Medical description of Hemolytic Anemia
Anemia, by definition, involves a decrease in red blood cells, or hemoglobin levels. The term “hemolytic anemia” encompasses different types of anemia where red blood cells are prematurely destroyed in the blood. The term “hemolysis” means destruction of red blood cells (hemo = blood, lysis = destruction).
Bone marrow has some spare capacity. That is, it can increase its production of red blood cells to a certain level to compensate for their increased destruction. Normally, red blood cells circulate in the blood vessels for about 120 days. At the end of their life, they are destroyed by the spleen and the liver (see also Anemia sheet – overview). The accelerated destruction of red blood cells is an important stimulus to the production of new red blood cells, which is mediated by a hormone produced by the kidneys, erythropoietin (EPO). In some cases, the bone marrow can produce as many red blood cells as the amount that is abnormally destroyed, so the hemoglobin level does not drop. We talk about compensated hemolysis without anemia. This is important because some factors may cause the situation to decompose in relation to factors that will interfere with the production of EPO such as pregnancy, kidney failure, folic acid deficiency, or acute infection.
Causes of Hemolytic Anemia
Haemolytic anemia is usually classified as being caused by a red blood cell that is itself abnormal (intracorpuscular), or a factor that is outside the red blood cell (extracorporeal). Hereditary and acquired haemolytic anemias are also distinguished.
Hereditary and intracorporeal causes
- Hemoglobinopathies (eg sickle cell anemia, …)
- Enzymopathies (eg G6-PD deficiency)
- Membrane and cytoskeletal abnormalities (eg congenital spherocytosis)
- Hereditary and extracorporeal cause
- Familial haemolytic-uremic syndrome (atypical)
- Acquired and intracorporeal cause
- Paroxysmal nocturnal hemoglobinuria
Acquired and extra corporeal cause
- Mechanical destruction (microangiopathy)
- Toxic agents
- Let’s discuss some examples, since it’s impossible to describe them all in the context of this document.
Immune Haemolytic Anemias :
Autoimmune reactions. In this case, the body, for various reasons, produces antibodies against its own red blood cells: they are called autoantibodies. There are two types: hot autoantibody and cold autoantibody, depending on whether the optimal temperature of antibody activity is 37 ° C or 4 ° C. This distinction is important because treatment varies from one form to another.
– Hot auto-antibodies: affect mostly adults and cause chronic and sometimes severe hemolytic anemia. They account for 80% of autoimmune haemolytic anemias. In half of the cases, they can be triggered by certain drugs (alpha-methyldopa, L-dopa) or certain diseases (ovarian tumor, lymphoproliferative syndrome, etc.). We then speak of “secondary” autoimmune haemolytic anemias, since they appear as a consequence of another disease.
– Cold autoantibodies: are associated with acute episodes of red blood cell destruction caused by cold. In 30% of cases, there is a secondary autoimmune reaction that can be explained by a viral infection or mycoplasma, an intermediate microorganism between viruses and bacteria.
Immunoallergic reactions. In case of immunoallergic (non-autoimmune) drug haemolysis, the antibodies do not attack red blood cells, but certain drugs: penicillin, cefalotin, cephalosporins, rifampicin, phenacetin, quinine, etc.
Congenital Hemolytic Anemias:
There are three essential components in red blood cells. There is hemoglobin, the membrane-cytoskeleton complex, and the enzymatic “machinery” to make everything work. Genetic abnormalities of any of these three factors can cause hemolytic anemia.
Hereditary abnormalities of the red blood cell membrane. The main one is congenital spherocytosis, so named because of the spherical shape that then characterizes the red blood cells and makes them particularly fragile. It is relatively frequent: 1 case out of 5000. Several genetic anomalies are in question, the classical form is autosomal dominate, but recessive forms also exist. It can cause some complications: gallstones, ulcers on the legs.
Enzymopathies. There are several forms of enzyme deficiency that can cause hemolytic anemia. They are usually hereditary. The most common is the deficiency of an enzyme called “glucose-6-phosphate dehydrogenase”, which causes premature destruction of red blood cells and, subsequently, haemolytic anemia.
The genetic anomaly that is involved is related to the X chromosome, therefore, only men can be affected. Women can carry the genetic anomaly, and pass it on to their children. In people with this enzymatic deficiency, hemolytic anemia usually occurs following exposure to oxidizing agents.
People with G6PD deficiency can develop acute hemolysis when exposed to certain agents such as:
- Consumption of the variety of beans called faba bean ( Vicia faba ) or exposure to pollen from this plant (this variety of beans is used for livestock feed). This contact causes acute haemolytic anemia also called favism.
- The use of certain drugs: antimalarials, methyldopa (lowers blood pressure), sulfonamides (antibacterials), aspirin, non-steroidal anti-inflammatory drugs, quinidine, quinine, etc.
- Exposure to certain chemicals such as mothballs.
- Some infections.
This disease is frequently diagnosed in people of Mediterranean origin (particularly in the Greek islands) and among those of black Africa and the United States (where prevalence is 10% to 14%). In some parts of the world, 20% or more of the population is affected.
