Hemolytic anemia
Hemolytic anemia | |
---|---|
Other names | Haemolytic anaemia |
Figure shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin.[1] | |
Specialty | Hematology |
Causes | Hemolysis |
Hemolytic anemia or haemolytic anaemia 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).[2] This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically (prosthetic valve damage).[2] Hemolytic anemia accounts for 5% of all existing anemias.[2] It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects.[2] The general classification of hemolytic anemia is either intrinsic or extrinsic.[3] Treatment depends on the type and cause of the hemolytic anemia.[2]
Symptoms of hemolytic anemia are similar to other forms of anemia (
Signs and symptoms
Symptoms of hemolytic anemia are similar to the general signs of anemia.
Chronic hemolysis leads to an increased excretion of bilirubin into the biliary tract, which in turn may lead to gallstones.[8] 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.[9] 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).[9]
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.[10] 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).[2][3]
Intrinsic causes
Hereditary (inherited) hemolytic anemia can be due to :
- Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis).[2]
- Defects in hemoglobin production (as in sickle-cell disease and congenital dyserythropoietic anemia).[2]
- Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency).[11][12]
- Wilson's disease may infrequently present with hemolytic anemia without due to excessive inorganic copper in blood circulation, which destroys red blood cells (though the mechanism of hemolysis is still unclear).[13]
Extrinsic causes
Acquired hemolytic anemia may be caused by immune-mediated causes, drugs, and other miscellaneous causes.[2]
- Immune-mediated causes could include transient factors as in chronic lymphocytic leukemia).[2]
- Spur cell hemolytic anemia[16]
- Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension.[17]
- Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria).[15][18]
- 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.[19]
- Lead poisoning resulting from the environment causes non-immune hemolytic anemia.[20]
- Similarly, poisoning by arsine or stibine also causes hemolytic anemia.[21]
- Runners can develop hemolytic anemia due to "footstrike hemolysis", owing to the destruction of red blood cells in feet at foot impact.[22][23]
- Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%.[24]
Mechanism
In hemolytic anemia, there are two principal mechanisms of hemolysis; intravascular and extravascular.[25]
Intravascular hemolysis
Intravascular hemolysis describes hemolysis that happens mainly inside the
Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as Babesia.[29]
Extravascular hemolysis
Extravascular hemolysis refers to hemolysis taking place in the
If extravascular hemolysis is extensive, hemosiderin can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in hemosiderosis.[28]
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.
In conditions where the rate of RBC breakdown is increased, the body initially compensates by producing more RBCs; however, breakdown of RBCs can exceed the rate that the body can make RBCs, and so anemia can develop.[34] Bilirubin, a breakdown product of hemoglobin, can accumulate in the blood, causing jaundice.[29]
In general, hemolytic anemia occurs as a modification of the RBC life cycle.[35][unreliable medical source?] That is, instead of being collected at the end of its useful life and disposed of normally, the RBC disintegrates in a manner allowing free iron-containing molecules to reach the blood.[35] With their complete lack of mitochondria, RBCs rely on pentose phosphate pathway (PPP) for the materials needed to reduce oxidative damage. Any limitations of PPP can result in more susceptibility to oxidative damage and a short or abnormal lifecycle.[36][unreliable medical source?] If the cell is unable to signal to the reticuloendothelial phagocytes by externalizing phosphatidylserine, it is likely to lyse through uncontrolled means.[37][38][39]
The distinguishing feature of intravascular hemolysis is the release of RBC contents into the blood stream. The metabolism and elimination of these products, largely iron-containing compounds capable of doing damage through
Additional effects of free hemoglobin seem to be due to specific reactions with NO.[43]
Diagnosis
The diagnosis of hemolytic anemia can be suspected on the basis of a constellation of symptoms and is largely based on the presence of anemia, an increased proportion of immature red cells (reticulocytes) and a decrease in the level of haptoglobin, a protein that binds free hemoglobin. Examination of a
Treatment
Definitive therapy depends on the cause:
- Symptomatic treatment can be given by blood transfusion, if there is marked anemia. A positive Coombs test is a relative contraindication to transfuse the patient. In cold hemolytic anemia there is advantage in transfusing warmed blood.
- In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary.
- In steroid resistant cases, consideration can be given to rituximab or addition of an immunosuppressant (azathioprine, cyclophosphamide).
- Association of methylprednisolone and intravenous immunoglobulin can control hemolysis in acute severe cases.
- Sometimes splenectomy can be helpful where extravascular hemolysis, or hereditary spherocytosis, is predominant (i.e., most of the red blood cells are being removed by the spleen).[45]
Mitapivat was approved for medical use in the United States in February 2022.[46]
Other animals
Hemolytic anemia affects nonhuman species as well as humans. It has been found, in a number of animal species, to result from specific triggers.[47]
Some notable cases include hemolytic anemia found in
Dogs and cats differ slightly from humans in some details of their RBC composition and have altered susceptibility to damage, notably, increased susceptibility to oxidative damage from consumption of onion. Garlic is less toxic to dogs than onion.[52]
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- ^ "Agios Announces FDA Approval of Pyrukynd (mitapivat) as First Disease-Modifying Therapy for Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency" (Press release). Agios Pharmaceuticals. 17 February 2022. Retrieved 19 February 2022 – via GlobeNewswire.
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