Anti-D alloimmunization after D-mismatched allogeneic hematopoietic stem cell transplantation in patients with hematologic diseases

BACKGROUND: The de novo development of anti-D after D-mismatched allogeneic hematopoietic stem cell transplantation (AHSCT) is a possibility that must be considered. The transfusion of D- blood components after AHSCT has been recommended but anti-D alloimmunization in this setting has been studied little. Thus, the aim of this study was to analyze anti-D formation after D-mismatched AHSCT. STUDY DESIGN AND METHODS: Thirty patients with a hematologic disease who underwent D-mismatched AHSCT were retrospectively studied. Support therapy included red blood cells (RBCs) and platelet (PLT) concentrates (PCs) from whole-blood donations and PLTs from apheresis. After AHSCT, patients received D+ PCs without administering Rh immunoglobulin (RhIG). An antibody screening to detect anti-D was performed by low-ionic-strength saline-indirect antiglobulin test with the tube test. RESULTS: Fifteen D+ patients received stem cells (SCs) of D- donors and 15 D- patients received SCs of D+ donors. After AHSCT, patients received a median of 11.5 (range, 0-32) D- RBC units. D+ patients received 682 (83%) of 825 PLT units from D+ donors, and D- patients received 573 (85%) of 678 PLT units from D+ donors. None of the 30 patients developed anti-D after a median follow-up of 32 weeks (range, 4-310 weeks). CONCLUSION: Anti-D alloimmunization after performing a D-mismatched AHSCT is infrequent in patients with hematologic diseases although patients receive D-mismatched PLT transfusions without RhIG administration.     

Detection of multiple passively acquired alloantibodies following infusions of IV Rh immune globulin

BACKGROUND: Passively acquired blood group alloantibodies are detected regularly after infusions of IV Rh immune globulin (RhIG) for the treatment of immune thrombocytopenic purpura (ITP) in D+ patients. STUDY DESIGN AND METHODS: Blood samples from 16 D+ patients with ITP were tested after treatment with IV RhIG for the presence of passively acquired alloantibodies. Similar studies were conducted for three D- patients after injections of IM RhIG for Rh immunoprophyl-axis. Four production lots of IV RhIG and 2 lots of IM RhIG were tested for the presence of alloantibodies. RESULTS: All 16 D+ patients with ITP developed a positive DAT, as well as positive antibody detection test results, after infusions of IV RhIG. All postinfusion plasma samples contained anti-D, as well as one or more additional antibodies, usually anti-C, -E, -G, -V, or -Fy(a). Eluates from patients' RBCs with positive DAT results contained multiple passively acquired alloantibodies. Multiple alloantibodies were detected in samples of different production lots of IV RhIG or IM RhIG. No acute transfusion reactions were observed in five D+ patients with ITP who had been treated with IV RhIG and had been given serologically incompatible D+ RBCs. After injections of IM RhIG, the only passively acquired alloantibody detected was anti-D. CONCLUSION: Plasma samples from D+ patients with ITP treated with IV RhIG regularly contained anti-D and multiple other passively acquired Rh, Duffy, or Kidd system alloantibodies. Postinfusion RBC samples all had positive DAT results with eluates containing anti-D and multiple other Rh, Duffy, or Kidd system antibodies. The consistent detection of multiple passively acquired alloantibodies after IV RhIG, in contrast to the detection of anti-D only after IM RhIG, reflects the immediate effect of the entire (bolus) dose of RhIG by the IV route, the dose for treating ITP that is approximately 10 times the dose for Rh immunoprophylaxis, and the expected serologic incompatibility with recipients' D+ RBCs.     

Prevention of immunization to D+ red blood cells with red blood cell exchange and intravenous Rh immune globulin

BACKGROUND: Although young women who are D- occasionally receive unintentional transfusions with D+ red blood cells (RBCs), there are little data to assist with management of such an event. Two cases of D- girls transfused with D+ RBCs are reported. In an effort to prevent formation of anti-D, RBC exchange followed by administration of intravenous (IV) Rh immune globulin (RhIg) was used. CASE REPORTS: Patient 1, a 56-kg, 16-year-old D- girl, was involved in a motor vehicle crash. She received 4 units of Group O uncrossmatched D+ RBCs. Thirty-six hours after admission, she underwent RBC exchange with 10 units of D- RBCs, followed by a total of 2718 microg of IV RhIg over 32 hours. Six months later, her antibody screen was negative. Patient 2, a 39-kg, 10-year-old D- girl with aplastic anemia, received 1 unit of D+ RBCs. She underwent RBC exchange on the same day with 5 units of D- RBCs, followed by a total of 900 microg of IV RhIg over 8 hours. Six months later her antibody screen was negative. CONCLUSION: RBC exchange followed by a calculated dose of IV RhIg was successful in preventing allo-immunization to D. Several small studies suggest that both trauma and hematology patients may be less capable of becoming immunized with the transfusion of D+ blood components. Until these findings are more clearly defined, there will be times when prevention of immunization of any D- girl is desired. RBC exchange followed by RhIg appears to be one way to achieve this goal.     

