Summary
Paroxysmal nocturnal hemoglobinuria, first described in the late 19th century, is an acquired disorder characterized by hemoglobinemia and hemoglobinuria.
The major clinical manifestation of PNH is chronic intravascular hemolysis of various severity. Patients-mostly young adults — may also present with episodes of abdominal or back pain. Common cause of death is thrombosis especially of the hepatic veins. Granulocytopenia and thrombocytopenia may be the initial manifestation of PNH, indicating that the disorder is a primary bone-marrow disease, affecting not only the erythrocytes but also other peripheral blood cells and the haematopoietic stem cell. The course of the disease is variable. Partial complete recovery was described, but also fatal thrombosis. The major phenotypic expression of PNH is an increased susceptibility of the erythrocytes to the lytic action of complement in vitro. The enhanced complement susceptibility is most probably due to membrane defects: two membrane proteins regulating the complement cascade in PNH cells were missing, the decay-accelerating factor, DAF, inhibiting the activation of the lytic complement complex and the C8 binding protein, C8bp, which interferes with the lytic process. Aside from the lack of the complement regulators also other membrane defects have been described (e.g. of acetylcholinesterase or alkaline phosphatase). The proteins as well as DAF and C8bp are linked to the cell membrane via a phosphatidylinositol (PI) anchor, leading to the speculation that the disease results from a deficiency in the posttranslational PI anchoring mechanism.
The diagnosis of PNH is based on the Hamtest, but will be extended to the quantitation of the above described membrane proteins.
Therapy of PNH is restricted to treatment of symptoms: Transfusion of washed erythrocytesnecessary when the hemoglobin level is critically low, iron supplementation, or in cases of thrombosis anticoagulans. Ideal treatment of PNH would be a replacement of the abnormal stem cells by bone-marrow transplantation. Due to its limitations bone-marrow transplantation have been done only in a few cases.
Similar content being viewed by others
Abbreviations
- PNH:
-
paroxysmale nächtliche Hämoglobinurie
- PNH-E:
-
PNH-Erythrozyten
- C56, C7, C8, C9:
-
Komplement-Komponenten 56, 7, 8 und 9
- DAF:
-
decay accelerating factor
- C8bp:
-
C8 binding protein
- PI:
-
phosphatidyl-inositol-Anker
Literatur
Aster RH, Enright SE (1969) A platelet and granulocyte membrane defect in paroxysmal nocturnal hemoglobinuria: usefulness for the detection of platelet antibodies. J Clin Invest 48:1199–1210
Auditore JV, Hartmann RC, Flexner JM, Balchum OJ (1960) The erythrocyte acetylcholinesterase enzyme in paroxysmal nocturnal hemoglobinuria. Arch Pathol 69:534–541
Beresford GH, Gudex DJ, Symmans WA (1986) Paroxysmal nocturnal haemoglobinuria and pregnancy. Lancet i:1396–1397
Blaas P, Berger B, Weber S, Peter HH, Hänsch GM (1988) Paroxysmal nocturnal hemoglobinuria: Enhanced stimulation of platelets by the terminal complement components is related to the lack of C8bp in the membrane. J Immunol 140:3045–3051
Blum SF, Gardner FH (1966) Intestinal infarction in paroxysmal nocturnal hemoglobinuria. N Eng J Med 274:1137–1138
