Rhesus System with Transfusion Reaction in Blood Bank


Thesis Proposal

Topic: Significant and relation between Rhesus system with transfusion reaction in blood bank

Aim: To study the relation and significant of Rh antibodies in blood transfusion reaction cases.


  1. To study the significant of Rh system (D,d,E,e,C,c,Cw) in transfusion reaction cases
  2. To determine the percentage of antibodies cause the reaction
  3. To examine different technique to detect the problem early
  4. To create a new policy to avoid transfusion reaction

please follow the structure of thesis proposal


Provision towards safe blood supply is the main responsibility for every transfusion facility. Testing for the presence of infectious pathogens along with preventions towards ABO blood group induced haemolytic transfusion reactions arising out of alloimmunization is of the prime importance (Makroo, Agrawal & Chowdhry, 2017). However, the adverse transfusion reaction arising out of the rhesus (Rh) system is gradually gaining immunogenic significance in transfusion reaction after ABO blood group (Sachan et al., 2015). According to the reports published by Vamvakas and Blajchman (2009), apart from haemolytic transfusion reaction,, transfusion reactions is also regarded as a prime thereat towards the development of transfusion related acute lung injury (TRALI) and transfusion-associated sepsis. Rh antibody mediated haemolytic transfusion reactions results in extravascular haemolysis along with delayed haemolytic transfusion reaction. The commonly reported Rh antigens which are involved in eliciting transfusion reaction include Diego, Kidd and P-antigens (Sachan et al., 2015). Apart from these anti-C RH antibodies is also gaining prominence in the domain of haemolytic reaction (Sachan et al., 2015). However, relation between the Rh antibody and intravascular haemolysis is unclear (Sachan et al., 2015). A detailed analysis of the relationship between Rh antigen and transfusion reaction will be important in generating proper action plan for the early detection of the transfusion reaction and subsequent policy to implement transfusion reaction control measures.

Aim of the research
So the aim of this research is to study the relation and significant of Rh antibodies in blood transfusion reaction cases.

Objective of the research

  1. To study the significant of Rh system (D,d,E,e,C,c,Cw) in transfusion reaction cases
  2. To determine the percentage of antibodies cause the reaction
  3. To examine different technique to detect the problem early
  4. To create a new policy to avoid transfusion reaction

Review of Literature

Significance of Rh system in blood transfusion cases
Rh system is classified into Rh-positive or negative based on the presence or absence of antibodies in the blood. Five main Rh antigens are present on red blood cells for which an individual can be either positive or negative: D, C/c, and E/e. The significance and need of including antibody screening during pre-transfusion testing was validated by a study that emphasised on the role of Rh mediated hemolytic transfusions delaying onset (Sachan et al., 2015). Findings suggested that Rh antibodies belong to the IgG class of immunoglobulins are found to exert no action on complement activation. Furthermore, a series of complement activation gets initiated upon interaction of the antigen and antibody, provided the RBC antibodies are capable of complement binding (Berséus et al., 2013). Similar findings were presented by other studies that provided evidence for the role of Rh antigen-antibody reaction in case of hemolytic transfusions (Tanhehco & Berns, 2012). Evidences further suggest that acute forms of hemolytic reactions occur upon interaction of the transfused RBCs with the antibodies that have been performed in the recipients.

Several cases of AHTR were also reported by studies that established its correlation with multiple alloantibodies, which led to the development of intravascular hemolysis. Other research articles, also confirmed association between hemolyyic disease of newborns and DHTR with Rh antibodies (anti-c) in combination with anti-E (Sachan et al., 2015). Authors have also established the need of conducting a screening for pre-transfusion antibodies during compatibility testing. Necessity for conducting transfusion of Kell and Rh matched antibodies have been confirmed by many articled, with the primary aim of preventing alloantibody development among individuals requiring multiple transfusions or suffering from a range of chronic disorders (Makroo, Agrawal & Chowdhry, 2017). Studies suggest that cross-matching, antibody screening, followed by their identification are the most essential steps that need to be performed before blood transfusion (Hijji, Parahoo, Hussein & Barr, 2013). Another study also provided evidence that established the sequence of antigenicity of the Kell and Rh antigens in the order of D>K>c>E>C>c. Blood transfusion is considered as an essential component of treating sickle celled patients (Sharma et al., 2013). Furthermore, it has been confirmed that alteration in Rh alleles in patients suffering from sickle cell anemia and their donors showed a high prevalence of Rh alloimmunisation. Rates of blood transfusion have been found indispensible in several regions of sub-Saharan Africa.

