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Allogeneic Red Blood Cell Adsorption for Removal of Warm Autoantibody

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Allogeneic Red Blood Cell Adsorption for Removal of Warm Autoantibody Allogeneic red blood cell adsorption for removal of warm autoantibody C. Barron Adsorption studies are usually required to confirm or rule out Reagents/Supplies the presence of underlying alloantibodies in samples containing warm autoantibody. Allogeneic adsorptions are necessary if the Treatment patient has been recently transfused. Most commonly, allogeneic Method Reagents Supplies adsorptions are performed using a trio of phenotyped reagent Papain • 1% cysteine-activated red blood cells to rule out clinically significant alloantibodies to papain common antigens. The adsorbing cells may be used untreated • Pipettes or treated with enzymes or with ZZAP before adsorption. Ficin • 1% ficin • Isotonic • 37°C water Adsorption may also be performed using enhancement such ZZAP • 1% cysteine-activated saline bath SEROLOGIC METHOD REVIEW as low-ionic strength saline or polyethylene glycol added to papain or 1% ficin • Allogeneic the mixture. Multiple adsorptions may be necessary to remove RBCs • Large-bore • 0.2 M DTT test tubes strongly reactive autoantibodies. Allogeneic adsorptions • Glycine max • Commercial LISS will not detect alloantibodies to high-prevalence antigens. var. soja • Calibrated enhancement reagent centrifuge Immunohematology 2014;30:153–155. • 20% PEG or commercial PEG enhancement Key Words: AIHA, adsorption, autoantibody, alloantibody, DTT = dithiothreitol; RBCs = red blood cells; LISS = low-ionic-strength allogeneic RBCs saline; PEG = polyethylene glycol. The serum from patients with warm autoimmune Procedural Steps hemolytic anemia (WAIHA) typically demonstrates broad Preparation of RBCs for adsorption reactivity with all reagent red blood cells (RBCs). This • Select reagent RBCs for use as adsorbing cells. reactivity usually necessitates the use of incompatible blood for • Treat the adsorbing cells with the desired enzyme or ZZAP. transfusion. When blood is incompatible as a result of an RBC Adsorption autoantibody, transfused RBCs will survive at a rate similar • Add 1 to 2 volumes of treated adsorbing cells to 1 volume of to that of the patient’s own RBCs.1 However, autoantibody patient serum or plasma and 1 volume of enhancement reagent (if applicable). reactivity may mask the reactions of underlying clinically • Incubate for 30–60 minutes at 37°C without enhancement, or 15 significant alloantibodies to common antigens, which can minutes at 37°C with LISS or PEG enhancement. • Harvest the adsorbed serum or plasma and test for the presence of cause rapid RBC destruction. The rate of alloimmunization in underlying alloantibodies. patients with warm autoantibodies varies among investigators. RBCs = red blood cells. Reported alloimmunization rates range from 17.5 to 38 percent, with an average rate of 32 percent.2–7 Issitt et al.4 found that 47 percent of alloantibody specificities identified after adsorption were actually partially adsorbed autoantibodies autoantibody has been removed and whether alloantibody with mimicking specificities. Mimicking autoantibody is present.8 Although this may be useful as a screening tool, specificities were found most often when autologous adsorption this method has been shown to be unreliable in consistently was used to remove autoantibody reactivity. Identification of detecting alloantibody underlying autoantibody.9 Autologous alloantibody specificities underlying a warm autoantibody is adsorption, which uses the patient’s own RBCs to remove critical for a safe and effective transfusion. the autoantibody, is a preferred method. Using autologous Methods used to determine the presence of an alloantibody RBCs ensures that only autoantibodies are removed from the underlying an autoantibody include serum dilution, autologous serum, leaving intact any alloantibody the patient may have adsorption, and allogeneic adsorption. The dilution screening produced, including antibodies to high-prevalence antigens. method uses a 1:5 dilution of serum in phosphate-buffered However, autologous adsorptions may only be performed saline. The diluted serum is tested to determine whether the when the patient has not been recently transfused or pregnant, IMMUNOHEMATOLOGY, Volume 30, Number 4, 2014 153 C. Barron commonly defined as having no transfusions or pregnancy in specificity corresponding to an antigen that is destroyed by the prior 3 months. Alloantibody may be removed from the enzymes (e.g., anti-Ge2) or ZZAP (e.g., anti-LWa or Kell system test system if autologous adsorptions are performed using antibodies). In these cases, adsorption with untreated reagent a sample from a recently transfused patient. Laine et al.10 RBCs is necessary. showed that even small amounts of transfused RBCs are The addition of enhancement media to the adsorbing capable of removing all alloantibody reactivity. Allogeneic mixture has also become commonplace and can be used in RBC adsorption is the method of choice for removal of warm place of RBC pretreatment. The addition of low-ionic-strength autoantibody reactivity in patients with recent