- Hemolytic anemia
, ICD9|283, ICD9|773
MedlinePlus = 000571
eMedicineSubj = med
eMedicineTopic = 979
MeshID = D000743
Hemolytic anemia is
anemiadue to hemolysis, the abnormal breakdown of red blood cells (RBCs) either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular). It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either acquired or inherited. Treatment depends on the cause and nature of the breakdown.
In a healthy person, a red blood cell survives 90 to 120 days (on average) 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 which removes old and damaged RBCs from the circulation. In healthy individuals, the break down and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow.
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.
Bilirubin, a breakdown product of hemoglobin, can accumulate in the blood causing jaundice, and be excreted in the urine causing the urine to become a dark brown colour.
anemiaare generally present (fatigue, later heart failure). Jaundice may be present.
*certain aspects of the medical history can suggest a cause for hemolysis (drugs,
fava beanor other sensitivity, prosthetic heart valve, or another medical illness)
Peripheral blood smearmicroscopy:
**fragments of the red blood cells ("
schistocytes") can be present
**some red blood cells may appear smaller and rounder than usual (
Reticulocytes are present in elevated numbers. This may be overlooked if a special stain is not used.
*The level of unconjugated
bilirubinin the blood is elevated. This may lead to jaundice.
*The level of
lactate dehydrogenase(LDH) in the blood is elevated
Haptoglobinlevels are decreased
*If the direct
Coombs testis positive, if hemolysis is caused by an immune process.
Haemosiderinin the urine indicates chronic intravascular haemolysis. There is also urobilinogenin the urine.
Clinical findings in haemolytic anaemias:
1. increased serum bilirubin levels in blood, therefore jaundice2. pallor in mucous membrane and skin3. increased urobilinogen in urine4.
Splenomegaly5. Pigmented gallstones may be found.
Classification of hemolytic anemias
Causes of hemolytic anemia can be either genetic or acquired.
*Genetic conditions of RBC Membrane
*Genetic conditions of RBC metabolism (
Glucose-6-phosphate dehydrogenase deficiency(G6PD or favism)
Pyruvate kinase deficiency
*Genetic conditions of hemoglobin
Sickle cell anemia
Acquired hemolytic anemia can be further divided into immune and non-immune mediated.
Immune mediated hemolytic anemia (direct
Coombs testis positive)
Autoimmune hemolytic anemia
Warm antibody autoimmune hemolytic anemia
Systemic lupus erythematosus(SLE)
Evans' syndrome(antiplatelet antibodies and hemolytic antibodies)
**Cold antibody autoimmune hemolytic anemia
Idiopathic cold hemagglutinin syndrome
Infectious mononucleosisand mycoplasma ( atypical) pneumonia
Paroxysmal cold hemoglobinuria(rare)
Haemolytic disease of the newborn(HDN)
Rh disease(Rh D)
ABO hemolytic disease of the newborn
Anti-Kell hemolytic disease of the newborn
Rhesus c hemolytic disease of the newborn
***Rhesus E hemolytic disease of the newborn
***Other blood group incompatibility (RhC, Rhe, Kidd, Duffy, MN, P and others)
**Alloimmune hemolytic blood transfusion reactions (ie from a non-compatible
*Drug induced immune mediated hemolytic anemia
Non-immune mediated hemolytic anemia (direct
Coombs testis negative)
*Drugs (i.e., some drugs and other ingested substances lead to haemolysis by direct action on RBCs, e.g.
Toxins (e.g., snakevenom)
heart valves, extensive vascular surgery, microvascular disease)
Microangiopathic hemolytic anemia(a specific subtype with causes such as TTP, HUS, DIC and HELLP syndrome)
*Infections (Note: Direct Coombs test is sometimes positive in hemolytic anemia due to infection)
Paroxysmal nocturnal hemoglobinuria(rare acquired clonal disorder of red blood cell surface proteins)
Drug induced hemolysis
Drug induced hemolysis has large clinical relevance. It occurs when drugs actively provoke red blood cell destruction. Four mechanisms are described below.
Penicillinin high doses can induce immune mediated hemolysis via the haptenmechanism in which antibodies are targeted against the combination of penicillin in association with red blood cells. Complement is activated by the attached antibody leading to the removal of red blood cells by the spleen.
The drug itself can be targeted by the immune system, e.g. by IgE in a Type I hypersensitivity reaction to penicillin, rarely leading to anaphylaxis.
Non-immune drug induced hemolysis can occur via oxidative mechanisms. This is particularly likely to occur when there is an enzyme deficiency in the antioxidant defence system of the red blood cells. An example is where antimalarial oxidant drugs like primaquine damage red blood cells in
Glucose-6-phosphate dehydrogenase deficiencyin which the red blood cells are more susceptible to oxidative stress due to reduced NADPH production consequent to the enzyme deficiency.
Some drugs cause RBC (red blood cell) lysis even in normal individuals. These include
Non-immune drug-induced hemolysis can also arise from drug-induced damage to cell volume control mechanisms; for example drugs can directly or indirectly impair regulatory volume decrease mechanisms, which become activated during
hypotonicRBC swelling to return the cell to a normal volume. The consequence of the drugs actions are irreversible cell swelling and lysis (e.g. ouabainat very high doses).
*Ineffective hematopoiesis is sometimes misdiagnosed as hemolysis.
** Clinically these conditions may share many features of hemolysis
** Red cell breakdown occurs before a fully developed red cell is released into the circulation.
thalassemia, myelodysplastic syndrome
Megaloblastic anemiadue to deficiency in vitamin B12or folic acid.
Definitive therapy depends on the cause.
*Symptomatic treatment can be given by
blood transfusion, if there is marked anemia.
*In severe immune-related hemolytic anemia,
steroidtherapy is sometimes necessary.
splenectomycan be helpful where extravascular hemolysis is predominant (ie most of the red blood cells are being removed by the spleen).
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