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2348 Part XIII: Transfusion Medicine Chapter 136: Erythrocyte Antigens and Antibodies 2349

suggest the absolute occurrence of Rh antibodies other than anti-D is antigens (Chap. 54). Production can be triggered by disease, viral
40
a
0.22 percent, other than anti-K is 0.19 percent, other than anti-Fy is infection, or drugs; from breakdown in immune system tolerance to
16
a
0.05 percent, and other than anti-Jk is 0.04 percent. The rate of allo- self-antigens; or from exposure to foreign antigens that induce anti-
immunization in patients with sickle cell anemia was 18.6 percent in bodies that crossreact with self-RBC antigens. Autologous specificity
one survey, and 55 percent of the immunized patients made more than is not always obvious because antigen expression can be depressed
one antibody. The most common specificities were anti-C, anti-E, and when autoantibody is present. 40
anti-K. 16 Warm autoantibodies react best at 37°C and are primarily IgG
b
(rarely IgM or IgA). Most are directed against the Rh protein, but Wr ,
Characteristics of Immune Antibodies Kell, Kidd, and U blood group specificities have been reported. 40
Immune antibodies most often are IgG but may be IgM and some- Cold-reactive autoantibodies are primarily IgM. They react best at
times are IgA. Most immune antibodies react at body temperature and temperatures below 25°C but can agglutinate RBCs or activate comple-
are considered clinically significant, except those directed against Bg, ment at or near 37°C, causing hemolysis or vascular occlusion upon
16
Knops, Cs , JMH, and sometimes Yt and Lutheran antigens. exposure to cold. Patients with cold agglutinin disease often have C3d
a
a
on their RBCs, which can provide some protection from hemolysis.
CLINICAL SIGNIFICANCE OF Most cold-reactive autoantibodies have anti-I activity. Reactivity with i,
H, Pr, P, or other antigenic specificities is much less common.
ERYTHROCYTE ANTIBODIES The biphasic cold-reactive IgG antibody associated with paroxys-
mal cold hemoglobinuria (“Donath-Landsteiner” antibody) typically
Information about the clinical significance of alloantibodies is available reacts with the high-prevalence antigen P (GLOB). It attaches to RBCs
at www.nybloodcenter.org. 59,60 in the cold and very efficiently activates complement before it dissoci-
ates at warmer temperatures.
HEMOLYTIC TRANSFUSION REACTIONS

Clinically significant antibodies are capable of destroying transfused
RBCs. The severity of the reaction varies with antigen density and anti- DISEASES ASSOCIATED WITH ANTIBODY
body characteristics. PRODUCTION
Antibodies commonly associated with intravascular hemoly- Table 136–4 lists diseases associated with specific antibody produc-
sis include anti-A, anti-B, anti-Jk , and anti-Jk . ABO incompatibility tion. These antibodies cause autoimmune hemolytic anemia only if the
b
a
is the most potent cause of immediate hemolytic reactions because A patient carries the corresponding antigen.
and B antigens are strongly expressed on RBCs and the antibodies so
efficiently bind complement. Kidd antibodies are associated more often
with delayed hemolytic reactions because they typically are difficult SEROLOGIC DETECTION OF
to detect and can disappear quickly from the circulation. IgG anti-
Jk appears to bind complement only when traces of IgM anti-Jk are ERYTHROCYTE ANTIGENS AND
a
a
present. Anti-PP1P , anti-Vel, and anti-Le have been associated with ANTIBODIES
16
k
a
hemolysis, but such examples are rare.
Extravascular hemolysis occurs with IgG and IgG antibodies that ABO
1
3
react at body temperature; that is, immune antibodies reactive with Rh,
Kidd, Kell, Duffy, or Ss antigens. These antibodies make up the bulk of ABO grouping is the single most important test performed in the
clinically significant antibodies. Antibodies not expected to cause RBC transfusion service because it is the fundamental basis for determining
destruction are those that react only at temperatures below 37°C and blood compatibility. ABO grouping is determined by testing RBCs with
IgG antibodies of the IgG or IgG subclass. 16 licensed antisera to identify the A or B antigens they carry (forward,
2 4 or cell, grouping) and by testing the corresponding serum or plasma
with known A and B cells to identify the antibodies present (reverse,
HEMOLYTIC DISEASE OF THE FETUS AND or serum, grouping). Positive reactions are seen as hemagglutination
NEWBORN or hemolysis, and the results of one test should confirm the results of
HDFN is caused by blood group incompatibility between a sensitized the other.
mother and her antigen-positive fetus (Chap. 55). The antibodies most If results are discrepant or reactions are weaker than expected, the
significant in HDFN are those that cross the placenta (IgG and IgG ), cause must be investigated before the ABO group can be interpreted
1
3
react at body temperature to cause red cell destruction, and are directed with confidence. Discrepancies can be related to RBC anomalies,
5,11,16
against well-developed RBC antigens. ABO incompatibility most com- serum anomalies, or both, and they may be associated with disease.
monly is seen, but ABO HDFN is clinically mild, presumably because Table 136–6 lists common causes, excluding clerical and technical error.
the antigens are not fully expressed at birth. Antibodies directed against If the ABO group of a patient cannot be determined, group O blood can
the D antigen can cause severe HDFN, and fetal health should be care- be used for transfusion.
fully monitored when anti-D titers are greater than 16. The severity of
HDFN is less predictable with other blood group antibodies and can Rh
vary from mild to severe. For example, anti-K and anti-Ge3 not only
causes red cell hemolysis but also may suppress erythropoiesis. 4,6, The D type is the next most important test performed for blood com-
patibility. Individuals whose RBCs type D+ are called Rh-positive, and
those who type D– are called Rh-negative, provided controls are accept-
AUTOIMMUNE HEMOLYTIC ANEMIA able. Blood donors who type D– using standard typing sera are tested
Autoimmune hemolytic anemia is caused by the production of further for weak D expression using more sensitive methods, such as an
“warm-” or “cold-” reactive autoantibodies directed against RBC indirect antiglobulin test. Donors with weak D antigen are considered

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