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.     

Lower alloimmunization rates in pediatric sickle cell patients on chronic erythrocytapheresis compared to chronic simple transfusions

BACKGROUND: Erythrocytapheresis (ECP), automated red blood cell exchange, is increasingly being used for chronic transfusion therapy in sickle cell disease (SCD) as it is an isovolumetric transfusion, is more effective in lowering hemoglobin (Hb)S, and can limit iron overload. Because ECP requires increased blood exposure compared to simple transfusions there is concern for increased transfusion complications, including alloimmunization. We compared alloimmunization rates between patients receiving simple or exchange chronic transfusions. STUDY DESIGN AND METHODS: Data were retrospectively collected for 45 SCD patients (n = 23 simple, n = 22 ECP) on a chronic transfusion program as of December 2010 to determine the rate of antibody formation (antibodies formed per 100 units transfused). RESULTS: The 45 patients received 10,949 units and formed six new alloantibodies during the study period (1994‐2010); therefore, the overall alloimmunization rate was 0.055 alloantibodies per 100 U. There were three antibodies formed in three patients on ECP, one allo (anti‐rh_i) and two autoantibodies. There were six antibodies in four patients on a simple transfusion program, five allo (anti‐Le^a, M, D, C, and Kp^a) and one autoantibody. The ECP group received significantly more blood (338.5 units/patient vs. 152.2 units/patient, p = 0.001). The rate of antibody formation (auto plus allo) was 0.040 antibodies per 100 U in the ECP group and 0.171 antibodies per 100 U in the simple transfusion group (p = 0.04). The alloantibodies formed per 100 units was 0.013 in the ECP group and 0.143 in the simple transfusion group (p = 0.03). CONCLUSION: Chronic ECP should be considered in patients requiring optimal management of HbS levels and iron burden. Concerns about increased alloimmunization with ECP may be unjustified.     

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.     

Alloimmunization to red cells in thalassemics: Emerging problem and future strategies

Aims and objectives

To evaluate the magnitude of red cell alloimmunization in regularly transfused patients with thalassemia major and analyse factors responsible for development of antibodies.

Materials and methods

This cross sectional study was conducted on 116 thalassemics receiving regular transfusions. All the patients underwent antibody screening. Patients with positive antibody screen were further tested for antibody identification. The data was analysed to find out the frequency, pattern and factors influencing red cell alloimmunization secondary to multiple transfusions.

Results

Mean age of the patients was 14 years (range 1.5–27 years). Red cell alloantibodies were found in 11 patients (9.48%). In four (36%) patients first transfusion was given before 6 months of age and in seven (64%) patients, first transfusion was given after two years of age. The interval between consecutive transfusions varied from 18 to 35 days. The most common antibody was Anti-E found in 4 (36.4%) patients, followed by Anti-K (three patients, 27.2%), Anti-Kp^a (two patients, 18.2%) and Anti-C_w (two patients, 18.2%). The interval from first transfusion to antibody development varied from 1.5 to 14 years. None of the eight out of 116 patients, who underwent splenectomy showed any antibody development.

Conclusions

The rate of red cell alloimmunization was found to be 9.48% in thalassemics receiving regular transfusions. The incidence of alloantibody development was higher if first transfusion was received at more than 2 years of age. Early institution of red cell transfusions and Rh and Kell phenotyping followed by provision of matched blood could prevent alloimmunization.     

