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Autoimmune Hemolytic Anemia
Autoimmune hemolytic anemia (AIHA) is characterized by premature intra- and extravascular lysis of erythrocytes due to antibodies.
Different antibodies (IgM, IgG) can be the cause of AIHA. AIHA is classified into forms with warm autoantibodies and those with cold autoantibodies. Approx. 50% of AIHA cases are idiopathic. The remaining 50% develop from infections, drugs, or in the context of proliferative and rheumatoid diseases.
Diagnostic: coombs test
Direct coombs test
The Coombs test is positive despite the form of AIHA, which is why it is the most important test for the general determination of AIHA. This test is also referred to as a direct antiglobulin test (DAT).
Generally, there are 2 possibilities for the Coombs test – the direct Coombs test and the indirect Coombs test. However, for the determination of AIHA, only the direct test is used, in which the examined erythrocytes are mixed with rabbit serum (Coombs serum). If an agglutination of the erythrocytes occurs, this is proof of an AIHA.
Indirect Coombs Test
Step I: Add test blood group O RBCs to the test tube to bind with IgG antibodies
Step II: Add Coombs reagent
|Direct Coombs test||Indirect Coombs test|
Autoimmune hemolytic anemia via warm antibodies
The optimal temperature for the warm antibodies belonging to the IgG class is 37.0°C (98.6°F). After the antibodies bind to the surface of the erythrocytes, they are not only recognized by the macrophages of the MMS (monocyte-macrophage system) but also destroyed. The patient shows non-specific symptoms like fatigue, tiredness, tachycardia, and tachypnea.
In the context of a hemolytic crisis, fever occurs, which can be accompanied by jaundice and beer-brown urine. Apart from the treatment of the underlying disease and the avoidance of AIHA-triggering factors, high-dose immunosuppressive corticoids can be administered. If the spleen, and not the liver, is the main location of erythrocyte degradation in the MMS, a splenectomy can be considered.
Autoimmune hemolytic anemia via cold antibodies
The optimal temperature of the cold antibodies, mainly belonging to the IgM class, is 4°C (39.2°F); thus, the risk of the antibodies binding to the surface of the erythrocytes is increased when the blood temperature is low, i.e. in the periphery. Chronic hemolytic anemia, which worsens with cold exposure, can develop.
Clinically, mild jaundice and splenomegaly can occur. Moreover, acrocyanosis in the nose, ears, fingers, and toes may be observed. The primary goal of therapy is to avoid exposure to cold. Since hemolysis can also be intravascular, the necessity of splenectomy must be examined thoroughly before it is performed. Splenectomy should only be performed for a severely enlarged spleen.
Drug-Induced Hemolytic Anemia
Generally, drug-induced hemolytic anemia is based on 3 different mechanisms, which is why different reactions between antibodies and complements occur.
- Autoimmune type: Antibodies do not activate complement and persist after the termination of medication (e.g. methyldopa, fludarabine).
- Immune-complex type: Antibodies activate complement and disappear with the termination of medication (e.g. NSAR, cephalosporins).
- Hapten-type: Antibodies react against a drug-erythrocyte-complex (e.g. penicillin, ampicillin).
For all 3 mechanisms, opsonized erythrocytes are degraded in the MMS and the resulting hemolytic anemia does not regress until the medication is terminated. One should consider that, for the autoimmune type, antibodies persist for several months even if the medication is terminated.
Rhesus-Incompatibility of Newborns
Etiology and pathogenesis
Rhesus incompatibility between the blood of the fetus and the blood of the mother results if an Rh-D-negative mother gives birth to an Rh-D-positive child, she is Rh-D sensitized and produces anti-D-antibodies of the IgG class, which can pass the placenta. As these antibodies are capable of passing the placenta during the next pregnancy, they lead to hemolysis of the fetal erythrocytes if the fetus is Rh-D positive.
In severe cases, rhesus incompatibility leads to the death of the fetus (hydrops fetalis). In milder cases, the newborn shows jaundice with hepatosplenomegaly at birth. Moreover, paleness, tachycardia, and edema can be present.
In the navel vein blood of the newborn, distinct anemia with increased reticulocytes can be observed and bilirubin levels are also elevated. The direct Coombs test is positive for the child; this also applies to the mother when the indirect Coombs test is performed.
With distinct signs of anemia, jaundice, possible heart insufficiency, and a positive direct Coombs test of the newborn, exchange transfusion can become necessary. For degradation of the bilirubin in the skin, the child can undergo phototherapy.
Due to the large amounts of unconjugated bilirubin residue in the basal ganglia, the risk of kernicterus, with accompanying damage to the central nervous system, is present after birth of the child (and only then). Deafness, epilepsy, and mental retardation can be irreversible consequences.
Further Possible Causes of Acquired Hemolytic Anemia
- RBC damage after long foot marches and long-distance runs (march hemoglobinuria)
- Infections (Malaria >>> Quotidian: variable; Falciparum; Tertian: vivax, every 48 hours; Quartan: malariae, every 72 hours)
- Intoxication (lead intoxication)
- Severely increased copper levels (Wilson’s disease)
- Hemolytic anemia via iso-antibodies (blood transfusion)
- Paroxysmal nocturnal hemoglobinuria (PNH)