Immunohematology and applications of blood groups

Dr. Topesh Patle

Introduction 

  • Immunohematology is the branch of immunology concerned with blood group antigens and antibodies

  • It deals with antigen–antibody reactions involving red blood cells

  • It forms the scientific basis of safe blood transfusion practices

  • It plays an essential role in blood banking and transfusion medicine

  • Immunohematology has applications beyond transfusion, including population genetics and forensic medicine

  • Knowledge of immunohematology helps prevent transfusion reactions and hemolytic diseases

  • It is an important subject for medical, paramedical, and laboratory professionals

Basic principles of immunohematology

Immunohematology is based on the specific interaction between red cell antigens and corresponding antibodies present in plasma or serum.

Red blood cell antigens

  • Antigens are genetically inherited structures located on the red cell membrane

  • They may be proteins, glycoproteins, or glycolipids

  • More than 300 red cell antigens have been identified

  • These antigens are arranged into well-defined blood group systems such as ABO, Rh, Kell, Duffy, Kidd, and MNS

Blood group antibodies

  • Antibodies are immunoglobulins produced in response to antigens

  • Naturally occurring antibodies are present without prior antigen exposure (e.g., anti-A and anti-B)

  • Immune antibodies are formed after exposure through transfusion or pregnancy (e.g., anti-D)

Antigen–antibody reaction

  • Occurs when an antibody binds to its corresponding antigen

  • Results in agglutination or hemolysis

  • Forms the basis of blood grouping, crossmatching, and compatibility testing

Classes of antibodies

  • IgM antibodies react at lower temperatures and cause direct agglutination

  • IgG antibodies react optimally at 37°C and require antiglobulin testing

Antiglobulin (Coombs) test

  • Detects IgG antibodies or complement attached to red cells

  • Includes direct antiglobulin test (DAT) and indirect antiglobulin test (IAT)

 

Blood group systems and their importance

  • A blood group system consists of one or more antigens controlled by a single gene or a closely linked group of genes

  • Each system is recognized by the International Society of Blood Transfusion (ISBT)

  • More than 40 blood group systems have been identified to date

ABO blood group system

  • Discovered by Karl Landsteiner

  • Most important blood group system in transfusion practice

  • Based on the presence of A and B antigens on red blood cells

  • Naturally occurring anti-A and anti-B antibodies are present in plasma

  • ABO incompatibility can cause severe, immediate hemolytic transfusion reactions

  • Essential in all blood transfusions and organ transplantation

Importance

  • Primary system for blood grouping

  • Major cause of fatal transfusion reactions if mismatched

Rh blood group system

  • Second most important blood group system

  • Rh-D antigen is highly immunogenic

  • Rh-negative individuals can develop anti-D antibodies after exposure

  • Major cause of hemolytic disease of the fetus and newborn (HDFN)

  • Also responsible for hemolytic transfusion reactions

Importance

  • Critical in pregnancy and neonatal care

  • Essential for safe transfusion practices

Kell blood group system

  • Kell antigens are highly immunogenic

  • Anti-K antibodies can cause severe hemolytic transfusion reactions

  • Can also cause HDFN

Importance

  • Important in patients requiring repeated transfusions

Duffy blood group system

  • Duffy antigens act as receptors for Plasmodium vivax

  • Duffy-negative individuals are resistant to P. vivax malaria

  • Anti-Duffy antibodies can cause delayed hemolytic transfusion reactions

Importance

  • Clinical relevance in transfusion medicine and malaria research

Kidd blood group system

  • Kidd antibodies are difficult to detect

  • Common cause of delayed hemolytic transfusion reactions

Importance

  • Significant in transfusion safety and antibody screening

MNS blood group system

  • Antigens present on glycophorin molecules

  • Some antibodies may be clinically significant

Importance

  • Occasional role in transfusion reactions

 

Application of blood groups in population genetics

Genetic basis of blood groups

  • Blood group antigens are controlled by specific genes inherited from parents

  • Inheritance follows Mendelian patterns

  • The ABO system is governed by multiple alleles (IA, IB, i)

  • The Rh system involves complex genetic inheritance with multiple genes

Study of population distribution

  • Blood group frequencies differ among populations and ethnic groups

  • Helps in understanding:

    • Racial and ethnic diversity

    • Population structure

    • Genetic variation within and between populations

Migration and evolutionary studies

  • Blood group patterns provide clues about human migration and evolutionary history

  • Similar blood group frequencies among populations suggest common ancestry

  • Differences indicate genetic drift, selection, or migration

Anthropological significance

  • Blood groups serve as biological markers in anthropological research

  • Used to study relationships among tribes, castes, and ethnic groups

  • Helps in reconstructing population history

Disease association studies

  • Certain blood groups are associated with specific diseases

  • Examples include:

