Blood Group Antigen Abnormality, Blood Transfusion, Rhesus Isoimmunisation Due to Anti-D
Conditions
Brief summary
Red blood cells (RBCs) from Asian-type DEL blood group express very weak RhD antigen and are falsely typed as RhD-negative blood group in routine RhD testing. Until now, Asian-type DEL (D-eluate) patients still be treated as rare RhD-negative patients in the clinic. Previous study from the Asian-type DEL pregnant women with RhD+ fetus showed no occurrence of alloanti-D immunization. This result, however, does not directly be applied for Asian-type DEL patients receiving RhD+ blood transfusions, as lacking of direct evidence regarding the safety and underlying mechanism. In this study, the patients with Asian-type DEL were identified and received RhD+ blood transfusion, then evaluations of any adverse reactions, especially the active follow-up alloantibody test, were prospectively conducted.
Detailed description
Red blood cells (RBCs) from Asian-type DEL individuals express very weak RhD antigen and are falsely typed as RhD-negative in routine RhD testing. Recent studies have shown that 9-30% of individuals with a serologically apparent RhD-negative phenotype in East and Southeast Asian populations, including Chinese, Korean, Japanese, Thai and Myanmar, actually are not truly RhD-negative but exhibit the DEL (D-eluate) phenotype, which represents almost 1.7 million Asian-type DEL individuals in China, 250,000 in Korea, Japan, Thailand, and Myanmar as well as at least 90,000 in the US among Asian immigrants. Nowadays, Asian-type DEL patients are conventionally transfused with RhD-negative RBC, which are difficult to organize because of the undersupply of the rare RhD-negative blood in these Asian countries, due to low frequency distribution (0.3-0.4%). However, our previous study demonstrated that Asian-type DEL pregnant women with RhD+ fetus did not develop alloanti-D during the pregnancy. Latter, this phenomenon was confirmed by different medical centers in China. Accordingly, Asian-type DEL patients may also not be able to produce alloanti-D after transfusion with RhD+ RBC and consequently the use of RhD-negative RBCs for the transfusion management of Asian-type patients may be superfluous. However, this hypothesis needs to be carefully proved. In this study, we were able to verify this assumption. Blood samples from 2,011 Chinese patients with a primary RhD-negative phenotype from the hospitals in Guangzhou of China were typed for Asian-type DEL blood group in the Guangzhou Blood Center. DEL phenotyping was performed by the serological adsorption/elution antibody testing and genotyping for the Asian-type DEL specific allele (RHD\*1227A) detection was conducted using a well validated high-resolution melting (HRM) approach. Then, transfusions of RhD+ RBC were performed in a cohort of Asian-type DEL patients. After RhD+ blood transfusion, evaluations of any adverse reactions, especially the active follow-up alloantibody test, were conducted to evaluate the alloanti-D immunization. Besides, effectiveness of transfusion (Hb changes) was also recorded.
Interventions
OTHERBlood transfusion
Transfusion with RhD+ blood product rather than rare RhD-negative blood to Asian-type DEL recipients
Sponsors
Sun Yat-sen University
Southern Medical University, China
Guangdong Provincial People's Hospital
Third Affiliated Hospital, Sun Yat-Sen University
Zhujiang Hospital
Second Affiliated Hospital of Guangzhou Medical University
Guangdong Provincial Hospital of Traditional Chinese Medicine
The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
Guangdong Second Provincial General Hospital
First Affiliated Hospital, Sun Yat-Sen University
Guangdong Provincial Institute of Biological Products And Materia Medica
Shenzhen Second People's Hospital
Koo Foundation Sun Yat-Sen Cancer Center
Guangzhou Blood Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A single-arm clinical trial of Chinese Asian-type DEL patients receiving RhD+ RBC transfusion was conducted. Although truly RhD-negative patients receiving RhD+ RBC transfusion were recognized as the ideal control group, they were not included in this study because it did not comply with the Chinese Clinical Blood Transfusion Standard and ethics principles. The truly RhD-negative patients could receive RhD+ blood only in emergency situations under conditions of an insufficient stock of RhD-negative RBCs. Thus, the summarized alloanti-D rate (203/720, 28.2%; 95% CI, 19%-32%) in truly RhD-negative patients with similar mixed diseases after RhD+ RBC transfusion reported in the meta-analysis （Vox Sang 2021, http://doi.org/10.1111/vox.13232）was used as the control for comparison.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
for eligible participants were as follows: (1) Asian-type DEL blood group; (2) male patients, or female patients ≥ 49 years of age, or female with severe illness and no plan for further pregnancy; (3) needing blood transfusion in line with guidelines for internal medicine or surgery; and (4) signed voluntary informed consent for blood transfusion treatment before the trial. The
Exclusion criteria
were: (1) adverse reaction in a previous transfusion; (2) allergies to blood products or immunodeficiency diseases; (3) needing massive blood transfusion for acute blood loss; (4) positive pregnancy test results; (5) conscious dysfunction or severe mental illness; and (6) unsuitability for the study, as estimated by the principal investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Alloanti-D Immunization in Asian-type DEL Recipients Transfused With RhD+ RBCs | A median follow-up of 226 days (range, 32 to 1354 days) after RhD+ RBC transfusion | For the Chinese Asian-type DEL recipients identified by the serological adsorption/elution test and HRM genotyping analysis, RhD+ RBC transfusion was performed. Then, the new blood samples from the patients were obtained after transfusion of RhD+ RBCs. The clinical significant alloantibodies against the common antigens of RBC were re-tested by antibody screening test. And the antibody screening test was performed using ID-DiaCell I-II-III Asia Kit (BIO-RAD, Cressier, Switzerland) in saline by the tube method and an indirect antiglobulin test (IAT) with the DG Gel Coombs card (Diagnostic Grifols, Barcelona, Spain). Meanwhile, RhCE and Asian- type DEL typing were also tested again. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Transfusion Reaction Analysis in Asian-type DEL Recipients During or After RhD+ Blood Transfusion | During the blood transfusion and in the days of hospitalization | Matched D+ RBCs were provided to the 54 eligible Asian-type DEL patients by the Guangzhou Blood Center and transfused at their respective hospitals. Patients were monitored for any adverse events during transfusion and a few days thereafter, which mainly involved acute nor delayed hemolytic transfusion reactions, as well as nonhemolytic reactions, including allergic and febrile nonhemolytic reactions and circulatory overload during or after transfusion. If the symptoms of hemolysis were suspected, the laboratory biochemical measurements were also performed. |
Countries
China
Participant flow
Recruitment details
Recruitment ranged between October 2016 and November 2021 in all hospitals located in Guangzhou of China.
