Donor anti-Jk(a) causing hemolysis in a liver transplant recipient

BACKGROUND: Hemolytic transfusion reactions have been observed in recipients of ABO- and/or D-mismatched marrow, peripheral blood, and solid organs. Passenger lymphocyte syndrome occurs when immunocompetent donor lymphocytes transferred during transplantation produce alloantibodies against host antigens. CASE REPORT: The first case of a delayed, anti-Jk(a)-mediated hemolytic reaction in a liver transplant recipient, caused by passenger donor lymphocytes, is reported here. A 43-year-old man underwent liver transplantation. Six weeks later, the patient underwent a second liver transplant. On Day 10 of the second transplant, clinical hemolysis ensued; anti-Jk(a) was detected. The patient's DAT became positive, and anti-Jk(a) was eluted from his RBCs. On Day 35 of the patient's second transplant, 3 weeks after the last blood transfusion, the patients' DAT was still weakly positive with anti-Jk(a) in the eluate. Six months later, serum antibody screening was negative, but the DAT was still weakly positive. The patient's RBCs tested Jk(a+), whereas the second donor's RBCs were Jk(a-). CONCLUSION: This is the first documentation of clinically significant hemolysis caused by anti-Jk(a), produced by passenger lymphocytes transferred from the donor's liver to the transplant recipient.     

Prophylactic antigen-matched donor blood for patients with warm autoantibodies: an algorithm for transfusion management

BACKGROUND: Patients with warm autoantibodies are at high risk for delayed hemolytic transfusion reactions due to the presence of alloantibodies. To provide blood safe for transfusion and to avoid adsorption studies in some cases, the provision of prophylactic antigen-matched donor blood where feasible for patients with warm autoantibodies is advocated. STUDY DESIGN AND METHODS: Twenty consecutive adult patients with warm autoantibodies (January 1999 to February 2000) received chronic RBC transfusions by use of this protocol: the serology consistent with warm autoantibodies was confirmed; the alloantibodies were identified; the complete phenotype was determined (i.e., C, E, c, e, K, Jk(a), Jk(b), Fy(a), Fy(b), S, and s); and prophylactic antigen-matched (i.e., donor RBCs matched with the patient's phenotype), WBC-reduced donor RBCs were provided for transfusion. On subsequent admissions, samples were evaluated by panel studies and DATs. If the serology remained consistent with previous findings, prophylactic antigen-matched, WBC-reduced RBCs were transfused without further testing. RESULTS: Eight of 20 (40%) patients had existing, clinically significant alloantibodies. In 12 of 20 (60%) patients, a phenotype was determined and the patients received transfusion of a total of 149 prophylactic antigen-matched RBC units (mean, 15 units per patient) precluding adsorption studies on 51 pretransfusion samples. In 8 of 20 (40%) cases (2 with alloantibodies), phenotypes were indeterminant, necessitating differential allogeneic adsorption studies on 39 samples before transfusion of 144 RBC units (mean, 18 units per patient). CONCLUSIONS: Determining complete phenotypes should be a routine component of the serologic evaluation of patients with warm autoantibodies. Our algorithm for providing prophylactic antigen-matched RBCs to these patients when a complete phenotype can be determined provides flexibility in their transfusion management while maintaining safety and circumvents or simplifies pretransfusion adsorption studies.     

Transient anti-Gya in an untransfused man. Serologic characteristics and cell survival study

Anti-Gya was identified in the serum of a 71-year-old untransfused man of German descent. The anti-Gya was reactive in the antiglobulin test phase and was of the IgG1 subclass. The patient's red cells typed as Gy(a-). A survival study using 10 ml of ABO compatible Gy(a+) 51Cr labelled red blood cells indicated normal survival up to six days. The anti-Gya diminished in reaction strength, and three months after the patient's initial hospitalization the antibody was no longer demonstrable by standard manual techniques. We conclude that intravascular hemolysis would have been unlikely if this patient were transfused with Gy(a+) cells. However, due to the possibility of a delayed hemolytic transfusion reaction, Gy(a+) cells would have been given only if Gy(a-) cells were not available and the patient's red blood cell deficit were life-threatening.     

