognosis can be achieved by taking the right measures to ensure an early diagnosis and suitable treatment. PNH patients now have a better outlook overall thanks to advancements in medical treatment.

Management of Paroxysmal Nocturnal Hemoglobinuria

Lifestyle modifications can assist in managing PNH and enhance general health in addition to medical treatment. These include:

• Eating a healthy, balanced diet to ensure adequate nutrition
• Staying hydrated to prevent blood clots
• Avoiding activities that may increase the risk of bleeding, such as contact sports
• Exercising on a regular basis to enhance general health and lower blood clot risk
• Quitting smoking to enhance general health and lower the chance of blood clots

Coping With PNH

Living with a rare blood disorder like PNH can be challenging, both physically and emotionally. It is essential to have a strong support system and to seek help when needed. Here are some tips for coping with PNH:

• Educate yourself about the disorder and its treatment options
• Connect with others who have PNH through support groups or online communities
• Seek counseling or therapy to manage the emotional impact of living with a chronic illness
• Prioritize your physical and emotional well-being and practice self-care.
• Ask questions about your treatment plan and engage in open communication with your healthcare team.

Managing Pregnancy With PNH

PNH can pose unique challenges for pregnant women. Careful management of pregnancy is necessary for women with PNH in order to protect the mother's and the baby's health and safety.

Hormonal changes and altered blood flow during pregnancy may make blood clots more likely. Women with PNH may be at higher risk of complications such as thrombosis and hemolysis during pregnancy. Therefore, it is important for pregnant women with PNH to work closely with their healthcare team to develop a comprehensive management plan.^[7]

Some key considerations for managing PNH during pregnancy include:

• Regular monitoring: Regular blood tests and check-ups are essential to monitor the levels of hemoglobin and other blood parameters. This helps to detect any changes or complications early on.
• Close monitoring of the baby: Regular ultrasound scans may be performed to monitor the growth and development of the baby. The healthcare team will also assess the baby's blood cell counts to ensure their well-being.^[8]
• Medication adjustments: The use of medication to manage PNH during pregnancy should be carefully evaluated by the healthcare team. Some medications used to treat PNH may not be safe during pregnancy, so adjustments may be necessary.
• Thromboprophylaxis: Anticoagulants may be prescribed to expectant PNH patients in order to lower their risk of blood clots. The type and duration of thromboprophylaxis will depend on the individual's specific case and should be discussed with the healthcare team.

Pregnant women diagnosed with PNH must have open communication with their healthcare team and adhere to their advice for the management of the condition during pregnancy. By taking the necessary precautions, women with PNH can have successful pregnancies while prioritizing their health and the health of their babies.

Conclusion

Paroxysmal nocturnal hemoglobinuria is a rare blood disorder that can significantly affect a person's life. However, with proper management and treatment, it is possible to live a fulfilling life with PNH. If you experience any symptoms, it is essential to seek medical attention and get a proper diagnosis. With early detection and treatment, the symptoms of PNH can be managed, and the risk of complications can be reduced.

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