Page 1913 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 110 Human Blood Group Antigens and Antibodies 1693

Indirect Antiglobulin Test and Direct Antiglobulin Test Approaches to Supplying Red Blood Cell Products to
TABLE Prevent Alloimmunization in Patients With Sickle Cell
110.4
The indirect antiglobulin test (IAT) is used to detect alloantibodies in Disease or Other Transfusion-Dependent Anemia
patient sera in vitro following incubation at 37°C and includes antibody
screening and identification and crossmatching with donor red blood Phenotype or genotype for clinically significant antigens before
cells (RBCs). IAT is also sometimes used for antigen typing to detect transfusion
RBCs coated with antibody following incubation with reagent antisera. Provide antigen-matched blood for C, E, and K prophylactically
After incubation, unbound antibodies are removed by washing with Provide blood negative for the major antigens that the patient lacks
saline and an antiglobulin reagent containing either antihuman IgG after the patient makes an antibody
(AHG) or a mixture of AHG and monoclonal antihuman complement
is added. Differential agglutination suggests the presence of antibodies
to one or more specific RBC antigens while agglutination of all cells
suggests the presence of an antibody to a high-prevalence antigen or
the presence of an autoantibody. antigen-negative blood will to some extent depend on the prevalence
The direct antiglobulin test (DAT) is used to detect the presence of of the target antigen(s) in the donor population. Transfusion service
antibody or complement (or both) on the surface of RBCs in vivo such staff are vital for communication between the patient’s physician and/
as autoantibodies coating the patient’s cells in warm autoimmune or consultant transfusion medicine specialist to determine the imme-
hemolytic anemia, cold hemagglutinin disease, or alloantibodies coating diate and ongoing transfusion needs of the patient and to ensure that
the patient’s cells in immediate or delayed transfusion reactions, or antigen-negative blood is available. Understanding the risks and
hemolytic disease of the fetus and newborn. Patient RBCs obtained benefits of transfusion are important, as well as understanding the
in ethylenediaminetetraacetic acid, to prevent in vitro complement potential clinical significance of the antibody and the urgency of
deposition on the RBCs, are washed with saline and then incubated
with a commercial antiglobulin reagent containing AHG or antihuman transfusion. When a patient’s antibody is directed at a high-prevalence
complement or a mixture of the two. Antiglobulin reagents contain- antigen, it is important to test siblings in the quest for compatible
ing anti-IgM or anti-IgA are available in specialized centers to detect blood and to urge the patient to donate blood for long-term storage
coating of RBCs by antibodies of these isotypes. when clinical status permits. In hemolytic anemia because of warm-
reactive autoantibodies, compatibility may be difficult to demonstrate.
In this scenario, the important issue is to be sure that there are no
clinically significant alloantibodies underlying the warm reactive
Rh Immune Globulin autoantibodies. Donor RBCs antigen-matched with the patient for
clinically significant blood group antigens should be considered in
Rh immune globulin (RhIG) is a human plasma-derived hyperim- lieu of transfusion with “least incompatible” blood to minimize
munoglobulin product consisting of IgG antibodies to D antigen that alloimmunization.
is administered to D-negative pregnant women who are at risk for
D sensitization. RhIG is administered (1) at 28 weeks gestational
age, (2) when there is a risk for fetal maternal hemorrhage through Prevention of Alloimmunization
amniocentesis, trauma, or other procedures, and (3) postpartum in the
case of a known or potential D-positive newborn or fetus. If the Rh(D)
typing of a pregnant woman is discrepant with prior results, or typing Transfusion management of patients who require chronic trans-
reactions are weaker than expected, or if variable reactivity is seen, fusion therapy, in particular patients with sickle cell disease can
RHD genotyping should be considered to guide RhIG prophylaxis and be challenging. 9–11 Many programs attempt to reduce or prevent
selection of blood for transfusion. alloimmunization by transfusion of RBCs that are prophylactically
RhIG is sometimes administered outside of pregnancy to D-negative antigen-matched, typically for C, E, and K, and some match for
12
patients who receive D-positive blood products, most commonly whole additional antigens. Some centers match for extended antigens once
blood derived platelet products. This is primarily considered for females the patient makes an antibody (Table 110.4). The goal is to prevent
of childbearing potential when the formation of anti-D has serious
consequences. Because the risk for D alloimmunization from whole hemolytic or delayed transfusion reactions, which are known to be
blood derived platelet transfusion is less than 4%, and even less for underreported because they can manifest as a sickle cell crisis and
apheresis platelets, the majority of D-incompatible platelets are given may result in decreasing the transfusion interval.
without RhIG administration. RhIG in significantly higher doses is used
to treat immune thrombocytopenic purpura (ITP) in patients who are
D-positive and have not been splenectomized. Blood Group Disease Association
For prevention of D-sensitization in the United States, 300 µg are
routinely administered, but dosing is increased if there is evidence The absence of some blood group antigens and their carrier molecules
of large fetal-maternal hemorrhage (300 µg for every 15 mL of RBC can result in disease. For example, an absence of the Rh and
exposure or 30 mL of whole blood exposure). The dose is calculated 13
based on the estimated volume of D-positive fetal RBCs from Kleihauer- Rh-associated glycoprotein (RhAG) proteins causes stomatocytosis
Betke or flow cytometry, which is more precise. RhIG dosing calculators and anemia, termed Rh null syndrome. The absence of Xk protein is
are available. RhIG should be given within 72 hours, which was the associated with the McLeod syndrome, which is associated with
time period for the original studies, but should not be withheld if not myopathy and neurodegeneration. RBCs and white blood cells from
administered within this time period. Adverse events to low doses patients with leukocyte adhesion deficiency II (also known as con-
used to prevent D immunization include fever, chills, and pain at the genital disorder of glycosylation type II) lack antigens that are dependent
injection site. Rarely, hypersensitivity reactions are noted. RhIG doses on fucose. The RBCs have the Le(a−b−) Bombay phenotype and the
used to treat ITP are substantial: 50 µg/kg for hemoglobin values white blood cells lack sialyl-Le , which explains the high white blood
x
≥10 g/dL and 25–40 µg/kg when hemoglobin is 8–10 g/dL. Adverse cell count and infections in these patients. Hemagglutination is a
events include possible anemia, hemolysis, disseminated intravascular
coagulopathy, and rarely, death (Chapter 131). simple test that can be used to diagnose these syndromes. In patients
with paroxysmal nocturnal hemoglobinuria, a proportion of the
RBCs will lack antigens carried on GPI-linked proteins. Other
associations between blood group antigens and diseases are summa-
transfused with antigen-negative RBCs only while the passive anti- rized in Table 110.1.
body is present. Selection of blood for transfusion to patients with Diseases associated with antibodies to blood group antigens
alloantibodies requires typing of donor units for the corresponding include hemolytic disease of the newborn, warm autoimmune hemo-
antigen to identify antigen-negative units and crossmatch of the lytic anemia, cold hemagglutinin disease, and paroxysmal cold
selected units with the patient’s plasma. Antigen-negative units are hemoglobinuria. Hemagglutination is a valuable aid in diagnosis of
provided by, or can be located by, most donor centers. Provision of these conditions.