Britishjournal of Haernatology, 1977,37, 167
Annotation PAROXYSMAL COLD HAEMOGLOBINURIA Although paroxysmal cold haemoglobinuria (PCH) is a rare disease, it was the first autoimmune haemolytic anaemia to be described. Elucidation of its pathogenesis by Donath & Landsteiner (1904) became the foundation of Clinical Immunohaematology, and the laboratory test for its diagnosis, the Donath-Landsteiner (DL) test, was the first immunohaematological diagnostic test to be used. PCH attracted the interest of some of the great scholars of the late nineteenth and early twentieth centuries, chiefly Ehrlich (1881),Chvostek (1894) and Widal (1913).Over 90% of patients were found to have a positive WR, and 30% showed unquestionable evidence of syphilis. The disease was at first called simply ‘paroxysmal haemoglobinuria’ and descriptions of PCH, written before Donath & Landsteiner’s paper, probably included various other forms of haemoglobinuria. A positive DL test enabled PCH clearly to be distinguished from other haemoglobinurias although cold haemagglutinin disease (CHAD) is still sometimes confused with PCH. The early literature has been reviewed by Mackenzie (1929). It should be of interest to readers of this Journal that the DL reaction was once called the ‘Eason phenomenon’ in some British publications, because Eason (1906) described what is essentially the DL test. Eason claimed priority on the basis of his having described his test at a meeting of the Galenical Society of Edinburgh in January 1904, whereas Donath & Landsteiner’s paper appeared in September of that year. However, no record of Eason’s communication has been traced. The present-day clinical and laboratory aspects of PCH are essentially the same as in Donath & Landsteiner’s classic description, except for three important criteria: first, the direct anti-human globulin test is usually positive; second, the antibody has blood group speclficity; and third, the disease may occur not only in association with syphilis but also with virus infections. Aetiology and Classification PCH is now divided into syphilitic and non-syphilitic types. Most, if not all, non-syphilitic examples are associated with viral disorders. Syphilis is not as common as it used to be so that most examples seen nowadays are of viral origin. Chicken pox (Kaiser & Bradford, I929), measles (O’Neill & Marshall, 1967) and mumps (Colley, 1964) have been implicated, and the disorder may be associated, particularly in children, with obscure febrile illnesses which are probably of viral origin (Nelson & Nicholl, 1960; Vogel et al, 1972; Bird et al, 1976). Bird et a1 (1976) studied three examples which occurred within a period of 16 d and which were probably due to a virus or viruses; a viral aetiology, however, could not definitely be established. An example of PCH after prophylactic immunization against measles was described by Bunch et a1 (1972). The role of viruses in the production of erythrocyte autoantibodies has been studied for some time but no clear explanation has yet been provided (Weens & Schwartz, 1974). It has Correspondence: Dr G. W . G. Bird, Regional Blood Transfusion Centre, Vincent Drive, Edgbaston, Birmingham B I S zSG.
167
168
Annotation
been suggested that structural alteration of the erythrocyte surface by viruses, and consequent failure of the self-recognition mechanism, leads to the production of antibodies to altered erythrocyte antigens, which crossreact with normal erythrocytes. The nature of the erythrocyte surface alteration and therefore the specdcity of the autoantibody differs from virus to virus. The viruses mentioned above are associated with the formation of DL haemolysins. Other microbes which evoke the production of erythrocyte autoantibodies are Mycoplasma pneumoniae which is associated with cold (IgM) anti-I autohaemagglutinins, the EB virus which evokes cold (IgM) anti-i autohaemagglutinins, and the Cytomegalovirus which may evoke, especially in children, warm (IgG) autohaemagglutinins with specificity within the Rhesus blood group system. A second hypothesis is that viruses stimulate the production of abnormal clones of immunologically competent cells. A third hypothesis is that viruses may alter the surface of lymphocytes in such a way as to induce T cells to stimulate autoantibody responses by B cells. Specijicity of DL Antibody The DL antibody is a bithermic haemolysin of the IgG class which combines with red cells at low temperatures (optimum: I'C) and fixes complement. It haemolyses red cells only when the temperature is raised to about 37" C. The DL antibody was held to be non-specdc until Levine et a1 (1963), Worlledge & Rousso (1965) and Kortekangas et al (1965) showed that it haemolysed P, and P, erythrocytes but not Plk,PZkor p and was therefore anti-P. Bithermic haemolysins which were apparently specific or relatively speclfic for p have been described (Engelfriet et al, 1971; Issitt et al, 1976). If a true anti-p antibody were to occur, it would be expected, ifit were strong enough, to act both on the red cells ofpp homozygotes and Pp heterozygotes. Pp heterozygotes are, however, so rare that this antibody almost certainly detects precursor material in the P biosynthetic pathway (Issitt et al, 1976). DL