Page 1917 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 110 Human Blood Group Antigens and Antibodies 1697

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Several phenotypes, including D− −, Dc−, and DC −, have an
enhanced expression of D antigen and no, or variant, CE antigens. Transfusion Management of Patients With Warm Autoimmune Hemolytic
Anemia
They are caused by replacement of portions of RHCE by RHD. The
RhD sequences in RhCE, along with a normal RhD, explain the Patients with warm autoimmune hemolytic anemia may present with
enhanced D and account for the lack, or reduced expression, of CE jaundice, fatigue, and anemia, or they may show no overt clinical
antigens. Immunized individuals with these CE-depleted phenotypes manifestations. The antibody screen and antibody identification panel
can make antibodies to high-prevalence Rh antigens. will show all red blood cells (RBCs) positive (panagglutinin) with anti-
C and c antigens differ by four amino acids, but only residue IgG in the indirect antiglobulin test. The autocontrol (patient’s own
Ser103Pro is predicted to be extracellular. E and e differ by one amino plasma and RBCs) will also be positive.
acid, Pro226Ala. The RhD and various combinations of RhCE History: A transfusion history should be obtained to differentiate
proteins (ce, Ce, cE, and CE) are typical for the majority of white these results from a hemolytic transfusion reaction or hemolysis
because of an alloantibody.
transfusion recipients. However, Rh proteins in other ethnic groups DAT: A direct antiglobulin test should be performed with anti-IgG
often carry additional polymorphisms, particularly in individuals of and anti-C3. In clinically significant hemolysis, the DAT is usually
African descent, and this fact often complicates transfusion in patients strongly positive.
with sickle cell disease. For example, the RBCs of more than 30% of Eluate: If patient has been recently transfused (3–4 months), an
blacks are VS+ because of a Leu245Val substitution in Rhce, and eluate should be prepared from the patient cells to remove the
expression of this antigen is associated with variant expression of e antibody(ies); the eluate should be tested to determine specificity.
antigen. Many other amino acid changes in Rhce, as well as in RhD, The eluate is usually reactive with all cells when tested by the IAT
are associated with production of Rh antibodies in patients with with anti-IgG.
sickle cell disease. RH genotyping by DNA methods allows enhanced Phenotype or genotype: Type the patient’s RBCs for minor blood
group antigens (Cc, Ee, K, Jka/b, Fya/b, Ss) if the patient has not
Rh antigen matching of patients and donors and is particularly been recently transfused. When possible, IgM typing reagents are
important in patients who present with Rh antibodies reacting with used because the patient’s own antibody-coated RBCs may result
all, or the majority, of cells tested. in false-positive typing. Some laboratories are able to remove the
The Rh null phenotype is very rare and occurs on two genetic IgG from the RBCs and perform a phenotype, but alternatively,
a/b
backgrounds: the “regulator” type, caused by mutations in RHAG, genotyping for minor blood group antigens including Do
which encodes an Rh-associated glycoprotein, and the “amorph” type, antigens (there is no serologic reagent) can be performed.
caused by mutations in RHCE on a D− (deleted RHD) background. Adsorption: Adsorb the serum autoantibody onto the patient’s own
Rh null RBCs are stomatocytic, fragile, and associated with anemia. RBCs to test for underlying alloantibody if the patient has not
RhAG is involved in maintenance of cation balance in RBCs. 13 been recently transfused (3–4 months). If the patient has been
recently transfused or if the low hematocrit results in insufficient
autologous RBCs, perform alloadsorption with well-characterized
Antibodies Most Rh antibodies are IgG and do not activate comple- RBCs (usually three with known antigen profiles). Test the
ment. As a result, primarily extravascular hemolysis, rather than adsorbed serum for underlying alloantibodies.
intravascular hemolysis, occurs in transfusion reactions involving Rh Crossmatch: Perform with neat and with adsorbed plasma.
antibodies. The antibodies are almost always caused by RBC immu- Crossmatch performed with neat plasma will usually be
nization from pregnancy or transfusion and usually persist for years. incompatible.
