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| ==Pathophysiology== | | ==Pathophysiology== |
| A hemolytic state exists whenever the red cell survival time is shortened from the normal average of 120 days. Hemolytic anemia is the hemolytic state in which anemia is present, and bone marrow function is inferentially unable to compensate for the shortened life-span of the red cell. Immune hemolytic states are those, both anemic and nonanemic, which involve immune mechanisms consisting of antigen-antibody reactions. These reactions may result from unrelated antigen-antibody complexes that fix to an innocent-bystander erythrocyte, or from related antigen-antibody combinations in which the host red cell or some part of its structure is or has become antigenic. The latter type of antigen-antibody reaction may be termed "autoimmune", and hemolytic anemias so produced are autoimmune hemolytic anemias.<ref name="pmid5267234">{{cite journal |author=Sawitsky A, Ozaeta PB |title=Disease-associated autoimmune hemolytic anemia |journal=[[Bulletin of the New York Academy of Medicine]] |volume=46 |issue=6 |pages=411–26 |year=1970 |month=June |pmid=5267234 |pmc=1749710 |doi= |url= |accessdate=2012-07-25}}</ref>
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| AIHA can be caused by a number of different classes of antibody, with [[IgG]] and [[IgM]] antibodies being the main causative classes. Depending on which is involved, the [[pathology]] will differ. As IgG is poor at activating [[complement system|complement]] but effectively binds the [[Fc receptor]] (FcR) of [[phagocytosis|phagocytic cells]],<ref>{{cite journal |author=Abramson N, Gelfand EW, Jandl JH, Rosen FS |title=The interaction between human monocytes and red cells. Specificity for IgG subclasses and IgG fragments |journal=J. Exp. Med. |volume=132 |issue=6 |pages=1207–15 |year=1970 |month=December |pmid=5511570 |pmc=2180500 |doi=10.1084/jem.132.6.1207 }}</ref> AIHA involving IgG is generally characterized by phagocytosis of RBCs. IgM is a potent activator of the [[classical complement pathway]], thus, AIHA involving IgM is characterized by complement mediated lysis of RBCs. IgM also leads to phagocytosis of RBCs however, because phagocytic cells have receptors for the bound complement (rather than FcRs as in IgG AIHA). IgG AIHA generally takes place in the [[spleen]], while IgM AIHA takes place in [[Kupffer cells]] – phagocytic cells of the [[liver]]. Phagocytic AIHA is termed extravascular, while complement mediated lysis of RBCs is termed intravascular AIHA. In order for intravascular AIHA to be recognizable it requires overwhelming complement activation, therefore most AIHA is extravascular – be it IgG or IgM mediated.<ref name="pmid11921020">{{cite journal |author=Gehrs BC, Friedberg RC |title=Autoimmune hemolytic anemia |journal=[[American Journal of Hematology]] |volume=69 |issue=4 |pages=258–71 |year=2002 |month=April |pmid=11921020 |doi= |url=http://dx.doi.org/10.1002/ajh.10062 |accessdate=2012-07-25}}</ref>
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| AIHA cannot be attributed to any single autoantibody. To determine the autoantibody or autoantibodies present in a patient, the [[Coombs test]], also known as the antiglobulin test, is performed . There are two types of Coombs test, direct and indirect; more commonly, the direct antiglobulin test (DAT) is used. Classification of the antibodies is based on their activity at different temperatures and their aetiology. Antibodies with high activity at physiological temperature (approximately 37°C) are termed warm autoantibodies. Cold autoantibodies act best at temperatures of 0–4°C. Patients with cold-type AIHA, therefore, have higher disease activity when body temperature falls into a hypothermic state. Usually, the antibody becomes active when it reaches the limbs, at which point it opsonizes RBCs. When these RBCs return to central regions, they are damaged by complement. Patients may present with one or both types of autoantibodies; if both are present, the disease is termed "mixed-type" AIHA.
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| When DAT is performed, the typical presentations of AIHA are as follows. Warm-type AIHA shows a positive reaction with [[antiserum|antisera]] to IgG antibodies with or without complement activation. Cases may also arise with complement alone or with [[IgA]], IgM or a combination of these three antibody classes and complement. Cold type AIHA usually reacts with antisera to complement and occasionally to the above antibodies. This is the case in both cold agglutinin disease and cold paroxysmal hematuria. Mixed warm and cold AIHA generally shows a positive reaction to IgG and complement, sometimes IgG alone and sometimes complement alone. Mixed type can, like the others, present unusually with positive reactions to other antisera.<ref name=Sokol81>{{cite journal |author=Sokol RJ, Hewitt S, Stamps BK |title=Autoimmune haemolysis: an 18-year study of 865 cases referred to a regional transfusion centre |journal=Br Med J (Clin Res Ed) |volume=282 |issue=6281 |pages=2023–7 |year=1981 |month=June |pmid=6788179 |pmc=1505955 |doi=10.1136/bmj.282.6281.2023 }}</ref>
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| ==References== | | ==References== |
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| [[Category:Disease]] | | [[Category:Disease]] |
| [[Category:Hematology]] | | [[Category:Hematology]] |