transfusions. saline (LISS) or polyethylene glycol (PEG) reduces the Note that the term “serum” is used to denote the patient sample processing time and may decrease the number of adsorptions throughout this article; however, either serum or plasma may required to remove the autoantibody.9,11,12 However, some be used for testing. investigators caution that some underlying alloantibodies may not be detected when PEG adsorptions are performed.13,14 Principle Indications Allogeneic adsorptions are used to remove broadly reactive autoantibody from a patient’s serum to allow for detection of Allogeneic adsorptions should be used when a patient has underlying clinically significant alloantibodies to common been recently transfused or when autologous cells are of limited antigens. The adsorbing cells will remove autoantibody along supply. Adsorption eliminates the reactivity of the warm with any additional antibody specificities to antigens that are autoantibody, allowing for the identification of alloantibodies present on the RBC. When performing allogeneic adsorptions, in the adsorbed serum. the goal is to eliminate or confirm the presence of those alloantibodies directed at the common antigens D, C, E, c, e, Procedure K, S, s, Fya, Fyb, Jka, and Jkb. Traditional allogeneic adsorptions use a set of three Select cells for adsorption. If the patient’s RBC phenotype is adsorbing cells with known phenotypes: R1R1, R2R2, and rr. known, select a phenotypically similar reagent RBC that lacks At least one of the adsorbing cells should be negative for K and the same common RBC antigens as the patient’s RBCs. If the Jka or Jkb. In addition, at least one of the reagent cells should patient’s RBC phenotype is unknown, select a trio of reagent a b also lack S or s and Fy or Fy unless the cells are pretreated RBCs: R1R1, R2R2, and rr. Additionally, at least one cell of the to denature the antigens. A separate aliquot of patient serum set should be negative for K and Jka or Jkb so that all common is incubated with each adsorbing cell. Once all autoantibody alloantibodies can be detected using the adsorbed serum. If reactivity is removed, the three adsorbed serums are tested to adsorptions will be performed using untreated reagent RBCs, eliminate or prove the presence of any underlying alloantibody. at least one cell should be negative for S or s and Fya or Fyb as Each aliquot of adsorbed serum contains alloantibody well.15–18 corresponding to those antigens for which the adsorbing cell If desired, treat the adsorbing cells with enzymes (ficin was negative. or papain) or ZZAP (ficin or papain and 0.2 M DTT). This If a patient’s RBC phenotype is known, it may be possible pretreatment will typically enhance the adsorbing process. to adsorb using a single phenotypically similar reagent RBC. Following pretreatment, wash the adsorbing cells, For instance, if a patient is only negative for E, K, S, and Fya, centrifuge, and remove all excess saline before use. Perform one reagent RBC negative for those antigens can be used for the adsorption by mixing one to two volumes of allogeneic adsorption. After adsorption, the adsorbed serum can be RBCs with one volume of patient serum at 37°C for 30 to 60 tested to confirm or eliminate the presence of anti-E, -K, -S, minutes. and/or -Fya. Another option is to perform the adsorption by mixing Various methods are used for performing the adsorption. one volume of patient serum and one volume of LISS or PEG19 Treatment of the adsorbing cells using enzymes or ZZAP may with one to two volumes of allogeneic reagent RBCs at 37°C enhance the uptake of the autoantibody.9 These cell treat- for 15 minutes.15–18 ments will also destroy some antigens, which may be After the adsorption, centrifuge the mixture and harvest advantageous when selecting cells for adsorption and testing the adsorbed serum. Test the adsorbed serum to determine the adsorbed serum. Rarely, autoantibodies may demonstrate whether adsorption is complete. This may be accomplished 154 IMMUNOHEMATOLOGY, Volume 30, Number 4, 2014 Allogeneic RBC adsorption for autoantibody removal by testing the adsorbed serum against the adsorbing cells 4. Issitt PD, Combs MR, Bumgarner DJ, Allen J, Kirkland or by testing the adsorbed serum against a reagent RBC A, Melroy-Carawan H. Studies of antibodies in the sera of patients who have made red cell autoantibodies. Transfusion phenotypically similar to the adsorbing cell. If necessary, 1996;36:481–6. repeat the adsorption using a new aliquot of adsorbing cells. 5. Laine EP, Leger RM, Arndt PA, Calhoun L, Garratty G, Once adsorption is complete, test the adsorbed serum Petz LD. In vitro studies of the impact of transfusion on the against reagent RBCs to rule out the presence of underlying detection of alloantibodies after autoadsorption. Transfusion 2000;40:1384–7. alloantibodies. For instance, if the adsorbing cell is R1R1, S–, 6. Young PP, Uzieblo A, Trulock E, Lublin DM, Goodnough LT. K– Jk(a–), then the following alloantibodies can be ruled out Autoantibody formation after alloimmunization: are blood in that aliquot of adsorbed serum; anti-E, -c, -S, -K, and -Jka. transfusions a risk factor for autoimmune hemolytic anemia? Transfusion 2004;44:67–72.
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