= uncommon disorders in which accelerated red cell destruction results from an autoantibody which reacts with a specific blood group antigen present on the subjects own red cells; recognized by positive antiglobulin test.
episode of intravascular hemolysis exposure to cold leads to intravascular Ag-Ab reaction with initiation of complement activation. On warming, transient hemoglobinemia and uria occurs as the complement cascade is completed to C9.
hemolytic process of extravascular hemolysis antibody usually anti-I; continuous Ag-Ab reaction
avoid cold exposure
; treat underlying disease
attempt to reduce antibody production Cytotoxic drugs
attempt to interfere with macrophage (C3b interaction) Steroids less effective, splenectomy helpful
Hemolytic Disease of the Newborn
= hemolytic disorder characterized by extravascular destruction of red cells of the fetus or neonate caused by specific IgG antibody transported across placenta from the maternal circulation to the fetal circulation.
fetus inherits from father a red cell antigen which the mother lacks (maternal-fetal blood group incompatibility)
mother previously alloimmunized (transfusion or pregnancy) to the red cell antigen (any antigen including A or B)
maternal antibody (always IgG) transported across placenta and reacts with antigen of fetal red cells
in the liver and spleen results bilirubin, unconjugated; anemia with reactive extramedullary erythropoiesis (reticulocytosis, erythroblastosis, hepatosplenomegaly); severe anemia Þ hypoxia Þ liver cell damage (hypoalbuminemia, edema, hydrops fetalis, pulm edema); intrauterine death; live birth with anemia and edema
= any IgG; anti-A most common; anti-Rh (D, C, E others); anti-KELL (1st application of Coombs serum)
administration of Rh immune globulin if no Rh antibody is detectable in the womans serum
all Rh negative women who have no demonstrable anti-Rh (D) antibody: during 3rd trimester; after delivery of Rh positive infant; after abortion, miscarriage, amniocentesis; received Rh positive platelets or Rh positive blood
Drug Related Immune Hemolytic Anemias
= disorders in which, by one of three mechanisms, a drug results in an Ab which causes immune red cell destruction
(1) Hapten type
(ex: Penicillin and some of its synthetic derivatives) large doses required (10 million units); drug binds to red cell firmly Þ IgG or IgM directed against the drug Þ Antibody (Fab portion) binds to drug on red cell which is then destroyed extravascularly in reticulo-endothelial system by macrophages.
rarely significant hemolysis; moderate anemia; drug can be continued
(2) Antigen Antibody Complex Innocent bystander type
drug (i.e., Stibophen, Quinine, Quinidine, others) binds to red cell surface forming a new-foreign-antigen ("neoantigen") which leads to antibody production (IgG or IgM). On re-exposure to drug (small amt required), antibody coats the red cell (an innocent bystander) and activates complement
demonstrable in vitro; reaction not inhibited by addition of drug in vitro
(3) Allergic - Autoimmune type
(ex: methyldopa) drug alters immune system (ß # of suppressor T cells (CD8)) and facilitates production of anti-Rh like antibody (IgG) which binds to red cells by Fab portion and triggers cell destruction by macrophages of the reticuloendothelial system (which cannot be stimulated in vitro)
gradual onset (3-6 mo) related to drug dose; reaction continues for days/wks after withdrawal of drug; moderate hemolytic anemia; not life threatening (drug may be continued); severity correlates with dose of Aldomet; drug not involved in antibody reaction; methyldopa, levodopa, mefenamic acid, procainamide all work in similar manner
Hemolytic Transfusion Reactions
= accelerated destruction of transfused red cells by specific alloantibodies resulting in intravascular or extravascular hemolysis. The reaction may occur immediately as the blood is transfused or be delayed 3 to10 days.
(1) Immediate Reactions often with intravascular hemolysis
usually human error; IgM antibody - anti-A or anti-B (complement activation, cascade complete to C9 Þ osmotic hemolysis, activation of coagulation cascade, conversion of plasminogen to plasmin Þ DIC); IgG antibody - Rh, Kell, Duffy (extravascular hemolysis, destruction by phagocytosis or membrane damage)
(2) Delayed Transfusion Reactions
(either IgM or IgG) - prior alloimmunization by transfusion or pregnancy; undetectable antibody present; transfusion re-exhibits antigen, anamnestic immune response occurs resulting in rapid rise in antibody titer and destruction of transfused cells (either intravascular or extra-vascular)