What Is Paroxysmal Nocturnal Hemoglobinuria?
Paroxysmal nocturnal hemoglobinuria is a rare disease, and it was first introduced by Ennekineg in 1925. It affects the blood-forming cells also called hematopoietic stem cells. Hematopoietic cells are found in the bone marrows of long bones. Paroxysmal nocturnal hemoglobinuria leads to the death of immature blood cells and causes the destruction in the formation of impaired red blood cells, white blood cells, and platelets.
Patients which paroxysmal nocturnal hemoglobinuria show paroxysmal symptoms like recurrent episodes of seizures because of some triggering factors like stress and infections, these episodes of paroxysmal symptoms lead to hemolysis of red blood cells and abnormal bleeding, causing hemorrhage or abnormal blood clotting called thrombosis in long veins. Affected patients may have blood loss through urine, presence of hemoglobin is detected to cause hemoglobinuria. Paroxysmal nocturnal hemoglobinuria increases the risk of developing leukemia, aplastic anemia, and other blood-related disorders.
What Is Hematopoiesis?
Hematopoiesis is the process of forming blood cells. The bone marrow has spongy tissue present in the long bones which forms the blood cells. Bone marrow contains blood-forming stem cells, also called hematopoietic stem cells. These cells proliferate to form three types of blood cells, white blood cells, red blood cells, and platelets. As the proliferation and maturation of the blood cells are completed in the bone marrow the blood cells are transmitted to the blood vessels and perform their functions like regulating the body temperature, fighting against infections, oxygen, and nutritional transportation.
What Are the Etiologies of Paroxysmal Nocturnal Hemoglobinuria?
Paroxysmal nocturnal hemoglobinuria is a rare X-linked disorder caused by two main factors.
An acquired somatic variation in gene PIGA and PIGT (phosphatidylinositol glycan class A and phosphatidylinositol glycan class T respectively). PIGA (phosphatidylinositol glycan class A) affects one or more hematopoietic stem cells and the defective process of multiplication of the cells. In addition, this mutation leads to the deficiency of GPI protein (glycosylphosphatidylinositol protein) which anchors to the surface of the cell membrane.
The deficiency of GPI protein anchors (glycosylphosphatidylinositol protein) does not allow the cells to attach to protein leading to the early destruction of the red blood cells. The mutation in PIGT (phosphatidylinositol glycan class T) leads to abnormal growth and development of the hematopoietic cells.
What Are the Clinical Features of Paroxysmal Nocturnal Hemoglobinuria?
The clinical features of paroxysmal nocturnal hemoglobinuria are as follows:
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Males and females are equally affected.
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Any age group can be involved.
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Hemolysis (destruction of red blood cells).
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Hemoglobinuria (abnormal presence of hemoglobin).
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Fatigue.
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Tachycardia (rapid heart rate).
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Headache.
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Chest pain.
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Breath difficulties.
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Abdominal discomfort.
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Swallowing problems.
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Venous thrombosis
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Thrombocytopenia (decreased platelets).
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Leukopenia (low white blood cell count).
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Pale skin color.
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Easily bleeding.
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Dizziness.
What Is the Pathology of Paroxysmal Nocturnal Hemoglobinuria?
Paroxysmal nocturnal hemoglobinuria leads to the destruction of blood cells. In normal conditions, the destroyed red blood cells by the process of hemolysis release free hemoglobin, which is dissolved by the haptoglobin or other clearing mechanisms. Still, in paroxysmal nocturnal hemoglobinuria, excessive hemolysis causes an overload on the body to digest the free hemoglobin, leading to the accumulation of free hemoglobin in the intravascular system.
In revert, the body binds the hemoglobin to nitric oxides present in the body, leading to a lower level of nitric oxide. Nitric oxide plays an important role in the body; nitric oxide depletion causes dystonia (it is a muscular disorder that causes involuntary contractions) of gastrointestinal walls, shortness of breath, abdominal pain, acute and chronic renal disorders, and erectile dysfunction in males.
What Are the Investigations for the Diagnosis of Paroxysmal Nocturnal Hemoglobinuria?
The diagnosis of paroxysmal nocturnal hemoglobin can be made advising the following investigations -
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Recording the personal and medical history of an individual.
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A complete blood count (CBC) is required to identify type of anemia and thrombocytopenia.
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Flow Cytometry- Flow cytometry is an investigation in which monoclonal antibodies and a special reagent is known as Fluorescent aerolysin reagent (FLAER), which attaches to the GPI protein (glycosylphosphatidylinositol protein); this test is capable of detecting affinity of the GPI protein (glycosylphosphatidylinositol protein). Flow cytometry is of two types: high and low sensitivity. Low sensitivity is sufficient to detect paroxysmal nocturnal hemoglobinuria, and high sensitivity can be used to detect paroxysmal nocturnal hemoglobinuria with other bone marrow disorders.
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Urine Test - It is advised to check the count of hemoglobin content in the urine caused due to hemoglobinuria.
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Liver Function Test- It is advised to check the level of bilirubin in the blood.
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Renal Function Test- To check chronic kidney dysfunction.
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Reticulocyte Count - Reticulocytes are the immature form of the red blood cells found in the bone marrow.
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Haptoglobin Test- Haptoglobin is a protein that clears the debris of the destroyed red blood cells. If the content of haptoglobin is low, this indicates the excessive destruction of red blood cells.
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Computerized Tomography (CT Scan) - CT scan of the head, chest, and abdomen is done to check the thrombosis.
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Lactate Dehydrogenase Test- Lactate dehydrogenase is an enzyme present in the red blood cells; if the count of lactate dehydrogenase is high in the blood it shows a possibility of red blood cell destruction.
What Are the Treatment Modalities of Paroxysmal Nocturnal Hemoglobinuria?
Paroxysmal nocturnal hemoglobinuria is a curable disorder sometimes; it can be a life-threatening disease involving other systemic problems.
Treatment for paroxysmal nocturnal hemoglobinuria involves:
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Iron supplementation for anemia.
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Blood transfusion is advised.
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Anti-thrombosis prophylaxis is given to prevent venous thrombosis.
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Drug administration involving Eculizumab and Ravulizumab.
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Eculizumab administration is a life-saving medical therapy preventing approximately 70 percent chance of a bone marrow transplant. Eculizumab inhibits the factors and reduces red blood cell destruction.
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Allogeneic hematopoietic stem cell transplantation is a surgical procedure for treating paroxysmal nocturnal hemoglobinuria.
Conclusion:
Paroxysmal nocturnal hemoglobinuria is an inherited or acquired rare blood disorder involving the destruction of red blood cells and clot formation. It can not be prevented if it is genetically transmitted or caused by some underlying disorders and by avoiding triggering factors like stress, infections, smoking, and consumption of alcohol. Chances of developing aplastic anemia or sometimes leukemia and myelodysplastic syndrome are higher. Living with paroxysmal nocturnal hemoglobinuria can be managed with proper treatment and by maintaining a healthy lifestyle.