Red blood cell alloimmunization in transfused patients with myelodysplastic syndrome or chronic myelomonocytic leukemia

BACKGROUND: Red blood cell (RBC) alloimmunization is a major problem in chronically transfused patients because of the risk of hemolytic reactions and limited availability of compatible blood. This study was aimed at determining the characteristics of RBC alloimmunization in transfusion‐dependent patients with myelodysplastic syndrome or chronic myelomonocytic leukemia (MDS/CMML). STUDY DESIGN AND METHODS: The transfusion and clinical records of all patients with MDS/CMML seen at our hospital from 1990 to 2009 were reviewed. The cumulative incidence of RBC alloimmunization was calculated by taking death as a competing risk. Incidence rates were compared by Poisson multivariate regression. RESULTS: A total of 272 patients were included. Median age was 74 years; 55% were men and had received a median of 33 (range, 4‐421) RBC units. Forty‐two (15%) patients formed 81 alloantibodies and seven autoantibodies. Three additional patients developed autoantibodies without alloantibodies. The incidence rate of RBC alloimmunization was 1 per 10.5 person‐years and was independent of sex, age, and MDS diagnostic category. The cumulative incidence of alloimmunization increased with the number of RBC transfusions, reaching a plateau at 19.5% after 130 RBC units. The most common antibody specificities were Kell (26 cases), E (19), c (5), and Jk^a (5). In 26 (62%) of the 42 alloimmunized patients, only the Rh system and Kell were involved. CONCLUSION: RBC alloimmunization occurs in 15% of MDS/CMML patients on chronic transfusion support and mostly involves the Rh system and Kell. Transfusing these patients with extended antigen‐matched blood, including Kell and CcEe antigens, would presumably reduce the RBC immunization rate.     

Red blood cell alloimmunization in myelodysplastic syndromes: Associations with sex,DAT-positivity,and increased transfusion needs

Background

Many patients with myelodysplastic syndromes (MDS) need repeated red blood cell transfusions which entails a risk of immunization and antibody formation. Associations between alloantibodies, autoantibodies and increased transfusion requirements have been reported, but their relationship remains unclear. In this study, we analyzed factors potentially associated with red blood cell alloimmunization, as well as changes in transfusion intensity and post-transfusion hemoglobin increments.

Methods

In a retrospective cohort study, we linked Swedish MDS patients diagnosed between 2003 and 2017 to transfusion and immunohematology data. Potentially associated factors were analyzed using Cox proportional hazards regression. The transfusion rate after detected alloimmunization was analyzed using a fixed effects Poisson regression. Post-transfusion hemoglobin increments before and after alloimmunization were compared using a mixed effects regression.

Results

Alloantibodies following MDS diagnosis were detected in 50 out of 429 patients (11.7%). Female sex and a positive direct antiglobulin test (DAT) were independently associated with alloimmunization, with hazard ratios of 2.02 (95% confidence interval [CI] 1.08–3.78) and 9.72 (95% CI, 5.31–17.74), respectively. The transfusion rate following alloimmunization was increased with an incidence rate ratio of 1.33 (95% CI, 0.98–1.80) and the post-transfusion hemoglobin increment after alloimmunization was 1.40 g/L (95% CI, 0.52–2.28) lower per red blood cell unit (p = .002) compared to before alloimmunization, in multivariable analyses.

Discussion

Alloimmunization against blood group antigens was associated with sex, DAT-positivity, increased transfusion needs, and lower post-transfusion hemoglobin increments. These findings warrant further investigation to evaluate the clinical significance of up-front typing and prophylactic antigen matching in patients with MDS.     

Genotyping of blood groups in alloimmunized patients with β-thalassemia major by T-ARMS-PCR and multiplex-aso-pcr

