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Platelet groups and types
Comments
o n C u r r e n t Literature
P L A T E L E T GROUPS AND T Y P E S ARLY observations 1,2 that the administration of heterologous E platelets to animals stimulates the production of specific antiplatelet " i m m u n e " serum, which, when injected into the circulation of the donor animals, results in marked thromboeytopenia, have been extended and verified. As has been summarized in a number of review articles, evidence for platelet iso- and autoantigenicity has accumulated from clinical and laboratory studies of the thrombocytopenic purpuras, and in the course of platelet transfusion studies, as well as from the experimental study of reactions following the injection of such modified plasma into normal recipients. ~, 3 The continued observation that platelets are antigenic suggested the existence of individual platelet groups and types comparable to the red cell groups, eight individual types being postulated originally. Within the past eighteen months to two years, several extensive investigations ~, 3 have been reported which focus attention upon the clinical importance of the platelets and their specificity, implying "the use of only compatible platelets for transfusions on the same lines as for whole blood. ''~ In 1953 Stefanini, Dameshek, and their co-workers 2 presented strong evidence for the antigenieity of platelets from observations obtained in the course of platelet transfusion studies. Patients with secondary, or amegakaryocytic, thromboeytopenic purpura show progressively less benefit from repeated platelet transfusions, the survival time of the transfused platelets being progressively shortened. At the same time these patients may
develop iso- and, occasionally, autoplatelet agglutinins, and their plasma may induce thrombocytopenia when injected into (normal) recipients who are v u l n e r a b l e . Development of platelet agglutinins o e c u r s more promptly when viable, well-preserved platelets are used for transfusion. By direct cross-testing techniques Stefanini and his group were able to detect naturally occurring platelet agglutinins in human subjects, suggesting the existence of four basic platelet groups: I, II, III (I + II), and IV (0 group :no antigen). The irtcidenee reported by these authors was based oft evidence o b t a i n e d f r o m a totaI of 285 individuals tested. Agglutinin absorption tests and in vivo immunization tests have confirmed the presence of such groups. They are not related to the ABO antigenic system of the red blood ceils, but since they can be detected by the use of naturally occurring' agglutinins, are considered to have an a~ltigenie significance similar to that of the ABO antigenic system. Occasional patients receiving multiple transfusions develop agglutinins against their own platelets (autoagglutinins) as well as isoagglutinins, and become thrombocytopenie as a result. These authors 2 have suggested that "some such mechanism with the development of platelet auto-sensitization, may result in idiopathic thromboeytopenia." In some instances of idiopathic thromboeytopenia, a platNet autoagglutinin can be detected. In a series of nine patients reported, the agglutinin disappeared in five of the nine following successful spleneetomy, although the plateIet isoagglutinin, also present, persisted
382
COM:MENTS ON
CURRENT LITERATURE
after the surgery. " T h i s finding may indicate that autoimmune thromboeytopenia is improved by spleneetomy, even if isoagghtinin production continues, and suggests an additional possible mechanism to explain the favorable effect of spleneetomy in many cases of the disease. ''2 In a summary of nine eases of thrombocytopenia and thrombopathia treated by means of repeated platelet transfusions, Van Creveld and his associates ~ (1953) stress the fact that they employed for such transfusion only blood of the same ABO and Rh groups, since the antigenic potentialities of the thrombocytes were not known to them. In all nine patients, a steady increase in the number of platclets was observed, and the patients showed benefit front the repeated platelet transfusions. Somewhat more recently investigations by Gurevitch and Nelken 4 have verified the four blood-group classification of platelets, corresponding to the ABO groups of erythrocytes; these authors describe in some detail the preparation of the specimen and the procedure of typing the platelet suspension. Control examinations of platelets were carried on simultaneously, the " c o n t r o l " thrombocytes being suspended in their own serum or in inactivated serum of the same group. Gurevitch and Nelken examined for their antigenic behavior eighty-five different samples of platelet suspensions, and in every instance the results showed exact correspondence between the erythrocyte and the thrombocyte groups. The identity of the A and B antigens in platelets and in red blood cells was verified by adsorption of isoagghtinins by erythrocytes and thromboeytes, by the inhibition of isoagglutinins with saliva, and the neutralization of sera by group-specific substances. Storage of platelet suspensions in the refrigerator up to seven days resulted in gradual loss of agglutinability by antisera. A recent preliminary publication in the Journal of Laboratory and CIini-
383
cat Medicine ~ (May, 1955) by Nicola, Rosti, and Zangaglia oE the University of Pavia, Italy, is of interest in conneetion with the group classification of tbromboeytes and the significance of their antigenic activity. Preliminary results described by these investigators indicate that, as might be expected from theoretical implications, platelet antibodies can be detected by means of a complement fixation test. The findings are based on studies of antiplatelet rabbit sera and guinea pig platelets. Complete inhibition of hemolysis took place at the serum dilution of 1:700; no inhibition of hemolysis was observed with serum specimens obtained from the same animals prior ~e immunization. This investigative lead is being pursued at present, especially with reference to possible correlations with human pathology. Such observations as these on platelet immunology have confirmed the heteroantigenicity of the thrombocytes, and have raised questions as to the significance of their iso- and autoantigenieity, not only in connection with patients having idiopathic thromboeytopenie purpura, and in relation to repeated platelet transfusion, but also in connection with the possibility that autoagghtinins might develop "in response to antigenic stimulation by platelet products or platelets damaged by various agents (viruses, etc.). ''~ F u r t h e r developments in this field concerning the antigenic behavior of the thromboeytes will be of consider: ~able interest. ]~USSELL g. BLATTNER REFERENCES 1. Marine, F.: Recherches sur ]es I~luquettes du Sang, Compt. rend. Soc. de Biol. 58: 194, 1905. 2. Stefanini, NIario, Plitman~ G. I.~ I)allleshek, William, Chatterjea~ J. B., and Mednicoff~ I. 9.: Studies on Platelets: XI. A n t i g e n i c i t y of P l a t e l e t s and Evidence of P l a t e l e t Groups and Types in 3~an~ J. Lab. & Clin. Med. 42: 723~ 1953. 3. Stefanini~ 3/Iario: Recent Observations on the P a t h o g e n e t i c 2r of Idiopathic Thromboeytopenic Purpura~ a. N t . Sinai ttosp. 19: 452~ 1952.
384
THE
JOURI'~AL
Stefaninl, ~ a r i o , Dameshek, William, Chatterjea, J. B., Adelson, E., and ~r coff, I. B.: Studies on Flate]ets: IX. Observations on the Properties and 5/[echanism of Action of a P o t e n t Platelet A g g l u t i n i a Detected in the Serum of a P a t i e n t W i t h I d i o p a t h i c Thromboeytopenic P u r p u r a ( W i t h a Note on the Pathogenesis of the Disease), Blood 8: 26, 1953. tIarrington, W. J., Sprague, C. C., Minnieh, V., Moore, C. V., Ahlvin, R. C., and Dubach, B.: Immunologic Mechanisms in Idiopathic and Neonatal Thromboeytopenie Purpura, Ann. Int. Med. 38: 433, 1953. Mushett, C. W., Reisner, E. J., Jr., Weiner, Leo, Nakashlma, Ritzu, and Col-
OF PEDIATRICS
lett, J a m e s : A n t i r a b b i t P l a t e l e t and Red-cell Factors in N o r m a l Blood, J. Lab. & Clin. ~V[ed. 42: 713, 1953. 4. Gurevitch, J., and Nelken, D.: ABe Groups in Blood Platelets, J. Lab. & Clin. 5/ied. 44: 562, 1954; 1Wature 173: 356, ]954. 5. V a n Creveld, S:, Paulssen, ~ . 1Y[. P., and Bartels, H. L. J. ~[.: T r a n s f u s i o n s of Suspensions of Blood P ] a t e l e t s in Thromb o c y t o p e n i a and T h r o m b o p a t h i a , J. Clin. P a t h . 6: 41, 1953. 6. de Nieola, Pierre, Bostl, Pietr0, and Zangaglia, Onorio: Complement Fixation Test Due to the I n t e r a c t i o n of Specific A~tiplatelet Serum and tIeterologous Platelet Antigen, J. Lab. & Clan. Med. 45: 725, 1955.