Absence of anti-D alloimmunization in hematologic patients after D-incompatible platelet transfusions

BACKGROUND: Rh antigens are not present on the platelet surface. However, platelet concentrates may contain enough RBCs to elicit an anti-D response. Thus, D status must be considered in platelet transfusion. In immunosuppressed patients, frequencies of D alloimmunization of up to 19 percent have been previously reported. STUDY DESIGN AND METHODS: Here a prospective study is reported in which 22 D- patients with hematologic disease received D+ platelet transfusions. Platelet concentrates were prepared from whole-blood donations according to the buffy coat method and were pooled before administration. The antibody screen test to detect anti-D was performed by LISS- IAT using the gel test. RESULTS: Our series comprises 22 immunosuppressed D+ patients with a median age of 56 years (range, 23-79). The patients received 121 D-incompatible pooled platelet transfusions. The mean +/- SD of RBC content was 4.17 +/- 1.74 mL. None of the 22 patients developed detectable anti-D after a median follow-up of 8 weeks (range, 1-37). CONCLUSION: The risk of D alloimmunization is low in patients with hematologic disease after D-incompatible platelet transfusions using platelet concentrates prepared by the buffy coat method.     

Detection of anti-D in D- recipients transfused with D+ red blood cells

BACKGROUND: The D antigen is highly immunogenic, requiring only a small quantity of transfused red blood cells (RBCs) to cause alloimmunization in D- immunocompetent recipients. The relatively low sensitization rate in oncology patients transfused with D+ platelets is well documented. A study of the alloimmunization rate of primarily nononcology D- recipients transfused with D+ RBCs was undertaken. STUDY DESIGN AND METHODS: Transfusion service records were examined to identify D- recipients who were not alloimmunized to the D antigen and who had a follow-up antibody screen performed at least 10 days after the initial D+ RBC transfusion(s). The age and sex of the recipients, date and number of D+ RBC transfusion(s) and their leukoreduction status, all subsequent serologic investigations, and the hospital ward where the units were issued were recorded. RESULTS: There were 98 study-eligible recipients identified who received a total of 445 D+ RBC units. The mean follow-up length was 182 days. Most recipients (87%) had antibody screens performed more than 21 days after the initial D+ RBC transfusion. In total, 24 recipients made 44 new alloantibodies: 22 anti-D (22%), 11 anti-E, 5 anti-C, 2 anti-K, and 1 each of anti-Kp(a), anti-Jk(a), anti-Bg, and anti-Fy(b). The rate of anti-D alloimmunization among recipients of entirely leukoreduced D+ units was 13 percent (1/8). Reexposure to D+ RBCs after the initial bleeding episode did not increase the rate of alloimmunization. CONCLUSIONS: The 22 percent rate of anti-D alloimmunization in patients requiring urgent RBC transfusion was intermediate between the rates previously reported for D- oncology patients transfused with D+ RBCs and that in immunocompetent volunteer recipients.     

Absence of D- alloimmunization in AIDS patients receiving D-mismatched RBCs

BACKGROUND: More than 80 percent of D- patients who receive D+ blood become alloimmunized to the D antigen. Anemia occurs in most AIDS patients at some point in the disease. D- patients with AIDS may require blood transfusion and, during times of blood shortage, may receive D+ RBCs. They would be expected to become alloimmunized to the d antigen. STUDY DESIGN AND METHODS: The records of the transfusion service between January 1996 and July 2000 were reviewed for D- patients who received D+ blood. IATs were performed before the initial transfusion and subsequently when the patient required further RBC transfusion. RESULTS: Eight D- AIDS patients who received multiple transfusions (three women and five men; age range, 31-44 years; mean, 44 years) who received between 2 and 11 units (mean, 6.25) of D+ RBCs were identified. Antibody screens were performed at 8 to 65 weeks after transfusion. It was found that none of the eight D- AIDS patients developed anti-D. ABO antibodies were found as expected. During the same period, it was found that six D- patients admitted with other diagnoses who received 1 to 9 units of D+ RBCs, all developed anti-D within 7 to 19 weeks of transfusion. CONCLUSION: Patients with AIDS may not form alloantibodies to the D antigen. This may be attributable to their immunodepressed state, particularly to the decrease in CD4+ T lymphocytes. Therefore, during blood shortages, transfusion of D+ blood to D- AIDS patients may be without any subsequent consequence.     

