Transfusion Reactions. Transfusion reactions are examples of antibody-dependent, complement-mediated cytotoxic reactions. The term transfusion reaction generally refers to the adverse consequences of incompatibility between patient and donor erythrocytes. Transfusion reactions can include hemolytic (red blood cell [RBC]–lysing) reactions occurring during or shortly after a transfusion, shortened posttransfusion survival of RBCs, an allergic response, or disease transmission.

Transfusion reactions can be divided into hemolytic and nonhemolytic types. Hemolytic reactions are associated with the infusion of incompatible erythrocytes. These reactions can be further classified into acute (immediate) or delayed in their manifestations (Box 1). Several factors influence whether a transfusion reaction will be acute or delayed, including the following:

• Number of incompatible erythrocytes infused

 • Antibody class or subclass

 • Achievement of the optimal temperature for antibody binding

Box1. Types of Transfusion Reactions

Immediate Hemolytic Reactions. The most common cause of an acute hemolytic transfusion reaction is the transfusion of ABO group–incompatible blood. In patients with preexisting anti bodies resulting from prior transfusion or pregnancy, other blood groups may be responsible.

Epidemiology. Acute hemolytic reactions are the most serious and potentially lethal transfusion reactions. Most fatalities resulting from acute hemolytic transfusion reactions occur in anesthetized or unconscious patients, with the immediate cause of death being uncontrollable hypotension.

Signs and Symptoms. Reactions can occur with the infusion of as little as 10 to 15 mL of incompatible blood. The most common initial symptoms are fever and chills, which mimic a febrile nonhemolytic reaction caused by leukocyte incompatibility. Back pain, shortness of breath, pain at the infusion site, and hypotension are additional symptoms. In addition to shock, the release of thromboplastic substances into the circulation can induce disseminated intravascular coagulation and acute renal failure.

Immunologic Manifestations. Acute hemolytic reactions occur during infusion or immediately after blood has been infused. Infusion of incompatible erythrocytes in the presence of preexisting antibodies initiates an antigen-antibody reaction, with activation of the complement, plasminogen, kinin, and coagulation systems. Other initiators of acute hemolytic reactions include bacterial contamination of blood or infusion of hemolyzed erythrocytes. Many reactions demonstrate extra vascular and intravascular hemolysis. If an antibody is capable of activating complement and is sufficiently active in vivo, intravascular hemolysis occurs, producing a rapid increase of free hemoglobin in the circulation. Although uncertain, the cause of the immediate clinical symptoms may be products released by the action of complement on the erythrocytes, which triggers multiple shock mechanisms.

Delayed Hemolytic Reaction. A delayed reaction may not manifest until 7 to 10 days after transfusion. In contrast to an immediate reaction, a delayed reaction occurs in the extravascular spaces. These reactions are associated with decreased RBC survival because of the coating of the RBCs (positive direct antiglobulin test), which promotes phagocytosis and premature removal of RBCs by the mononuclear phagocyte system. If an antibody does not activate complement or activates it very slowly, extravascular hemolysis occurs. Most IgG antibody–coated erythrocytes are destroyed extravascularly, mainly in the spleen.

A delayed hemolytic transfusion reaction may be of two types. It may represent an anamnestic antibody response in a previously immunized recipient on secondary exposure to transfused erythrocyte antigens, or it may result from primary alloimmunization. In an anamnestic response, the antibodies are directed against antigens to which the recipient has been previously immunized by transfusion or pregnancy.

Hemolytic Disease of the Fetus and Newborn. Hemolytic disease of the fetus and newborn (HDFN) results from excessive destruction of fetal RBCs by maternal antibodies. HDFN in the fetus or neonate is clinically characterized by anemia and jaundice. If the hemoglobin breakdown product that visibly produces jaundice (bilirubin) reaches excessive levels in the newborn’s circulation, it will accumulate in lipid-rich nervous system tissue and can result in mental retardation or death.

Etiology. Antigens possessed by the fetus that are foreign to the mother can provoke an antibody response in the mother. Any blood group antigen that occurs as an IgG antibody is capable of causing HDFN.

Although anti-A and anti-B are present in the absence of their corresponding antigens as environmentally stimulated (IgM) antibodies, infrequent IgG forms may be responsible for HDFN because of ABO incompatibility. High titers of anti-A, anti-B of the IgG type in group O mothers often cause mild HDFN. Anti-A and anti-B antibodies are usually 19S (IgM) in character and, as such, are unable to pass through the placental barrier. In addition, the A and B antigens are not fully expressed on the erythrocytes of the fetus and newborn. In a survey of antibodies that have caused HDFN, more than 70 different antibodies were identified.

Epidemiology. The incidence of HDFN resulting from ABO incompatibility ranges from 1 in 70 to 180, with an estimated average of 1 in 150 births. The most frequent form of ABO incompatibility occurs when the mother is type O and the baby is type A or type B, usually type A.

Until the early 1970s, the Rh antibody anti-D was the most frequent cause of moderate or severe forms of HDFN. Anti-D occurred alone or in combination with another Rh antibody such as anti-C. Anti-D accounted for approximately 93% of cases of non-ABO HDFN. Since the development of modern treatment to prevent primary immunization to the D antigen, the frequency of HDFN caused by anti-D has significantly decreased.

Signs and Symptoms. Hemolytic disease resulting from ABO incompatibility is usually mild because of fewer A and B anti gen sites on the fetal or newborn erythrocytes, weaker antigen strength of fetal or newborn A and B antigens, and competition for anti-A and anti-B between tissues and erythrocytes. The number and strength of A and B antigen sites on fetal erythrocytes are less than on adult RBC membranes. In addition, A and B substances are not confined to the RBCs, so only a small fraction of IgG anti-A and anti-B that crosses the placenta combines with the infant’s erythrocytes.

