RhD+ Blood Transfusion to Asian-type DEL Recipients

Single-arm Multicenter Clinical Trial of Blood Transfusion From RhD+ Donors to Asian-type DEL Recipients

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.

Study Overview

• Status: Completed
• Conditions: Blood Transfusion; Blood Group Antigen Abnormality; Rhesus Isoimmunisation Due to Anti-D
• Intervention / Treatment: Other: Blood transfusion

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Guangdong General Hospital
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510000
      • Guangdong Second Provincial General Hospital
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Guangzhou University of Chinese Medicine
    • Guangzhou, Guangdong, China, 510000
      • The Second Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510095
      • Guangzhou Blood Center
    • Guangzhou, Guangdong, China, 510000
      • ZhuJiang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510000
      • Guangdong Province Traditional Chinese Medical Hospital
    • Guangzhou, Guangdong, China, 510000
      • The Third Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Asian-type DEL recipients; First, to identify Asian-type DEL patients by phenotyping and genotyping methods in the Chinese recipients having a serologically apparent RhD-negative phenotype. Then, blood transfusion of RhD+ blood rather than rare RhD-negative blood to the Asian-type DEL recipients which met the inclusion criteria.	Other: Blood transfusion; Transfusion with RhD+ blood product rather than rare RhD-negative blood to Asian-type DEL recipients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	A median follow-up of 226 days (range, 32 to 1354 days) after RhD+ RBC transfusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	During the blood transfusion and in the days of hospitalization

Collaborators and Investigators

• Sponsor: Guangzhou Blood Center
• Collaborators: Guangdong Provincial Hospital of Traditional Chinese Medicine; Sun Yat-sen University; First Affiliated Hospital, Sun Yat-Sen University; Guangdong Provincial People's Hospital; Zhujiang Hospital; Third Affiliated Hospital, Sun Yat-Sen University; Guangdong Provincial Institute of Biological Products And Materia Medica; Shenzhen Second People's Hospital; Second Affiliated Hospital of Guangzhou Medical University; Southern Medical University, China; Koo Foundation Sun Yat-Sen Cancer Center; Guangdong Second Provincial General Hospital; The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
• Investigators: Study Chair: Yongshui Fu, MD, PhD, Guangzhou Blood Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): October 9, 2021
• Study Completion (Actual): November 30, 2021

Study Registration Dates

• First Submitted: October 26, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 1, 2018

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hematologic Diseases; Congenital Abnormalities
• Other Study ID Numbers: DEL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No