o n C u r r e n t Literature
P L A T E L E T GROUPS AND T Y P E S ARLY observations 1,2 that the administration of heterologous E platelets to animals stimulates the production of specific antiplatelet " i m m u n e " serum, which, when injected into the circulation of the donor animals, results in marked thromboeytopenia, have been extended and verified. As has been summarized in a number of review articles, evidence for platelet iso- and autoantigenicity has accumulated from clinical and laboratory studies of the thrombocytopenic purpuras, and in the course of platelet transfusion studies, as well as from the experimental study of reactions following the injection of such modified plasma into normal recipients. ~, 3 The continued observation that platelets are antigenic suggested the existence of individual platelet groups and types comparable to the red cell groups, eight individual types being postulated originally. Within the past eighteen months to two years, several extensive investigations ~, 3 have been reported which focus attention upon the clinical importance of the platelets and their specificity, implying "the use of only compatible platelets for transfusions on the same lines as for whole blood. ''~ In 1953 Stefanini, Dameshek, and their co-workers 2 presented strong evidence for the antigenieity of platelets from observations obtained in the course of platelet transfusion studies. Patients with secondary, or amegakaryocytic, thromboeytopenic purpura show progressively less benefit from repeated platelet transfusions, the survival time of the transfused platelets being progressively shortened. At the same time these patients may
develop iso- and, occasionally, autoplatelet agglutinins, and their plasma may induce thrombocytopenia when injected into (normal) recipients who are v u l n e r a b l e . Development of platelet agglutinins o e c u r s more promptly when viable, well-preserved platelets are used for transfusion. By direct cross-testing techniques Stefanini and his group were able to detect naturally occurring platelet agglutinins in human subjects, suggesting the existence of four basic platelet groups: I, II, III (I + II), and IV (0 group :no antigen). The irtcidenee reported by these authors was based oft evidence o b t a i n e d f r o m a totaI of 285 individuals tested. Agglutinin absorption tests and in vivo immunization tests have confirmed the presence of such groups. They are not related to the ABO antigenic system of the red blood ceils, but since they can be detected by the use of naturally occurring' agglutinins, are considered to have an a~ltigenie significance similar to that of the ABO antigenic system. Occasional patients receiving multiple transfusions develop agglutinins against their own platelets (autoagglutinins) as well as isoagglutinins, and become thrombocytopenie as a result. These authors 2 have suggested that "some such mechanism with the development of platelet auto-sensitization, may result in idiopathic thromboeytopenia." In some instances of idiopathic thromboeytopenia, a platNet autoagglutinin can be detected. In a series of nine patients reported, the agglutinin disappeared in five of the nine following successful spleneetomy, although the plateIet isoagglutinin, also present, persisted
382
COM:MENTS ON
CURRENT LITERATURE
after the surgery. " T h i s finding may indicate that autoimmune thromboeytopenia is improved by spleneetomy, even if isoagghtinin production continues, and suggests an additional possible mechanism to explain the favorable effect of spleneetomy in many cases of the disease. ''2 In a summary of nine eases of thrombocytopenia and thrombopathia treated by means of repeated platelet transfusions, Van Creveld and his associates ~ (1953) stress the fact that they employed for such transfusion only blood of the same ABO and Rh groups, since the antigenic potentialities of the thrombocytes were not known to them. In all nine patients, a steady increase in the number of platclets was observed, and the patients showed benefit front the repeated platelet transfusions. Somewhat more recently investigations by Gurevitch and Nelken 4 have verified the four blood-group classification of platelets, corresponding to