Secondary anti-D immunization by Del red blood cells

BACKGROUND: Recent molecular studies of the RHD gene have revealed that D(el) individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. No D(el) phenotype has yet been shown to induce a primary or secondary alloanti-D immunization, however. CASE REPORT: A 67-year-old D- Japanese woman with a history of allosensitization from transfusion of D+ red blood cells (RBCs) was negative for anti-D at admission. After she received RBCs from 19 apparently D- donors, she developed anti-D with an 8-fold titer. The titer of anti-D increased further to 128-fold after transfusions of cross-match-compatible D- negative RBCs from 40 donors over the next 2 years. Two of 59 donors were found to be RHD gene-positive and antigen D- with a D(el) phenotype, that is, RHD(K409K). CONCLUSION: This is the first case in which RBCs having the D(el) phenotype induced a secondary alloanti-D immunization. A D- donor with the RHD(K409K) allele was associated with the development of anti-D. Adverse episodes or evidence of hemolysis was not observed after the transfusion of RHD(K409K) RBCs. Further clinical evidence is needed to reveal whether the D(el) phenotype has a clinically relevant potential for anti-D immunization.     

Alloimmunization in preterm infants after repeated transfusions of WBC-reduced RBCs from the same donor

BACKGROUND: Preterm infants are among the most heavily transfused of patient groups, yet multiply transfused infants only rarely produce alloantibodies against RBC or WBC antigens. It is not known whether rates of alloimmunization might be increased by repeated exposure to RBCs and WBCs from the same donor, as in limited-donor-exposure programs, or whether infants might benefit from WBC-reduced RBC components as a means of diminishing the risk of possible alloimmunization. STUDY DESIGN AND METHODS: Preterm infants (birth weight 0.6-1.3 kg) received prestorage WBC-reduced RBCs from dedicated donors, collected in AS-3 as a means of limiting donor exposures. Blood samples were collected serially from infants shortly after birth until either discharge or age 6 months and were studied for RBC and WBC antibodies-the latter with reactivity against either HLA class I or neutrophil-specific antigens. RESULTS: Thirty preterm infants received 139 transfusions (mean, 4.6; median, 4 transfusions per infant), with 81 percent of transfusions obtained from one donor per infant. Eighty-four blood samples (mean, 2.7/infant) were studied, and no infant produced RBC antibodies. Twenty-seven percent of infants exhibited WBC antibodies, but only 13 percent actually produced WBC antibodies (passive maternal antibody excluded). Of the WBC antibodies produced by infants, three were against HLA class I and one was against neutrophil-specific antigens; none were linked to adverse effects. CONCLUSIONS: Because infants only rarely produce RBC antibodies, no changes in blood banking practices are necessary for limited-donor-exposure programs. Although the production of WBC antibodies by infants occurs, it seems to be uncommon; thus, the possible benefits, if any, of WBC reduction are uncertain, and further study is required before changes in practice can be justified.     

Multiple transfusion fail to provoke antibodies against blood cell antigens in human infants

We conducted studies of both red cell (RBC) and leukocyte (WBC) antibody formation in infants following multiple transfusions given during the first weeks of life. Fifty-three infants received 683 RBC transfusions from 503 different donors, plus 62 platelet, 4 granulocyte, and 53 fresh-frozen plasma units during the first 4 months of life. Three hundred fifty serum samples were obtained before, during, and after the transfusions. None of the infants formed unexpected RBC antibodies when tested at 37 degrees C by a two-cell low-ionic-strength solution antibody screen that included an anti-globulin phase. Twenty posttransfusion serums were negative when tested at room temperature. Lymphocytotoxic and granulocytotoxic WBC antibodies were measured in posttransfusion serums from 13 infants, and none were found. Despite exposure to many RBC and WBC antigens, no infants produced alloantibodies against blood cell antigens. Thus, immunologically mediated transfusion reactions should be quite rare in young infants, and this study supports recommendations of the American Association of Blood Banks Standards to omit repeat RBC compatibility testing during the first 4 months of life in infants whose initial RBC antibody screens reveal no unexpected antibodies.     

