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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3699-3709.
Prepublished online as a Blood First Edition Paper on July 28, 2005; DOI 10.1182/blood-2005-04-1717.
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Submitted April 27, 2005
Accepted July 19, 2005
Diagnosis and management of paroxysmal nocturnal hemoglobinuria
Charles Parker*, Mitsuhiro Omine, Stephen Richards, Jun-ichi Nishimura, Monica Bessler, Russell Ware, Peter Hillmen, Lucio Luzzatto, Neal Young, Taroh Kinoshita, Wendell Rosse, and Gerard Socie
Division of Hematology, University of Utah School of Medicine and the George E. Whalen VA Medical Center, Salt Lake City, Utah, USA
Department of Medicine, Division of Hematology, Showa University Fujigaoka Hospital, Kanagawa, Japan; The Research Committee for the Idiopathic Hematopoietic Disorders, Ministry of Health, Labor and Welfare, Government of Japan, Tokyo, Japan
HMDS, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
The Research Committee for the Idiopathic Hematopoietic Disorders, Ministry of Health, Labor and Welfare, Government of Japan, Tokyo, Japan; Department of Medicine, Division of Cellular Therapy, Duke University Medical Center, Durham, NC, USA
Division of Hematology, Washington University School of Medicine, St. Louis, MO, USA
Division of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA
Nazionale per la Ricerca sul Cancro, Genova, Italy
Hematology Branch, National Institutes of Health, Bethesda, MD, USA
The Research Committee for the Idiopathic Hematopoietic Disorders, Ministry of Health, Labor and Welfare, Government of Japan, Tokyo, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Duke University School of Medicine, Durham, NC, USA
Service d'Hematologie Greffe de Moelle, Hospital Saint Louis, Paris, France
* Corresponding author; email: Charles.Parker{at}hsc.utah.edu.
The primary clinical manifestations of PNH are hemolytic anemia, marrow failure, and thrombophilia. However, PNH is not a simple binary diagnosis and both flow cytometric characterization of glycosyl phosphatidylinositol-anchored protein expression on peripheral blood cells and marrow analysis are required for comprehensive disease classification. For optimum management, the contribution of both hemolysis and marrow failure to the complex anemia of PNH should be determined. Complement inhibition by eculizumab is a promising new approach to treating the hemolytic anemia. Stem cell transplant is potentially curative, but the decision on use is best made on a case-by-case basis because of the heterogeneous natural history of the disease. PNH clone size and ethnic/geographic factors appear to influence thrombophilic propensity, however, a consensus on prophylactic anticoagulation has not been reached. Involvement of unusual sites (hepatic, mesenteric, cerebral, dermal veins) is characteristic of the thrombophilia of PNH. Indefinite anticoagulation is recommended following a thromboembolic event and thrombolytic therapy should be considered for acute hepatic vein thrombosis (Budd-Chiari syndrome). Pregnancy in a patient with PNH is complicated and requires careful management including prophylactic anticoagulation. To obtain a broad overview of the natural history, approaches to management, and outcome, the International PNH Registry was recently established.
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