In contrast to intravascular hemolysis, this is the type of hemolysis typically seen when IgG antibodies (instead of IgM) coat incompatible RBCs. Since IgG isn’t generally great at activating the complement system, these antibodies do not immediately destroy the target RBCs. Instead, the RBCs are removed from the circulation when they pass through the spleen (or liver, to a lesser extent), where there are many macrophages with receptors that recognize IgG-coated RBCs (“Fc receptors”). The resulting hemolysis is typically less dramatic and rapid than that seen in intravascular hemolysis, and the clinical consequences are usually considerably less severe (though that is not always true!). RBC antibodies typically associated with this type of hemolysis include those in the Rh system, Kell system, Duffy system, and MNS system (anti-S and -s more than anti-M or -N). Kidd system antibodies are unique in that they can cause either intravascular or extravascular hemolysis. Most hemolysis seen in delayed hemolytic transfusion reactions is of the extravascular variety (again, with the exception of reactions associated with the Kidd system).
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