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RHESUS D NEGATIVE AND ANTIBODY SENSITIZATION AMONG PREGNANT WOMEN IN NIGERIA

CHAPTER ONE

INTRODUCTION

1.1     Background of Study

Antibody detection and identification are fundamental to the practice of immunohaematology. Antibody identification can be a guide towards the clinical importance of the antibody and provides information that aids in the selection of suitable blood for transfusion. Prenatal immunohaematologic care of pregnant women requires the investigation of unexpected blood group antibodies (especially Red Blood Cell and Rhesus blood group antibodies) in their sera during pregnancy (Jeremiah and Mordi, 2011). When blood cell antibody screening is on the positive, it is essential to determine specificity of the antibody, its clinical significance as well as the ability to cross the placenta and cause haemolytic disease of the foetus and newborn (HDFN). In some circumstances, it can be a difficult and time consuming process and thus cause a delay in patient care (Poole and Daniels, 2007). In 1940, Landsteiner and Wiener found that rhesus (Rh) immunization was because of fetal blood group antigen inherited from father invading the maternal circulation and causing maternal immunization. Anti-D occurring in Rh negative women was a main cause for severe haemolytic disease of the foetus and new born (HDFN) worldwide until the 1960s (Santavy, 2010). Furthermore, attention was called to the clinical importance of Rh immunization in 1941 and it was obvious that hemolytic disease of the newborn resulted from Rh sensitization and possibly in the death of fetus\newborn (William, 2007). Following successful implementation of prophylaxis, variations in birth order and enhanced quality of medical care, morbidity and mortality due to Rh -D related HDFN in many countries drastically reduced from 12-13 to 1-2 per cent (Velati, 2007; Joseph and Kramer, 2008). Meanwhile, other irregular antibodies that were observed to cause HDFN, mainly anti-c, anti-E, antibodies to antigens of Kell, Duffy, Kidd and MNS blood group systems, gained importance (Moise, 2000). Currently, the availability of wider screening panels has enabled the detection of various minor blood group antibodies, a number of which are well known to have importance in the antenatal setting (Velati, 2007). In developing countries the financial burden of routine screening for irregular antibodies, has to be weighed against the benefits and studies have shown that rhesus immunization is one of the primary reasons for perinatal mortality (Volkov, 2008).

1.2     Aim and Objectives

This study is aimed at providing the occurrence rate of rhesus D negative and antibody sensitization among pregnant women attending antenatal clinic in Federal Teaching Hospital Abakaliki.

The objectives include:

    1. Provide the frequencies of alloantibodies among pregnant women attending antenatal clinic in Federal Teaching Hospital Abakaliki.
    2. Provide the frequencies of alloantibodies among pregnant women attending antenatal clinic in Federal Teaching Hospital Abakaliki in relation to gravidity.
    3. Provide the frequencies of alloantibodies among pregnant women attending antenatal clinic in Federal Teaching Hospital Abakaliki in relation to the maternal gestational period.

1.3                   Significance of the Study

In Ebonyi State, as well in other developing parts of the world; type and screen procedure is not regularly carried out as part of the pre-transfusion test protocol, hence the incidence of maternal red cell alloantibodies and the prevalence of these unexpected antibodies in this locality are not known. With the high rate of neonatal jaundice in Nigeria (Jeremiah and Mordi, 2011), lack of information on this subject, it becomes essential for a study like this to be conducted. Hence this is the foremost attempt to provide the prevalence of unexpected antibodies in this part of the globe.

CHAPTER TWO

LITERATURE REVIEW

2.1     Rhesus Blood Group System

The Rh blood group system (including the Rh factor) is one of thirty-three current human blood group systems. It is the most important blood group system after ABO. At present, the Rh blood group system consists of 50 defined blood-group antigens, among which the five antigens D, C, c, E, and e are the most important.

