Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a serious health condition that destroys the blood cells and can even turn fatal if not treated. Read on to find out about the causes, symptoms and treatment options of this blood disorder.

Paroxysmal Nocturnal Hemoglobinuria Definition

It is an acquired genetic blood disorder which is caused by certain genetic mutation and may turn life threatening if left untreated. It affects the red blood cells or erythrocytes, white blood cells or leukocytes and platelets or thrombocytes. PNH breaks apart red blood cells in a process which is referred to as “Hemolysis”. Sufferers pass blood with urine, mainly at night (Nocturnal Hemoglobinuria), due to the breaking down of the blood cells during an episode of the disease.

The gene mutation responsible for the disease is generally acquired in adulthood. It is not an inherited condition and is not passed down to the next generation by affected individuals.

Paroxysmal Nocturnal Hemoglobinuria Incidence

This is a very rare genetic disorder, occurring in only 1 to 2 out of one million individuals. The condition affects males and females alike. Twenty-five percent of the PNH cases in females are diagnosed during pregnancy which increases the death risk of both the mother and child significantly.

Paroxysmal Nocturnal Hemoglobinuria Types

The disease is divided into three categories depending on the context of its diagnosis:

Picture 1 – Paroxysmal Nocturnal Hemoglobinuria

  • Classic Paroxysmal Nocturnal Hemoglobinuria: Evidence of this condition in absence of some other bone marrow disorder.
  • PNH present in setting of another particular bone marrow disease.
  • Subclinical Paroxysmal Nocturnal Hemoglobinuria: PNH abnormalities present on a flow cytometry report without any sign of hemolysis.

Paroxysmal Nocturnal Hemoglobinuria Causes

The main reason behind the occurrence of PNH is the mutation in the single stem cell gene named PIG-A. The gene is located on the X-chromosome in one’s bone marrow. The exact reasons responsible for triggering this gene mutation are not known yet. According to some doctors, some people have weaker-than-normal bone marrow which leads to this genetic mutation. The risk factors for weakened bone marrow include aplastic anemia and some other bone marrow failure disorders. Sometimes, a mild but undiagnosed and untreated bone marrow disease can lead to bone marrow weakness.

Paroxysmal Nocturnal Hemoglobinuria Pathophysiology

The PIG-A gene is responsible for handling the codes for a protein named glycosyl-phosphatidylinositol (GPI) which helps around 30 important proteins in attaching to the cell surface. This protects the cells from various substances (complement) present in the blood. Mutations in the PIG-A gene hamper the production of GPI which makes it impossible for the proteins to connect to the surface of the cells in order to protect them. This leads to premature break down of the red blood cells, leaking hemoglobin into blood which passes with the urine. It can occur any time in a day, but occurs more commonly during night or early in the morning.

Paroxysmal Nocturnal Hemoglobinuria Signs and Symptoms

Many PNH patients remain asymptomatic for all or most of their lives. The condition can lead to a wide range of mild to severe symptoms. The symptoms occur depending on whether the patient is suffering from hemolysis, thrombosis or deficient hematopoiesis. These are the three main health problems caused by PNH. The symptoms associated with them are mentioned below:

Hemolysis or destruction of RBC

Hemoglobinuria or dark colored urine, due to the presence of hemoglobin in urine, is the main symptom. Patients may also develop hemolytic anemia which can lead to symptoms like shortness of breath, tiredness and palpitations.

Thrombosis or blood clots

The location of the blood clot determines the symptoms. A patient may suffer from jaundice, Hepatomegaly (enlarged liver) and renal failure if the blood clot occurs in a liver vein. A clot in the abdomen generally results in moderate to severe abdominal pain. Severe headache results from a blood clot in the head. If the clots occur in skin, it can lead to painful and raised red lumps or swelling over large skin areas. High levels of bilirubin in the body may result in the development of gallstones. Some patients may suffer from ischemic stroke due to blood clotting in a blood vessel.

Deficient hematopoiesis or low blood cell count

A deficiency in RBC causes anemia while low amounts of WBC makes the patient susceptible to infections. An individual is likely to experience abnormal and excessive bleeding from wounds if there is a lack of platelets.