IntroductionBeta-thalassemia major is a severe hemolytic anemia requiring life-long blood transfusion. Planned random donor blood transfusion is associated with alloimmunization against incompatible antigens. Determination of the minor blood group systems phenotype or genotype, and administration of the compatible blood components can significantly reduce the rate of alloimmunization.The present study aimed to determine the prevalence of alloimmunization, and genotype/phenotype characteristics of the minor blood groups systems in patients with β-thalassemia major.Material and methodsThis study was conducted on 1147 β-thalassemia major patients. Initially, antibody screening and antibody identification were performed. Then, phenotyping and genotyping for the Rh, Kell, Kidd, and Duffy blood groups were done in alloimmunized patients using monoclonal antibodies and Multiplex-Allele Specific Oligonucleotide-Polymerase Chain Reaction (Multiplex-ASO-PCR) and Tetra-primer amplification refractory mutation system–PCR (T-ARMS-PCR), respectively. Any phenotype/genotype discrepancy was assessed by direct sequencing.ResultsNinety-seven (8.5 %) out of 1147 patients had alloantibodies against the minor blood group antigens (44 males, 45.4 %, and 53 female, 54.6 %). The most common alloantibodies were against the RH (n: 47, 48.5 %), and the Kell (n: 23, 23.7 %) blood groups systems. Twenty-three (2.1 %) genotype/phenotype discrepancies out of 1067 tests, including 9 in the Rh (9.3 %), 8 in Duffy (34.8 %), and 6 in Kidd (26.1 %) blood groups were detected. No discrepancy was found in the Kell blood group system. Direct sequencing revealed that the results of molecular methods were correct.ConclusionMultiplex-ASO-PCR and T-ARMS-PCR molecular methods are fast, reliable and cost-benefit molecular methods for the minor blood group genotyping in multi-transfused β-thalassemia major patients.     

Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes

BACKGROUND: Alloantibodies against the human platelet (PLT) alloantigen (HPA)-15 system residing on CD109 can cause fetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura, and PLT transfusion refractoriness. The detection of antibodies against HPA-15, however, is hampered by the variable low expression and instability of the CD109 molecule during preparation and storage. STUDY DESIGN AND METHODS: This study analyzed the occurrence of HPA-15 alloantibodies in 1403 patients: 930 FNAIT and 473 polytransfused (PT) patients by modified monoclonal antibody specific immobilization of PLT antigens (MAIPA) assay with well-defined phenotyped PLTs. A DNA typing technique was developed to confirm the phenotypes of PLT donors. B-cell lines were established as sources of reference DNA. RESULTS: Genotyping of 407 unrelated blood donors revealed the gene frequencies 0.512 and 0.488 for HPA-15a and -15b, respectively. Based on the selection of PLTs expressing high amounts of CD109 on the surface (mean fluorescence intensity ratio 4-5 on expression peak on Days 2-4 after apheresis) antibody screening by the MAIPA assay was performed. In total, 16 (1.1%) HPA-15 alloantibodies were found comprising four anti-HPA-15a and 12 anti-HPA-15b. Anti-HPA-15b without other PLT-reactive antibodies were detectable in three serum samples of PT patients. The incidence of HPA-15 alloimmunization in PT patients was significantly higher than in mothers with FNAIT (3.0% vs. 0.22%). In relation to all detected HPA-specific antibodies, HPA-15 is responsible for 6.2 percent of alloimmunizations. CONCLUSION: These observations indicate that alloimmunization against HPA-15 should be considered as a cause for immune thrombocytopenia, particularly in patients receiving multiple PLT transfusions.     

The incidence of development of irregular red cell antibodies in patients with sickle cell anemia

Two hundred and forty-five patients with SS hemoglobinopathy were screened for alloimmunization; they had all been transfused previously. Their median age was 10 years. Nineteen patients (7.75%) were found to be sensitized to various red cell antigens. The median number of transfusions received by sensitized patients was 23 compared to three in the unsensitized group, indicating an increased risk with more transfusion exposures. Thirteen sensitized patients were re-exposed to transfusion and four (30%) developed new alloantibodies. Once immunized, the risk of developing more alloantibodies on re-exposure did not increase with increasing number of exposures. The most frequently observed alloantibody was anti-K, accounting for 38 percent of all instances. Anti-Lea and -Leb were next in frequency (24%); Rh antibodies were seen in 14 percent of cases. Children with sickle cell anemia who were multiply transfused had a low frequency of alloimmunization. Responders had an increased rate of further sensitization which did not increase with number of subsequent exposures. Phenotypically matched blood is probably not warranted in most patients receiving transfusions for sickle cell anemia.     