Another study showed high prevalence of acute transfusion reactions at a rate of 213 per 1000 transfusions in KATH (Owusu ? Ofori, Owusu?Ofori & Bates, 2017). Research studies have also been conducted to elucidate the fact that in order to avoid transfusion reactions, blood from the donor must always be compatible and matched to that of the patient. Articles confirm that the blood donated must contain similar Rh antigen D that is lacking in the body of the patient or the receiver. However, authors have also argued that donors might still portray incompatibility due to presence of other antigens, which might not be routinely typed (Chou et al., 2013). Hence, it is essential to cross match the Rh systems with the aim of ensuring compatibility of the donor RBCs against the recipient’s serum. Although several studies have been conducted to elucidate the importance of Rh factor compatibility before conducting blood transfusions, there is a need to conduct more extensive literature searches for preventing risks related to sensitization of the receivers and hemolytic reactions following blood transfusions. Further studies should be conducted to investigate the concerns about alloimmunisation and future hemolytic reactions.

Percentage of antibodies that cause blood transfusion reaction
Blood transfusion reactions occur when the immune system of the recipient attacks the red blood cells that were given by the donor during transfusion. A retrospective study that aimed to determine prevalence of alloimmunisation among the Chinese population identified 83 patients with RBC antibodies. Estimates of the antibody percentages were found to be approximately 39.3% (anti-E), 13.1% (anti-c), 6.55% (anti-Jka), 38.4% (anti-E), and 7.7% (anti-Fyb) (Cheng, Lee & Lin, 2012). Another retrospective analysis were conducted to determine risks of hemolytic transfusion reactions following an emergency and provided evidences for positive antibody detection in 10.9% of the episodes. Alloantibodies and warm autoantibodies were found in 6.4% and 2.3% of the cases, respectively (Goodell, Uhl, Mohammed & Powers, 2010). Results from a prospective analysis that aimed to screen alloimmunisation after RBC transfusion suggested presence of a high proportion of individuals with O positive blood group (25%). 13.33% individuals without any history of blood transfusions were found to produce antibodies. Further estimates suggested presence of alloimmunisation among patients subjected to more than 10 episodes of blood transfusion (50%) (Alves et al., 2012).

Similar findings were reported by another study that aimed to determine transfusion complications that occur in thalassemia patients. The result analysis provided evidence for 19% transfused patients with reported allantibodies. 47% alloimmunised patients were found to contain multiple antibodies, such as, anti-K, anti-E, anti-C, anti-c, and anti-JKa at frequencies of 17%, 29%, 12%, 5% and 6%, respectively. Furthermore, rate of alloimmunisation was found to be maximum at the initiation age of 11-20years, for transfusion therapy (Vichinsky et al., 2014). A particular study was able to determine the prevalence of the Rh and kell systems and estimated their rates to be 58%, 93.6%, 87%, 98%, 20%, and 3.5% for ‘c’, ‘D’, ‘C’, ‘e’, ‘E’, and ‘K’ antigens respectively (Makroo et al., 2013). Similar results were demonstrated by another study that determined the prevalence to be around 58.3%, 91.6%, 84%, 78.5% and 25.6% (Sharma et al., 2013). Studies were also conducted to ascertain drawing of RBC components predominantly from Caucasian donors and stated that SCD patients having undergone blood transfusion were found to contain 2% K, 2% E, 1% C for antibody specificity (Wilkinson et al., 2012).

The major research gap exists in the fact that inadequate literature sources are available that have investigated the proportion of antibodies that are responsible for the onset of acute blood transfusion reactions. Good evidence is available for confirming the fact that blood transfusion is highly variable and often shows a deviation from the evidence-based guidelines. Owing to the fact that blood transfusions are life saving, it is extremely essential to identify the percentage and prevalence of the antibodies that significantly contribute to its associated adverse effects that might be life threatening. Therefore, there is a need to determine the percentage of allo- and auto-antibodies that lead to the manifestation of acute hemolytic transfusion reactions, post-transfusion.

To examine different technique to detect problem early
According to Sahu and Hemlata (2014), transfusion reactions are one of the most common adverse effects associated with the administration of blood products. Adverse transfusion reaction can lead to extreme discomfort to the patients along with extra burden of cost to the healthcare system. There, awareness in increasing the clinical efficacy towards restrictive transfusion thresholds along with early detection of the problem is crucial to reduce the fatal outcomes (Delaney et al., 2016). Sahu and Hemlata (2014) are of the opinion that detection of the early symptom is one of the crucial ways to detect the problem early. Allergic and anaphylactic transfusion reactions occur within 4 hours of transfusion and are associated with platelet transfusion. The symptoms caused by the primary mediators (histamine) are mild including rash, urticaria (hives), pruritus and severe reaction in include anaphylactic shock (Delaney et al., 2016). Acute haemolytic transfusion reactions are the common transfusion reactions. Since fever and chills are the few early signs and it is important to monitor the patients during transfusion and cease the transfusion immediately if there are any imbalance in the vital signs (Delaney et al., 2016). Early detection and prevention of delayed haemolytic or delayed serological transfusion reactions are common phenomenon among the patients with sickle cell anaemia (Delaney et al., 2016). Excretion of dark urine and jaundice are common symptoms that must be used to monitor the detection of the transfusion reaction (Delaney et al., 2016). However, the current management of delayed haemolytic transfusion reaction is controversial because proper mechanism behind the development of transfusion reaction is unclear because antibodies cannot be detected and lack of proper corticosteroid treatment in patients with sickle cell anaemia (Yazdanbakhsh, Ware & Noizat-Pirenne, 2012). Febrile non-haemolytic transfusion reactions have similar early symptoms like that of the haemolytic transfusion reactions such that monitoring of the fever or chills are main techniques or approaches that is utilised for the early detection of the adverse transfusion reaction. However, Delaney et al. (2016) is of the opinion that pre-storage of leukocyte can help in the prevention of the febrile non-haemolytic reactions. One of the challenging and most complex blood transfusion reactions is hyper haemolytic transfusion reaction. According to Delaney et al. (2016), serological analysis of the post-transfusion samples might not reveal additional red blood cell alloantibodies and direct antiglobulin test might provide negative results and thus creating confusion. Thus a high index suspicion is recommended for the early diagnosis of the hyper haemolytic transfusion reaction which occurs 7 days after the transfusion (Delaney et al., 2016).

Prevention and early detection relies on systems-based practises along with proper training of the healthcare professionals in order to ensure accurate patient identification at crucial steps in sample collection and transfusion process (Figueroa et al., 2006). Further review of literature will help in the elucidation for the proper system-based practices and detection methods that is employed for the early detection of the transfusion reactions along with detailed planning of the effective treatment procurement.