Hemoglobinopathies. Term used to describe genetic diseases where the production of hemoglobin inside red blood cells is affected. Sickle cell anemia (sickle cell anemia) and thalassemia are the two main categories of hemoglobin.
Sickle cell anemia (sickle cell anemia) 4,5 . This relatively serious disease is related to the presence of abnormal hemoglobin called hemoglobin S. It deforms the red blood cells and gives them the shape of a crescent or a false (sickle-like red blood cells), in addition to killing them prematurely. See the sheet Sickle Cell Anemia.
Thalassemia. Very widespread in some countries of the world, this serious disease is linked to a genetic anomaly that affects the production of hemoglobin, the blood pigment of red blood cells that allows the transport of oxygen to the organs. The affected red blood cells are fragile and rapidly degraded. The term “thalassemia” comes from the Greek word “thalassa”, which means “sea” because it was first observed in people from the Mediterranean basin. The genetic defect can affect two places in the synthesis of hemoglobin: the alpha chain or the beta chain. Depending on the type of chain affected, there are two forms of thalassemia: alpha-thalassemia and beta-thalassemia.
Other causes of Hemolytic Anemia
Mechanical causes. Red blood cells can be damaged during certain treatments related to mechanical devices:
- Prostheses (artificial valves for the heart, etc.);
- Extra corporeal blood purification (hemodialysis);
- Machine to oxygenate the blood (used in case of heart-lung surgery), etc.
Rarely, a marathoner may have mechanical haemolysis while the capillaries of the feet are crushed repeatedly. This situation has also been described after some very long ritual dances, barefoot.
Exposure to toxic elements :-
- Industrial or domestic toxic products: aniline, arsenic hydrogen, nitrobenzene, naphthalene, paradichlorobenzene, etc.
- Toxic animal: spider bite, wasp sting, snake venom.
- Toxic plant: some mushrooms.
Infections. Severe gastroenteritis caused by E. coli , pneumococcal or staphylococcal infections, hepatitis, typhoid fever, malaria, etc. Malaria (or malaria) is the most important cause in this category. Malaria is caused by a parasite that develops inside red blood cells.
Hyperfunction of the spleen. It is normal for red blood cells to be destroyed in the spleen at the end of their 120-day journey, but if this organ works excessively, the destruction is too fast and haemolytic anemia ensues.
Emoglobinurie paroxysmal nocturnal . This chronic condition associates a presence of hemoglobin in the urine due to excessive destruction of red blood cells. Nocturnal seizures are caused by any form of stress, stimulation of the immune system or certain medications. Sometimes the disease causes lower back pain and discomfort.
Possible complications: thrombosis, medullary hypoplasia , secondary infections.
SYMPTOMS of Hemolytic Anemia
Those who are linked to a low level of red blood cells: pale complexion, fatigue, weakness, dizziness, fast heart rate, etc.
- Dark urine.
- Enlargement of the spleen.
- Those that is specific to each form of hemolytic anemia. See “Medical Description”.
People at Risk
- For congenital forms of hemolytic anemia:
- Those with a family history.
- People from the Mediterranean Basin, Africa, South Asia, Southeast Asia and the Caribbean.
Other Risk Factors
In persons with a deficiency of the enzyme glucose-6-phosphate dehydrogenase: exposure to oxidizing agents (certain drugs, faba bean, etc.).
For other forms of hemolytic anemias:
- Certain diseases: hepatitis, infection with streptococcus or E. coli , autoimmune disorders (such as lupus), ovarian tumor.
- Some drugs (antimalarial, penicillin, rifampicin, sulfonamides, etc.) or toxic agents (aniline, arsenic hydrogen, etc.).
- Some mechanical devices used in medicine: artificial valves, devices to purify or oxygenate the blood.
At present, hereditary forms cannot be prevented except by consulting a genetic counselor before conceiving a child. The specialist will be able to determine the risk of having a child with hemolytic anemia when one or both of the potential parents have a family history (see also Sickle Cell Anemia for more details on genetic risks with regard to this form of hemolytic anemia).
If a specific substance is responsible for the disease, it must be avoided to prevent recurrence.
For many forms of hemolytic anemia, it is also important to guard against certain infections.
They vary according to the type of hemolytic anemia.
The treatment is based primarily on a general support to the body and the underlying cause when possible
A folic acid supplement is usually indicated for patients with chronic hemolytic anemia
Vaccination against common infections is important for these patients who have altered immune defenses, especially in those with splenectomies (removal of the spleen 6 )
Blood transfusions are sometimes indicated
A splenectomy is sometimes suggested, especially in people with hereditary spherocytosis, thalassemias that often require transfusions but also sometimes in other forms of chronic hemolytic anemias. Indeed, it is largely in the spleen that the red blood cells are destroyed.
Cortisone is sometimes prescribed in case of autoimmune anemia with hot antibodies and to be considered in case of cold-antibody anemia. It is sometimes used in case of paroxysmal nocturnal haemoglobinuria and in particular for thrombotic thrombocytopenic purpura. More potent immunosuppressive agents, such as rituximab, intravenous immunoglobulins, azathioprine, cyclophosphamide, and cyclosporine may be considered in immunological haemolytic anemias. Plasmapheresis is sometimes used, especially in case of thrombotic thrombocytopenic purpura.