Pre-assignment details
The enrolled participants are the Asian-type DEL patients with application for RBCs product from Guangzhou Blood Center, which is the only institute responsible for blood supply in Guangzhou city of China. Guangzhou is the capital city of Guangdong province in South China, with 15 million inhabitants. When any enrolled participants did not receive any blood transfusion finally, because of no need of blood transfusion in the clinic, they were excluded from the study.
Participants by arm
| Arm | Count |
|---|---|
| Asian-type DEL Recipients After identification of Asian-type DEL patients by phenotyping and genotyping methods, then D+ RBCs rather than rare D-negative RBCs were transfused to the Aisa-type DEL recipients who met the inclusion criteria.
Blood transfusion: Transfusion with D+ blood rather than the rare D-negative blood to Asian-type DEL recipients | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 12 |
Baseline characteristics
| Characteristic | Asian-type DEL Recipients |
|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 21.5 |
| Asian-type DEL patients received D+ RBC transfusion | 54 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 54 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 54 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 54 |
| other Total, other adverse events | 0 / 54 |
| serious Total, serious adverse events | 0 / 54 |
Outcome results
Primary
Occurrence of Alloanti-D Immunization in Asian-type DEL Recipients Transfused With RhD+ RBCs
For the Chinese Asian-type DEL recipients identified by the serological adsorption/elution test and HRM genotyping analysis, RhD+ RBC transfusion was performed. Then, the new blood samples from the patients were obtained after transfusion of RhD+ RBCs. The clinical significant alloantibodies against the common antigens of RBC were re-tested by antibody screening test. And the antibody screening test was performed using ID-DiaCell I-II-III Asia Kit (BIO-RAD, Cressier, Switzerland) in saline by the tube method and an indirect antiglobulin test (IAT) with the DG Gel Coombs card (Diagnostic Grifols, Barcelona, Spain). Meanwhile, RhCE and Asian- type DEL typing were also tested again.
Time frame: A median follow-up of 226 days (range, 32 to 1354 days) after RhD+ RBC transfusion
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Asian-type DEL Recipients | Occurrence of Alloanti-D Immunization in Asian-type DEL Recipients Transfused With RhD+ RBCs | No occurrence of alloanti-D immunization | 42 Participants |
| Asian-type DEL Recipients | Occurrence of Alloanti-D Immunization in Asian-type DEL Recipients Transfused With RhD+ RBCs | Lost of follow-up | 12 Participants |
Comparison: In this study, a single-arm clinical trial was conducted. The summarized alloanti-D rate (203/720, 28.2%; 95% CI, 19%-32%) in truly RhD-negative patients with similar mixed diseases after RhD+ RBC transfusion reported in the meta-analysis (Ji YL, et al. Vox Sang 2022; 117: 633-40) was used as the control for comparison with alloanti-D rate identified in Asian-type DEL patients after RhD+ RBC transfusion in the clinical trial.p-value: <0.001Chi-squared
Secondary
Adverse Transfusion Reaction Analysis in Asian-type DEL Recipients During or After RhD+ Blood Transfusion
Matched D+ RBCs were provided to the 54 eligible Asian-type DEL patients by the Guangzhou Blood Center and transfused at their respective hospitals. Patients were monitored for any adverse events during transfusion and a few days thereafter, which mainly involved acute nor delayed hemolytic transfusion reactions, as well as nonhemolytic reactions, including allergic and febrile nonhemolytic reactions and circulatory overload during or after transfusion. If the symptoms of hemolysis were suspected, the laboratory biochemical measurements were also performed.
Time frame: During the blood transfusion and in the days of hospitalization
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Asian-type DEL Recipients | Adverse Transfusion Reaction Analysis in Asian-type DEL Recipients During or After RhD+ Blood Transfusion | Without adverse transfusion reaction | 54 Participants |
| Asian-type DEL Recipients | Adverse Transfusion Reaction Analysis in Asian-type DEL Recipients During or After RhD+ Blood Transfusion | With adverse transfusion reaction | 0 Participants |