A MAR-like antibody in a DCWe/DCWe person

BACKGROUND: MAR (RH51), a high-incidence antigen in the Rh blood group system, is absent from RBCs with a double dose of CW or CX or a single dose each of CW and CX antigens, as well as from rare Rh phenotypes including D- - and Rh(null). The MAR antigen is associated with the presence of Ala36 and Gln41 on the RhCe protein. The original example of anti-MAR, described in 1994, was made by a DCWe/DCXe woman. It was possible that the antibody directed against a high-incidence antigen in the Rh system made by a DCXe/DCXe woman (CM) in 1983 was anti-MAR. CASE REPORT: A 52-year-old, multiply transfused, white woman (CJ) with pre-existing anti-c, -E, and -Jk(a) presented for preoperative work-up for her fifth open heart procedure. The strength of the reaction of her RBCs with anti-CW suggested a double dose of CW antigen. Her serum, which unexpectedly was strongly reactive with c-, E-, Jk(a-) RBCs by PEG indirect antiglobulin test, was incubated with E-c-, Jk(a-) RBCs, and an eluate was prepared. This eluate reacted 3+ with E-c-, Jk(a-) RBCs but did not react with Rh(null) (n = 5), - - (3), DCW- (2), Dc- (1), or DCWe/DCWe (1) RBCs. Two related DCXe/DCXe and two unrelated DCWe/DCXe RBC samples were weakly agglutinated. The patient's RBCs were negative with the original anti-MAR but reacted as strongly as the positive control RBCs with the antibody made by the DCXe/DCXe person. CONCLUSION: This is the first example of a MAR-like antibody made by a DCWe/DCWe woman. The specificity cannot be called anti-MAR, because some MAR-negative samples react, albeit weakly. The original anti-MAR, made by a DCWe/DCXe woman, did not react with DCWe/DCWe, DCWe/DCXe, or DCXe/DCXe RBCs. It is apparent that the specificity of "anti-MAR" differs slightly, depending on the CW/CX status of the antibody maker.     

Acute hemolysis of transfused A2 red cells by an auto-HI antibody

BACKGROUND: Anti-HI is a common cold autoantibody that complicates serologic testing for underlying alloantibodies and has only rarely been associated with hemolysis. An unusual case of an acute hemolytic transfusion reaction (AHTR) due to an anti-HI autoantibody in a subgroup A1 patient transfused with A2 red blood cells (RBCs) is reported. CASE REPORT: A 56-year-old man presented to the hospital with anemia and gastrointestinal tract bleeding. His medical history was significant for congestive heart failure, obesity, and pulmonary hypertension. On admission, he was noted to have a hemoglobin level of 7.7 g per dL and therefore transfusion of RBCs was ordered. The patient was group A, D- with a reactive antibody screen due to a cold autoantibody with HI specificity. Further serologic investigation did not detect any alloantibodies. The patient was issued an electronically cross-matched group A, D- unit of RBCs. Several hours after the transfusion, he was found to be producing "Coca-cola"-colored urine with gross hemoglobinemia visible in a posttransfusion specimen, indicating an AHTR. A transfusion reaction investigation excluded mistransfusion or a missed alloantibody and instead revealed that the patient's anti-HI had a high thermal amplitude and that the implicated unit of RBCs was from the A2 subgroup. The patient subsequently tolerated transfusion of a unit of group A1 RBCs through a blood warmer without any signs or symptoms of hemolysis. CONCLUSION: This case illustrates that anti-HI autoantibodies rarely may behave like alloantibodies and cause AHTRs. Subsequent RBC transfusion with an appropriate ABO group or subgroup through a blood warmer is well tolerated.     