Bordet J (1900) Les serums hemolytiques, les antitoxins et les théories des serums cytoliques. Ann de l'Institut Pasteur 14:257–271
Braren V, Jenkins DE Jr., Phythyon JM, Hartmann RC (1981) Perioperative management of patients with paroxysmal nocturnal hemoglobinuria. Surg Gynecol Obstet 153:515–520
Carmel R, Coltmann CA, Yatteau RF, Costanji JJ (1970) Association of PNH with erythroleukemia. N Engl J Med 283:1329–1331
Chow FL, Telen MJ, Rosse WF (1985) The acetylcholinesterase in paroxysmal nocturnal hemoglobinuria: Evidence that the enzyme is absent from the cell membrane. Blood 66:940–945
Conzelmann A, Spiazzi A, Bron C (1987) Glycolipid anchors are attached to Thy-1 glycoprotein rapidly after translation. Biochem J 246:324
Crookston JH, Crookston MC, Burnic KL, Davis JA, Lewis SM (1969) Hereditary erythroblastic multinuclearity associated with a positive acidified-serum test: a type of congenital dyserythropoietic anaemia. Br J Haemat 17:890–894
Crosby WH, Damashek W (1950) Paroxysmal nocturnal hemoglobinuria. The mechanism of hemolysis and its relation to the coagulation system Blood 5:822
Crosby WH (1951) PNH-A classical description of Paul Strübing in 1882, and a bibliography of the disease. Blood 6:270–284
Dacie JV, Firtin D (1943) Blood transfusion in nocturnal hemoglobinuria. Br Med J 1:626–628
Dacie JV (1967) The hemolytic anemias: congenital and acquired, 2nd Ed, part 4, Churchill, London
Dacie JV, Lewis SM (1972) Paroxysmal nocturnal haemoglobinuria: clinical manifestations, haematology, and nature of the disease. Ser Haematol 5:3–23
Davitz MA, Low NG, Nussenzweig V (1986) Release of decay accelerating factor (DAF) from the cell membrane by phosphatidylinositol specific phospholipase C (PIPLC). J Exp Med 163:1150–1161
Dessypris EN, Clark DA, Luckee LC Jr., Krantz SB (1983) Increased sensitivity to complement of erythroid and myeloid progenitors in paroxysmal nocturnal hemoglobinuria. N Engl J Med 309:690–693
Devine DV, Gluck WL, Rosse WE, Weinberg JB (1987) Acute lymphoblastic leukemia in paroxysmal nocturnal hemoglobinuria. Evidence of evolution from the abnormal paroxysmal nocturnal hemoglobinuria clone. J Clin Invest 79:314–317
Dixon RH, Rosse WF (1977) Mechanisms of complement-mediated activation of human blood platelets in vitro: Comparison of normal and paroxysmal nocturnal hemoglobinuria platelets. J Clin Invest 59:360–368
Donhowe SP, Lazaro RP (1984) Dural sinus thrombosis in paroxysmal nocturnal hemoglobinuria. Clin Neurol Neurosurg 86:149–152
Doukas MA, DiLorenzo PE, Mohler DN (1984) Intestinal infarction caused by paroxysmal nocturnal hemoglobinuria. Am J Hematol 16:75–81
Forman K, Sokol RJ, Hewitt S, Stamps BK (1984) Paroxysmal nocturnal haemoglobinuria. A clinico-pathological study of 26 cases. Acta Haematol 71:217–226
DeGramont A, Krulik M, Debray J (1987) Paroxysmal nocturnal hemoglobinurie and pregnancy. Lancet ii:868
Greenwood LH, Yrizzary JM, Hallett GW, jr (1983) Urokinase treatment of Budd-Chiari syndrome. Am J Radiol 141:1057–1059
Hänsch GM, Voigtländer V, Rother U (1980) Effect of aspirin on the complement system in vitro. Int Arch Allergy Appl Immunol 61:150–158
Hänsch GM, Hammer CH, Vanguri P, Shin ML (1981) Homologous species restriction in lysis of erythrocytes by terminal complement proteins. Proc Natl Acad Sci USA 78:5118–5121
