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Blood type

Blood type

A blood type (also known as a blood group ) is a classification of blood based on the presence and absence of antibodies and inherited antigenic substances on…

A blood type, also known as a blood group, represents a classification of blood determined by the presence or absence of specific antibodies and inherited antigenic substances located on the surface of red blood cells (RBCs). These antigens can comprise proteins, carbohydrates, glycoproteins, or glycolipids, varying according to the particular blood group system. Furthermore, certain antigens may also be found on the surface of other cell types within diverse tissues. Multiple red blood cell surface antigens can originate from a single allele—an alternative form of a gene—thereby collectively constituting a blood group system.

Blood types are genetically inherited, reflecting contributions from both biological parents. As of June 2025, the International Society of Blood Transfusion (ISBT) officially recognizes 48 distinct human blood group systems. The ABO and Rh systems are paramount, as they define an individual's blood type (A, B, AB, or O, with RhD status indicated by + or −) and are critical for assessing compatibility in blood transfusions.

Blood Group Systems

A comprehensive blood type characterization would encompass all 48 recognized blood groups, with an individual's specific blood type representing one of numerous potential combinations of blood-group antigens. Typically, an individual's blood group remains constant throughout their life; however, in rare instances, changes can occur due to the addition or suppression of an antigen during infection, malignancy, or autoimmune disease. A more frequent cause of altered blood type is a bone marrow transplant. These transplants are utilized in the treatment of various conditions, including numerous leukemias and lymphomas. Should a recipient receive bone marrow from a donor with a distinct ABO type (e.g., a type O patient receiving type A bone marrow), the recipient's blood type is expected to convert to that of the donor. This transformation occurs because the patient's hematopoietic stem cells (HSCs) are eliminated, either through bone marrow ablation or by the donor's T-cells. Following the demise of the patient's original red blood cells, they are entirely supplanted by new cells originating from the donor's HSCs. If the donor possessed a different ABO type, the surface antigens of these newly formed cells will consequently differ from those present on the patient's initial red blood cells.

Certain blood types exhibit associations with the inheritance of other pathologies; for instance, the Kell antigen has been linked to McLeod syndrome. Furthermore, particular blood types can influence susceptibility to infections, exemplified by the resistance to specific malaria species observed in individuals deficient in the Duffy antigen. The Duffy antigen is notably less prevalent in populations residing in regions with a high incidence of malaria, a phenomenon presumed to be a consequence of natural selection.

The ABO Blood Group System

The ABO blood group system is characterized by the presence of two primary antigens and two corresponding antibodies within human blood. Specifically, these include antigen A and antigen B, along with antibody A and antibody B. Antigens are located on the surface of red blood cells, while antibodies circulate in the serum. Based on the antigenic properties of their blood, all individuals are categorized into four main groups: Group A (possessing antigen A), Group B (possessing antigen B), Group AB (possessing both antigen A and antigen B), and Group O (lacking both antigens). The corresponding antibodies found in conjunction with these antigens are as follows:

  1. Group A: Antigen A with antibody B.
  2. Group B: Antigen B with antibody A.
  3. Group AB: Both antigen A and antigen B, with neither antibody A nor antibody B.
  4. Group O: Absence of both antigens (antigen null), with both antibody A and antibody B.

An agglutination reaction occurs when a specific antigen encounters its corresponding antibody (e.g., antigen A agglutinates antibody A, and antigen B agglutinates antibody B). Consequently, a blood transfusion is deemed safe only if the recipient's serum lacks antibodies that would react with the donor's red blood cell antigens.

The ABO system holds paramount importance in human blood transfusion practices. The anti-A and anti-B antibodies associated with this system are typically immunoglobulin M (IgM) antibodies. A prevailing hypothesis suggests that ABO IgM antibodies develop during the initial years of life through sensitization to environmental agents, including various foods, bacteria, and viruses. Karl Landsteiner's original classification in 1901 employed the terminology A/B/C; subsequently, in later publications, 'C' was replaced by 'O'. In other languages, Type O is frequently referred to as 0 (zero or null).