Hemolytic Transfusion Reactions

SUMMARY: The risk of hemolytic transfusion reactions (HTRs) is approximately 1:70,000 per unit. Acute HTRs occurring during or within 24 h after administration of a blood product are usually caused by transfusion of incompatible red blood cells (RBCs), and, more rarely, of a large volume of incompatible plasma. Delayed HTRs are caused by a secondary immune response to an antigen on the donor's RBCs. In some patients with delayed HTRs, an additional bystander hemolysis of the patient's RBCs can be assumed. Different mechanisms lead to intra- and extra-vascular hemolysis, such as complete complement activation, phagocytosis of RBCs covered with C3b by macrophages after incomplete complement activation, or destruction of RBCs covered only with IgG by direct cell-cell contact with K cells. The clinical consequences of HTRs are triggered via several pathophysiological pathways like formation of anaphylatoxins, release of cytokines causing a systemic inflammatory response syndrome, activation of the kinin system, the intrinsic clotting cascade and fibrinolysis resulting in hypotension, disseminated intravascular coagulation, diffuse bleeding, and disruption of microcirculation leading to renal failure and shock. In the following, the symptoms of HTR are introduced, laboratory investigations and treatment are described, and some recommendations for prevention are given.     

Delayed immune hemolysis in a patient receiving cyclosporine after orthotopic liver transplantation

Immune hemolytic anemia in patients after organ transplantation has been reported generally to be graft-cell-derived due to elaboration by the donor's "passenger" lymphocytes of the antibodies directed against the recipient's red cell antigens. In contrast, this report presents a case that illustrates postoperative red cell alloantibody production by the recipient of an orthotopic liver transplant. Anti-Jka, -c, and -S, detected in the recipient's serum 9 days after transplantation, resulted in significant hemolysis. These alloantibodies had not been present in the recipient's serum before transplantation or in the sera of the liver or blood donors. In addition, anti-Jka and -c were eluted from posttransfusion red cells. The patient was transfused during surgery with crossmatch-compatible blood, that carried the alloantigens Jka, c, and S. The liver donor's red cells also carried the Jka, c, and S antigens. The recipient's pretransplantation red cell phenotyping was Jk(a-), c-, S-. The recipient had received only one transfusion 10 years prior to this operation, after which time he was noted to have anti-K. Immunosuppression initially consisted of cyclosporine, azathioprine, and prednisolone. This is believed to be the first report of delayed immune hemolysis due to non-ABO antibodies in a liver transplant patient treated with cyclosporine.     

In vitro studies of the impact of transfusion on the detection of alloantibodies after autoadsorption

BACKGROUND: In a patient with warm autoantibodies who has recently received a transfusion, it is not recommended to perform adsorptions using autologous RBCs to detect alloantibodies. Although not scientifically documented, this position is based on the theory that transfused RBCs in the patient's circulation would be capable of adsorbing alloantibodies that may be present. This in vitro study was designed to determine what percentage of transfused RBCs might completely remove alloantibodies in vivo. STUDY DESIGN AND METHODS: Selected D, E, K, Fy(a), and Jk(a) antibodies were adsorbed with mixtures of antigen-positive and antigen-negative RBCs to determine the lowest concentration of antigen-positive RBCs capable of removing all alloantibody reactivity. The percentage of antigen-positive RBCs in each mixture was determined by flow cytometry. RESULTS: Small amounts of antigen-positive RBCs (2-6%, as determined by flow cytometry) completely removed anti-D, -E, and -Fy(a) reactivity. Reactivity of two examples of anti-K was removed by 11 percent and 17 percent of K+ RBCs, respectively. Anti-Jk(a) reactivity was completely removed by 4 to 5 percent Jk(a+) RBCs using a PEG adsorption; the endpoint (>11%) was estimated, but complete adsorption with ZZAP-treated RBCs was not performed. CONCLUSION: Small amounts of antigen-positive RBCs are generally capable of removing all alloantibody reactivity. Thus, waiting for 3 months after transfusion before performing autologous adsorptions is a prudent policy.     