Passive anti-C acquired in the setting of Rh immune globulin administration following Rh mismatched apheresis platelet transfusion: A case series

Rh immune globulin (RhIG) may be administered to Rh(D)-negative recipients of Rh(D)-positive platelet (PLT) transfusions to mitigate anti-D alloantibody formation. We report a series of seven patients in which anti-C was detected as a result of RhIG administered as immunoprophylaxis following Rh-mismatched apheresis PLT transfusion, persisting for a range of 27 to 167 days post-RhIG. The passively transferred anti-C antibodies created complexities for subsequent transfusion support. Based on these challenges, in combination with emerging evidence supporting an extremely low anti-D alloimmunization risk following Rh-mismatched apheresis PLTs, we have changed our practice and now limit RhIG immunoprophylaxis in this setting to women of reproductive age. In summary, the blood bank and apheresis communities should be aware that passive transfer of non-D antibodies is possible following RhIG administration. This phenomenon represents a compelling reason to consider the risk/benefit ratio of RhIG and to limit its use to situations in which it is clinically necessary.     

Anti-G in a pregnant patient

BACKGROUND: Anti-G is a red cell (RBC) antibody of the Rh system. It has been described in pregnant women only in association with anti-D or anti-C; therefore, the ability of this antibody alone to cause hemolytic disease of the newborn is uncertain. One case in which this antibody caused no clinical sequelae is reported. CASE REPORT: The patient was a 35-year-old primigravida with type O, D-, C-, E-, c+ RBCs who was given 4 units of type O, D- allogeneic RBCs and 2 units of autologous RBCs 2 years antepartum. She was found to have anti-D and anti-C by an outside laboratory as part of a routine prenatal work-up. Further evaluation by our laboratory revealed the presence of anti-G and possible anti-C without anti-D. Titers at 22 weeks' gestation were 64 against r'r RBCs and 16 against R2R2 RBCs; these remained unchanged throughout the pregnancy. Amniocentesis performed at Weeks 28 and 32 showed no evidence of hemolytic disease of the newborn. A healthy 3.3-kg infant was delivered at 36 weeks' gestation. Prophylactic Rh immune globulin was administered antepartum and postpartum. The infant's RBCs were type O, D+, c+ C-, E-, and the direct antiglobulin test was positive. An acid eluate prepared from the baby's RBCs revealed anti-G. The total bilirubin was 5.5 mg per dL at birth, and the hematocrit was 66 percent. Total bilirubin peaked on Day 5 at 11.9 mg per dL, and no therapeutic intervention was required. CONCLUSIONS: Anti-G alone caused little if any fetal or neonatal hemolysis in this case. Although further study is needed, invasive fetal monitoring may be unnecessary if anti-G is the sole cause of fetomaternal RBC incompatibility.     

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.     

Red cell alloimmunization in multitransfused HLA-typed patients

The authors studied retrospectively the formation of clinically significant red cell (RBC) alloantibodies in 958 HLA-typed, multiply transfused patients receiving kidney (603 patients) or liver (263 patients) transplants or plateletpheresis transfusions (92 patients). RBC alloantibodies were found in 91 (9.5%) of these patients and multiple antibodies in 35 (3.7%). Rh (D, C, c, and E) antibodies accounted for 49 percent of the total and Kell antibodies for 31 percent. Antibodies were found in 15 percent of apheresis recipients and in 8.6 percent of renal and 9.5 percent of liver transplantation patients. No association was found between any HLA-A, HLA-B, or HLA-DR phenotype and the presence of RBC alloantibodies, either in general or when analyzed according to the specific antibody. Renal transplant patients with RBC alloantibodies were somewhat more broadly HLA-alloimmunized than were those without RBC alloantibodies. Patient gender did not affect these results. The authors concluded that the immune response to RBC alloantigens is independent of HLA type but is associated with an increased level of HLA antibody formation.     

Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated. STUDY DESIGN AND METHODS: Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified. RESULTS: The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1. CONCLUSION: First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.     

