Variants of RhD – current testing and clinical consequences

Abstract

Anti-D (-RH1) of the Rh blood group system is clinically important as it causes haemolytic transfusion reactions and haemolytic disease of the fetus and newborn. Although most people are either D+ or DÀ, there is a plethora of D variants, often categorized as either weak D or partial D. These two types are inadequately defined and the dichotomy is potentially misleading. DVI is the D variant most commonly associated with anti-D production and UK guidelines recommend that patients are tested with anti-D reagents that do not react with DVI. Weak D types 1, 2, and 3 are seldom, if ever, associated with alloanti-D production, so a policy recommendation would be to treat patients with those D variants as D+, to preserve DÀ stocks, whereas patients with all other D variants would be treated as DÀ. All donors with D variant red cells, including DVI, should be treated as D+. The frequency of the D+ phenotype is about 85% in Caucasians, around 95% in sub-Saharan Africa, and greater than 99Á5% in eastern Asia (Daniels, 2013). Although most people are either D+ or DÀ, a grey area exists in the form of a plethora of D variants: the so-called weak D, partial D, and DEL phenotypes. These ill-defined terms are often a cause of consternation beyond their clinical relevance. Over its history of well over a century, blood group serology has been fraught with problems arising from nomenclature, and the terminology applied to D variants has led to confusion.In this review I will attempt to clarify the situation, recommend a testing and transfusion strategy that minimizes the risk of alloimmunization without undue waste of DÀ blood stocks, and describe the clinical issues relating to these aberrant forms of D.

Red Blood Cell Alloimmunization in Sickle Cell Disease: Listen to Your Ancestors

“…RHD and RHCE are a pair of genes which share 93.8% homology over all introns and coding exons. They are closely linked but in opposite orientation: 5′-RHD-3′-3′-RHCE-5′[11]. In Rh(D)-negative persons, there is usually a complete absence of the D protein, with the C/c and E/e antigens present.…”

Molecular basis of D-negative phenotype (literature review and case reports)

“…Вариантом антигена D, не распознаваемым моно-клональными анти-D-реактивами, но идентифициру-емым методами адсорбции-элюции [37], является фенотип DEL (D el ), часто встречающийся у предста-вителей монголоидной расы [38][39][40]. Молекулярная основа данного варианта гена RHD -делеция 1013 пар оснований между интронами 8 и 9, выпадение почти всего экзона 9 и присутствие аллеля 1227А [41,42].…”

Case of rhesus antigen weak D type 4.2. (DAR category) detection

“…Среди множества его вариантов принято выделять 3 основных: слабый антиген D -D weak (его количество на эритроците снижено), пар-циальный, у которого отсутствует какой-либо из эпи-топов (лица с таким антигеном D могут вырабатывать антитела к отсутствующим у них эпитопам), и DEL [2]. Эритроциты с антигеном DEL обычно идентифици-руют как RhD-отрицательные при использовании се-рологических методов.…”