Paroxysmal Nocturnal Hemoglobinuria Diagnosis

A 3-stage investigation is performed for making its diagnosis. The first test is comprised of a flow cytometry analysis, which helps to determine if any blood cell lacks the GPI-anchored proteins. The second test is carried out to analyze markers in blood for establishing the presence of hemolysis. Once these two tests have been completed, the diagnostician performs bone marrow analysis for detecting signs of another blood disorder such as aplastic anemia, myelodysplastic syndrome and myelofibrosis.

The diagnostic tests used for this condition include:

  • Complete blood count (CBC)
  • Coombes’ test
  • Ham test or acid hemolysin test
  • Sucrose hemolysis test (Sugar-Water Hemolysis Test)
  • Urinalysis or urine test

Imaging tests like abdominal ultrasound and MRI may be required to detect blood clots in the abdomen and any kidney or renal abnormality.

Paroxysmal Nocturnal Hemoglobinuria Differential Diagnosis

The following disorders are characterized by symptoms similar to that of PNH:

  • Hemolytic Anemia
  • Portal Vein Thrombosis
  • Paroxysmal Cold Hemoglobinuria
  • Renal Vein Thrombosis
  • Mesenteric Artery Ischemia
  • Mesenteric Artery Thrombosis

Differential Diagnosis should aim at ensuring the absence of such conditions in sufferers.

Paroxysmal Nocturnal Hemoglobinuria Treatment and Management

PNH is a chronic condition which cannot be completely cured by any treatment procedure. The treatment mainly focuses on relieving the symptoms of hemolysis, anemia and bone marrow problems.

Treatment for Hemolysis and Anemia

In majority of the cases, Hemolysis leads to anemia and causes several serious health problems. The symptoms are usually treated by:

Blood Transfusions

Patients suffering from severe anemia are treated in this process. It involves transferring blood from a donor directly into the blood streams of the patient. There are two types of blood transfusions: RBC transfusion and Platelet transfusion.

Iron Therapy

This condition can cause iron deficiency in the patient which can be managed by taking iron supplements. However, iron pills are not recommended for individuals receiving RBC transfusion. ( Recommended reading:  Food high in iron list)

Fulfilling Nutritional Requirements

Folate is a nutrient that can help to keep the symptoms under control. Folate (a B-vitamin) assists the bone marrow to produce normal blood cells, thus helping to control anemia. It is advisable for PNH patients to take folic acid (a form of folate) tablets every day.

Treatment of Bone Marrow Failure

Doctors may suggest surgical intervention if all the above-mentioned treatment options fail to stop the progression of hemolysis, blood clotting and bone marrow weakness. In extremely severe cases, a bone marrow transplantation surgery may be necessary for fighting complete bone marrow failure.

Paroxysmal Nocturnal Hemoglobinuria Prognosis

The outcome of this disorder is usually positive with early diagnosis and proper treatment. Patients generally have a 10 to 15 year life expectancy after a successful treatment. However, it is important to go for regular checkups for any signs of recurrence. In some less common cases, serious complications like complete bone marrow failure and thrombosis may result in the death of a sufferer.

Paroxysmal Nocturnal Hemoglobinuria Complications

The possible complications of PNH include:

Picture 2 – Paroxysmal Nocturnal Hemoglobinuria Image

  • Acute Myelogenous Leukemia
  • Hemolytic anemia
  • Myelodysplasia
  • Iron deficiency anemia

Paroxysmal Nocturnal Hemoglobinuria Prevention

There are no known ways to prevent PNH because it is not possible to gain advance knowledge of who will develop the disease. Yearly screening tests are performed in people with a history of aplastic anemia and any other bone marrow weakening condition for any early sign of this blood disorder.

Paroxysmal Nocturnal Hemoglobinuria is a serious and potentially fatal blood disorder. Early diagnosis is very crucial to avoid the life-threatening consequences of the condition. There are many support groups and foundations that provide proper guideline regarding the treatment options of PNH to help the patient survive.

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