Hänsch GM, Hammer C, Jiji R, Rother U, Shin ML (1983) Lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by acid-activated serum. Immunobiol 164:118–126
Hänsch GM, Schönermark S, Roelcke D (1987) Paroxysmal nocturnal hemoglobinuria type III: Lack of an erythrocyte membrane protein restricting the lysis by C5b-9. J Clin Invest 80:7–12
Hänsch GM, Weller PF, Nicholson-Weller A (1988) Release of C8bp by phosphatidylinositol-specific phospholipase C. Blood 72:1089–1092
Ham TH (1937) Chronic hemolytic anemia with paroxysmal nocturnal hemoglobinuria: study of the mechanism of hemolysis in relation to acid-base equilibrium. N Engl J Med 217:915–917
Ham TH, Dingle JH (1939) Studies on disfunction of red blood cells. II. Chronic hemolytic anemia with paroxysmal nocturnal hemoglobinuria: Certain immunological aspects of the hemolytic mechanism with special reference to serum complement. J Clin Invest 18:657–672
Hartmann RC, Jenkins DE Jr (1966) The “sugar-water” test for paroxysmal nocturnal hemoglobinuria. N Engl J Med 275:155–157
Hartmann RC, Jenkins DE Jr, McKee LC, Heyssel RM (1966) Paroxysmal nocturnal hemoglobinuria; clinal and laboratory studies relating to iron metabolism and therapy with androgen and iron. Medicine 45:331
Hartmann RC, Luther AB, Jenkins DE, Jr, Tenorio LE, Saba HI (1980) Fulminant hepatic venous thrombosis (Budd-Chiari syndrome) in paroxysmal nocturnal hemoglobinuria: definition of a medical emergency. Johns Hopkins Med J 146:247–254
Heilmann L, Siekmann U, Ludwig H (1980) Paroxysmale nächtliche Hämoglobinurie (PNH) und Schwangerschaft. Geburtsh. und Frauenheilk. 40:682–687
Jacobs P, Wood L (1986) Paroxysmal nocturnal haemoglobinuria and pregnancy. Lancet i:1099
Jehn U, Sauer H, Kolb HJ, Fink M, Ledderose G, Brehm G, Wilmanns W, Eckstein R, Heim M, Mempel W et al. (1983) Knochenmarktransplantation im Erwachsenenalter bei akuter Leukämie, aplastischer Anämie und paroxysmaler nächtlicher Hämoglobinurie. Klin Wochenschr 61:321–328
Jenkins DE, Hartmann RC (1969) Paroxysmal nocturnal hemoglobinuria terminating in acute myeloblastic leukemia. Blood 33:274–282
Krause JR (1983) Paroxysmal nocturnal hemoglobinuria and acute non-lymphocytic leukemia. A report of three cases exhibiting different cytologic types. Cancer 51:2078–2082
Kruatrachue M, Was P, Na-Nakorn S (1978) Paroxysmal nocturnal haemoglobinuria in Thailand with special reference to an association with aplastic anaemia. Br J Haemat 39:267–276
Künstling TR, Rosse WF (1969) Erythrocyte acetylcholinesterase deficiency in paroxysmal nocturnal hemoglobinuria (PNH) — a comparison of the complement-sensitive and — insensitive population. Blood 33:607–616
Leibowitz AI, Hartmann RC (1981) The Budd-Chiari-Syndrome and paroxysmal nocturnal hemoglobinuria. Br J Haematol 48:1–6
Lewis SM (1965) Electron-microscope studies of the red cell in paroxysmal nocturnal haemoglobinuria. Br J Haematol 11:689–695
Lewis SM, Dacie JV (1965) Neutrophil (leucocyte) alkaline phosphatase in paroxysmal nocturnal haemoglobinuria. Br J Haematol 11:549–556
Lewis SM, Dacie JV (1967) The aplastic anaemia-paroxysmal nocturnal haemoglobinuria syndrome. Br J Haematol 13:236–251
Lewis SM, Petit JE, Tattershall MHN, Pepys MB (1971) Myelosclerosis and PNH. Scand J Haematol 8:451–460
