Transfusionsmedizin 2016; 6(02): 57-64
DOI: 10.1055/s-0042-104711
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Zur klinischen Bedeutung des Antigen D und seiner Varianten

Clinical Implications of the D Antigen and its Variants
S. Wienzek-Lischka
1   Zentrum für Transfusionsmedizin und Hämotherapie, Deutsches Zentrum für fetomaternale Inkompatibilität (DZFI), Universitätsklinikum Gießen und Marburg GmbH, Gießen
,
W. A. Flegel
2   Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
01 June 2016 (online)

Zusammenfassung

Varianten des Antigen D stellen infolge ihrer komplexen genetischen Grundlage für das immunhämatologische Labor und die transfundierenden bzw. behandelnden Ärzte eine Herausforderung dar. Schwache oder diskrepante serologische Bestimmungen des Antigen D sorgen für Unklarheiten in der Versorgung mit Erythrozytenpräparaten, aber auch bei der Gabe der Rh-Prophylaxe im Rahmen der Schwangerschaft. Die vorliegende Arbeit gibt, unter Berücksichtigung aktueller Empfehlungen und Richtlinien, einen Überblick zur klinischen Bedeutung der RhD-Varianten sowie zur Diagnostik, Transfusionspraxis und Mutterschaftsvorsorge. Neben den deutschen Richtlinien werden auch die schweizerischen Empfehlungen und österreichischen Standards berücksichtigt. Ein strukturiertes Vorgehen kann kostensparend und sollte aus ethischer Hinsicht geboten sein.

Abstract

The variants of the D antigen may pose a challenge for immunohematology laboratories and attending physicians, which is caused by the complex genetic basis. Weak or discrepant serologic typing results for the D antigen can lead to uncertainties with regard to both red blood cell transfusion and administration of RhIg prophylaxis during pregnancy. Using current recommendations and guidelines, the present article reviews the clinical implications of RhD variants for diagnostics, transfusion strategies and obstetrical care. The German regulations, the Swiss recommendations and the Austrian standards were considered. A defined strategy may reduce health care costs and should be implemented for ethical reasons.

