User:Dshan19/Hemolytic anemia

Intro/Lead:
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically (prosthetic valve damage). Hemolytic anemia accounts for 5% of all existing anemias. It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects. The general classification of hemolytic anemia is either intrinsic or extrinsic. Treatment depends on the type and cause of the hemolytic anemia.

Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition, the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications, such as gallstones and pulmonary hypertension. ** Already have citations**

S/S:
Symptoms of hemolytic anemia are similar to the general signs of anemia. General signs and symptoms include: fatigue, pallor, shortness of breath, and tachycardia. In small children, failure to thrive may occur in any form of anemia. In addition, symptoms related to hemolysis may be present such as chills, jaundice, dark urine, and an enlarged spleen. Certain aspects of the medical history can suggest a cause for hemolysis, such as drugs, medication side effects, autoimmune disorders, blood transfusion reactions, the presence of prosthetic heart valve, or other medical illness.

Chronic hemolysis leads to an increased excretion of bilirubin into the biliary tract, which in turn may lead to gallstones. The continuous release of free hemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery); this, in turn, leads to episodes of syncope (fainting), chest pain, and progressive breathlessness. Pulmonary hypertension eventually causes right ventricular heart failure, the symptoms of which are peripheral edema (fluid accumulation in the skin of the legs) and ascites (fluid accumulation in the abdominal cavity).

Causes:
They may be classified according to the means of hemolysis, being either intrinsic in cases where the cause is related to the red blood cell (RBC) itself, or extrinsic in cases where factors external to the RBC dominate. (Has citation) Intrinsic effects may include problems with RBC proteins or oxidative stress handling, whereas external factors include immune attack and microvascular angiopathies (RBCs are mechanically damaged in circulation).

Intrinsic causes
Hereditary (inherited) hemolytic anemia can be due to :


 * Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis).
 * Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia).
 * Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency).
 * Paroxysmal nocturnal hemoglobinuria (PNH), sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterized by complement-induced intravascular hemolytic anemia.

Extrinsic causes
Acquired hemolytic anemia may be caused by immune-mediated causes, drugs, and other miscellaneous causes.


 * Immune-mediated causes could include transient factors as in Mycoplasma pneumoniae infection (cold agglutinin disease) or permanent factors as in autoimmune diseases like autoimmune hemolytic anemia (itself more common in diseases such as systemic lupus erythematosus, rheumatoid arthritis, Hodgkin's lymphoma, and chronic lymphocytic leukemia).
 * Spur cell hemolytic anemia
 * Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension.
 * Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria).
 * Lead poisoning resulting from the environment causes non-immune hemolytic anemia.
 * Similarly, poisoning by arsine or stibine also causes hemolytic anemia.
 * Runners can suffer hemolytic anemia due to "footstrike hemolysis", owing to the destruction of red blood cells in feet at foot impact. Citations present
 * Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%. Citations present

Mechanism:
In hemolytic anemia, there are two principal mechanisms of hemolysis; intravascular and extravascular.

Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia and increasing the risk of ensuing hyperbilirubinemia.

Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as Babesia.

Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes. In this case little hemoglobin escapes into blood plasma. The macrophages of the reticuloendothelial system in these organs engulf and destroy structurally-defective red blood cells, or those with antibodies attached, and release unconjugated bilirubin into the blood plasma circulation. Typically, the spleen destroys mildly abnormal red blood cells or those coated with IgG-type antibodies, while severely abnormal red blood cells or those coated with IgM-type antibodies are destroyed in the circulation or in the liver.

If extravascular hemolysis is extensive, hemosiderin can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in hemosiderosis.

In a healthy person, a red blood cell survives 90 to 120 days in the circulation, so about 1% of human red blood cells break down each day. The spleen (part of the reticulo-endothelial system) is the main organ that removes old and damaged RBCs from the circulation. In healthy individuals, the breakdown and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow.