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Physiology · Blood

Blood groups

Blood groups are a strictly individual, genetically determined set of specific antigens on cell membranes and their corresponding antibodies in the plasma. To date, more than three hundred such systems have been discovered, but the AB0 system and the Rhesus factor play a primary role in clinical practice.

Variety of systemsModern physiology identifies over 300 different antigen–antibody systems.
Antibody classAgglutinins circulating in the plasma are immunoglobulins of class M (IgM) in their chemical nature.
Development in childrenNewborn plasma lacks agglutinins; their production begins and occurs during the first year of life.
HeredityThe presence of blood group antigens is genetically determined and serves as an individual characteristic.
6 min readFor medical studentsUpdated 09/24/2026
Material prepared by WhiteCoat Pro editorial team based on platform study guidesReviewed by medical editor: Aulov A. A., general practitioner · 09/24/2026

Structural components: antigens and antibodies

The basis of the physiological doctrine of blood groups relies on the interaction of two key components. It is their unique combination that determines the individual blood profile of each specific person.

Agglutinogens (Antigens) Chemically, agglutinogens are specific carbohydrate components of molecules belonging to the glycolipid class. Their primary localization is the outer surface of the erythrocyte membrane. It is important to note that these antigens are not exclusive to red blood cells alone; they are also found on the membranes of other formed blood elements, such as leukocytes and platelets. Within the AB0 system, there are two basic antigens: antigen A and antigen B. The complete absence of both is considered separately. An erythrocyte can contain only antigen A, only antigen B, bear both antigens simultaneously on its surface, or contain neither.

Agglutinins (Antibodies) Agglutinins are located exclusively in the liquid part of the blood—the plasma. By nature, these are proteins of the immune system, specifically class M immunoglobulins (IgM). The key rule governing this system states that agglutinins possess strict specificity: they are produced exclusively against the antigen that is absent from the membranes of a person's own erythrocytes. An interesting physiological feature is that agglutinins are completely absent in infant blood plasma at birth; their active synthesis and accumulation occur gradually throughout the first year of life.

AB0 system classification

In modern medical science, more than 300 antigen–antibody systems are known, but only two are of substantial clinical and practical significance: the AB0 system and the Rhesus system. Blood classification according to the expression of AB0 system agglutinogens involves four groups:

  1. Group I (0). Characterized by the fact that erythrocytes contain no agglutinogens at all (both A and B are absent). Meanwhile, both types of antibodies circulate in the plasma—$\alpha$- and $\beta$-agglutinins.
  2. Group II (A). Only agglutinogen A is present on the erythrocyte membrane. $\beta$-agglutinin is found in the plasma, since antigen B is absent from the cells themselves.
  3. Group III (B). Erythrocytes bear only agglutinogen B. $\alpha$-agglutinins are present in the plasma compensatorily.
  4. Group IV (AB). Erythrocytes express both agglutinogens simultaneously (both A and B). Blood plasma contains no agglutinins at all.

The physiological norm is that in the blood of one healthy person, homologous antigens and antibodies against them never meet. This is a genetically determined mechanism protecting one's own blood from destruction.

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Mechanism of the agglutination reaction

The main danger during incompatible blood transfusion is the development of an agglutination reaction. This pathological mechanism is inevitably triggered if homologous components interact within the bloodstream.

The interaction of an antibody with its corresponding antigen (for example, the meeting of agglutinogen A with $\alpha$-agglutinin or agglutinogen B with $\beta$-agglutinin) leads to agglutination, i.e., the clumping of erythrocytes together. The formation of such massive red blood cell clusters blocks normal blood flow and disrupts blood functions.

Blood groupAgglutinogens on erythrocytesAgglutinins in plasma
I (0)No$\alpha$, $\beta$
II (A)A$\beta$
III (B)B$\alpha$
IV (AB)A, BNo

Briefly: answers to topical questions

What are the main antigens included in the Rhesus (Rh) system?

The main antigens forming the Rhesus system are six antigens combined into three pairs.