 
  • Literatur

  • 1 Wagner FF, Flegel WA. RHD gene deletion occurred in the Rhesus box. Blood 2000; 95: 3662-3668
  • 2 Okuda H, Suganuma H, Kamesaki T et al. The analysis of nucleotide substitutions, gaps, and recombination events between RHD and RHCE genes through complete sequencing. Biochem Biophys Res Commun 2000; 274: 670-683
  • 3 Flegel WA. Molecular genetics and clinical applications for RH. Transfus Apher Sci 2011; 44: 81-91
  • 4 Colin Y, Chbrif-Zahar B, Le Van Kim C et al. Genetic basis of the RhD-positive and RhD-negative blood group polymorphism as determined by Southern Analysis. Blood 1991; 78: 2747-2752
  • 5 Stratton F. A new Rh allelomorph. Nature 1946; 158: 25-26
  • 6 Flegel WA, Wagner FF. Molecular biology of partial D and weak D: Implications for blood bank practice. Clin Lab 2002; 48: 53-59
  • 7 Flegel WA. Molecular genetics of RH and its clinical application. Transfus Clin Biol 2006; 13: 4-12
  • 8 Flegel WA. Genetik des Rhesus-Blutgruppensystems. Dtsch Arztebl 2007; 104: 651-657
  • 9 Wagner FF, Eicher NI, Jørgensen JR et al. DNB: a partial D with anti-D frequent in Central Europe. Blood 2002; 100: 2253-2256
  • 10 Wagner FF, Kasulke D, Kerowgan M et al. Frequencies of the blood groups ABO, Rhesus, D category VI, Kell, and of clinically relevant high-frequency antigens in south-western Germany. Infusionsther Transfusionsmed 1995; 22: 285-290
  • 11 von Zabern I, Wagner FF, Moulds JM et al. D category IV: a group of clinically relevant and phylogenetically diverse partial D. Transfusion 2013; 53: 2960-2973
  • 12 Fung MK ed. Technical Manual. 18th ed. Bethesda, MD: American Association of Blood Banks; 2014
  • 13 Wagner FF, Flegel WA. The Rhesus Site. Transfus Med Hemother 2014; 41: 357-363
  • 14 Wagner FF, Gassner C, Müller TH et al. Molecular basis of weak D phenotypes. Blood 1999; 93: 385-393
  • 15 Wagner FF, Frohmajer A, Ladewig B et al. Weak D alleles express distinct phenotypes. Blood 2000; 95: 2699-2708
  • 16 Müller TH, Wagner FF, Trockenbacher A et al. PCR screening for common weak D types shows different distributions in three Central European populations. Transfusion 2001; 41: 45-52
  • 17 Garratty G. Do we need to be more concerned about weak D antigens?. Transfusion 2005; 45: 1547-1551
  • 18 Flegel WA. How I manage donors and patients with a weak D phenotype. Curr Opin Hematol 2006; 13: 476-483
  • 19 McGann H, Wenk RE. Alloimmunization to the D antigen by a patient with weak D type 21. Immunohematology 2010; 26: 27-29
  • 20 Le Maréchal C, Guerry C, Benech C et al. Identification of 12 novel RHD alleles in western France by denaturing high-performance liquid chromatography analysis. Transfusion 2007; 47: 858-863
  • 21 Körmöczi GF, Gassner C, Shao C et al. A comprehensive analysis of DEL types: partial DEL individuals are prone to anti-D alloimmunization. Transfusion 2005; 45: 1561-1567
  • 22 Wagner FF, Frohmajer A, Flegel WA. RHD positive haplotypes in D negative Europeans. BMC Genet 2001; DOI: 10.1186/1471-2156-2-10.
  • 23 Gassner C, Doescher A, Drnovsek TD et al. Presence of RHD in serologically D-, C/E+ individuals: a European multicenter study. Transfusion 2005; 45: 527-538
  • 24 Flegel WA. Are weak D RBCs really immunogenic?. Transfusion 2006; 46: 1063-1064
  • 25 Wagner T, Körmöczi GF, Buchta C et al. Anti-D immunization by DEL red blood cells. Transfusion 2005; 45: 520-526
  • 26 Shao C. Transfusion of RhD-positive blood in “Asia type” DEL recipients. N Engl J Med 2010; 362: 472-473
  • 27 Sandler SG, Flegel WA, Westhoff CM et al. Itʼs time to phase in RHD genotyping for patients with a serologic weak D phenotype. Transfusion 2015; 55: 680-689
  • 28 Kacker S, Vassallo R, Keller MA et al. Financial implications of RHD genotyping of pregnant women with a serologic weak D phenotype. Transfusion 2015; 55: 2095-2103
  • 29 Paxton A. Groups urge phase-in of RHD genotyping. CAP Today 2015; 29: 56-58
  • 30 Sandler SG, Roseff SD, Domen RE et al. Policies and procedures related to testing for weak D phenotypes and administration of Rh immune globulin: results and recommendations related to supplemental questions in the Comprehensive Transfusion Medicine survey of the College of American Pathologists. Arch Pathol Lab Med 2014; 138: 620-625
  • 31 Crottet SL, Henny C, Meyer S et al. Implementation of a mandatory donor RHD screening in Switzerland. Transfus Apher Sci 2014; 50: 169-174
  • 32 Gowland P, Gassner C, Hustinx H et al. Molecular RHD screening of RhD negative donors can replace standard serological testing for RhD negative donors. Transfus Apher Sci 2014; 50: 163-168
  • 33 Flegel WA, von Zabern I, Wagner FF. Six yearsʼ experience performing RHD genotyping to confirm D- red blood cell units in Germany for preventing anti-D immunizations. Transfusion 2009; 49: 465-471