Transfusion of incompatible RBCs to a patient with alloanti-Kp(b)

BACKGROUND: The finding of an antibody that reacts against a high-incidence blood group antigen always constitutes a complex transfusion problem because of the difficulty in finding compatible units. When the transfusion of incompatible RBCs is imperative, it would be of great interest to have access to techniques facilitating the prediction of the transfusion outcome. STUDY DESIGN AND METHODS: The case of a patient with alloanti-Kp(b) who required RBC transfusions is reported. The functional activity of this antibody was assessed by both the chemiluminescence test (CLT) and the survival of 51Cr-labeled RBCS: RESULTS: The CLT showed an opsonic index of 0.8 with Kp(b)-positive RBCs (normal values up to 1.6) in pretransfusion studies. During an elective surgical procedure, the patient required the transfusion of one incompatible unit of RBCs, which did not produce hemolysis. Two weeks after this incompatible transfusion, the opsonic index had risen to 11. Results of the 51Cr in vivo study, also performed at that time, indicated 24.3 percent survival of Kp(b)-positive RBCs at 60 minutes and 2.0 percent at 24 hours. CONCLUSION: Results of the CLT correlated with the in vivo transfusion outcome and later with the 51Cr survival study.     

Hyperhemolysis syndrome in sickle cell disease: case report (recurrent episode) and literature review

BACKGROUND: Hyperhemolysis syndrome (HS) has been well described both in sickle cell disease (SCD) and non-SCD patients. The pathogenesis remains unclear. The possible mechanisms include bystander hemolysis, suppression of erythropoiesis, and destruction of red cells (RBCs) due to contact lysis via activated macrophages. CASE REPORT: This study reports a child with SCD who presented with recurrent episode of HS. In the first episode, the hemoglobin (Hb) level decreased to 4.1 g per dL. He was treated with intravenous immunoglobulin (IVIG) and oral steroids, and transfusion was avoided. Six months later he had another episode of HS. The nadir Hb level decreased to 3.2 g per dL, and further transfusions were given with IVIG-IV methylprednisolone cover. RESULTS: RBC alloantibodies were not identified in pre- and posttransfusion samples in patient's serum in both episodes. HLA antibodies were also not detected. CONCLUSION: This is the second reported case of recurrent HS in a child. Recent studies have shown that the adhesion molecules expressed on RBC erythroid precursor cells and reticulocytes can interact with macrophages and can cause hemolysis. Because RBC alloantibodies and HLA antibodies were not identified in this case, it is believed that the patient's cells and transfused cells were destroyed by macrophages either by direct contact lysis or by erythrophagocytosis. The possible mechanism of IVIG and steroids on suppression of macrophages resulting in cessation of hemolysis is discussed. Our case illustrates the danger of recurrent HS and the difficulty of balancing this against the need for transfusions in patients presented with severe hemolysis.     

Antibody to c antigen consequent to renal transplantation

A case of apparent red cell (RBC) autoimmunity due to anti-c is described in the recipient of a cadaveric renal transplant. Although the patient suffered little hemolysis as a result, a strong direct anti-c agglutinin was detectable on the patient's RBCs 8 days after transplantation and in his serum only 4 days after transplantation. We believe that the antibody was produced by passively transferred B lymphocytes in the donor kidney, and that the recipient may have been protected from more serious hemolysis by immunosuppressive agents administered at the time of transplantation. The donor received multiple transfusions before transplantation, but his serum lacked anti-c in a screen performed shortly before his death. This case raises the possibility that donor alloantibodies to other Rh antigens on recipient RBCs can arise after transplantation, if the donor has been transfused.     

Acute intravascular hemolysis secondaryto out-of-group platelet transfusion

BACKGROUND: Acute intravascular hemolysis is rarely associated with platelet transfusion. Out-of-group single-donor platelets may cause hemolysis if the donor has high-titer ABO hemagglutinins. CASE REPORT: A 44-year-old woman, blood group A, was recently diagnosed with acute myeloid leukemia and was receiving chemotherapy. After the transfusion of apheresis platelets from a group O donor, back pain, hemoglobinuria, and hemoglobinemia developed, and her Hb dropped by 2.3 g per dL, despite the transfusion of 2 units of RBCs. RESULTS: Investigation revealed acute intravascular hemolysis with a positive DAT due to anti-A(1) on her RBCs. The donor's titer of anti-A(1) was greater than 16,000. CONCLUSION: Review of published cases raises the possibility that hemolytic reactions to out-of-group platelets may be more frequent since the use of apheresis platelets has increased.     