Logue GL, Rosse WF, Adams JP (1973) Mechanisms of immune lysis of red blood cells in vitro. I. Paroxysmal nocturnal hemoglobinuria cells. J Clin Invest 52:1129–1137
Marchiafava E, Nazari A (1911) Nuovo contributo alla stidio degli itteri cronici emolitica. Policlinico 18:241
Medof MF, Kinoshita T, Nussenzweig V (1984) Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. J Exp Med 160:1558–1578
Moore JC, Frank MM, Müller-Eberhard HJ, Young NS (1985) Decay accelerating factor is present in PNH erythroid progenitors and lost during erythropoesis in vitro. J Exp Med 162:1182–1192
Nicholson-Weller A, Burge J, Feanov DT, Weller PF, Austen KF (1982) Isolation of a human erythrocyte membrane glycoprotein with decay accelerating activity for C3-convertase of the complement system. J Immunol 129:184–189
Nicholson-Weller JP, March S, Rosenfeld I, Austen KF (1983) Affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria are deficient in the complement regulatory protein, decay accelerating factor. Proc Natl Acad Sci USA 80:5066–5070
Nicholson-Weller A, Douglas MD, Spice DB, Austen MD (1985) Deficiency of the complement regulatory protein, “decay accelerating factor”, on membranes of granulocytes, monocytes, and platelets in paroxysmal nocturnal hemoglobinuria. N Engl J Med 312:1091–1097
Oni SB, Osunkoya BO, Kuzzatto L (1970) Paroxysmal nocturnal hemoglobinuria: evidence for monoclonal origin of abnormal red cells. Blood 36:145–152
Ostering H, Brunner G, Heimburg P et al. (1971) Thrombolysis in the Budd-Chiari syndrome induced by partial thromboses of the inferior vena cava and the hepatic veins. Dtsch Med Wochenschr 96:1532–1534
Packman CH, Rosenfeld SI, Jenkins DE, Thiem PA, Leddy JP (1979) Complement lysis of human erythrocytes: differing susceptibility of two types of paroxysmal nocturnal hemoglobinuria cells to C5b-9. J Clin Invest 64:428–433
Parker CJ, Baker PJ, Rosse WF (1982) Increased enzymatic activity of the alternative pathway convertase when bound to the erythrocytes of paroxysmal nocturnal hemoglobinuria. J Clin Invest 69:337–346
Payne PR, Holt JM, Neame PB (1968) Paroxysmal nocturnal haemoglobinuria parturition complicated by presumed hepatic vein thrombosis. J Obst Gynec Brt Cwlth 75:1066
Rosse WF, Dacie JV (1966) Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody. J Clin Invest 45:736–748
Rosse WF, Gutterman LA (1970) The effect of iron therapy in paroxysmal nocturnal hemoglobinuria. Blood 36:559
Rosse WF (1973) Variations in the complement sensitive cells in paroxysmal nocturnal haemoglobinuria. Br J Haematol 24:327–342
Rosse WF, Adams JP, Thorpe AM (1974) The population of cells in paroxysmal nocturnal hemoglobinuria of intermediate sensitivity to complement lysis: significance and mechanism of increased immune lysis. Br J Haematol 28:181–190
Rosse WF (1982) Treatment of paroxysmal nocturnal hemoglobinuria. Blood 60:20–23
Rotoli B, Robledo R, Luzzatto L (1982) Decreased number of circulating BFU-Es in paroxysmal nocturnal hemoglobinuria. Blood 60:157–159
Roualt TA, Rosse WF, Bell S, Shelburne J (1978) Differences in the terminal steps of complement lysis of normal and paroxysmal nocturnal hemoglobinuria red cells. Blood 51:325–330
Schönermark S, Rauterberg EW, Shin ML, Löke S, Roelcke D, Hänsch GM (1986) Homologous species restriction in lysis of human erythrocytes: a membrane derived protein with C-8-binding capacity functions as an inhibitor. J Immunol 136:1772–1776
