PNH (Paroxysmal Nocturnal Hemoglobinuria) Diagnosis: Challenges and Advances

Introduction:

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare blood disorder that occurs when the immune system attacks and damages the red blood cells and platelets. In this disorder, red, brown, or dark urine is noticed during late-night or early-morning trips to the bathroom. If not treated timely paroxysmal nocturnal hemoglobinuria (PNH) can result in hemolytic anemia, kidney disease, or thrombosis. Doctors treat it with certain medications that help prevent blood cell damage.

What Is Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare type of blood disorder that occurs when the immune system attacks and damages the red blood cells and platelets. In this disorder, red, brown, or dark urine is noticed late at night or early morning while going to the bathroom. “Paroxysmal” refers to sudden; “nocturnal” refers to night; and “hemoglobinuria” refers to urine stained with blood. The urine becomes dark since the immune system breaks down red blood cells. This is known as hemolysis. Dark-colored urine is only one of many PHN symptoms that might signal potentially serious illnesses. If left untreated, PNH may cause hemolytic anemia, chronic kidney disease, or thrombosis (blood clots in the blood vessels). Healthcare providers treat PNH with medication that prevents blood cell damage.

What Causes Paroxysmal Nocturnal Hemoglobinuria (PNH)?

PNH occurs when a genetic flaw affects the functioning of red blood cells and platelets. The flaw launches a series of events that create critical and potentially life-threatening medical issues. The series starts in the bone marrow, where the body forms stem cells that gradually become mature red blood cells, white blood cells, and platelets. In PNH, the PIGA gene in one stem cell undergoes mutation or changes into an abnormal stem cell. This cell divides and forms additional abnormal stem cells that turn into red blood cells and platelets.

What Are the Challenges Faced In Diagnosing Paroxysmal Nocturnal Hemoglobinuria?

The symptoms of PNH are different amongst different individuals, and most affected people do not show all the associated symptoms. Patients with PNH are more prone to develop blood clots, which are potentially life-threatening and might be repeatedly seen. Also, there might be a certain degree of underlying bone marrow dysfunction. Because of the multifactorial symptoms of PNH, the diagnosis often becomes lengthy and complex. Timely diagnosis is an essential factor for the treatment and prognosis of paroxysmal nocturnal hemoglobinuria. Certain high-risk patients should undergo screening tests for paroxysmal nocturnal hemoglobinuria. These high-risk patients include:

• Patients with unexplained hemolysis.

• Coombs-negative hemolytic anemia.

• Hemoglobinuria or hemosiderinuria.

• Hemolysis with renal dysfunction.

Patients with unexplained thrombosis and evidence of hemolysis without reasonable cause.

Venous and arterial thrombosis in unusual sites (eg, intra-abdominal veins, cerebral veins, dermal veins) or with cytopenia.

• Nonresponsive to anticoagulants.

• Young age patients.

Patients with unexplained clinical symptoms:

• Dyspnea.

• Abdominal pain, headache, low back pain.

• Dysphagia.

• Erectile dysfunction.

• Weight loss.

What Are the Advances in PNH (Paroxysmal Nocturnal Hemoglobinuria) Diagnosis?

Doctors use various tests to diagnose paroxysmal nocturnal hemoglobinuria. They might use a flow cytometry test to evaluate the blood cells based on those test results. When combined with other monoclonal antibodies in multicolor flow cytometry, the fluorescent aerolysin offered an improved assay for diagnosing and monitoring PNH clones. It is very important to diagnose this rare entity with higher suspicion. Some of these tests that might be used are:

1. Complete Blood Count with Differential: Doctors check for signs of blood issues like anemia, thrombocytopenia, and anemia.

2. Basic metabolic panel (BMP): Doctors check for the signs of chronic kidney disease and renal dysfunction.

3. Urinalysis: Urinalysis might reveal the signs of hemoglobinuria (blood in urine) and hemosiderosis (too much iron deposits).

4. Reticulocyte count: A reticulocyte count evaluates the number of immature red blood cells (reticulocytes) in the bone marrow. Doctors measure the reticulocytes to determine if the bone marrow produces sufficient healthy red blood cells.

5. Haptoglobin test: Haptoglobin is a protein that eradicates the debris formed by damaged red blood cells. Low haptoglobin levels might be a sign of damaged red blood cells.

6. Lactate dehydrogenase (LDH): LDH is an enzyme in red blood cells. A high LDH level might indicate increased red blood cell distortion.

7. Liver function: This test checks for the bilirubin levels that might elevate when red blood cells break down.

What Are the Treatment Options for PNH (Paroxysmal Nocturnal Hemoglobinuria)?

The treatment of PMH becomes challenging as the symptoms vary greatly. Doctors might prescribe one or more of the treatment options described below to manage symptoms and complications of PNH.:

Complement Inhibitors

The Food and Drug Administration (FDA) has approved multiple medications to treat PNH:

• Eculizumab (Soliris) was approved in 2007.

• Ravulizumab (Ultomiris) was approved in 2018.

• Pegcetacoplan (Empaveli) was approved in 2021.

These medications are complement inhibitors that block the complement system from the breakdown of red blood cells. They do not cure PNH, but they might help alleviate its symptoms, lower the risk of complications, and improve the quality of life.

Medication to Prevent and Treat Blood Clots:

To prevent the formation of blood clots, doctors might prescribe anticoagulation therapy. This type of medication is also called a blood thinner. If the development or signs or symptoms of a blood clot are present, doctors might prescribe medication to help break it down. This is known as thrombolytic therapy. Various types of blood thinners and thrombolytic therapies are available. If doctors prescribe any of these medications, they will monitor the patient closely for potential side effects, including too much bleeding.

Immunosuppressants

If severe bone marrow failure is developed, the doctor might prescribe immunosuppressive medication to reduce the activity of the immune system.

Conclusion:

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare autoimmune blood disorder in which urine color becomes red, brown, or dark late at night or early morning. The diagnosis of PNH remains challenging due to its multifactorial symptoms and the resemblance to other disorders. However, correctly diagnosing PNH can significantly provide better outcomes and improve patients' lives along with their quality. Various advancements have been made to enable earlier diagnoses of PNH. Researchers are also working further to improve diagnostic methodologies for this rare disorder.