Anti-D can cause severe hemolytic transfusion reactions and HDFN, Communication: Inform ordering physician of reactivity and of delay
but the incidence of anti-D has decreased with the prophylactic use in receiving crossmatched RBCs. Provide emergency-release
of Rh immune globulin. Most Rh antibodies should be considered RBCs if patient’s clinical situation warrants. Inform the physician
that the patient may hemolyze transfused RBCs similar to
as having the potential to be clinically significant for HDFN and hemolysis of his or her own RBCs.
hemolytic transfusion reactions. If serum antibody levels fall below Transfusion: Consider providing RBC units negative for minor
detectable levels, subsequent exposure to the antigen characteristically antigens that the patient also lacks. Consider matching for Cc,
produces a rapid secondary immune response. Autoantibodies in the Ee, K, Jka/b, Fya/b, Ss (and Doa/b if possible). This potentially
sera of patients with warm autoimmune hemolytic anemia, as well as enables RBC units to be available before completion of the
in some cases of drug-induced autoimmune hemolytic anemia, antibody identification testing. Transfusion with antigen-matched
appear to demonstrate relative specificity to high-prevalence Rh units potentially allows continued transfusion without need for
antigens, although specificity for other members of the Rh complex autoadsorption or alloadsorption unless signs and symptoms
have not been ruled out (see box on Transfusion Management of of RBC destruction occur or there is a change in reactivity in
antibody screening or the DAT.
Patients With Warm Autoimmune Hemolytic Anemia).
RHAG Blood Group System
RhAG glycoprotein, encoded by RHAG, is highly similar to the RhD
and RhCE proteins. It carries four blood group antigens: two of high membrane. Kell is highly polymorphic because of single amino acid
prevalence (RHAG1 and 3) and two of low prevalence (RHAG 2 and substitutions in the glycoprotein that account for 35 of 36 antigens
4). Antibodies to RHAG4 cause HDFN. RhAG is important for described to date. The K antigen is remarkably immunogenic even-
erythrocyte ion balance in RBCs and is required for the expression though it differs from wild-type (k, small k) by only one amino acid,
of RhD and RhCE proteins forming the core of the Rh-complex. and it appears that loss of an N-glycan exposes the peptide, thereby
rendering it immunogenic.
LW Blood Group System Inherited weak expression of Kell antigens, termed K mod pheno-
a
Rh and LW are independent blood group systems but have a pheno- type, occurs with amino acid changes in the protein, with Kp in cis,
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typic relationship. In adults, D-positive RBCs have a stronger expres- and in the McLeod phenotype. Transient depression of Kell system
sion of LW antigen than D-negative RBCs, and anti-LW can be antigens may also occur in autoimmune hemolytic anemia, in micro-
confused with anti-D. Transient loss of LW antigens from RBCs has bial infections, and was reported in two cases of idiopathic thrombo-
been described in pregnancy and in patients with diseases, particularly cytopenia purpura. The lack of Kell antigens (the K 0 or K null
Hodgkin disease, lymphoma, leukemia, sarcoma, and other forms of phenotype) is caused by multiple different gene defects.
malignancy. Loss of LW antigens is usually associated with the pro- HDFN caused by anti-K can result in severe neonatal anemia, and
duction of antibodies that appear to be alloanti-LW. unlike anti-D, maternal antibody titers and amniotic bilirubin levels
are not good predictors of the severity of the disease. Kell antigens
Kell and Kx Systems are expressed very early during erythropoiesis, and anti-K has been
The Kell glycoprotein is highly folded through multiple intrachain shown to suppress erythropoiesis in vitro. This may explain the low
disulfide bonds and is covalently linked to the XK protein in the RBC level of bilirubin observed in cases of neonatal anemia; thus Doppler