MAHE 2006 Hemolytic Anemia
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- Hereditory spherocytosis
- PNH
- Thalassemia
Review:
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterised by hemolytic anemia, thrombosis and red urine due to breakdown of red blood cells. PNH is the only hemolytic anemia caused by an acquired intrinsic defect in the cell membrane.
Signs and symptoms
- Quite paradoxically, the destruction of red blood cells (hemolysis) is neither paroxysmal or nocturnal the majority of the time (this constellation of symptoms is seen in only 25% of patients).
- On-going hemolysis is a more common characteristic.
- A common finding in PNH is the presence of breakdown products of RBCs (hemoglobin and hemosiderin) in the urine.
- An inconsistent, but potentially life-threatening, complication of PNH is the development of clot in the veins (venous thrombosis).
- These clots (thrombi) are often found in the hepatic (causing Budd-Chiari syndrome), portal (causing portal vein thrombosis), and cerebral veins (causing cerebral venous thrombosis).
- Many patients with bone marrow failure (aplastic anemia) develop PNH (10-33%).
- Aplastic anemia can be caused by an attack by the immune system against the bone marrow.
- For this reason, drugs that suppress the immune system are being researched as a therapy for PNH.
Classification
PNH is classified:
Classic PNH. Evidence of PNH in the absence of another bone marrow disorder.
PNH in the setting of another specified bone marrow disorder.
Subclinical PNH. PNH abnormalities on flow cytometry without signs of hemolysis.
Pathophysiology
All cells have proteins attached to their membranes and they are responsible for performing a vast array of functions. There are several ways for proteins to be attached to a cell membrane. PNH occurs as a result of a defect in one of these mechanisms.
A molecule called PIGA (phosphatidylinositol glycan A) is needed to make a cell membrane anchor for proteins called GPI (glycosylphosphatidylinositol). The gene that codes for PIGA is inherited in an X-linked fashion, which means that only one active copy of the gene for PIGA may exist. If a mutation occurs in this gene then PIGA may be defective, which leads to a defect in the GPI anchor. When this mutation occurs in a bone marrow stem cell (which are used to make red blood cells as well as white blood cells and platelets), all of the cells it produces will also have the defect. Several of the proteins that anchor to GPI on the cell membrane are used to protect the cell from destruction by the complement system. The complement system is part of the immune system and helps to destroy invading microorganisms. Without the proteins that protect them from complement, red blood cells are destroyed. The main proteins which carry out this function are CD16, CD55 and CD59 (CD is an acronym for cluster of differentiation).
The increased destruction of red blood cells results in anemia. The increased rate of thrombosis is due to dysfunction of platelets. They are also made by the bone marrow stem cells and will have the same GPI anchor defect as the red blood cells. The proteins which use this anchor are needed for platelts to clot properly, and their absence leads to a hypercoagulable state.
Category: MAHE 2006 MCQs
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