antibodies with other speclficities have been reported. PCH thought to be due to anti-I or anti-HI were probably examples of transient CHAD, or cold agglutinins may have been present together with DL antibody. Furthermore, because of known associations between the ABH, Ii and P blood systems (Bird, 1977), it may have been that the specficity of the atypical antibodies did in fact involve the P blood group system. In future investigations of PCH, bithermic haemolysins with atypical specficity should be carefully investigated for possible interrelationships with the P system. The DL test, properly carried out, is fundamental to the differential diagnosis of autoimmune haemolytic anaemia. It would be wise to remember: (i) that the DL antibody elutes easily, so that, if a specimen is not tested quickly enough, the direct Coombs test may be negative, (ii) complement may be used up during a haemolytic episode so that the DL test may be negative unless complement is added, and (iii) the DL antibody is always haemolytic and never haemagglutinating: cold agglutinins, on the other hand, are haemagglutinating and some may be haemolytic as well. There is controversy over whether complement is fixed during the cold phase or the warm phase. The question is largely academic; the weight of evidence, however, is in favour of its being fixed during the cold phase (Dacie, 1962). Biochemical studies have shown that the P-determinant has a structure apparently identical with that of globoside (Naiki & Marcus, 1975). DL antibody, however, does not seem to be identical with anti-globoside. Hakomori (1969) raised antibodies in animals against globoside
Annotation
169
extracted from red cells and found that they reacted weakly or not at all against human red cells, whereas the DL antibody is the most powerful of all known immune haemolysins.* Haemolysis by the DL antibody is much more powerful than that caused by complement-fixing antibodies such as anti-A, anti-B or anti-I. It is not known why Treponema pallidurn or certain viruses stimulate the production of this powerful haemolysin. According to Rosenfield (1976),the fact that globoside is a shorter structure than ABH glycosphingolipids may explain the capacity ofanti-P to cause much greater haemolysis than anti-A, anti-B or anti-I. This view was said to be based on studies of poly-DL-alanines coupled to human red cells by Sela who suggested that short chains predispose to lysis and longer chains to agglutination. However, anti-Tn antibodies are haemagglutinating rather than haemolytic and, since the T n receptor consists ofjust a single sugar attached to a protein backbone (Dahr et al, 1974; Springer & Desai, 1974),it would seem that other factors besides the length of glycolipid or glycoprotein chains are involved. Clinical Aspects Textbook descriptions of PCH are usually a conglomerate of every reported sign and symptom, and not all of these clinical features may be observed in a single patient. Unfortunately, various features of CHAD have intruded into textbook descriptions of PCH. Dacie (1962), however, makes a clear distinction between the two conditions. The literature contains several examples of CHAD which were evidently mistaken for PCH (Bird et al, 1976). The situation is made more difficult by those who classify CHAD as a form of paroxysmal cold haemoglobinuria (van Loghem et al, 1963). There are serological differences in the syphilitic and non-syphilitic types of PCH. The thermal amplitude of erythrocyte sensitization in the non-syphilitic type is much greater than in the syphilitic type. Antibody binding in the non-syphilitic type may occur at temperatures as high as 32°C (Reis et al, 1971), whereas it usually occurs below 20°C in the syphilitic type. Furthermore, in the syphilitic type the antibody is usually persistent, whereas it is transient in the non-syphilitic variety. In the syphilitic type, paroxysms are provoked by cold weather, or even by drinking cold water or washing the hands in it. In the non-syphilitic type, haemolytic episodes may be induced by just slight surface chilling so that they may occur in warmer weather. Symptoms include fever, headache, malaise, anorexia, cough, rigors, abdominal pain, vomiting and diarrhoea and severe pain in the back and legs. Patients usually complain of passing ‘red’ urine. The urine contains haemoglobin and is the colour of port wine. The paroxysm subsides within a few hours and may be followed by jaundice. Raynaud’s syndrome, still a poorly understood condition, is described in PCH. Although Raynaud’s syndrome may be associated with some examples of CHAD the present author has not seen it in 40 cases of PCH studied over a period of 3 5 years. Attacks of PCH described as ‘abortive’, ‘rudimentary’, ‘frustrated’ or ‘larval’ may also occur in which there is either haemoglobinuria without other symptoms, or constitutional symptoms and jaundice with haemoglobinuria (Mackenzie, 1929). In a remarkable case described by Hoppe & Witte (1960), DL antibody is said to have caused haemolytic disease of the newborn. The child’s mother had syphilitic PCH. In syphilitic PCH, the primary disease should of course be treated. Haemolytic episodes in *See Notes added in proof on page 170.
