What is Paroxysmal Nocturnal Hemoglobinuria (PNH)?
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by the destruction of red blood cells (hemolysis), blood clots (thrombosis), and impaired bone marrow function. The condition is caused by a mutation in the PIGA gene, which results in the absence of certain proteins on the surface of blood cells, making them more susceptible to destruction by the immune system.
Histological Features of PNH
In the context of histology, PNH is notable for the absence of glycosylphosphatidylinositol (GPI)-anchored proteins on the surface of hematopoietic cells. This absence can be observed using flow cytometry, a technique that analyzes the physical and chemical characteristics of cells or particles. The lack of GPI-anchored proteins, such as CD55 and CD59, leads to increased sensitivity to complement-mediated lysis.What Are GPI-Anchored Proteins?
GPI-anchored proteins are a diverse group of proteins that are attached to the cell membrane via a glycosylphosphatidylinositol anchor. These proteins play crucial roles in various cellular functions, including signal transduction, cell adhesion, and enzymatic processes. In PNH, the deficiency of these proteins, particularly CD55 and CD59, on red blood cells leads to uncontrolled activation of the complement system, resulting in hemolysis.
How is PNH Diagnosed?
PNH diagnosis often involves a combination of clinical evaluation, laboratory tests, and histological analysis. A key diagnostic tool is flow cytometry, which can identify the absence of GPI-anchored proteins on the surface of blood cells. Bone marrow examination may also be performed to assess the degree of bone marrow failure and to rule out other hematological conditions. Additionally, tests for hemoglobinuria (presence of hemoglobin in the urine) and elevated levels of lactate dehydrogenase (LDH) are indicative of hemolysis.
Histological Impact on Bone Marrow
In PNH patients, bone marrow biopsy may reveal varying degrees of hypocellularity, indicative of bone marrow failure. The marrow may show a reduced number of erythroid, myeloid, and megakaryocytic cells. Some patients might present with features suggestive of aplastic anemia, a condition that can coexist with PNH.Treatment and Management
The management of PNH includes supportive care and targeted therapies. Eculizumab, a monoclonal antibody, is a primary treatment that inhibits the complement protein C5, thereby reducing hemolysis. Bone marrow transplantation may be considered in severe cases. Regular monitoring of blood counts, renal function, and thrombotic risk is essential for managing the disease.Prognosis and Complications
The prognosis of PNH varies depending on the severity of the disease and the effectiveness of treatment. Thrombosis is one of the most serious complications and can occur in unusual sites such as the hepatic, cerebral, and abdominal veins. Chronic kidney disease and pulmonary hypertension are other potential complications due to ongoing hemolysis and iron deposition in the kidneys.
