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Volume 9, Issue 3 (August 2022)                   IJML 2022, 9(3): 164-168 | Back to browse issues page


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Bahramian H, Hashemzehi J, Nayebzadeh M, Khosravi S. Identification of First Patient with Rh null Phenotype in Southeast Iran. IJML 2022; 9 (3) :164-168
URL: http://ijml.ssu.ac.ir/article-1-400-en.html
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Zahedan, Iran
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Introduction
Rhnull is an extremely rare autosomal recessive blood group phenotype with an estimated prevalence of one per 6,000,000 individuals [1, 2]. The Rh blood group system with about 50 different antigens is the most polymorphic human blood group and the most clinically significant blood group next to ABO [3]. The Rh blood group system is one of the most complex blood group systems with a significant effect on the erythrocyte structure [4]. Patients with Rhnull phenotype do not express any Rh antigens and therefore have red blood cells with somatotype phenotype and experience chronic hemolytic anemia [3]. In addition, patients
with Rhnull syndrome have other erythrocyte abnormalities, including spherocytosis, increased osmotic fragility, elevated Na1/K1 ATPase activity, and others [3, 5]. A patient with a
Rhnull  phenotype may be Rhnull -amorph or Rhnull -regulator; both may produce an antibody against all Rh antigens, which is also known as anti-total Rh or anti-Rh29, which is a significant clinical and laboratory challenge [3, 4]. The main difference between these two forms of Rhnull is the molecular basis of the disorders [5]. Due to the rarity of the syndrome, patients with Rhnull are at a high risk of a lack of blood supplements in emergencies like surgery. Therefore early identification and registration of patients with rare blood groups is of special importance. Due to this requirement, an International Society for Blood Transfusion (ISBT) working party report on rare blood donors was established to facilitate blood availability for patients with rare blood groups [6]. Due to the importance of this issue in the present study, we reported the first family with Rhnull phenotype in southeast Iran.