Prevalence of HLA antibodies in transfused patients with and without red cell antibodies

BACKGROUND: Multiply transfused patients are at increased risk of developing red cell (RBC) antibodies, as well as antibodies to HLA. Although pretransfusion testing screens for RBC antibodies, no such testing is routinely performed for HLA antibodies. Determining which patients are more likely to make HLA antibodies may be important for patients undergoing elective surgery where platelets (PLTs) may be required. It is hypothesized that patients with RBC alloantibodies may be more likely to have HLA antibodies than previously transfused patients without RBC antibodies. STUDY DESIGN AND METHODS: Blood was collected from 53 adult male surgical patients with RBC alloantibodies and a control group of 69 similar male patients with a history of previous transfusions but no evidence of RBC alloimmunization. The samples were tested for the presence of immunoglobulin G Class I HLA antibodies by enzyme-linked immunosorbent assay. RESULTS: Of the 53 samples from patients with RBC alloantibodies, 12 (22.6%) also had HLA antibodies, whereas only 7 (10.1%) of the 69 patients in the control group had HLA antibodies (p < 0.03). CONCLUSIONS: There is a significant difference between the rates of HLA alloimmunization in male patients with RBC antibodies versus multiply transfused patients without RBC antibodies. Screening for HLA antibodies may be warranted in patients with RBC alloantibodies who might require PLT transfusion support for elective surgery.     

Labeling D+ RBCs for flow cytometric quantification of fetomaternal hemorrhage after the RBCs have been coated with anti-D

BACKGROUND: D- patients may receive Rh immunoglobulin (RhIg) before blood samples are taken for estimation of the volume of fetomaternal hemorrhage (FMH) by flow cytometry. Anti-D bound to the fetal D+ cells may then block the binding of conjugated D MoAb. This may reduce the fluorescence of the D+ cells, which would lead to ambiguity over setting the positions of the markers on histograms and may result in erroneous values of FMH. STUDY DESIGN AND METHODS: Labeling methods were compared by using FITC-BRAD 3 (anti-D) and/or FITC-anti-IgG (Fab fragment) with mixtures of D+ (R1r) and D- (rr) cells when the D+ cells had first been coated with various amounts (0 molecules/cell and 600-13,000 molecules/cell) of anti-D (RhIg). Variables examined were antibody concentrations, the order and times of incubation with the antibodies, and the effect of washing between the uptake of the antibodies used. RESULTS: In all cases, D+ cells were strongly labeled after incubation with 50 microL of FITC-BRAD-3 and then after washing with 50 microL of FITC-anti-human IgG, with both incubations being for 30 minutes at 37 degrees C. With this double-staining procedure, the fluorescence of D+ cells was found to be similar regardless of how much anti-D (RhIg) was previously bound and greater than that with FITC-BRAD-3 alone, giving an enhanced signal-to-noise ratio. CONCLUSION: As the testing laboratory may not know if the patient has received prophylactic RhIg, this labeling method would be suitable for all samples.     

Red blood cell alloimmunization in sickle cell disease patients in Uganda

BACKGROUND: Blood transfusion is an integral part in the management of sickle cell disease (SCD) patients. Alloimmunization is a recognized complication of red blood cell (RBC) transfusions with consequences including delayed hemolytic transfusion reactions and difficulties in getting compatible blood for future transfusions. The objective of this study was to determine the frequency of RBC alloimmunization in SCD patients in Uganda where pretransfusion screening for alloantibodies is not practiced.
STUDY DESIGN AND METHODS: In a cross-sectional study, SCD patients at Mulago Hospital Sickle Cell Clinic, Kampala, Uganda, were investigated. The demographic characteristics and transfusion history were recorded. Blood samples were drawn from consenting, previously transfused patients and RBC alloimmunization was demonstrated using immunohematologic techniques.
RESULTS: There were 428 patients (median age, 12 years; female/male ratio, 1.0) and they had received a median of 3 units in a median of three transfusion episodes. Twenty-six patients (6.1%) possessed RBC alloantibodies and 21 (80.7%) of them had received up to 10 transfusions. A total of 30 alloantibodies was found; 20 (66.7%) and 5 (16.6%) belonged to Rh and MNS blood groups, respectively. Five of the alloimmunized patients had multiple antibodies.
CONCLUSIONS: The rate of RBC alloimmunization in Ugandan SCD patients was 6.1%. The homogeneity between donors and SCD patients plus the low transfusion load may explain this immunization frequency. Nevertheless, our study confirms the significance of RBC alloimmunization as a complication in Ugandan SCD patients. Therefore, there is need to improve immunohematologic testing in Uganda so that RBC alloimmunization and its consequences may be prevented.     