1 70
Annotation
both types of PCH are best treated by rest in a warm bed. The transient non-syphilitic type is usually self-limiting. Transfusion is seldom necessary and, in any event, should if possible, be avoided because P-negative blood is unlikely to be readily available. P-positive blood of homologous ABO and Rhesus group, kept at about body temperature, may be given if absolutely necessary, provided the patient is kept warm. Notes Added in Proof Marcus & Schwarting (1976) Advancer in Immunology, Vol. 23, p 2 1 8 , Academic Press, New York, have reported that globoside inhibits DL antibody and that yurijied antigloboside antibodies give a typical DL reaction. Further studies by Marcus and his colleagues (Schwarting, G.A., Marcus, D.M. 81 Metaxas, M. (1977) V o x Sanguinis, 32, 257) have shown that the antibody which reacts preferentially with p erythrocytes is strongly inhibited by sialosylparagloboside. This substance is not a biosynthetic precursor of any of the P blood group antigens, but contains a chemical grouping which is also part of the PI glycolipid. Schwarting et a1 believe that steric factors may be involved in the enhanced reactions of the antibody with P, and p red cells. G. W. G. BIRD
Regional Blood Transjiusion Centre, Vincent D r i v e , Edgbaston, Birmingham REFERENCES BIRD,G.W.G. (1977) Interrelationshipsofsomeblood group antigens and cryptantigens. Handbook Series in Clinical Laboratory Science, Section D, Vol. I, Blood Banking, pp 489-492. CRC Press, Cleveland, Ohio. BIRD,G.W.G., WINGHAM, J., MARTIN, A.J., RICHARDS O N , S.G.N., COLE, A.P., PAYNE, R.W. & SAVAGE, B.F. (1976) Idiopathic non-syphilitic paroxysmal cold haemoglobinuria in children.Journal ofclinical Pathology, 3 , 2 1 5 . BUNCH,C., SCHWARTZ, F.C.M. & BIRD,G.W.G. (1972) Paroxysmal cold haemoglobinuria following measles immunization. Archives of Disease in Chiidhood, 47, 299. CHVOSTEK, F. ( I 894) Ueber das Wesen der Paroxysmalen Himoglobinurie. Deutike, Vienna. COLLEY, E.W. (1964) Paroxysmal cold haemoglobinuria after mumps. Briiish MedicalJournal, i, I 5 5 2 . DACIE, J.V. (1962) The Haemolytic Anaemias. Congential and Acquired. Pt. 2. The Auto-immune Anaemias, p 545. Churchill, London. DAHR,W., UHLENBRUCK, G. & BIRD,G.W.G. (1974) Cryptic A-like receptor sites in human erythrocyte glycoproteins: proposed nature of Tn-antigen. Vox Sanguinis, 27, 29. DONATH, J. & LANDSTEINER, K. (1904) Ueber paroxysmale hamoglobinurie. Muenchener Medizinische Wochenshrgt, 51. 1590. EASON, J. (1906) Pathology of paroxysmal haemoglobinuria. Edinburgh Medical Journal, 19, 43.
