Rh system: anti-Cw

Authors: Danielle Meunier, MD; Sophia Peng, MD; and Gwen Clarke, MD, FRCPC
Publication date: September 2019
Primary target audiences: Medical laboratory technologists (MLT) in a hospital laboratory, transfusion medicine physicians

Key points

• Anti-C^w may be clinically significant.
• Patients with anti-C^w should receive red blood cell units crossmatch compatible by IAT at 37°C for transfusion.
• Patients with sickle cell disease who have anti-C^w should be provided with C^w-negative red blood cell units for transfusion.

Background

C^w (RH8) is one of 54 antigens in the complex Rhesus (Rh) blood group system. The Rh antigens are located on large, multi-looped glycoprotein products of two closely linked genes.

C^w is a relatively low-frequency antigen, occurring at an estimated 2% in the general Caucasian population, and up to 7–9% in the Latvian, Laplander and Finnish populations. Its antithetical antigens include C^X (RH9, an abnormal C^w) and the high-incidence MAR (RH51) antigen.

Due to the location of C^w on the RHCE gene, gene linkage dictates that it almost always coincides with the C antigen (particularly of the DCe (R1) haplotype). When associated with C^w, the C antigen shows weakened expression, hence an alloanti-C may rarely be made in C+C^w+ individuals.

Anti-C^w was first described in 1946 in a patient with lupus (who also produced anti-Lu^a). It was named for its association with the C antigen and in recognition of the red blood cell donor, Willis.

Anti-C^w is a relatively common antibody and usually occurs naturally, although it may be immune stimulated (i.e. by transfusion or pregnancy-related red blood cell exposure). It is almost always an IgG antibody, with rare case reports of IgM, and often occurs in association with other antibodies.

Patient management: pre-transfusion and prenatal testing

Unlike many other Rh antigens, in the context of transfusion, anti-C^w is not typically clinically significant. There are no case reports associating anti-C^w with acute or delayed hemolytic transfusion reactions. However, it has been associated with mild to moderate hemolytic disease of the fetus and newborn (HDFN), with rare case reports of severe HDFN, including at least one case of hydrops fetalis.

When anti-C^w is detected in a patient’s pre-transfusion sample, there is usually no requirement for selection of C^w-negative donor red blood cells. In fact, 98% of donor units are C^w-negative. Routine donor antigen typing (phenotyping) at Canadian Blood Services does not include C^w typing; therefore, a request for C^w-negative red blood cell units results in additional manual phenotyping and/or genotyping. For current and historic anti-C^w, red blood cell units that are crossmatch compatible at 37°C IAT phase should be selected for transfusion.  See Table 1 for a summary of recommendations for red blood cell transfusion in patients with non-ABO antibodies.

Patients with sickle cell disease

For sickle cell disease patients without antibodies, most guidelines recommend transfusion of Rh(DCcEe)- and Kell-matched units. For those patients with one or more antibodies (current or historical), complete donor phenotype/genotype matching is often recommended. Typically, this matching includes the Rh(DCcEe), Kell, Kidd and Duffy blood group systems along with the S/s antigens. If a patient with sickle cell disease develops an anti-C^w, then C^w-negative units should be provided, along with matching for the full phenotype, as above. Given the increased risk of hyperhemolysis in patients with sickle cell disease, this clinical context necessitates full compatibility with the patient’s antigen and antibody profile.

* Note: Patients with sickle cell disease who develop any one of the antibodies listed here should be provided with antigen-negative red blood cell units for transfusion.

Additional resources

For an introduction to immunohematology and the foundations of blood bank compatibility testing, visit LearnSerology.ca, an online educational resource developed by transfusion medicine specialists in Canada. The curriculum consists of six modules and includes an interactive module for completing an antibody investigation panel.

Suggested citation

Meunier D, Peng S, Clarke G. Rh System: Anti-C^w  [Internet]. Ottawa: Canadian Blood Services; 2019 Sept 25 [cited YYYY MM DD]. Available from: https://profedu.blood.ca/en/transfusion/best-practices/serological-best-practices

Resources

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5. Reid M, Lomas Francis C and Olsson M. The Blood Group Antigens Facts Book, 3rd ed. San Diego: Elsevier Science & Technology; 2012. Section II: The blood group systems and antigens; Rh Blood Group System, C^W antigen. p. 213-4.
6. Saini N, Sood T, Kaur R, Mittal K, Kumar R, Kaur P. Clinically Significant IgM Anti-C: A Rare Report. Indian J Hematol Blood Transfus. 2017;33(2):298-299.
7. The Canadian Haemoglobinopathy Association. Transfusion. In: Consensus Statement on the Care of Patients with Sickle Cell disease in Canada. Version 2.0. Ottawa; 2018. p. 12-20. Available from: https://www.canhaem.org/wp-content/uploads/2018/05/Sickle-Cell-Consensus.pdf