Presence of the red cell alloantibody anti-E in an 11-week-old infant

The development of red cell (RBC) alloantibodies in infants less than 4 months of age is believed to be rare. Though there are no well-documented published accounts, the formation of alloanti-E in a multiply transfused 11-week-old infant is reported here. The infant, blood group B, D +, developed necrotizing enterocolitis and renal failure requiring 31 transfusions of washed and unwashed RBCs (group B and group O), as well as fresh-frozen plasma and platelets. Six weeks after the first blood transfusion, alloanti-E was detected. The anti-E weakly agglutinated R2R2 screening RBCs at 37 degrees C and sensitized these RBCs to react with anti-IgG. The infant's RBCs were typed as E-. Passive transfer of alloanti-E was ruled out by the negative antibody screening tests of each donor unit and the absence of any RBC alloantibodies in the mother's serum. Stored samples of the infant's sera were tested, and anti-E was shown to be present approximately 11 days after exposure to a known E+ RBC unit. The appearance of alloanti-E in this time frame is consistent with a secondary immune response. Primary immunization most likely took place in the first 4 weeks of transfusion therapy.     

''Immune complex'' mediated intravascular hemolysis due to IgM cephalosporin-dependent antibody

Immune hemolytic anemia (IHA) related to cephalosporins is rare and generally considered to be the result of a drug-adsorption mechanism. In previously reported cases, the hemolysis was usually extravascular and the causative antibodies were IgG, incapable of activating complement, and demonstrable by the direct or indirect antiglobulin test using red cells (RBCs) pretreated in vitro with cephalosporin. The authors report a patient in whom acute intravascular hemolysis developed while she was receiving cefotaxime (a cephalosporin as yet not reported to cause IHA). The patient's RBCs were coated only with complement fragments (C3d), even at the peak of the hemolytic episode. Her serum and eluates repeatedly yielded negative results when tested against normal or cephalosporin-coated RBCs. However, strong hemagglutination and C5b-9-mediated hemolysis were observed if the patient's serum was tested against RBCs in the presence of the drug, its ex vivo antigen and, to a lesser degree, cephalothin and ceftriaxon, but not in the presence of penicillin and other related cephalosporins. The positive reactions were not changed by preincubating the serum with different amounts of the drugs. All of these findings reflect the typical picture of drug-induced IHA by the so-called "immune complex" mechanism and not by the drug-adsorption mechanism. The authors conclude that cephalosporin can cause immune hemolysis in two ways: the drug-adsorption mechanism and, as described here, the "immune complex" mechanism.     

Predicting the effect of transfusing only phenotype-matched RBCs to patients with sickle cell disease: theoretical and practical implications

BACKGROUND: Transfusing only phenotype-matched RBCs has been recommended to reduce the incidence of alloimmunization to blood group antigens in patients with sickle cell disease (SCD). STUDY DESIGN AND METHODS: The expected benefit of phenotype matching was determined by identifying which of the existing blood group alloantibodies in patients with SCD who received conventional transfusions would not have been formed if they had received only phenotype-matched RBCs. By use of each patient's alloantibodies as a baseline, it was possible to identify specific alloantibodies that would not have been formed if each of five different phenotype-matching protocols had been used. RESULTS: During a 12-year period, 351 patients received transfusions with 8939 units of ABO- and D-matched RBCs. Of these, 102 patients (29.1%) formed at least one blood group alloantibody. An additional 35 patients with SCD with alloantibodies were identified by reviewing clinical records, yielding a total of 137 alloimmunized patients for inclusion in this study. If all transfusions had been selected by limited phenotype matching (C, c, E, e, and K, as well as for ABO and D), all alloantibodies would have been prevented for more than half (53.3%) of the 137 alloimmunized patients. If all transfusions had been matched for C, c, E, e, K, S, Fya, and Jkb, all antibodies would have been prevented for 70.8 percent of the 137 alloimmunized patients. Approximately 13.6 percent of random white blood donors would be expected to match a limited phenotype-matching protocol, whereas only 0.6 percent would match an extended phenotype-matching protocol. CONCLUSION: Limited phenotype matching would have prevented all alloantibodies in 53.3 percent of the patients who formed alloantibodies. This protocol requires RBCs that are readily available. Extended phenotype matching would have prevented alloimmunization in 70.8 percent of patients who formed alloantibodies. However, this would require phenotypes that are 22.7 times less prevalent among random blood donors and is therefore impractical for a long-term strategy.     

