What is the clinical significance of the C antigen in blood type?

Clinical Significance of C Antigen in Blood Type

The C antigen is a clinically significant blood group antigen in the Rh system that requires prophylactic matching for patients with sickle cell disease to prevent alloimmunization and associated transfusion reactions. 1

Overview of C Antigen

• Part of the Rh blood group system (second most important after ABO)
• Found in approximately 95.5% of the general population 1
• Encoded by the RHCE gene, which can express either C or c antigens along with E or e antigens 1
• Distribution varies by ethnicity and geographic region, with studies showing prevalence of 92.38% in some populations 2

Clinical Significance

Alloimmunization Risk

• C antigen mismatch is a major cause of alloimmunization in transfusion recipients, particularly in patients with sickle cell disease 3
• Anti-C antibodies can develop when C-negative individuals are exposed to C-positive blood through transfusion or pregnancy 4
• These antibodies can be both IgM and IgG type, though most Rh antibodies are predominantly IgG 4

Transfusion Reactions

• Anti-C antibodies can cause both acute and delayed hemolytic transfusion reactions 4
• In patients with sickle cell disease who have partial C antigens, exposure to normal C antigen can lead to anti-C production in approximately 30% of cases 5
• Some patients with anti-C antibodies may experience significant hemolysis requiring clinical intervention 5

Pregnancy Implications

• Anti-C antibodies can cause hemolytic disease of the fetus and newborn (HDFN) 4
• Maternal sensitization can occur during pregnancy if the fetus is C-positive and the mother is C-negative

Partial C Antigens

• Partial C antigens are more common in individuals of African descent 5

• Carriers of partial C antigens are at risk of developing anti-C when exposed to normal C antigens 5

• Specific genetic variants associated with partial C include:

  • (C)ce(s) haplotype
  • R(N) haplotype
  • RHD*DIIIa-CE (4-7)-D
  • RHCE*CeRN alleles 3, 1

• Patients with these genetic variants should receive C-negative blood to prevent alloimmunization 1

Recommendations for Transfusion Practice

Extended Antigen Typing

• The American Society of Hematology (ASH) strongly recommends prophylactic red cell antigen matching for Rh (C, E or C/c, E/e) and K antigens for patients with sickle cell disease 3, 1
• This recommendation is based on moderate certainty evidence showing significant reduction in alloimmunization rates 1
• Extended red cell antigen profiling should be performed at the earliest opportunity, optimally before the first transfusion 3

Testing Methods

• C antigen typing can be performed using:

  • Serologic methods (hemagglutination or gel column techniques)
  • Molecular genotyping 1

• Molecular genotyping provides improved accuracy for C antigen determination, especially in:

  • Recently transfused patients (within 3 months)
  • Patients with interfering antibodies
  • Patients with suspected variant antigens 3, 1

Patient Populations Requiring Special Attention

1. Patients with sickle cell disease
2. Chronically transfused patients
3. Patients who have already developed alloantibodies
4. Pregnant women with history of HDFN 1

Clinical Implications for Specific Scenarios

For Patients with Sickle Cell Disease

• Rh (C, E or C/c, E/e) and K antigen matching reduces alloimmunization incidence from 1.94 to 0.40 new alloantibodies per 100 units transfused 3
• Patients with partial C antigen should receive C-negative blood 1
• Extended matching may include additional antigens (Jka/Jkb, Fya/Fyb, S/s) for further protection 3

For Transfusion Medicine Practice

• Having extended red cell antigen profiles available expedites compatibility workup and aids in selection of compatible donor units 3
• Molecular genotyping should be considered for accurate C antigen determination in patients with African ancestry due to higher prevalence of variant alleles 5

Challenges and Considerations

• C-negative units may be in short supply, particularly for patients with sickle cell disease who are C-negative 5
• Distinguishing between auto-antibodies and allo-antibodies against C antigen can be difficult by serological tests alone; molecular methods can help determine the nature of the antibody 6
• Prevention of anti-C immunization for individuals with partial C antigen requires increased availability of C-negative RBC units 5

By understanding the clinical significance of the C antigen and implementing appropriate matching strategies, clinicians can significantly reduce transfusion-related complications and improve patient outcomes, particularly in high-risk populations such as those with sickle cell disease.