Paroxysmal nocturnal hemoglobinuria

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 30, 2016
StartDiseasesParoxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (or PNH) is a rare but often devastating blood disorder. The disease is life-threatening and the many symptoms associated with the disorder can greatly affect the quality of life experienced by PNH patients. 

Contents

Definition & Facts

Paroxysmal nocturnal hemoglobinuria was named by the doctors who discovered it in the 19th century because they believed the occurrences of hemoglobinuria - the release of hemoglobin in the urine - to be intermittent or paroxysmal and to only occur at night. It has since been discovered that while the hemoglobinuria does occur intermittently and does tend to happen more often at night, it can occur at any time of the day.

PNH is an extremely rare disease; it affects somewhere between 0.5 and 2 people per million. While the disease seems to affect males and females more or less equally and has appeared in all races all around the world, it appears to be more prevalent in Southeast Asia and the Far East. Researchers are unsure as of yet why this is.

The survival rate of this condition is approximately 10 years. Family history does not play a role in this condition.

Symptoms & Complaints

Symptoms associated with paroxysmal nocturnal hemoglobinuria are many and varied. Patients typically suffer from chronic pain of the abdomen and back, along with frequent severe headaches. Extreme fatigue, debilitating weakness, and recurring infections are common in PNH patients.

The symptom most closely associated with PNH is the appearance of bright red blood cells in the urine, particularly in the morning. Research has discovered, however, that this indication only occurs in less than half of PNH patients. It is more common for the urine to be the color of dark tea. Typically, it is darker in the morning and clears up throughout the day.

The most serious of all PNH symptoms is thrombosis, or blood clotting. These blood clots typically appear in veins (which carry oxygen to the heart) more often than in arteries (which carry oxygen from the heart to the body). While they can occur anywhere in the body, the veins in the abdomen are more prone to blood clots. Patients who die as a result of PNH are most often killed by a blood clot. 

Causes

Paroxysmal nocturnal hemoglobinuria develops due to a deficiency in glycosyl-phosphatidylinositol anchor protein, which plays a role in protecting cells, clotting, and fighting infection. This protein is absent in the red blood cells, platelets, and white blood cells of those with this condition. Red blood cells break down in absence of this protein which can cause hemoglobin to enter the circulatory system.

Researchers have discovered that an acquired somatic mutation of the stem cell, PIGA gene, which affects the development of blood cells in the bone marrow is the cause of the defective anchors. The cause of the PIGA mutation is unknown, though it is acquired as opposed to inherited, and it is somatic, meaning it occurs after conception.

Diagnosis & Tests

Diagnosis of paroxysmal nocturnal hemoglobinuria begins with the patient describing their symptoms and medical history. Doctors who suspect PNH can order a range of blood tests to confirm their initial hypothesis. While the sucrose hemolysis, or sugar water test, and the Ham test are readily available, the results can report false negatives if the patient has received a recent blood transfusion.

The ideal blood test for diagnosing PNH is flow cytometry. In this test, the blood flows through a device called a flow cytometer, which counts the blood cells and determines their size and shape. This information provides the doctor with a more clear picture of what is happening with the blood cells. While the results of flow cytometry are not affected by recent blood transfusions, it is not commonly performed by labs and can be more difficult to procure. 

Treatment & Therapy

The treatment options of paroxysmal nocturnal hemoglobinuria are varied and depend on the severity of the symptoms exhibited by the individual patient. For patients who demonstrate mild symptoms, doctors prescribe folic acid and iron supplements in an effort to increase red blood cell production.

For those with more severe symptoms, prednisone can be used to try to slow down the rate of red blood cell destruction. It is important, however, that the physicians closely monitor patients while they are taking prednisone because of the side effects of the drug. It is usually recommended that patients who show no improvement after six weeks of taking the drug be taken off to prevent other problems.

For patients with potentially life-threatening acute thrombosis, physicians typically prescribe thrombolytic therapy. This is the administration of a group of powerful drugs known as lytics. These drugs have been nicknamed "clot busters" because of their ability to dissolve dangerous blood clots. Anticoagulants, aspirin, and ibuprofen can all also be used in the treatment of thrombosis. The FDA has also recently approved a new drug, eculizumab, for the treatment of thrombosis.

For patients with the most severe cases of PNH, an allogeneic bone marrow transplantation may be a viable option. In this procedure the patient's damaged bone marrow is destroyed by radiation or chemotherapy and replaced with the bone marrow of a genetically similar but not identical donor such as a brother or sister. Ideally, the new marrow will travel to the bones and begin producing healthy blood cells.

This treatment option is a dangerous one, though. There is a 15 to 20% chance of death for the patient receiving the transplant. Those chances go up if the donor is not a full sibling. Because of the associated risks, bone marrow transplants from non-related donors are only performed in the most severe cases and typically in very young patients. 

Prevention & Prophylaxis

Preventing paroxysmal nocturnal hemoglobinuria has proved to be difficult because researchers still know so little about what causes the PIGA mutation. Currently, the best course of action is to prevent as many symptoms as possible once the diagnosis has been confirmed. The hope is that the PNH patient's prognosis and quality of life can be improved if the disease is caught early and symptoms are proactively treated.