To create a new policy to avoid transfusion reaction
One of the main policy that is utilised to control the blood transfusion reaction include detailed analysis of the patient’s allergic history before initiation of the blood transfusion along with proper blood typing (Delaney et al., 2016). In the domain of allergic and anaphylactic transfusion reaction, Tinegate et al. (2012) is of the opinion that the transfusion can be resumed with the same unit but at a reduced rate if the symptoms resolved but if the symptoms reoccur, then the transfusion must be discontinued immediately. Antihistamine drug along with administration of epinephrine is recommended in order to treat the anaphylactic transfusion reactions (Delaney et al., 2016). For the juvenile patients suffering from cerebral palsy multiple intravenous infusions done via allogenic ABO/Rh-indentical umbilical cord blood cells is considered to be safe and effective procedure in order to prevent the blood transfusion reaction (Romanov et al., 2015). However, policy framing in order to implement this procedure is still under way as further trails are require to validate the efficacy of the results. The study conducted by Owusu?Ofori, Owusu?Ofori and Bates (2017) in Ghana elucidated that there is a significant number of discontinued blood transfusion reaction cases. They are of the opinion that this incidence suggests that proper guidelines on how to manage the transfusion reactions would help to preserve the scarcity of the blood stocks. They are also of the opinion that step-by-step implementation of haemovigilance system, starting with monitoring the negative transfusion reaction is a pragmatic way under resource limited settings. Overall, Fung et al. (2010) is of the opinion that the health-care organisations must establish policies that define the vitals sign change that will facilitate quick evaluation of suspected transfusion reaction. Thus there lies a gap in the domain of proper framing of the blood transfusion policies which will help to prevent the adverse effects arising out of the blood transfusion reaction. According to Milkins et al. (2013), any abbreviation of the ABO group must be assessed in a comprehensive manner. They also further opined that fully automated systems should be employed in order to reduce the risks associated with the interpretation and transcription errors. Milkins et al. (2013) also vouched in favour of proper analysis of the patient’s demographics against the computer-generated record before validation of the transfusion results this will ensure that the samples are matched and that no errors are done during the encryption of the data in the laboratory information management system. Milkins et al. (2013) further opined that indirect antiglobulin test (IAT) cross match should be used as the default technique when the electronic issue is contra-indicated. IAT cross match technique should be used only if the patient’s plasma contains allo-antibodies of the red blood cells. Gender and a unique identification number are proper by Milkins et al. (2013) as the general identifier for the unknown patient; this will help to track the root cause of the adverse transfusion reaction.

However, these blood transfusion polices are only related to the pre-transfusion protocols. A detailed analysis of the governmental policies across the world in relation of blood transfusion reaction will help to frame concrete transfusion policies which will in turn provide an effective means to reduce the fatal outcomes of the transfusion reactions.

This qualitative research will be conducted based on positivism research philosophy as this will help the researcher to analyse the topic with logical flow of information. The research design which will be used by researcher include descriptive approach as this will help the research to analyse various approaches in a descriptive manner. Research strategy that will be suitable for this research is secondary and this will aid qualitative data analysis (Parahoo et al., 2014). The sampling or the collection of sample in this research generally deals with search of the literary articles. The search of the articles will mostly be based on the broad key-word search of the articles in the electronic data base include PubMed, Medline and Crochane. The main keywords which will be used for the search of the literary articles include “blood transfusion”, “transfusion reaction”, “transfusion reaction” AND “ABO blood group”, “transfusion reaction” AND adverse events”. The main inclusion criteria that will be selected for the study include, literary articles published within last 10 years (2008 to 2018) and in English language. The main exclusion criteria that will be selected for the study include the articles focused on the plasma derivatives.

Time Plan

Gantt Chart

Task 1st month 2nd month 3rd month 4th month 5th month
Search of the literary articles ·        
Sorting of the literary articles · ·      
Performing review of literature (thematic analysis)   · ·    
Data analysis       ·  
Results and recommendation          

Alves, V. M., Martins, P. R. J., Soares, S., Araújo, G., Schmidt, L. C., Costa, S. S. D. M., … & Moraes-Souza, H. (2012). Alloimmunization screening after transfusion of red blood cells in a prospective study. Revista brasileira de hematologia e hemoterapia, 34(3), 206-211.

Berséus, O., Boman, K., Nessen, S. C., & Westerberg, L. A. (2013). Risks of hemolysis due to anti ? A and anti ? B caused by the transfusion of blood or blood components containing ABO? incompatible plasma. Transfusion, 53(S1), 114S-123S.

Cheng, C. K., Lee, C. K., & Lin, C. K. (2012). Clinically significant red blood cell antibodies in chronically transfused patients: a survey of Chinese thalassemia major patients and literature review. Transfusion, 52(10), 2220-2224.

Chou, S. T., Jackson, T., Vege, S., Smith-Whitley, K., Friedman, D. F., & Westhoff, C. M. (2013). High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. Blood, 122(6), 1062-1071.

Delaney, M., Wendel, S., Bercovitz, R. S., Cid, J., Cohn, C., Dunbar, N. M., … & Van De Watering, L. (2016). Transfusion reactions: prevention, diagnosis, and treatment. The Lancet, 388(10061), 2825-2836.