Management of patients refractory to platelet transfusion.

This article discusses the causes and management of platelet refractoriness. Improvements in the quality of platelets and leukoreduction have reduced the morbidity and mortality related to alloimmunization and refractoriness of patients to platelet transfusion. Alloimmunization can be distinguished from other causes of poor post-transfusion platelet increments by the measurement of platelet alloantibodies. Options for managing platelet refractoriness caused by alloimmunization include platelet transfusion from human leukocyte antigen-matched or donor-recipient cross-matched platelets. Prevention strategies include efforts to limit recipients' exposure to human leukocyte antigen specificities by using single-donor platelets, filtration to reduce the number of human leukocyte antigen-bearing leukocytes, and pretransfusion ultraviolet B irradiation to decrease their immunogenicity. For appropriate management of patients refractory to platelets, close cooperation and good communication are necessary between clinicians and blood centers.     

Maternal immunization to Gov system alloantigens on human platelets

BACKGROUND: Immunization to platelet alloantigens can occur during pregnancy or after the transfusion of blood components. Platelet alloantibodies can cause neonatal alloimmune thrombocytopenia and posttransfusion purpura. Transfusion-induced alloimmunization to a novel platelet alloantigen system, Gov, expressed on the 175-kDa glycosyl phosphatidylinositol-anchored platelet glycoprotein, CD109, was previously described. This report describes three unrelated patients who were alloimmunized to Gov(a) or Gov(b) during pregnancy. STUDY DESIGN AND METHODS: Platelets were typed by using radioimmunoprecipitation for HPA-1a, -3a, -5a, -5b, Gov(a), and Gov(b) and by polymerase chain reaction-restriction fragment length polymorphism for HPA-1a, -1b, -3a, and -3b. Maternal sera were screened for platelet antibodies by using radioimmunoprecipitation and the antigen capture assay. RESULTS: Patients 1 and 2 were investigated after the diagnosis of neonatal alloimmune thrombocytopenia in their children, and alloantibodies specific for Gov(b) and Gov(a), respectively, were detected in maternal serum. Serum from patient 3, who had mild idiopathic thrombocytopenia purpura with no detectable autoantibody, was found to contain alloantibodies to Gov(b) and to HPA- 5b, presumably as a result of immunization during pregnancy. Platelet typings confirmed that the patients were at risk for alloimmunization to the respective antigen. CONCLUSION: This report of three cases of maternal alloimmunization to antigens in the Gov system indicates that immunization can occur via placental transfer of antigen and that Gov system alloantibodies may be associated with neonatal alloimmune thrombocytopenia.     

Red blood cell alloantibodies after transfusion: factors influencing incidence and specificity

BACKGROUND:  Alloimmunization after exposure to red cell (RBC) alloantigens depends on genetic and acquired patient-related factors, dose and route of administration, and the immunogenicity of the antigen, but exact kinetics are still unknown.
STUDY DESIGN and METHODS:  A 5-year retrospective multicenter study analyzing factors influencing the rate and specificity of RBC alloimmunization was performed, with special emphasis on the time interval between transfusion event and antibody detection. Included were clinically significant alloantibodies against the Rhesus, Kell, Duffy, Kidd, and MSs blood group systems.
RESULTS:  Multivariate analysis involving 1710 immunized patients revealed that time interval between transfusion and antibody tests was strongly associated with the antibody specificity. Anti-Jk^a and anti-Jk^b were predominantly found in patients tested within 3 months, whereas anti-K and anti-Fy^a were the most encountered antibodies at more than 5 years after transfusion. Of all immunized patients, new antibodies were detected within 14 days after transfusion in 299 patients (16.8%) and in 1479 patients (83.2%) after more than 14 days. Fifty percent of transfusion recipients were retested for alloimmunization because of a new transfusion indication. Eleven of 2932 patients (0.4%) retested up to 3 days after transfusion had formed new antibodies.
CONCLUSION:  The time interval between transfusion and antibody test was associated with RBC antibody specificity. Because RBC antibody tests after transfusion are not routinely performed, many antibodies may (not) be detected at the time of a new transfusion event, posing the transfusion recipient at risk for transfusion delay or a (delayed) hemolytic transfusion reaction. Routine RBC antibody screening at set time intervals after transfusion would reduce these risks.     

Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion

BACKGROUND: Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients.
STUDY DESIGN AND METHODS: A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity.
RESULTS: Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations.
CONCLUSION: This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.     

Alloimmunization in transfused patients with constitutional anemias in Norway

Background and ObjectivesThe status of red blood cell alloimmunization in patients with constitutional anemias including hemoglobinopathies is not known in Norway. The study objective was to investigate the impact of a strategy based on phenotype-matching for C, c, E, e, K, Jka, Jkb, Fya, Fyb, S and s on alloimmunization.Materials and MethodsWe reviewed transfusions of 40 patients retrospectively using the computerized blood bank management system and medical records; including diagnosis, age at start of transfusion therapy, gender, number and age of packed red blood cell units transfused, follow-up time, phenotypes of the donors and patients, antigen-negative patients exposed to antigen-positive packed red blood cell units, transfusion reactions and alloantibody specificities.ResultsForty patients received 5402 packed red blood cell units. Alloimmunization frequency was 20 % for the whole group, being 7%, 25 % and 30 % in patients with sickle cell disease (n = 14), thalassemia (n = 16) and other conditions (n = 10), respectively. The alloantibodies detected were anti-E, -c, -C, -Cw, -K, -Jka and -Lua.ConclusionGood communication between the clinicians and the transfusion services is essential for successful management of patients with constitutional anemias. Providing full phenotype-matched units was not always possible. Extended pheno-/genotyping before the first transfusion and providing antigen-negative units for antigen-negative patients for at least C, c, E and K in every red cell transfusion would probably have reduced the alloimmunization rate. Non-phenotype-matched transfusions seem to be the main reason for alloimmunization. Finding markers for identifying responders prone to alloimmunization will ensure targeted transfusion strategies.     

Transfusion-Induced Bone Marrow Transplant Rejection Due to Minor Histocompatibility Antigens

Traditionally, alloimmunization to transfused blood products has focused exclusively on recipient antibodies recognizing donor alloantigens present on the cell surface. Accordingly, the immunologic sequelae of alloimmunization have been antibody mediated effects (ie, hemolytic transfusion reactions, platelet refractoriness, anti-HLA and anti-HNA effects, etc). However, in addition to the above sequelae, there is also a correlation between the number of antecedent transfusions in humans and the rate of bone marrow transplant (BMT) rejection—under reduced intensity conditioning with HLA-matched or HLA-identical marrow. Bone marrow transplant of this nature is the only existing cure for a series of nonmalignant hematologic diseases (eg, sickle cell disease, thalassemias, etc); however, rejection remains a clinical problem. It has been hypothesized that transfusion induces subsequent BMT rejection through immunization. Studies in animal models have observed the same effect and have demonstrated that transfusion-induced BMT rejection can occur in response to alloimmunization. However, unlike traditional antibody responses, sensitization in this case results in cellular immune effects, involving populations such as T cell or natural killer cells. In this case, rejection occurs in the absence of alloantibodies and would not be detected by existing immune-hematologic methods. We review human and animal studies in light of the hypothesis that, for distinct clinical populations, enhanced rejection of BMT may be an unappreciated adverse consequence of transfusion, which current blood bank methodologies are unable to detect.     