    • Blood group O and peptic ulcer disease

    • Blood group A and gastric carcinoma

  • Useful in epidemiological and genetic susceptibility studies

Role in genetic counseling

  • Blood group inheritance patterns assist in genetic counseling

  • Useful in understanding inheritance risks and family studies

Public health importance

  • Helps blood banks estimate donor availability

  • Assists in planning transfusion services for specific populations

 

Application of blood groups in forensic medicine

Identification from biological stains

  • Blood group antigens can be detected in blood, semen, saliva, and other body fluids

  • Useful in examining stains found at crime scenes

  • Helps to link or exclude suspects from forensic evidence

Secretor status

  • Individuals may be secretors or non-secretors

  • Secretors secrete ABO antigens in body fluids such as saliva and semen

  • Determination of secretor status increases the usefulness of blood group analysis in forensic investigations

Disputed paternity cases

  • Blood group testing is used to exclude paternity

  • Based on inheritance patterns of ABO and Rh blood groups

  • Cannot conclusively prove paternity but can definitively exclude it in certain cases

Medico-legal investigations

  • Assists in criminal cases involving assault, rape, or homicide

  • Helps correlate biological evidence with individuals

  • Used as supporting evidence in courts of law

Identification in mass disasters

  • Useful in mass casualty events when bodies are mutilated or decomposed

  • Blood group data may aid in narrowing down identities when combined with other findings

Limitations of blood group analysis

  • Cannot provide individual-specific identification

  • Less discriminatory compared to DNA profiling

  • Results must be interpreted cautiously and in conjunction with other evidence

Importance in forensic practice

  • Simple, cost-effective, and rapid technique

  • Useful where DNA testing facilities are unavailable

  • Serves as an important preliminary or supplementary forensic tool

Application of blood groups in transfusion medicine

Blood grouping and typing

  • Determination of ABO and Rh blood groups of donors and recipients

  • Mandatory before any blood transfusion

  • Prevents incompatible transfusions and serious transfusion reactions

Pre-transfusion testing

  • Includes:

    • ABO and Rh typing

    • Antibody screening

    • Antibody identification (if screening is positive)

    • Crossmatching between donor and recipient blood

  • Ensures selection of compatible blood units

Prevention of transfusion reactions

  • Detection of clinically significant alloantibodies

  • Avoids hemolytic transfusion reactions, both acute and delayed

  • Essential for patients with a history of multiple transfusions

Selection of antigen-negative blood

  • Required for patients who have developed specific antibodies

  • Involves matching beyond ABO and Rh systems (e.g., Kell, Duffy, Kidd)

  • Reduces risk of alloimmunization and transfusion complications

Management of special transfusion situations

  • Neonatal and pediatric transfusions

  • Massive transfusion protocols

  • Transfusion in patients with hemoglobinopathies (e.g., thalassemia, sickle cell disease)

  • Transfusion in patients with autoimmune hemolytic anemia

Prevention and management of hemolytic disease of the fetus and newborn (HDFN)

  • Identification of Rh-negative mothers

  • Antibody screening during pregnancy

  • Selection of compatible blood for intrauterine or exchange transfusions

Component therapy

  • Proper selection of blood components such as PRBCs, platelets, FFP, and cryoprecipitate

  • Ensures targeted therapy and optimal patient outcomes

Role in hemovigilance

  • Helps in investigation and reporting of adverse transfusion reactions

  • Supports quality assurance and patient safety programs

Clinical and public health significance

Clinical significance

  • Ensures safe blood transfusion
    Accurate blood grouping, antibody screening, and compatibility testing prevent incompatible transfusions and life-threatening hemolytic reactions.

  • Prevention of transfusion reactions
    Identification of clinically significant antibodies reduces the risk of acute and delayed transfusion reactions.

  • Management of hemolytic disease of the fetus and newborn (HDFN)
    Early detection of maternal antibodies, especially anti-D, helps prevent and manage HDFN through appropriate monitoring and intervention.

  • Support in complex clinical conditions
    Essential in patients requiring repeated transfusions such as thalassemia, sickle cell disease, and aplastic anemia.

  • Diagnosis of immune-mediated hemolytic disorders
    Plays a role in diagnosing autoimmune hemolytic anemia using antiglobulin testing.

Public health significance

  • Strengthens national blood transfusion services
    Helps in planning donor recruitment, blood group inventory management, and distribution of blood components.

  • Improves transfusion safety at population level
    Standardized immunohematology practices reduce transfusion-related morbidity and mortality.

  • Supports hemovigilance programs
    Enables monitoring, reporting, and prevention of adverse transfusion events.

  • Aids in disaster management and emergency preparedness
    Knowledge of blood group distribution helps in planning transfusion support during mass casualty situations.

  • Contributes to epidemiological and genetic studies
    Blood group data assist in studying disease associations and population health trends.

  • Enhances healthcare quality and patient trust
    Safe and reliable transfusion practices increase public confidence in healthcare systems.