The Rh Blood Group System

The Rh system, named after the Rhesus macaque, constitutes the second most critical blood-group system in human transfusion medicine, encompassing 50 distinct antigens. Among these, the D antigen holds paramount importance due to its pronounced immunogenicity, making it the most probable of the five primary Rh antigens to elicit an immune response. Typically, D-negative individuals do not possess anti-D IgG or IgM antibodies, as these are not commonly generated through sensitization to environmental agents. Nevertheless, D-negative individuals can develop IgG anti-D antibodies subsequent to a sensitizing event, such as a fetomaternal transfusion during pregnancy or, less frequently, a transfusion involving D-positive red blood cells (RBCs). The prevalence of Rh-negative blood types varies geographically, being significantly lower in Asian populations (0.3%) compared to European populations (15%).

The designation of an individual's Rh status, specifically concerning the Rh(D) antigen, is indicated by a '+' or '−' suffix. For instance, an A− blood group signifies an ABO type A individual who lacks the Rh(D) antigen.

Geographic Distribution of ABO and Rh Blood Groups

Consistent with numerous other genetic characteristics, the prevalence of ABO and Rh blood groups demonstrates substantial variation across different human populations. Although the precise evolutionary mechanisms and geographical variations of blood types remain subjects of ongoing scientific debate, compelling evidence indicates that their evolution may be influenced by genetic selection. This selection favors blood types whose antigens provide resistance to specific diseases prevalent in certain geographical areas, exemplified by the higher prevalence and survival rates of individuals with blood type O in regions endemic for malaria.

Additional Blood Group Systems

As of June 2025, the International Society for Blood Transfusion officially recognizes 48 distinct blood-group systems. Consequently, beyond the well-known ABO and Rh antigens, numerous other antigens are expressed on the surface membrane of red blood cells (RBCs). For instance, an individual might possess an AB, D positive phenotype, while simultaneously being M and N positive (MNS system), K positive (Kell system), and either Lea or Leb negative (Lewis system). Historically, many blood group systems were named after the patients in whom the respective antibodies were first identified. While blood group systems other than ABO and Rh present a potential risk of complications during blood mixing, this risk is generally considered relatively low.

A comparative analysis of the clinically significant characteristics of antibodies targeting the primary human blood group systems is presented below:

Clinical Relevance

Blood Transfusion Procedures

Transfusion medicine, a specialized discipline within hematology, encompasses the comprehensive study of blood groups and the operational functions of blood banks, which supply blood and other blood products for transfusion services. Globally, the prescription of blood products, analogous to pharmaceutical medications, is exclusively reserved for licensed medical practitioners, including physicians and surgeons.

A significant portion of routine blood bank operations is dedicated to testing donor and recipient blood to guarantee that each recipient receives compatible and maximally safe blood. Transfusion of incompatible blood can precipitate a severe acute hemolytic reaction, characterized by hemolysis (red blood cell destruction), renal failure, and shock, with a potential fatal outcome. Such antibodies exhibit high activity, capable of attacking red blood cells and activating components of the complement system, thereby inducing massive hemolysis of the transfused blood.

To minimize the risk of transfusion reactions, patients should ideally receive either autologous blood or type-specific blood products. Autologous blood transfusion, which involves using the patient's own blood, ensures complete compatibility. The process for washing a patient's red blood cells involves collecting the lost blood and subsequently washing it with a saline solution. This washing procedure produces concentrated, washed red blood cells. The final step is the reinfusion of these packed red blood cells into the patient. Red blood cells can be washed using various methods, with the primary techniques including centrifugation and filtration. Microfiltration devices can also facilitate this procedure. Blood cross-matching can further mitigate risks, though it may be omitted in emergency situations where immediate transfusion is critical. Historically, cross-matching entailed combining a recipient's serum sample with a donor's red blood cell sample to observe for agglutination or clump formation. Should agglutination not be visually apparent, a blood bank technologist may employ a microscope to detect it. The presence of agglutination indicates that the donor's blood is incompatible with that specific recipient and cannot be transfused. Within blood transfusion services, accurate identification of all blood specimens is paramount, leading to the standardization of labeling through the ISBT 128 barcode system.