Figueroa, P. I., Ziman, A., Wheeler, C., Gornbein, J., Monson, M., & Calhoun, L. (2006). Nearly two decades using the check-type to prevent ABO-incompatible transfusions: one institution’s experience. American journal of clinical pathology, 126(3), 422-426.

Fung M, Grossman BJ, Hillyer CD & Westhoff CM. (2014). Technical Manual, 18th edn. Glen Burnie, MD: AABB Press.

Goodell, P. P., Uhl, L., Mohammed, M., & Powers, A. A. (2010). Risk of hemolytic transfusion reactions following emergency-release RBC transfusion. American journal of clinical pathology, 134(2), 202-206.

Hijji, B., Parahoo, K., Hussein, M. M., & Barr, O. (2013). Knowledge of blood transfusion among nurses. Journal of clinical nursing, 22(17-18), 2536-2550.

Makroo, R. N., Agrawal, S., & Chowdhry, M. (2017). Rh and Kell Phenotype Matched Blood Versus Randomly Selected and Conventionally Cross Matched Blood on Incidence of Alloimmunization. Indian Journal of Hematology and Blood Transfusion, 33(2), 264-270.

Makroo, R. N., Bhatia, A., Gupta, R., & Phillip, J. (2013). Prevalence of Rh, Duffy, Kell, Kidd & MNSs blood group antigens in the Indian blood donor population. The Indian Journal of Medical Research, 137(3), 521.

Milkins, C., Berryman, J., Cantwell, C., Elliott, C., Haggas, R., Jones, J., … & Win, N., (2013). Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories.

Owusu ? Ofori, A. K., Owusu ? Ofori, S. P., & Bates, I. (2017). Detection of adverse events of transfusion in a teaching hospital in Ghana. Transfusion Medicine, 27(3), 175-180.

Parahoo, K., 2014. Nursing research: principles, process and issues. Palgrave Macmillan

Romanov, Y. A., Tarakanov, O. P., Radaev, S. M., Dugina, T. N., Ryaskina, S. S., Darevskaya, A. N., … & Burkova, A. S. (2015). Human allogeneic AB0/Rh-identical umbilical cord blood cells in the treatment of juvenile patients with cerebral palsy. Cytotherapy, 17(7), 969-978.

Sachan, D., Jayakumar, R., Varghese, J., & Rela, M. (2015). An acute hemolytic transfusion reaction due to the “anti-c” rhesus antibody: A case report emphasizing the role of transfusion medicine. Asian journal of transfusion science, 9(2), 213.

Sahu, S. & Hemlata, A.V. (2014). Adverse events related to blood transfusion. Indian journal of anaesthesia, 58(5), p.543.

Sharma DC, Singhal S, Rai S, Iyenger S, Sao S, Jain B (2013) Incidence of Rh Antigens, Phenotype & Probable Genotype in the Population of Gwalior and Chambal Region, Central India. Int Blood Res Rev. 1(1), 29–43.

Tanhehco, Y. C., & Berns, J. S. (2012, September). Red Blood Cell Transfusion Risks in Patients with End ? Stage Renal Disease. In Seminars in dialysis, 25(5), 539-544.

Tinegate, H., Birchall, J., Gray, A., Haggas, R., Massey, E., Norfolk, D., … & Allard, S. (2012). Guideline on the investigation and management of acute transfusion reactions Prepared by the BCSH Blood Transfusion Task Force. British journal of haematology, 159(2), 143-153.

Vamvakas, E. C., & Blajchman, M. A. (2009). Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood, 113(15), 3406-3417.

Vichinsky, E., Neumayr, L., Trimble, S., Giardina, P. J., Cohen, A. R., Coates, T., … & Thompson, A. A. (2014). Transfusion complications in thalassemia patients: a report from the Centers for Disease Control and Prevention (CME). Transfusion, 54(4), 972-981.

Wilkinson, K., Harris, S., Gaur, P., Haile, A., Armour, R., Teramura, G., & Delaney, M. (2012). Molecular blood typing augments serologic testing and allows for enhanced matching of red blood cells for transfusion in patients with sickle cell disease. Transfusion, 52(2), 381-388.

Yazdanbakhsh, K., Ware, R. E., & Noizat-Pirenne, F. (2012). Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management. Blood, 120(3), 528-537.

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