Materials and Methods
The patient was referred to the immuno-hematology laboratory of Zahedan Blood Transfusion Organization for compatibility testing. Initially, blood grouping was performed on the patient's fresh samples using anti-A, anti-B, and anti-AB negative, A-cell, and B-cell. In the next step, antibody screening with a homemade 3-cell panel was performed to determine the presence of any unexpected antibody in the patient's serum. After observation of a positive reaction on the antibody screening step, antibody identification was performed using the Iranian Blood Transfusion Organization (IBTO) homemade antibody identification 11- cell panel. Finally, red blood cell phenotyping of the patient was performed by anti-C, anti-c, anti-E, and anti-e antibodies.
Due to a lack of specific assays in the immunohematology laboratory of the Zahedan Transfusion Organization, the patient's sample was sent to the immunohematology reference laboratory of the IBTO in Tehran. Confirmatory tests were performed for the index cases in the immunohematology reference laboratory, as previously described in detail [7]. The study was proved by the ethical committee of the Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Zahedan, Iran.
Results and Discussion
In her first delivery, a 21-year-old woman with positive parents' consanguineous marriages was referred to the immunohematology laboratory of Zahedan Blood Transfusion Organization for pretransfusion testing. In the hospital cross-match of the patient, they found a strong reaction (+4) of the patient's serum with all available red blood cell units. Therefore, the patient's sample was sent to the immuno-hematology laboratory of Zahedan Blood Transfusion Organization for compatibility testing. In blood grouping, the following reactions were observed: Anti-A, anti-B, and anti-AB negative, A-cell, and B-cell positive (4+), which were compatible with O negative blood group. Antibody screening with a homemade 3-cell panel revealed a positive reaction with all panel cells, which was highly suspected to be an antibody against a common panel cell antigen or multiple alloantibodies against the patient's absence antigens. Further studies on the Iranian Blood Transfusion Organization (IBTO) homemade antibody identification panel (11 cell panel) revealed a widespread reaction with all panel cells. Following this reaction, further red blood cell phenotyping was performed by anti-C, anti-c, anti-E, and anti-e, which showed a negative reaction for all antibodies, highly suspected of Rhnull phenotype (Table 1).
Table 1. Characteristics of a family with Rhnull phenotype
Case Anti-A Anti-B Anti-AB Anti-D Anti-C Anti-c Anti-E Anti-e
Index case Neg Neg Neg Neg Neg Neg Neg Neg
Son Neg Neg Neg Neg Pos Neg Neg Pos
Sister Neg Neg Neg Neg Neg Pos Neg Pos
Brother Neg Neg Neg Neg Neg Pos Neg Pos 
Father Neg Neg Neg Neg Neg Neg Neg Neg
Mother Neg Neg Neg Neg Neg Neg Neg Neg
Immunohematology reference laboratory confirmed the Rhnull phenotype of the patient. Due to the requirement of the patient for blood transfusion and the autosomal recessive inheritance pattern of Rhnull, we called her family members for blood donation. Her parents and sister were referred to the immunohematology laboratory of the Zahedan Transfusion Organization for further assessments (Table 1). She had a sister, and primary and confirmatory serological testing, including the Rh system phenotyping, revealed that she is also a Rhnull individual. Blood was collected from the patient's sister and transfused to the patient, and the pregnancy ended without complications.
Rhnull is an extremely rare condition that could be found in one per 6,000,000 individuals worldwide. Although the precise incidence of the syndrome is unknown, societies with a high rate of consanguineous marriages have a high rate of this condition. A few individuals with Rhnull syndrome have been reported in different counties, including Iran, India, Europe, the United States, and others [3, 7, 8]. Most patients with Rhnull syndrome have been identified randomly in pretransfusion testing, similar to the present case and previously reported Iranian case [3, 7].
In patients with Rhnull syndrome, all the Rh blood group system antigens are absent [3]. Patients with Rhnull syndrome could have a severe blood transfusion reaction following Rh-positive blood transfusion. Thus, appropriate management of patients, particularly during surgery, is an important issue. Patients with Rhnull phenotype can produce anti-Rh29, anti-Rh17, or a mixture of antibodies. The transfusion process in patients with these antibodies, particularly anti-Rh29, which is a total Rh antibody, is a significant challenge and only can give blood from an individual with a Rhnull phenotype, as observed in the present case [3, 4].
Identifying one case with Rhnull is a significant diagnostic clue for identifying other family members with the same phenotype. In the present study, randomly diagnosing one individual with Rhnull syndrome leads to diagnosing another family member with the syndrome. Previous studies have reported chronic hemolytic anemia with stomatocytosis in patients with Rhnull syndrome [3, 7]. In this study, we observed erythrocytes with somatotype morphology and chronic anemia in the patient. Anemia is mild and does not require any blood transfusion, as observed in the present case. There are only a few reported cases with Rhnull phenotype in Iran, and supply of blood supplements for patients with such a rare blood group phenotype is a significant challenge, and autologous blood transfusion is a crucial lifesaving choice for patients with such a rare phenotype. Establishing the ISBT, working party on rare donors, and identifying such individuals and their blood supply may be less challenging [6]. Alternatively, close-relative such as brothers and sisters may have a common blood group phenotype with patients with Rhnull phenotype and can be selected for blood transfusion, especially in emergencies, as described previously by other Iranian researchers (7). In the present study, we also used a close relative of the patient─her sister─ as a selective donor to manage her complicated pregnancy that required two units packed red blood cells for blood transfusion.
Conclusion
Early identification of patients with rare blood group phenotypes is an important issue that can help in the timely management and appropriate treatment of patients in emergencies. Identifying and registering patients with rare blood phenotypes is straightforward for the early management of the individuals.
Conflict of Interest
The authors declare that they have no competing interests.
Acknowledgments
We would like to thank the Zahedan blood transfusion organization staff, the selected patient, and her family for their kind cooperation during the study project.
References
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  3.  Avent ND, Reid ME. The Rh blood group system: a review. Blood 2000; 95(2): 375-87.
  4.  Huang CH, Liu PZ, Cheng JG. Molecular biology and genetics of the Rh blood group system. Semin Hematol. 2000; 37(2): 150-65.
  5.  Agre P, Cartron JP. Molecular biology of the Rh antigens. Blood 1991; 78: 551-563.
  6.  Mourant AE: The establishment of the international panel of rare blood donors. Vox Sang. 1965; 10(2): 129-32
  7.  Shahverdi E, Moghaddam M, Abolghasemi H. First report of known rare Rh null phenotype individuals in Iran. Int J Hematol Oncol Stem Cell Res. 2018; 12(3): 181-84.
  8.  Seidl S, Spielmann W, Martin H. Two siblings with Rhnull disease. Vox Sang. 1972; 23(1): 182-89.
Type of Study: case report | Subject: Hematology & Blood Banking
Received: 2021/02/2 | Accepted: 2022/08/4 | Published: 2022/10/15

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