Schreiber AD (1983) Paroxysmal nocturnal hemoglobinuria revisited. N Engl J Med 309:723–725
Schubothe H, Weber S (1979) Paroxysmal nocturnal hemoglobinuria. Vortrag auf dem 5th. Meeting of the International Society of Hematology (Abstract)
Selvaray P, Dustin ML, Silber R, Low MG, Springer TA (1987) Deficiency of lymphocytefunction-associated antigen 3 (LFA-3) in paroxysmal nocturnal hemoglobinuria. Functional correlates and evidence for a phosphatidylinositol membrane anchor. J Exp Med 166:1011–1025
Sherman SP, Taswell HF (1977) The need for transfusion of saline washed blood cells in patients with paroxysmal nocturnal hemoglobinuria; a myth. Transfusion 17:683
Shin ML, Hänsch GM, Hu VW, Nicholson-Weller A (1986) Membrane factors responsible for homologous species restriction of complement-mediated lysis: evidence for a factor other than DAF operating at the stage of C8 and C9. J Immunol 136:1777–1782
Sholar PW, Bell WR (1985) Thrombolytic therapy for inferior cava thrombosis in paroxysmal nocturnal hemoglobinuria. Ann Int Med 103:539–541
Spencer JA (1980) Paroxysmal nocturnal haemoglobinuria in pregnancy: a case report. Br J Obstet Gynaecol 87:246–248
Stafford HA, Tykocinski ML, Lublin DM, Holers VM, Rosse WF, Atkinson JP, Medof ME (1988) Normal polymorphic variations and transcription of the decay accelerating factor gene in paroxysmal nocturnal hemoglobinuria cells. Proc Natl Acad Sci USA 85 (3):880–884
Stern M, Rosse WF (1979) Two populations of granulocytes in paroxysmal nocturnal hemoglobinuria. Blood 53:928–934
Storb R, Evans RS, Thomas ED, Buckner CD, Clift RA, Fefer A, Newman P, Wright SE (1973) Paroxysmal nocturnal hemoglobinuria and refractory marrow failure treated by marrow transplantation. Br J Haematol 24:743–750
Strübing P (1982) Paroxysmale Hämoglobinurie. Dtsch Med Wochenschr 81:1–3, 2:2–21
Szer J, Deeg HJ, Witherspoon RP, Fefer A, Buckner CD, Thomas ED, Storb R (1984) Long-term survival after bone marrow transplantation for paroxysmal nocturnal hemoglobinuria with aplastic anemia. Ann Intern Med 101:193–195
Tumen J, Kline LB, Fay JW, Scullin DC, Reisner EG, Rosse WF, Huang AT (1980) Complement sensitivity of paroxysmal nocturnal hemoglobinuria bone marrow cells. Blood 55:1040–1046
Vellenga E, Mulder NH, Gips CH, Krom RGF (1982) Vascular problems in paroxysmal nocturnal hemoglobinuria. A report of two cases. Blut 45:261–265
Warren RL, Schlant RC, Wenger NK et al. (1972) Treatment of Budd-Chiari syndrome with streptokinase. Gastroenterology 62:200
Wozniak AJ, Kitchens CS (1982) Prospective hemostatic studies in a patient having paroxysmal nocturnal hemoglobinuria, pregnancy, and cerebral venous thrombosis. Am J Obstet Gynecol 142:591–593
Zaccaria A, Rosti G, Betti S, Testoni N, Baccarani M (1982) Normal karyotype in seven patients with paroxysmal nocturnal hemoglobinuria. Br J Haematol 51:333–334
Zimmermann D, Bell WR (1980) Venous thrombosis and splenic rupture in paroxysmal nocturnal hemoglobinuria. Am J Med 68:275–279
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Blaas, P., Weber, S., Hänsch, G.M. et al. Paroxysmale nächtliche Hämoglobinurie. Klin Wochenschr 68, 247–255 (1990). https://doi.org/10.1007/BF02116052
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02116052