EHRLICH, P. (1881) Ueber paroxysmale hamoglobinurie. Deutscke Medizinische Wochenshrijt, 7.224. ENGELFRIET, C.P., BECKERS, D., V O N DEM BORNE, A.E.G.KR., REYNIERSE, E. & V A N LOGHEM, J.J. (1971) Haemolysins probably recognizing the antigen p. Vox Sanguinis, 23. 176. HAKOMORI, S. (1969) Differential reactivities of fetal and adult human erythrocytes to antisera directed against glycolipids of human erythrocytes. Vox Sanguinis, 16,478. HOPPE,H. & WITTE, A. (1960)Hamolytische Erkrankungen eines Neugebornen bei paroxysmaler Kaltehamglobinurie der Mutter. Vox Sanguinis, 5,425. Issrrr, C.H., DUCKETT, J.B., OSBORNE, B.M., GUT, J.B. & BEASLEY, J. (1976) Another example of an antibody reacting optimally with p cells. British Journal of Haematology, 34, 19. KAISER,A.D. & BRADFORD, W.L. (1929) Severe haemoglobinuria in a child occurring in the prodroma1 stage of chicken pox. Archives ofPediatrics, 46, 571. KORTEKANGAS, A.E., KAARSALO, E., MELARTIN, L., TIPPETT, P., GAVIN, J., NOADES, J., SANGER, R. & RACE,R.R. (1965) The red cell antigen P' and its relationship to the P system: the evidence of three more P' families. Vox Sanguinis, 10. 385. LEVINE, P., CELANO, M.J. & FALKOWSKI, B.S. (1963) The specificity of the antibody in paroxysmal cold hemoglobinuria. Transjusion ('Philad.), 3. 278. MACKENZIE, G.M. (1929) Paroxysmal haemoglo-
Annotation
171
binuria. A review. Medicine (Baltimore), 8, 159. 61,470. NAIKI,M. & MARCUS, D.M. (1975) An immunoVANLOGHEM, J.J., PEETOOM, F., VANDER HART,M., chemical study of the human blood group P I , P, M., PRINS, VANDER VEER,M., VANDER GIESSEN, and Pkglycosphingolipid antigens. Biochemishy ,14, H.K., ZURCHER, C. & ENGELFRIE, C.P. (1963) Serological and immunochemical studies in haemo4837NELSON, M.G. & NICHOLL, B. (1960)Paroxysmal cold lytic anaemia with high-titre cold agglutinins. Vox haemoglobinuria. Irish Journal of Medical Science, Sanguinis, 8, 3 3 . 6th Series, 49. VOGEL, J.M., HELLMAN, M. & MOLOSHOK, R.E. (1972) O’NEILL, B.J. & MARSHALL, W.C. (1967) Paroxysmal Paroxysmal cold hemoglobinuria of nonsyphilitic cold haemoglobinuria and measles. Archives of etiology in two children. Journal of Pediatrics, 81, Disease in Childhood, 42, I 83. 974. REIS,C.A., GARRAITY, G., PETZ,L.D. & FUDENBERG, WEENS, J.J. & SCHWARTZ, R.S. (1974)Etiologic factors H.H. (1971) Paroxysmal cold hemoglobinuria: in autoimmune hemolytic anemia. Series Haematoreport of a case with an exceptionally high thermal logica, 7, 303. range Donath-Landsteiner antibody. Blood, 38,491. WIDAL,F., ABRAMI,P. & BRISSAUD, E. (1913) ROSENFIELD, R.E. (1976) Quantitation of erythrocytic Recherches sur l’hkmoglobinurie paroxsystique “i frigore”. Semaine Mldicale, 33. 5 8 5 . antigens. A Seminar on Performance Evaluation, p 93. American Association of Blood Banks, WashingWORLLEDGE, S.M. & Rousso, C. (1965)Studieson the ton. serology of paroxysmal cold haemoglobinuria SPRINGER, G.F. & DESAI,P.R. (1974) Common pre(P.C.H.) with special reference to its relationship cursors of human blood group M N specificities. with the P blood group system. Vox Sanguinis, 10, Biochewiical and Biophysical Research Communications, 293.
