Chapter 30
Paroxysmal Nocturnal Hemoglobinuria (PNH) Analysis
Stephen J. Richards PhD, FRCPath,
Stephen J. Richards PhD, FRCPath
Department of Haematology, St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Search for more papers by this authorStephen J. Richards PhD, FRCPath,
Stephen J. Richards PhD, FRCPath
Department of Haematology, St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Search for more papers by this authorBook Editor(s):Kandice Kottke-Marchant MD, PhD,
Bruce H. Davis MD,
Kandice Kottke-Marchant MD, PhD
Pathology & Laboratory Medicine Institute, Cleveland, OH, USA
Department of Pathology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA
Hemostasis and Thrombosis, Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA
Search for more papers by this authorFirst published: 10 April 2012
Summary
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder closely related to aplastic anemia. Its main clinical manifestations are hemolytic anemia, bone marrow failure, and life-threatening thrombosis. Rapid diagnosis is essential and flow cytometry plays a prominent role in the laboratory investigation of PNH. The availability of a rapid diagnostic test means that for patients with suspected PNH, a definitive diagnosis can be rapidly established by demonstrating the absence of cell membrane glycosylphosphatidylinositol (GPI)-anchored proteins from granulocytes and/or erythrocytes. With the successful development and clinical trial of a complement inhibition-based monoclonal antibody therapy (eculizumab) for PNH, accurate and timely diagnosis can have a considerable impact on patient management and outcome.
References
- Parker CJ. Historical aspects of paroxysmal nocturnal haemoglobinuria: “defining the disease”. Br J Haematol 2002; 117: 3–22.
- Hillmen P, Lewis SM, Bessler M et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995; 333: 1253–1258.
- Socie G, Mary JY, de Gramont A et al. Paroxysmal nocturnal haemoglobinuria: long term follow-up and prognostic factors. French society for haematology. Lancet 1996; 348; 573–577.
- Hill A, Platts PJ, Smith A et al. The incidence and prevalence of paroxysmal nocturnal hemoglobinuria (PNH) and survival of patients in Yorkshire [abstract]. Blood 2006; 108 Suppl 1: 294a.
- Hillmen P, Hall C, Marsh JC et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 2000; 350: 552–559.
- Hillmen P, Young NS, Schubert J et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006; 355: 1233–1243.
- Hillmen P, Muus P, D ü hrsen U et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007; 110: 4123–4128.
- Borowitz MJ, Craig FE, DiGiuseppe JA et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin Cytom 2010; 78: 211–230.
- Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol 2007; 137: 181–192.
- Auditore JV, Hartmann RC. Paroxysmal Nocturnal Hemoglobinuria. II. Erythrocyte acetylcholine esterase defect. Am J Med 1959; 27: 401–410.
- Beck WS, Valentine WN. Biochemical studies on leucocytes. II. Phosphatase activity in chronic lymphatic leukemia, acute leukemia, and miscellaneous hematologic conditions. J Lab Clin Med 1951; 38: 245–253.
- Medof ME, Kinoshita T, Silber R et al. Amelioration of lytic abnormalities of paroxysmal nocturnal hemoglobinuria with decay-accelerating factor. Proc Natl Acad Sci USA 1985; 82: 2980–2984.
- Nicholson-Weller A, Spicer DB, Austen KF. Deficiency of the complement regulatory protein, “decay-accelerating factor,” on membranes of granulocytes, monocytes, and platelets in paroxysmal nocturnal hemoglobinuria. N Engl J Med 1985; 312: 1091–1097.
- Alfinito F, Del Vecchio L, Rocco S et al. Blood cell flow cytometry in paroxysmal nocturnal hemoglobinuria: A tool for measuring the extent of the PNH clone. Leukemia 1996; 10: 1326–1330.
- Navenot JM, Bernard D, Harousseau JL et al. Expression of glycosyl-phosphotidylinositol-linked glycoproteins in blood cells from paroxysmal nocturnal hemoglobinuria patients. A flow cytometry study using CD55, CD58, and CD59 monoclonal antibodies. Leuk Lymphoma 1996; 21: 143–151.
- Hall SE, Rosse WF. The use of monoclonal antibodies and flow cytometry in the diagnosis of paroxysmal nocturnal hemoglobinuria. Blood 1996; 87: 5332–5340.