Manifestations of HDFN caused by other antibodies can range from mild to severe. In addition to possible death in utero, newborns may demonstrate severe anemia and an increase in RBC breakdown products, such as bilirubin. Accumulation of bilirubin causes jaundice and may result in mental retardation if the bilirubin is not cleared from the infant’s body. Immunologic Mechanisms. For antibody formation to take place, the mother must lack the antigen and the fetus must express the antigen (gene product). The fetus would inherit the gene for antigen expression from the father. HDFN results from the production of maternal antibodies that have been stimulated by the presence of these foreign fetal antigens. The actual production of antibodies depends on a variety of factors: the genetic makeup of the mother, the antigenicity of a specific antigen, and the actual amount of antigen introduced into the maternal circulation.

Transplacental hemorrhage (TPH) can occur at any stage of pregnancy. Immunization resulting from TPH can result from negligible doses during the first 6 months in utero; however, significant immunizing hemorrhage usually occurs during the third trimester or at delivery. Fetal erythrocytes can also enter the maternal circulation as the result of physical trauma from an injury, abortion, ectopic pregnancy, amniocentesis, or normal delivery. Abruptio placentae, cesarean section, and manual removal of the placenta are often associated with a consider able increase in TPH.

An example of the normal pattern of immunization is demonstrated by the case of an Rh(D)-negative mother whose primary immunization (sensitization) was caused by a previously incompatible Rh(D)-positive pregnancy or a blood transfusion, which stimulates the production of low-titered anti-D, pre dominantly of the IgM class. Subsequent antigenic stimulation, such as fetal-maternal hemorrhage during pregnancy with an Rh(D)-positive fetus, can elicit a secondary (anamnestic) response, characterized by the predominance of increasing titers of anti-D of the IgG class.

Immune antibodies subsequently react with fetal antigens. Erythrocytic antigens, as well as leukocyte and platelet antigens, can induce maternal immunization by the formation of IgG antibodies. In HDFN, the erythrocytes of the fetus become coated with maternal antibodies that correspond to specific fetal antigens. Antibodies to IgG, the only immunoglobulin selectively transported to the fetus, are transferred from the maternal circulation to the fetal circulation through the placenta. The mechanism whereby IgG passes through the placenta has not been definitively established. Most research on transplacental passage supports the hypothesis that all IgG subclasses are capable of crossing the placental barrier between mother and fetus.

When the antigen and its corresponding antibody combine in vivo, increased lysis of RBCs results. Because of this hemolytic process, the normal 45- to 70-day lifespan of the fetal erythrocytes is reduced. To compensate for RBC loss, the fetal liver, spleen, and bone marrow respond by increasing production of erythrocytes. Increased RBC production outside the bone marrow, extramedullary hematopoiesis, can result in enlargement of the liver and spleen and premature release of nucleated erythrocytes from the bone marrow into the fetal circulation. If increased RBC production cannot compensate for the cell being destroyed, a progressively severe anemia develops that can cause the fetus to develop cardiac failure, with generalized edema and death in utero. Less severely affected infants continue to experience erythrocyte destruction after birth, which generates large quantities of unconjugated bilirubin. Bilirubin resulting from excessive hemolysis could result in the accumulation of free bilirubin in lipid-rich tissue of the central nervous system.

Diagnostic Evaluation. The following procedures are generally used for the prenatal or postnatal diagnostic evaluation of HDFN:

 • ABO blood grouping

 • Rh testing

• Screening for irregular antibodies; identification and titering of any antibodies

• Amniocentesis (prenatal)

• Serum bilirubin of cord or infant blood

 • Direct antiglobulin test of cord or infant blood

• Peripheral blood smear

• Kleihauer-Betke test

Prevention. Independent researchers have shown that a passive antibody, Rh IgG, could protect most Rh-negative mothers from becoming immunized after the delivery of Rh(D)-positive infants or similar obstetric conditions. In 1968, Rh IgG was licensed for administration in the United States. Since that time, the incidence of HDFN caused by anti-D has decreased dramatically, although complete elimination may never occur because of the cases in which anti-D is formed before delivery. All pregnant Rh-negative women should receive Rh IgG, even if the Rh status of the fetus is unknown, because fetal D antigen is present on fetal erythrocytes as early as 38 days from conception.

Autoimmune Hemolytic Anemia. Autoimmune hemolytic anemia is an example of a type II hypersensitivity reaction directed against self antigens on RBCs. It can take two forms, cold autoagglutinins and warm autoagglutinins.

Cold Autoimmune Hemolytic Anemia. Cold autoagglutinins, usually IgM, represent about one third of cases of immune hemolytic anemia. Cold agglutinins react best at room temperature or lower.

Warm Autoimmune Hemolytic Anemia. In contrast to the cold form, warm autoagglutinins, usually IgG, represent most cases of autoimmune hemolytic anemia. Although the source of antigen exposure may be unknown, antibodies can be formed to microorganisms or drugs. Warm autoagglutinins react best at 37° C (98.6° F).

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مواضيع ذات صلة

Immunologic Manifestations of Rubella infection

Antigen presentation

Cytokines

Structure of MHC Molecule

MHC Genes and Their Products

Macrophage

B Lymphocytes

T Lymphocytes

Immunologic Manifestations of Infectious Mononucleosis

Peripheral Lymphoid Organs

Central Lymphoid Organs

Effector Functions of Complement