Annotation PAROXYSMAL COLD HAEMOGLOBINURIA Although paroxysmal cold haemoglobinuria (PCH) is a rare disease, it was the first autoimmune haemolytic anaemia to be described. Elucidation of its pathogenesis by Donath & Landsteiner (1904) became the foundation of Clinical Immunohaematology, and the laboratory test for its diagnosis, the Donath-Landsteiner (DL) test, was the first immunohaematological diagnostic test to be used. PCH attracted the interest of some of the great scholars of the late nineteenth and early twentieth centuries, chiefly Ehrlich (1881),Chvostek (1894) and Widal (1913).Over 90% of patients were found to have a positive WR, and 30% showed unquestionable evidence of syphilis. The disease was at first called simply ‘paroxysmal haemoglobinuria’ and descriptions of PCH, written before Donath & Landsteiner’s paper, probably included various other forms of haemoglobinuria. A positive DL test enabled PCH clearly to be distinguished from other haemoglobinurias although cold haemagglutinin disease (CHAD) is still sometimes confused with PCH. The early literature has been reviewed by Mackenzie (1929). It should be of interest to readers of this Journal that the DL reaction was once called the ‘Eason phenomenon’ in some British publications, because Eason (1906) described what is essentially the DL test. Eason claimed priority on the basis of his having described his test at a meeting of the Galenical Society of Edinburgh in January 1904, whereas Donath & Landsteiner’s paper appeared in September of that year. However, no record of Eason’s communication has been traced. The present-day clinical and laboratory aspects of PCH are essentially the same as in Donath & Landsteiner’s classic description, except for three important criteria: first, the direct anti-human globulin test is usually positive; second, the antibody has blood group speclficity; and third, the disease may occur not only in association with syphilis but also with virus infections. Aetiology and Classification PCH is now divided into syphilitic and non-syphilitic types. Most, if not all, non-syphilitic examples are associated with viral disorders. Syphilis is not as common as it used to be so that most examples seen nowadays are of viral origin. Chicken pox (Kaiser & Bradford, I929), measles (O’Neill & Marshall, 1967) and mumps (Colley, 1964) have been implicated, and the disorder may be associated, particularly in children, with obscure febrile illnesses which are probably of viral origin (Nelson & Nicholl, 1960; Vogel et al, 1972; Bird et al, 1976). Bird et a1 (1976) studied three examples which occurred within a period of 16 d and which were probably due to a virus or viruses; a viral aetiology, however, could not definitely be established. An example of PCH after prophylactic immunization against measles was described by Bunch et a1 (1972). The role of viruses in the production of erythrocyte autoantibodies has been studied for some time but no clear explanation has yet been provided (Weens & Schwartz, 1974). It has Correspondence: Dr G. W . G. Bird, Regional Blood Transfusion Centre, Vincent Drive, Edgbaston, Birmingham B I S zSG.
167
168
Annotation
been suggested that structural alteration of the erythrocyte surface by viruses, and consequent failure of the self-recognition mechanism, leads to the production of antibodies to altered erythrocyte antigens, which crossreact with normal erythrocytes. The nature of the erythrocyte surface alteration and therefore the specdcity of the autoantibody differs from virus to virus. The viruses mentioned above are associated with the formation of DL haemolysins. Other microbes which evoke the production of erythrocyte autoantibodies are Mycoplasma pneumoniae which is associated with cold (IgM) anti-I autohaemagglutinins, the EB virus which evokes cold (IgM) anti-i autohaemagglutinins, and the Cytomegalovirus which may evoke, especially in children, warm (IgG) autohaemagglutinins with specificity within the Rhesus blood group system. A second hypothesis is that viruses stimulate the production of abnormal clones of immunologically competent cells. A third hypothesis is that viruses may alter the surface of lymphocytes in such a way as to induce T cells to stimulate autoantibody responses by B cells. Specijicity of DL Antibody The DL antibody is a bithermic haemolysin of the IgG class which combines with red cells at low temperatures (optimum: I'C) and fixes complement. It haemolyses red cells only when the temperature is raised to about 37" C. The DL antibody was held to be non-specdc until Levine et a1 (1963), Worlledge & Rousso (1965) and Kortekangas et al (1965) showed that it haemolysed P, and P, erythrocytes but not Plk,PZkor p and was therefore anti-P. Bithermic haemolysins which were apparently specific or relatively speclfic for p have been described (Engelfriet et al, 1971; Issitt et al, 1976). If a true anti-p antibody were to occur, it would be expected, ifit were strong enough, to act both on the red cells ofpp homozygotes and Pp heterozygotes. Pp heterozygotes are, however, so rare that this antibody almost certainly detects precursor material in the P biosynthetic pathway (Issitt et al, 1976). DL antibodies with