Prognostic Value Evaluation of HLA-DRB1*07:01, *10, *12, *13:01 Alleles for Alloimmunization in Transfusion-Dependent Thalassemia

BackgroundTransfusion is a lifesaving treatment for lots of patients. However, in chronic blood recipients such as thalassemia patients, there are high concerns about alloantibody production that affects the quality of their life. Therefore, research on risk factors of alloimmunization has been started and followed. This study aimed at the determination of correlation probability between some HLADRB1 alleles and alloimmunization in Iranian thalassemia patients.Materials and methodsThe present study was conducted on 60 alloimmunized and 60 non-alloimmunized transfusion-dependent thalassemia patients. Antibody screening and identification tests were carried out using the tube method, and HLA-DRB1 genotyping was done using a single specific primer-polymerase chain reaction (PCRSSP).ResultsThe results of antibody screening showed that the most prevalent alloantibodies were Anti-K (46.7 %), and followed by Anti-E (32.5 %), Anti-C (15.8 %), Anti-D (13.3 %), Anti-e (8 %), and Anti-c (5.8 %), respectively. DRB1*07:01 was detected more in non-responder patients (28.3 %). However, data analysis showed that there is no significant relationship between DRB1*07:01, *10, *13:01 frequency among responder and non-responder groups (p = 0·195, 0.648, 0.402, respectively). There was not any significant correlation between HLA-DRB1*10 and *13:01 allele and alloimmunization. There was a significant association between HLA-DRB1*12 and alloimmunization (p < 0·05, OR = 2.071, CI: 1.716–2.501).ConclusionThe findings of this study represented that there is a significant relationship between HLADRB1*12 and Kell and E alloantibodies. Although more developed studies on other HLA alleles are demanded, these findings can be valuable in determining important alloimmunization risk factors to better management of transfusion complications.     

Transfusion‐induced platelet antibodies and regulatory T cells in multiply transfused patients

BackgroundPlatelet transfusion refractoriness (PTR) remains a difficult problem in patients requiring long‐term platelet supportive care. However, there are little data on the frequency of platelet antibodies in multiply transfused Chinese patients. Moreover, the relationship between peripheral regulatory T cells (Tregs) and PTR remains unclear.MethodsWe retrospectively studied the frequency of alloimmunization against platelet antigens in patients receiving multiple transfusions between 2013 and 2017. Monoclonal antibody solid‐phase platelet antibody test (MASPAT) kits were used to screen for platelet antibodies before each platelet transfusion. Peripheral Tregs and CD4⁺CD25⁺CD127⁻ T cells were detected by flow cytometry, while transforming growth factor‐beta (TGF‐β) and interleukin (IL)‐17 cytokines were detected by enzyme‐linked immunosorbent assay.ResultsA total of 399 patients who met the inclusion criteria were enrolled for the analysis of platelet antibodies and refractoriness. Among these patients, 10 (2.5%) were positive for platelet antibodies before transfusion and 47 (11.8%) became antibody‐positive during the study period. The number of alloimmunized patients was significantly higher in patients with hematological disease as compared with other disease groups (p < 0.05). Refractoriness and alloimmunization occurred in 77 (19.3%) and 22 (28.6%) patients, respectively. There were no significant differences in CD4⁺, CD8⁺, and CD4⁺CD25⁺CD127⁻ T cell numbers and plasma levels of TGF‐β1 and IL‐17 between patients with PTR and the control group.ConclusionsRefractoriness was common in patients undergoing multiple platelet transfusions (19.3%), with alloimmunization observed in 28.6% of patients. However, Tregs in peripheral blood may not play a key role in PTR.     