- van der Schoot CE, Huizinga TW, van't Veer-Korthof ET et al. Deficiency of glycosyl-phosphatidylinositol-linked membrane glycoproteins of leukocytes in paroxysmal nocturnal hemoglobinuria, description of a new diagnostic cytofluorometric assay. Blood 1990; 76: 1853–1859.
- Bessler M, Mason PJ, Hillmen P et al. Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. EMBO J 1994; 13: 110–117.
- Takeda J, Miyata T, Kawagoe K et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell 1993; 73: 703–711.
- Hall C, Richards SJ, Hillmen P. The glycosylphosphatidylinositol anchor and paroxysmal nocturnal haemoglobinuria/aplasia model. Acta Haematol 2002; 108: 219–230.
- Mortazavi Y, Merk B, McIntosh J et al. Pathophysiology and Treatment of Aplastic Anaemia Study Group. The spectrum of PIG-A gene mutations in aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple muta-tions and evidence of a mutational hot spot. Blood 2003; 101: 2833–2841.
- Parker C, Omine M, Richards S et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005; 106: 3699–3709.
- Yamashina M, Ueda E, Kinoshita T et al. Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1990; 323: 1184–1189.
- Reid ME, Mallinson G, Sim RB et al. Biochemical studies on red blood cells from a patient with the Inab phenotype (decay-accelerating factor deficiency). Blood 1991; 78: 3291–3297.
- Sugimori C, Chuhjo T, Feng X et al. Minor population of CD55 - CD59-blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood 2006; 107: 1308–1314.
- Wang H, Chuhjo T, Yasue S et al. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome. Blood 2002; 100: 3897–3902.
- Hernandez-Campo PM, Almeida J, Sanchez ML et al. Normal patterns of expression of glycosylphosphatidylinositol-anchored proteins on different subsets of peripheral blood cells: A frame of reference for the diagnosis of paroxysmal nocturnal hemoglobinuria. Cytometry B Clin Cytom 2006; 70: 71–81.
- Hernandez-Campo PM, Almeida J, Matarraz S et al. Quantitative analysis of the expression of glycosylphosphatidylinositol-anchored proteins during the maturation of different hematopoietic cell compartments of normal bone marrow. Cytometry B Clin Cytom 2007; 72: 34–42.
- Nakakuma H, Nagakura S, Kawaguchi T et al. Persistence of affected T lymphocytes in long-term clinical remission in paroxysmal nocturnal hemoglobinuria. Blood 1994; 84: 3925–3928.
- Richards SJ, Norfolk DR, Swirsky DM et al. Lymphocyte subset analysis and glycosylphosphatidylinositol phenotype in patients with paroxysmal nocturnal hemoglobinuria. Blood 1998; 92: 1799–1806.
-
Keeney M, Gratama JW, Chin-Yee IH et al. Isotype controls in the analysis of lymphocytes and CD34 + stem and progenitor cells by flow cytometry — time to let go! Cytometry B Clin Cytom 1998; 34: 280–283.
10.1002/(SICI)1097-0320(19981215)34:6<280::AID-CYTO6>3.0.CO;2-H CAS PubMed Web of Science® Google Scholar
- Brodsky RA, Mukhina GL, Li S et al. Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin. Am J Clin Pathol 2000; 114: 459–466.
- Richards SJ, Hillmen P. Immunophenotypic analysis of PNH cells. In: Robinson JP, Darzynkiewicz Z, Dean P et al. (eds.) Current Protocols in Cytometry. New York, NY: John Wiley & Sons, Inc.; 2000; 6.11.1–6.11.16.
- Richards SJ, Rawstron AC, Hillmen P. The Application Of Flow Cytometry To The Diagnosis Of Paroxysmal Nocturnal Hemoglobinuria. Cytometry B Clin Cytom 2000; 42: 223–233.
- Hillmen P, Richards SJ. Flow Cytometry in PNH: serial analysis and the prediction of outcome [abstract ]. Blood 1999; 94 Suppl 1: 412a.
- Moyo VM, Mukhina GL, Garrett ES et al. Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol 2004; 126: 133–138.
- Hall C, Richards SJ, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 2003; 102: 3587–3591.