other speclficities have been reported. PCH thought to be due to anti-I or anti-HI were probably examples of transient CHAD, or cold agglutinins may have been present together with DL antibody. Furthermore, because of known associations between the ABH, Ii and P blood systems (Bird, 1977), it may have been that the specficity of the atypical antibodies did in fact involve the P blood group system. In future investigations of PCH, bithermic haemolysins with atypical specficity should be carefully investigated for possible interrelationships with the P system. The DL test, properly carried out, is fundamental to the differential diagnosis of autoimmune haemolytic anaemia. It would be wise to remember: (i) that the DL antibody elutes easily, so that, if a specimen is not tested quickly enough, the direct Coombs test may be negative, (ii) complement may be used up during a haemolytic episode so that the DL test may be negative unless complement is added, and (iii) the DL antibody is always haemolytic and never haemagglutinating: cold agglutinins, on the other hand, are haemagglutinating and some may be haemolytic as well. There is controversy over whether complement is fixed during the cold phase or the warm phase. The question is largely academic; the weight of evidence, however, is in favour of its being fixed during the cold phase (Dacie, 1962). Biochemical studies have shown that the P-determinant has a structure apparently identical with that of globoside (Naiki & Marcus, 1975). DL antibody, however, does not seem to be identical with anti-globoside. Hakomori (1969) raised antibodies in animals against globoside
Annotation
169
extracted from red cells and found that they reacted weakly or not at all against human red cells, whereas the DL antibody is the most powerful of all known immune haemolysins.* Haemolysis by the DL antibody is much more powerful than that caused by complement-fixing antibodies such as anti-A, anti-B or anti-I. It is not known why Treponema pallidurn or certain viruses stimulate the production of this powerful haemolysin. According to Rosenfield (1976),the fact that globoside is a shorter structure than ABH glycosphingolipids may explain the capacity ofanti-P to cause much greater haemolysis than anti-A, anti-B or anti-I. This view was said to be based on studies of poly-DL-alanines coupled to human red cells by Sela who suggested that short chains predispose to lysis and longer chains to agglutination. However, anti-Tn antibodies are haemagglutinating rather than haemolytic and, since the T n receptor consists ofjust a single sugar attached to a protein backbone (Dahr et al, 1974; Springer & Desai, 1974),it would seem that other factors besides the length of glycolipid or glycoprotein chains are involved. Clinical Aspects Textbook descriptions of PCH are usually a conglomerate of every reported sign and symptom, and not all of these clinical features may be observed in a single patient. Unfortunately, various features of CHAD have intruded into textbook descriptions of PCH. Dacie (1962), however, makes a clear distinction between the two conditions. The literature contains several examples of CHAD which were evidently mistaken for PCH (Bird et al, 1976). The situation is made more difficult by those who classify CHAD as a form of paroxysmal cold haemoglobinuria (van Loghem et al, 1963). There are serological differences in the syphilitic and non-syphilitic types of PCH. The thermal amplitude of erythrocyte sensitization in the non-syphilitic type is much greater than in the syphilitic type. Antibody binding in the non-syphilitic type may occur at temperatures as high as 32°C (Reis et al, 1971), whereas it usually occurs below 20°C in the syphilitic type. Furthermore, in the syphilitic type the antibody is usually persistent, whereas it is transient in the non-syphilitic variety. In the syphilitic type, paroxysms are provoked by cold weather, or even by drinking cold water or washing the hands in it. In the non-syphilitic type, haemolytic episodes may be induced by just slight surface chilling so that they may occur in warmer weather. Symptoms include fever, headache, malaise, anorexia, cough, rigors, abdominal pain, vomiting and diarrhoea and severe pain in the back and legs. Patients usually complain of passing ‘red’ urine. The urine contains haemoglobin and is the colour of port wine. The paroxysm subsides within a few hours and may be followed by jaundice. Raynaud’s syndrome, still a poorly understood condition, is described in PCH. Although Raynaud’s syndrome may be associated with some examples of CHAD the present author has not seen it in 40 cases of PCH studied over a period of 3 5 years. Attacks of PCH described as ‘abortive’, ‘rudimentary’, ‘frustrated’ or ‘larval’ may also occur in which there is either haemoglobinuria without other symptoms, or constitutional symptoms and jaundice with haemoglobinuria (Mackenzie, 1929). In a remarkable case described by Hoppe & Witte (1960), DL antibody is said to have caused haemolytic disease of the newborn. The child’s mother had syphilitic PCH. In syphilitic PCH, the primary disease should of course be treated. Haemolytic episodes in *See Notes added in proof on page 170.