Red blood cell alloantibody frequency, specificity, and properties in a population of male military veterans

BACKGROUND: The prevalence of red blood cell (RBC) alloantibodies among general, hospital‐based patients typically has averaged approximately 1 percent in various studies. The frequency and properties of RBC alloantibodies in military veterans has never been examined. STUDY DESIGN AND METHODS: Transfusion records of 18,750 military veterans at a Department of Veterans Affairs (VA) medical center were retrospectively reviewed. For patients with RBC alloantibodies, the following were collected: sex, race/ethnicity, decade of birth, transfusion history, alloantibody specificity, reaction phase(s), and whether alloantibodies were detected at the initial type and screen or later. RESULTS: The RBC alloantibody prevalence was 2.4 percent among predominantly male military veterans. Alloantibody prevalence varied with decade of birth, ranging up to 3.3 percent (1911‐1920). The 10 most frequent alloantibodies in males, as a percentage of total male antibodies, were K (21.9%), E (19.4%), D (9.1%), Le^a (7.4%), Fy^a (5.4%), c (4.8%), C (4.6%), P₁ (3.9%), Jk^a (3.7%), and Le^b (3.5%). Investigation of D alloimmunization in men revealed that antibody development occurred before VA care in 80 percent (39/49) of cases. For alloimmunization during VA care, anti‐D was mostly associated with the transfusion of D+ platelets (7/10). The majority of alloantibodies in males reacted at the antiglobulin (AG) phase, even anti‐Le^a, ‐Le^b, M, ‐Lu^a, and ‐P₁. CONCLUSION: Military veterans have a relatively high prevalence of RBC alloantibodies, including anti‐D, despite a large male predominance and lack of pregnancy‐related alloimmunization. Alloantibody prevalence was highest in World War II veterans. The majority of male alloantibodies reacted with AG, even those traditionally considered to be clinically insignificant.     

Human Leukocyte Antigen Alloimmunization and Alloimmune Platelet Refractoriness

Despite significant advancements in the production of platelet products, storage, and transfusion, transfusion refractoriness remains a significant clinical problem, affecting up to 14% of hematological patients receiving platelet transfusions. Human leukocyte antigen (HLA) alloimmunization is a major cause of immune platelet refractoriness, and its rate can be significantly reduced by implementation of leukoreduction. Despite promising preclinical results, pathogen reduction does not reduce HLA alloimmunization. Patients with HLA alloimmune refractoriness are usually managed with HLA-selected platelet transfusions. In this review, we describe the pathophysiology of HLA alloimmunization and alloimmune refractoriness, as well as options to prevent and treat these transfusion complications. We discuss the evidence supporting these options and point out the outstanding gaps. Finally, we review the possible future directions for prevention and treatment of alloimmune refractoriness.     

Transfusion‐related alloimmune neutropenia with no pulmonary complications: one donor—five cases

BACKGROUND: Neutrophil alloantibodies are well‐known triggers of transfusion‐related acute lung injury (TRALI) and also cause immune neutropenia. Alloimmune neutropenia due to transfusion is an isolated phenomenon that is only rarely identified. Its incidence is specified in the literature as being less than one in 10,000 transfused plasma‐containing units. We expect that this phenomenon is underreported. STUDY DESIGN AND METHODS: We observed five cases of alloimmune neutropenia with no respiratory complications with only one case initially reported as a suspected transfusion reaction. The other four cases were detected in the course of the subsequent lookback investigation. RESULTS: The first case was reported as a potential transfusion reaction when a female patient showed a decrease in the white blood cell count after a platelet (PLT) transfusion. Examinations of the donor blood revealed an antibody against the human neutrophil antigen HNA‐1b; the recipient was typed HNA‐1b positive and HNA‐1a negative. After examining the blood counts of other patients who previously received PLT concentrates from the same donor, we identified four other patients with an unreported decrease in the leukocyte and/or granulocyte count of more than approximately 50% after transfusion. CONCLUSION: HNA antibodies are generally regarded as potential triggers of TRALI. Here we describe an HNA antibody that reproducibly caused transfusion‐related neutropenia only without pulmonary complications. Factors predisposing patients to TRALI development are widely discussed. Our case suggests that antibody characteristics are also relevant in the development of TRALI. Current measures to prevent TRALI should also prevent transfusion‐related alloimmune neutropenia.