  • Antigen D (Rh0(D)) is the strongest antigen with a pronounced immunogenic effect, the presence of which defines the blood as Rhesus-positive.
  • Antigen d is a conventional designation for the absence of antigen D (the gene for it has not been found).
  • Antigens C, c, E, e are antigenic determinants present in various combinations in gene complexes.

What is Ottenberg's rule in blood transfusion?

Ottenberg's rule states that during blood transfusion, only the donor's erythrocytes are agglutinated. The mechanism is due to the fact that donor blood agglutinins are significantly diluted in the recipient's plasma, and their concentration becomes insufficient to clump the recipient's erythrocytes.

This rule has strict limitations:

  • Applicable only when transfusing small volumes (up to 500 ml) of blood.
  • During massive transfusion, donor agglutinins do not have time to dilute and may cause agglutination of the recipient's erythrocytes.
  • In children, the use of this rule (universal donor blood transfusion) is absolutely unacceptable.

How does erythrocyte agglutination differ from blood coagulation (clotting)?

The main difference according to the cited sources: erythrocyte agglutination is associated with the interaction of corresponding agglutinogens and agglutinins, whereas coagulation hemostasis is triggered by vascular injury and described through the formation of a fibrin mesh and a red thrombus.

CharacteristicErythrocyte agglutinationCoagulation hemostasis
MechanismInteraction of an antibody with the corresponding antigen; in case of incompatibility—the meeting of homologous antigen and antibody: A + α, B + β, Rh-antigen + anti-Rh antibodiesFibrin strands form a network associated with the platelet aggregate and tissues
ResultClumping of erythrocytesFormed blood elements, mainly erythrocytes, are incorporated into the network; a red thrombus is formed
Trigger conditionMeeting of corresponding agglutinogens and agglutininsVascular injury

What methods are used to determine AB0 blood groups in clinical practice?

The cited sources describe two methods for determining AB0 blood groups:

  • Determination using standard isohemagglutinating sera. The agglutination reaction is evaluated with sera of groups I(0), II(A), and III(B). In case of a positive reaction with all three sera, a control reaction with standard group IV(AB) serum is performed for final confirmation of the IV(AB) group; the absence of agglutination with it confirms IV(AB).
  • Determination using standard washed erythrocytes—a method for detecting antibodies in the patient's serum. After obtaining the serum, standard erythrocytes of known groups I, II, and III are added to its drops, and agglutination is evaluated.
How to memorize

To easily remember the principle of agglutination, use the rule of "rejection of identical letters": if A and $\alpha$ or B and $\beta$ meet in the blood, clumping occurs. Normally, the body never produces antibodies against its own antigens, so only those antibodies for which there are no glycolipids on the erythrocyte membranes can be present in the plasma.

Class and exam questions

Where exactly are blood group antigens and antibodies located?

Antigens (agglutinogens) are firmly fixed on the outer surface of the erythrocyte membrane, and can also be found on platelets and leukocytes. Antibodies (agglutinins) freely circulate exclusively in the blood plasma.

Why don't human erythrocytes agglutinate with each other?

This is a strict physiological norm: the absence of homologous antigens and antibodies is genetically determined in the blood of a single person. Antibodies are synthesized exclusively against those antigens that are physically absent from one's own erythrocytes.

Which blood group systems have the greatest practical significance?

Despite the fact that fundamental science knows more than 300 antigen–antibody systems, only two have critical clinical significance during transfusion: the AB0 system and the Rhesus system.

Are there agglutinins in the blood of a newborn child?

No, agglutinins are completely absent in newborn plasma. Their production and gradual accumulation in the blood occur throughout the child's first year of life.

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What else to study on this topic

  • Detailed cellular mechanism of the erythrocyte agglutination reaction
  • Rhesus system: characteristics of antigens, antibodies, and clinical significance
  • Genetic principles of AB0 blood group inheritance
  • Specific role of blood group antigens on leukocyte and platelet membranes

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