1 70
Annotation
both types of PCH are best treated by rest in a warm bed. The transient non-syphilitic type is usually self-limiting. Transfusion is seldom necessary and, in any event, should if possible, be avoided because P-negative blood is unlikely to be readily available. P-positive blood of homologous ABO and Rhesus group, kept at about body temperature, may be given if absolutely necessary, provided the patient is kept warm. Notes Added in Proof Marcus & Schwarting (1976) Advancer in Immunology, Vol. 23, p 2 1 8 , Academic Press, New York, have reported that globoside inhibits DL antibody and that yurijied antigloboside antibodies give a typical DL reaction. Further studies by Marcus and his colleagues (Schwarting, G.A., Marcus, D.M. 81 Metaxas, M. (1977) V o x Sanguinis, 32, 257) have shown that the antibody which reacts preferentially with p erythrocytes is strongly inhibited by sialosylparagloboside. This substance is not a biosynthetic precursor of any of the P blood group antigens, but contains a chemical grouping which is also part of the PI glycolipid. Schwarting et a1 believe that steric factors may be involved in the enhanced reactions of the antibody with P, and p red cells. G. W. G. BIRD
Regional Blood Transjiusion Centre, Vincent D r i v e , Edgbaston, Birmingham REFERENCES BIRD,G.W.G. (1977) Interrelationshipsofsomeblood group antigens and cryptantigens. Handbook Series in Clinical Laboratory Science, Section D, Vol. I, Blood Banking, pp 489-492. CRC Press, Cleveland, Ohio. BIRD,G.W.G., WINGHAM, J., MARTIN, A.J., RICHARDS O N , S.G.N., COLE, A.P., PAYNE, R.W. & SAVAGE, B.F. (1976) Idiopathic non-syphilitic paroxysmal cold haemoglobinuria in children.Journal ofclinical Pathology, 3 , 2 1 5 . BUNCH,C., SCHWARTZ, F.C.M. & BIRD,G.W.G. (1972) Paroxysmal cold haemoglobinuria following measles immunization. Archives of Disease in Chiidhood, 47, 299. CHVOSTEK, F. ( I 894) Ueber das Wesen der Paroxysmalen Himoglobinurie. Deutike, Vienna. COLLEY, E.W. (1964) Paroxysmal cold haemoglobinuria after mumps. Briiish MedicalJournal, i, I 5 5 2 . DACIE, J.V. (1962) The Haemolytic Anaemias. Congential and Acquired. Pt. 2. The Auto-immune Anaemias, p 545. Churchill, London. DAHR,W., UHLENBRUCK, G. & BIRD,G.W.G. (1974) Cryptic A-like receptor sites in human erythrocyte glycoproteins: proposed nature of Tn-antigen. Vox Sanguinis, 27, 29. DONATH, J. & LANDSTEINER, K. (1904) Ueber paroxysmale hamoglobinurie. Muenchener Medizinische Wochenshrgt, 51. 1590. EASON, J. (1906) Pathology of paroxysmal haemoglobinuria. Edinburgh Medical Journal, 19, 43.
EHRLICH, P. (1881) Ueber paroxysmale hamoglobinurie. Deutscke Medizinische Wochenshrijt, 7.224. ENGELFRIET, C.P., BECKERS, D., V O N DEM BORNE, A.E.G.KR., REYNIERSE, E. & V A N LOGHEM, J.J. (1971) Haemolysins probably recognizing the antigen p. Vox Sanguinis, 23. 176. HAKOMORI, S. (1969) Differential reactivities of fetal and adult human erythrocytes to antisera directed against glycolipids of human erythrocytes. Vox Sanguinis, 16,478. HOPPE,H. & WITTE, A. (1960)Hamolytische Erkrankungen eines Neugebornen bei paroxysmaler Kaltehamglobinurie der Mutter. Vox Sanguinis, 5,425. Issrrr, C.H., DUCKETT, J.B., OSBORNE, B.M., GUT, J.B. & BEASLEY, J. (1976) Another example of an antibody reacting optimally with p cells. British Journal of Haematology, 34, 19. KAISER,A.D. & BRADFORD, W.L. (1929) Severe haemoglobinuria in a child occurring in the prodroma1 stage of chicken pox. Archives ofPediatrics, 46, 571. KORTEKANGAS, A.E., KAARSALO, E., MELARTIN, L., TIPPETT, P., GAVIN, J., NOADES, J., SANGER, R. & RACE,R.R. (1965) The red cell antigen P' and its relationship to the P system: the evidence of three more P' families. Vox Sanguinis, 10. 385. LEVINE, P., CELANO, M.J. & FALKOWSKI, B.S. (1963) The specificity of the antibody in paroxysmal cold hemoglobinuria. Transjusion ('Philad.), 3. 278. MACKENZIE, G.M. (1929) Paroxysmal haemoglo-
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