Blood group information may be inscribed on identification tags or, historically, tattooed on military personnel to facilitate emergency blood transfusions. During World War II, frontline German Waffen-SS personnel were known to have blood group tattoos.

Rare blood types frequently present significant supply challenges for blood banks and healthcare facilities. For instance, Duffy-negative blood is considerably more prevalent among individuals of African descent; its scarcity in other populations can lead to critical shortages for patients requiring this specific blood type. Likewise, RhD-negative individuals face risks when traveling to regions with limited RhD-negative blood supplies, particularly in East Asia, where blood services might actively solicit donations from Westerners.

Hemolytic Disease of the Newborn (HDN)

A pregnant woman may carry a fetus with a blood type distinct from her own. This typically becomes problematic when an RhD-negative mother conceives a child with an RhD-positive father, resulting in an Rh-positive fetus. In such instances, the mother's immune system can produce IgG blood group antibodies. This sensitization can occur if fetal blood cells enter the maternal circulation, such as during a minor fetomaternal hemorrhage at childbirth, obstetric interventions, or occasionally following a therapeutic blood transfusion. Such sensitization can lead to hemolytic disease of the newborn (HDN) in the current or subsequent pregnancies. In severe cases, this condition can be lethal for the fetus, manifesting as hydrops fetalis. For pregnant women with known anti-D antibodies, the fetal RhD blood type can be determined through analysis of fetal DNA in maternal plasma to evaluate the risk of Rh disease to the fetus. Cell-free DNA testing allows for the determination of the fetal RHD genotype from a maternal plasma sample after 10 weeks of gestation. A significant twentieth-century medical advancement involved preventing this disease by inhibiting anti-D antibody formation in D-negative mothers through an injectable medication known as Rho(D) immune globulin. While antibodies linked to certain blood groups can induce severe HDN, others may only cause mild forms, and some are not associated with HDN development.

Blood Products

To maximize the utility of each blood donation and prolong shelf-life, blood banks fractionate whole blood into various components. The most frequently utilized products include red blood cells (RBCs), plasma, platelets, cryoprecipitate, and fresh frozen plasma (FFP). FFP is rapidly frozen to preserve labile clotting factors V and VIII; it is typically administered to patients experiencing potentially fatal clotting disorders stemming from conditions like advanced liver disease, anticoagulant overdose, or disseminated intravascular coagulation (DIC).

Packed red cell units are produced by extracting the maximum possible volume of plasma from whole blood units.

Modern recombinant methods now routinely synthesize clotting factors for hemophilia treatment, thereby eliminating the infection transmission risks inherent in pooled blood products.

Red Blood Cell Compatibility

Table Note
1. This assumes the absence of atypical antibodies that could induce incompatibility between donor and recipient blood, a condition typically verified during cross-matching procedures.

An Rh D-negative patient who has not developed anti-D antibodies (i.e., has never been previously sensitized to D-positive erythrocytes) may receive a transfusion of D-positive blood. However, this administration carries the risk of inducing sensitization to the D antigen, which could subsequently place a female patient at risk for hemolytic disease of the newborn. Should a D-negative patient have already developed anti-D antibodies, any subsequent exposure to D-positive blood could precipitate a potentially perilous transfusion reaction. Consequently, Rh D-positive blood must never be administered to D-negative women of childbearing age or to any patient possessing D antibodies; blood banks are therefore mandated to conserve Rh-negative blood for these specific patient populations. Under extreme circumstances, such as during a major hemorrhage when the inventory of D-negative blood units is severely depleted at the blood bank, D-positive blood might be considered for D-negative females beyond childbearing age or for Rh-negative males, provided they do not possess anti-D antibodies, in order to preserve the D-negative blood supply. Conversely, Rh D-positive patients do not exhibit adverse reactions to D-negative blood.

Analogous matching procedures are implemented for other antigens within the Rh system, including C, c, E, and e, as well as for other blood group systems associated with a recognized risk of alloimmunization, such as the Kell system, particularly in patients undergoing chronic transfusion therapy.