Red blood cell alloimmunization in transfusion-dependent Egyptian patients with thalassemia in a limited donor exposure program

BACKGROUND: Thalassemia is considered the most common hemoglobinopathy in Egypt and is one of its major health problems. Lifelong red blood cell (RBC) transfusion remains the main treatment for severe forms; however, RBC alloimmunization results as a complication of regular transfusions due to repeated exposure to foreign antigens. The objective was to compare the frequency of alloantibodies in a group of patients in a limited donor exposure program (LDEP) with those receiving RBCs from multiple donors in Egyptian transfusion‐dependent patients with thalassemia. STUDY DESIGN AND METHODS: A total of 235 regularly transfused patients with thalassemia were studied, 36 of which were on LDEP. All patients were investigated for the presence of RBC autoantibodies and alloantibodies, followed by antibody identification for positive patients. RESULTS: Forty‐six (19.5%) patients developed RBC alloantibodies. The most common clinically significant alloantibodies were directed against antigens in the Kell and Rh systems. Development of alloantibodies was associated with older age, higher transfusion frequency, and splenectomy. A trend toward lower alloimmunization was elicited in the LDEP group, where 8.3% (3/36) patients were alloimmunized compared to 21.6% (43/199) in the non‐LDEP one (p = 0.057). CONCLUSIONS: Examination of donor RBCs for presence of Kell and Rh(E) antigens before transfusion can help decrease RBC alloimmunization. Further larger studies are required to assess the frequency of alloantibody production in patients on LDEP.     

RBC alloimmunization and autoimmunization among transfusion-dependent Arab thalassemia patients

BACKGROUND: Thalassemia major is a common hemoglobinopathy in the Arabian Gulf region. However, limited data are available on the frequency of RBC alloimmunization and autoimmunization in transfusion-dependent Arab thalassemia patients. STUDY DESIGN AND METHODS: A total of 190 thalassemia major patients were classified as Kuwaiti Arab and non-Kuwaiti Arab. Pretransfusion investigation records were reviewed for the presence of RBC alloantibody and autoantibody, and the age at which RBC alloantibody was developed. RESULTS: Fifty-seven (30%) patients developed RBC alloantibodies. The most common clinically significant alloantibodies were directed against antigens in the Kell and Rh systems. Anti-K developed in 41 (72%) patients followed by anti-E in 26 (45.6%). RBC autoantibodies developed in 21 (11%) patients with and without underlying RBC alloantibodies. Sixty-six (49.6%) RBC alloantibodies developed between the ages of 2 and 10 years. CONCLUSION: Several factors might have contributed to the high alloimmunization and autoimmunization rate observed in this study, including the heterogeneity of the population living in Kuwait, lack of better-matched donors for those patients, and the use of poststorage leukodepleted blood. It is recommended that thalassemia patients receive blood matched for Rh and Kell antigens and prestorage leukodepleted RBCs.     

Prospective evaluation of a transfusion policy of D+ red blood cells into D- patients.

BACKGROUND: Although D- patients should receive red blood cells (RBCs) from D- donors, the scarcity of D- blood components in certain situations makes the transfusion of D+ RBCs unavoidable. Therefore it is recommended that guidelines be developed in order to standardize transfusion policy in these scenarios. STUDY DESIGN AND METHODS: We have prospectively evaluated a policy for the use of D+ RBCs in 905 D- patients. The amount of D- RBCs saved as well as the incidence of hemolytic reactions and anti-D alloimmunization were assessed. RESULTS: 554 patients received D- RBCs while 351 received a total of 1032 D+ RBCs, all of them within our criteria for the acceptable use of D+ RBCs. This strategy allowed us to save 25.6 percent of D- RBCs (1032 out of 4024 RBCs requested). No hemolytic reactions were reported. The incidence of alloimmunization was 21.4 percent. Most patients who developed anti-D did so within the first 2 or 4 RBCs transfused (64% after the first 2 RBCs transfused and 88% after the first 4). In multivariate analysis the age of less than 77 years was the only predictor for alloimmuization (HR = 2.48 [95% CI = 1.21-3.81]; p = 0.014). CONCLUSION: The use of D+ RBCs in selected D- patients does not induce adverse reactions and allows the saving of a significant number of D- RBCs.