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CMAJ : Canadian Medical Association Journal logoLink to CMAJ : Canadian Medical Association Journal
. 2021 Jan 25;193(4):E124. doi: 10.1503/cmaj.201212

Modern Rhesus (Rh) typing in transfusion and pregnancy

Willy Albert Flegel 1,
PMCID: PMC7954563  PMID: 33667181

Patients who are Rhesus (Rh) negative lack the D antigen on their red blood cells

Patients who are Rh negative, if transfused with Rh-positive blood, can become immunized for anti-D immunoglobulin (Ig).1 These patients are at risk of severe transfusion reactions, and if they become pregnant, the fetus is at risk of severe anemia. A small number (0.5%) of patients have a serologic “weak D” phenotype, and when these patients need a transfusion, providers are left wondering if Rh-negative red blood cells and RhIg prophylaxis are needed.

More than 160 distinct molecular weak D types are known

Weak D types are clustered by ethnic origin. Types 1 to 3 are typical in White people, type 4 variants cluster in Black people and type 15 is found most often in East Asian people. Other weak D types are encountered sporadically.

Molecular typing of weak D improves patient safety without increasing costs

Although the technology for molecular typing has been established for 2 decades, only the serologic test is routinely applied. Molecular typing is reliable, and applying this precision medicine approach can avoid unnecessary therapies, but it must be specially requested in many hospitals.2

Patients with the 5 most prevalent weak D types can be safely treated as Rh positive

Patients carrying the molecular weak D types 1, 2, 3, 4.0 or 4.1 should be treated as Rh positive.3 Pregnant women with these weak D phenotypes do not benefit from RhIg prophylaxis.4 They should not be exposed to RhIg, which is pooled from thousands of immunized donors. This approach conserves the limited supply of Rh-negative blood.5

Patients carrying less common molecular weak D types should be treated as Rh negative

Less common types include the weak D type 4.2, though it is more prevalent among people of African descent.6 An exhaustive list of weak D types that should be treated as Rh negative is maintained by the International Society of Blood Transfusion.7 If providers are unsure about whether types should be treated as Rh positive or negative, an immunohematology reference laboratory should be contacted.

Footnotes

Competing interests: None declared.

This article has been peer reviewed.

Funding: The author is supported by the NIH Clinical Center, Intramural Research Program, ID ZIA CL002128.

Disclaimer: The views expressed do not necessarily represent the view of the National Institutes of Health, the Department of Health and Human Services, or the US Federal Government.

References

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