Plasma Compatibility

Blood plasma compatibility operates inversely to red blood cell compatibility. Type AB plasma contains neither anti-A nor anti-B antibodies, rendering it suitable for transfusion to individuals of any blood group; however, patients with type AB blood can exclusively receive type AB plasma. Conversely, type O plasma contains both anti-A and anti-B antibodies, which means individuals of blood group O are able to receive plasma from any blood group, but type O plasma is restricted to use by type O recipients only.

Table Note
1. This premise relies on the absence of potent atypical antibodies within the donor plasma.

Universal Donors and Universal Recipients

"Universal donor" status is frequently attributed to individuals with O Rh D-negative blood, while those with AB Rh D-positive blood are often termed "universal recipients" in the context of red blood cell transfusions. Nevertheless, these designations are broadly accurate primarily concerning potential reactions involving recipient anti-A and anti-B antibodies to transfused red blood cells, and the possibility of Rh D antigen sensitization. A notable exception involves individuals possessing the hh antigen system, also known as the Bombay phenotype, who can exclusively receive blood safely from other hh donors due to their production of antibodies targeting the H antigen found on all other red blood cells.

Donors exhibiting exceptionally potent anti-A, anti-B, or other atypical blood group antibodies might be deemed ineligible for donating high plasma volume blood products. Generally, although the plasma component of a transfusion can introduce donor antibodies absent in the recipient, the likelihood of a substantial adverse reaction is diminished due to dilution effects.

Furthermore, red blood cell surface antigens beyond A, B, and Rh D can induce adverse reactions and sensitization if they bind to their cognate antibodies, thereby eliciting an immune response. Transfusions are additionally complicated by the fact that platelets and white blood cells (WBCs) possess distinct surface antigen systems, and sensitization to these platelet or WBC antigens may arise from transfusion events.

In the context of plasma transfusions, the dynamics are inverted. Type O plasma, which contains both anti-A and anti-B antibodies, is restricted to O recipients, as these antibodies would otherwise target the antigens present in other blood types. Conversely, AB plasma is compatible with patients of any ABO blood group, given its absence of anti-A or anti-B antibodies.

Blood Group Determination

Standard blood typing procedures involve combining a blood sample with solutions containing antibodies specific to each antigen. The occurrence of agglutination signifies the presence of a particular antigen on the surface of the red blood cells.

Genotypic Analysis of Blood Groups

Complementing conventional serologic blood typing, advancements in molecular diagnostics are facilitating the growing application of blood group genotyping, often referred to as red cell genotyping. Unlike serologic assays that directly identify a blood type phenotype, genotyping enables the prediction of a phenotype by leveraging knowledge of the molecular underpinnings of known antigens. This methodology provides a more comprehensive assessment of blood type, leading to improved transfusion compatibility, which is especially vital for patients requiring numerous transfusions to mitigate alloimmunization risks.

Historical Context

The initial discovery of blood types is credited to Karl Landsteiner, an Austrian physician affiliated with the Pathological-Anatomical Institute of the University of Vienna (presently the Medical University of Vienna). In 1900, Landsteiner observed that blood sera from various individuals would agglutinate, or clump, when combined in test tubes; furthermore, some human blood also agglutinated with animal blood. He documented this finding in a two-sentence footnote:

The serum of healthy human beings not only agglutinates animal red cells, but also often those of human origin, from other individuals. It remains to be seen whether this appearance is related to inborn differences between individuals or is the result of some damage of a bacterial kind.

This observation constituted the initial evidence for the existence of blood variation among humans. The following year, in 1901, Landsteiner made the conclusive finding that an individual's blood serum would only agglutinate with the blood of specific other individuals. From this, he categorized human blood into three distinct groups: A, B, and C. He established that Group A blood agglutinates with Group B blood but not with its own type. Likewise, Group B blood agglutinates with Group A. Group C blood was unique in its agglutination with both A and B types. This groundbreaking discovery of blood groups earned Landsteiner the Nobel Prize in Physiology or Medicine in 1930. (Group C was subsequently re-designated as O, derived from the German term Ohne, signifying "without," "zero," or "null.") A fourth group, later designated AB, was identified a year later by Landsteiner's students, Adriano Sturli and Alfred von Decastello, who initially described it simply as "no particular type" without assigning a formal name. Consequently, Landsteiner's initial work recognized three primary blood types: A, B, and C.