Severe hemolytic anemia due to multiple red cell alloantibodies after an ABO-incompatible allogeneic bone marrow transplant

BACKGROUND: A patient who received an ABO-incompatible allogeneic bone marrow transplant experienced three episodes of immune hemolytic anemia due to multiple red cell (RBC) alloantibodies. CASE REPORT: A 41-year- old man with chronic myeloid leukemia received an ABO-incompatible bone marrow graft from his HLA-identical brother. Selective removal of RBCs from donor marrow before transfusion was performed by centrifugation using a continuous-flow blood cell separator. The patient was given group O Rh-positive RBCs and group A Rh-positive platelets. Prophylaxis for graft-versus-host disease consisted of cyclosporine and methotrexate. The patient experienced three hemolytic episodes, on Days 21, 35, and 160 which were due to different RBC alloantibodies (anti-K, anti-Jk(b), anti-M, IgG anti-A) produced by host lymphocytes surviving the conditioning regimen. RESULTS: The patient was group O, Jk(b-), and the marrow donor was group A, Jk(b+). After the first hemolytic episode (Day 21), immunohematologic studies showed group O RBCs and a positive direct antiglobulin test (IgG+, C3d+). Antibody screening test and eluate studies detected anti-M, anti-Jk(b), and anti-K. During the second hemolytic episode (Day 35), the patient's blood group showed a mixed population of group A and group O RBCs. The direct antiglobulin test was positive (IgG+, C3d+). Anti-M, anti-Jk(b), and IgG anti-A were detected in the serum. Eluates made from the recipient's RBCs showed the same specificity as serum antibodies. During the third hemolytic episode (Day 160), a mixture of group O and group A RBCs was still present, the direct antiglobulin test was positive (IgG+, C3d-), and anti-Jk(b) and IgG anti-A were observed in the serum and in an eluate made from the patient's RBCs. CONCLUSION: This is the first reported case of severe immune hemolytic anemia due to multiple RBC alloantibodies after an allogeneic bone marrow transplant. The time of appearance and the specificity of the antibodies strongly suggest that they were produced by residual recipient lymphoid cells.     

Methods for the detection of Jk heterozygotes: interpretations and applications

The lytic properties of red cells from Jk(a+,b+), Jk(a-, b+) and Jk(a+b-) (normal), Jk(a-b-), and obligate Jk heterozygotes were studied. The Jk(a-b-) cells did not hemolyze for at least 15 minutes in either 2 M urea or methylurea, whereas normal cells were completely hemolyzed in 2 minutes. Red cells from Jk heterozygotes demonstrated intermediate levels of hemolysis when compared to normal and Jk(a-b-) red cells. In addition, these cells had less than 10 percent hemolysis when suspended in 2 M methylurea prepared in 0.4 percent phosphate-buffered saline (pH 7.2). This method may be an alternative to hemagglutination titration scoring for the detection of Jk, especially in paternity cases.     

