Int J Hematol (2010) 91:159–160 DOI 10.1007/s12185-010-0493-0
IMAGES IN HEMATOLOGY
Paroxysmal nocturnal hemoglobinuria turning Coombs-positive Alexander Ro¨th • Sven Peine • Ulrich Du¨hrsen
Received: 13 September 2009 / Revised: 28 October 2009 / Accepted: 4 January 2010 / Published online: 9 February 2010 Ó The Japanese Society of Hematology 2010
Paroxysmal nocturnal hemoglobinuria (PNH) represents a Coombs-negative hemolytic anemia. Due to mutations of the PIG-A gene, the affected progeny cells are deficient in all GPI-anchored surface proteins, including the complement regulators CD55 and CD59. Therefore, PNH RBCs are highly vulnerable to activated complement with the formation of the membrane attack complex (MAC) resulting in chronic intravascular hemolysis as the underlying cause of morbidities and mortality in PNH. Eculizumab is a humanized monoclonal antibody blocking C5 of the terminal complement cascade. Therefore, the MAC formation along with the intravascular hemolysis is effectively inhibited leading to a marked decrease of anemia, fatigue, transfusion requirements, renal impairment, pulmonary hypertension, the risk of severe thromboembolic events and an improvement in the quality of life. However, early stages of complement activation occur leading to the binding of C3 cleavage products to CD55/CD59-deficient RBCs, as they survive and no longer undergo intravascular hemolysis. As shown here in a 46year-old woman, PNH patients chronically treated with eculizumab may develop a positive monospecific direct antiglobulin test (DAT) for C3d and—with lesser
intensity—also for C3c (Fig. 1a). This may explain why mild extravascular hemolysis due to sequestration of affected PNH red blood cells can sometimes be observed
A. Ro¨th (&) U. Du¨hrsen Department of Hematology, University Hospital, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany e-mail:
[email protected] S. Peine Institute for Transfusion Medicine, University Hospital, University of Duisburg-Essen, Essen, Germany
Fig. 1 a Positive monospecific Coombs-test (C3d, slightly C3c) in a PNH patient treated with eculizumab. b The peripheral blood film of this patient shows anisocytosis, tear drop like cells and spherocytes
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during otherwise successful treament with eculizumab. Morphologically marked anisocytosis, tear drop like cells and spherocytes may be present (Fig. 1b). If clinically relevant, low dose steroids or splenectomy have been reported to normalize extravascular hemolysis [1].
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Reference 1. Risitano AM, Marando L, Seneca E, Rotoli B. Hemoglobin normalization after splenectomy in a paroxysmal nocturnal hemoglobinuria patient treated by eculizumab. Blood. 2008;112:449–51.