In 1907, Czech serologist Jan Janský became the first to identify and categorize four distinct blood types, publishing his findings in a local journal. He employed Roman numerals I, II, III, and IV, which correspond to the contemporary O, A, B, and AB classifications, respectively. Unbeknownst to Janský, American physician William L. Moss introduced a nearly identical classification system in 1910, though with a crucial difference: Moss's types I and IV corresponded to Janský's IV and I. This duplication of systems immediately generated considerable confusion and posed potential risks in medical applications. Moss's system gained acceptance in Britain, France, and the United States, whereas Janský's system was favored across most other European nations and certain regions of the U.S. Reports indicated that "The practically universal use of the Moss classification at that time was completely and purposely cast aside. Therefore, in place of bringing order out of chaos, chaos was increased in the larger cities." To address this escalating confusion, a joint recommendation was issued in 1921 by the American Association of Immunologists, the Society of American Bacteriologists, and the Association of Pathologists and Bacteriologists, advocating for the adoption of Janský's classification based on its priority. However, this recommendation was not widely implemented, particularly in areas where Moss's system was already established.

By 1927, Karl Landsteiner, then affiliated with the Rockefeller Institute for Medical Research in New York and serving on a National Research Council committee focused on blood grouping, proposed replacing the Janský and Moss systems with the letter-based nomenclature O, A, B, and AB. A separate ambiguity arose concerning the designation "O," which Polish physician Ludwik Hirszfeld and German physician Emil von Dungern had introduced in 1910. It remained unclear whether "O" represented the numeral 0, the German term null (meaning zero), or the uppercase letter O, signifying ohne (meaning "without"). Landsteiner ultimately opted for the letter.

In 1928, the Permanent Commission on Biological Standardization formally endorsed Landsteiner's proposal, declaring:

The Commission notes with satisfaction that, through the initiative of the Health Organization of the League of Nations, the nomenclature for blood group classification proposed by von Dungern and Hirszfeld has achieved widespread acceptance. It therefore recommends the adoption of this nomenclature for international application as follows: 0 A B AB. To streamline the transition from previously utilized nomenclatures, the subsequent guideline is proposed:

  • Janský ....O(I) A(II) B(III) AB(IV)
  • Moss ... O(IV) A(II) B(III) AB(I)

This standardized classification gained extensive acceptance and was universally adopted following the early 1950s.

In 1910, Hirszfeld and Dungern elucidated the Mendelian inheritance patterns of blood types and, in 1911, identified the existence of A subtypes. Subsequently, in 1927, Landsteiner, collaborating with Philip Levine, discovered both the MN blood group system and the P system. The subsequent development of the Coombs test in 1945, coupled with advancements in transfusion medicine and a deeper comprehension of ABO hemolytic disease of the newborn, facilitated the identification of numerous additional blood groups. As of June 2025, the International Society of Blood Transfusion (ISBT) officially acknowledges 48 distinct blood group systems.

Society and Culture

In several East Asian nations, particularly Japan and South Korea, a prevalent pseudoscientific belief asserts that an individual's ABO blood type can predict their personality, character traits, and interpersonal compatibility. However, researchers have definitively determined that no scientific foundation supports blood type-based personality categorization. Studies have consistently revealed "no significant relationship between personality and blood type, rendering the theory 'obsolete' and concluding that no basis exists to assume that personality is anything more than randomly associated with blood type."

References

Dean, Laura (2005). Blood Groups and Red Cell Antigens: A Guide to the Differences in Our Blood Types That Complicate Blood Transfusions and Pregnancy. Bethesda, MD: National Center for Biotechnology Information. ISBN 1-932811-05-2. NBK2261.

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