Hyperhemolysis syndrome in anemia of chronic disease

BACKGROUND: Occasional cases of delayed hemolytic transfusion reaction (DHTR) demonstrate severe and persistent hemolysis and are referred to as hyperhemolysis syndrome. This syndrome usually occurs in patients with sickle cell disease and possibly thalassemia who receive multiple transfusions. There are few such clinical reports in patients without hemoglobinopathies. CASE REPORT: A 67-year-old woman with anemia and a history of four previous transfusions was admitted with shortness of breath and a hematocrit (Hct) level of 27 percent. The patient was group O with a negative antibody screen. She received 1 unit of electronically cross-matched red blood cells (RBCs) and was discharged. Thirteen days later she returned to hospital with weakness and a Hct level of 23 percent. The antibody screen now demonstrated anti-K alloantibody. The direct antigloblulin test (DAT) was positive with both anti-immunoglobulin G and anti-complement (C3). Anti-K was recovered in the eluate. The previously transfused RBC unit was positive for presence of the K antigen. The patient's RBCs were negative for the presence of K antigen. Other laboratory data confirmed ongoing hemolysis, and a diagnosis of DHTR was made. She continued to display findings of active hemolysis for 9 more weeks requiring 19 units of RBCs. Thirty-four days after the original transfusion, her DAT remained positive and both the plasma sample and a RBC eluate demonstrated anti-K. CONCLUSION: The delayed hemolytic transfusion reaction with hyperhemolysis can occur among patients without hemoglobinopathies.     

Anti-i causing acute hemolysis following a negative immediate-spin crossmatch

A unique case of acute hemolysis following transfusion of red cells (RBCs) that were found compatible by immediate-spin (IS) crossmatch technique is reported. Screening tests for unexpected antibodies, using low-ionic-strength saline (LISS), 10 minutes' incubation at 37 degrees C, and anti-IgG, were nonreactive; however, 1 transfused unit was found crossmatch incompatible by indirect antiglobulin technique (IAT). An anti-i (titer 512 at 4 degrees C) that was not an autoantibody was identified in the patient's serum. Unlike the incriminated donor RBCs, most I+ RBCs did not react by LISS-IAT. Variable reactivity was seen with ficin-treated I+ RBCs, and there was marked hemolysis of iadult and icord RBCs. In marked contrast, dominant Lu(a-b-) RBCs, with reduced expression of i, did not react by any test method; nor did autologous I+, Lu(b+) RBCs. The in vivo clinical significance of this anti-i was confirmed by monocyte monolayer assay and RBC survival studies. The patient's i antigen may have been altered, by either chemotherapy or disease, and lacked part of the i antigen-mosaic. Her antibody was directed at epitopes of i that were absent from her RBCs. Those i epitopes missing from her RBCs are also absent on dominant Lu(a-b-) RBCs. This anti-i represents a unique cause of an acute hemolytic transfusion reaction. It also represents a case of acute immune-mediated hemolysis following transfusion of IS crossmatch-compatible blood when screening tests for unexpected antibodies are nonreactive. Because of the rarity of such cases (less than 1/200,000 RBC units transfused), modifications to pretransfusion testing protocols are not proposed.     

Fetal hemolytic anemia and intrauterine death caused by anti-M immunization

BACKGROUND: Antibodies with anti-M specificity are detected in 10 percent of pregnant women with a positive antibody screen, but anti-M is only rarely associated with hemolytic anemia in the fetus. STUDY DESIGN AND METHODS: This study reports on three pregnancies in one family that all resulted in severe fetal anemia. The first fetus died in utero with hydrops fetalis during the 20th gestational week and the second child was delivered after 28 weeks of gestation with hydrops fetalis and a hemoglobin level of 16 g per L whereas the third affected child was treated with intrauterine red cell (RBC) transfusions before delivery at 28 weeks of gestation. RESULTS: The direct antiglobulin test was negative but anti-M in a low titer was detected through the three pregnancies, and its clinical relevance, which initially was uncertain, was confirmed by pronounced in vivo hemolysis in maternal blood of chromate ((51)Cr)-labeled M+ RBCs and normal survival of (51)Cr labeled M- RBCs. CONCLUSION: It is concluded that anti-M immunization in a few cases may cause severe fetal hemolytic anemia and intrauterine death. It remains to be elucidated why a normally clinically insignificant antibody is this aggressive in a small proportion of cases. Because the condition is treatable, anti-M must be considered as a possible cause of fetal anemia and intrauterine death.