The commonly used terms Rh factor, Rh positive and Rh negative refer to the D antigen only. Besides its role in blood transfusion, the Rh blood group system—specifically, the D antigen—is used to determine the risk of hemolytic disease of the newborn (or erythroblastosis fetalis) as prevention is the best approach to the management of this condition (Wagner and Flegel, 2002). As part of prenatal care, a blood test may be used to find out the blood type of a fetus. If the Rh antigen is lacking, the blood is called Rh-negative. If the antigen is present, it is called Rh-positive. When the mother is Rh-negative and the father is Rh-positive, the fetus can inherit the Rh factor from the father. This makes the fetus Rh-positive too. Problems can arise when the fetus’s blood has the Rh factor and the mother’s blood does not.

2.2     Rh factor

An individual either has, or does not have, the “Rh factor” on the surface of their red blood cells. This term strictly refers only to the most immunogenic D antigen of the Rh blood group system, or the Rh− blood group system. The status is usually indicated by Rh positive (Rh+ does have the D antigen) or Rh negative (Rh− does not have the D antigen) suffix to the ABO blood type. However, other antigens of this blood group system are also clinically relevant. These antigens are listed separately (see below: Rh nomenclature). In contrast to the ABO blood group, immunization against Rh can generally only occur through blood transfusion or placental exposure during pregnancy in women (Wagner and Flegel, 2002).

2.3     History of discoveries

In 1939, Philip Levine and Rufus Stetson published in a first case report the clinical consequences of non-recognized Rh factor, hemolytic transfusion reaction and hemolytic disease of the newborn in its most severe form (Levine and Stetson, 2009). It was recognized that the serum of the reported woman agglutinated with red blood cells of about 80% of the people although the then known blood groups, in particular ABO were matched. No name was given to this agglutinin when described for the first time. In 1940, Karl Landsteiner and Alexander S. Wiener reported a serum that also reacted with about 85% of different human red blood cells (Landsteiner and Weiner, 2010). This serum was produced by immunizing rabbits with red blood cells from Rhesus macaque.

Based on the serologic similarities Rh factor was later also used for antigens, and anti-Rh for antibodies, found in humans such as the previously described by Levine and Stetson. Although differences between these two sera were shown already in 1942 and clearly demonstrated in 1963, the already widely used term “Rh” was kept for the clinically described human antibodies which are different from the ones related to the Rhesus monkey. This real factor found in Rhesus macaque was classified in the Landsteiner-Wiener antigen system (antigen LW, antibody anti-LW) in honor of the discoverers (Scott, 2004). It was recognized that the Rh factor was just one in a system of various antigens. Based on different models of genetic inheritance, two different terminologies were developed; both of them are still in use.

The clinical significance of this highly immunizing D antigen (i.e. Rh factor) was soon realized. Some keystones were to recognize its importance for blood transfusion including reliable diagnostic tests, and hemolytic disease of the newborn including exchange transfusion and very importantly the prevention of it by screening and prophylaxis.

Rh nomenclature

The Rh blood group system has two sets of nomenclatures: one developed by Ronald Fisher and R.R. Race, the other by Wiener. Both systems reflected alternative theories of inheritance. The Fisher-Race system, which is more commonly in use today, uses the CDE nomenclature. This system was based on the theory that a separate gene controls the product of each corresponding antigen (e.g., a “D gene” produces D antigen, and so on). However, the d gene was hypothetical, not actual.

The Wiener system used the Rh–Hr nomenclature. This system was based on the theory that there was one gene at a single locus on each chromosome, each contributing to production of multiple antigens. In this theory, a gene R1 is supposed to give rise to the “blood factors” Rh0, rh’, and hr” (corresponding to modern nomenclature of the D, C and e antigens) and the gene r to produce hr’ and hr” (corresponding to modern nomenclature of the c and e antigens) (Weiner, 2009).

Notations of the two theories are used interchangeably in blood banking (e.g., Rho(D) meaning RhD positive). Wiener’s notation is more complex and cumbersome for routine use. Because it is simpler to explain, the Fisher-Race theory has become more widely used.

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