the ABO groups of erythrocytes; these authors describe in some detail the preparation of the specimen and the procedure of typing the platelet suspension. Control examinations of platelets were carried on simultaneously, the " c o n t r o l " thrombocytes being suspended in their own serum or in inactivated serum of the same group. Gurevitch and Nelken examined for their antigenic behavior eighty-five different samples of platelet suspensions, and in every instance the results showed exact correspondence between the erythrocyte and the thrombocyte groups. The identity of the A and B antigens in platelets and in red blood cells was verified by adsorption of isoagghtinins by erythrocytes and thromboeytes, by the inhibition of isoagglutinins with saliva, and the neutralization of sera by group-specific substances. Storage of platelet suspensions in the refrigerator up to seven days resulted in gradual loss of agglutinability by antisera. A recent preliminary publication in the Journal of Laboratory and CIini-
383
cat Medicine ~ (May, 1955) by Nicola, Rosti, and Zangaglia oE the University of Pavia, Italy, is of interest in conneetion with the group classification of tbromboeytes and the significance of their antigenic activity. Preliminary results described by these investigators indicate that, as might be expected from theoretical implications, platelet antibodies can be detected by means of a complement fixation test. The findings are based on studies of antiplatelet rabbit sera and guinea pig platelets. Complete inhibition of hemolysis took place at the serum dilution of 1:700; no inhibition of hemolysis was observed with serum specimens obtained from the same animals prior ~e immunization. This investigative lead is being pursued at present, especially with reference to possible correlations with human pathology. Such observations as these on platelet immunology have confirmed the heteroantigenicity of the thrombocytes, and have raised questions as to the significance of their iso- and autoantigenieity, not only in connection with patients having idiopathic thromboeytopenie purpura, and in relation to repeated platelet transfusion, but also in connection with the possibility that autoagghtinins might develop "in response to antigenic stimulation by platelet products or platelets damaged by various agents (viruses, etc.). ''~ F u r t h e r developments in this field concerning the antigenic behavior of the thromboeytes will be of consider: ~able interest. ]~USSELL g. BLATTNER REFERENCES 1. Marine, F.: Recherches sur ]es I~luquettes du Sang, Compt. rend. Soc. de Biol. 58: 194, 1905. 2. Stefanini, NIario, Plitman~ G. I.~ I)allleshek, William, Chatterjea~ J. B., and Mednicoff~ I. 9.: Studies on Platelets: XI. A n t i g e n i c i t y of P l a t e l e t s and Evidence of P l a t e l e t Groups and Types in 3~an~ J. Lab. & Clin. Med. 42: 723~ 1953. 3. Stefanini~ 3/Iario: Recent Observations on the P a t h o g e n e t i c 2r of Idiopathic Thromboeytopenic Purpura~ a. N t . Sinai ttosp. 19: 452~ 1952.
384
THE
JOURI'~AL
Stefaninl, ~ a r i o , Dameshek, William, Chatterjea, J. B., Adelson, E., and ~r coff, I. B.: Studies on Flate]ets: IX. Observations on the Properties and 5/[echanism of Action of a P o t e n t Platelet A g g l u t i n i a Detected in the Serum of a P a t i e n t W i t h I d i o p a t h i c Thromboeytopenic P u r p u r a ( W i t h a Note on the Pathogenesis of the Disease), Blood 8: 26, 1953. tIarrington, W. J., Sprague, C. C., Minnieh, V., Moore, C. V., Ahlvin, R. C., and Dubach, B.: Immunologic Mechanisms in Idiopathic and Neonatal Thromboeytopenie Purpura, Ann. Int. Med. 38: 433, 1953. Mushett, C. W., Reisner, E. J., Jr., Weiner, Leo, Nakashlma, Ritzu, and Col-
OF PEDIATRICS
lett, J a m e s : A n t i r a b b i t P l a t e l e t and Red-cell Factors in N o r m a l Blood, J. Lab. & Clin. ~V[ed. 42: 713, 1953. 4. Gurevitch, J., and Nelken, D.: ABe Groups in Blood Platelets, J. Lab. & Clin. 5/ied. 44: 562, 1954; 1Wature 173: 356, ]954. 5. V a n Creveld, S:, Paulssen, ~ . 1Y[. P., and Bartels, H. L. J. ~[.: T r a n s f u s i o n s of Suspensions of Blood P ] a t e l e t s in Thromb o c y t o p e n i a and T h r o m b o p a t h i a , J. Clin. P a t h . 6: 41, 1953. 6. de Nieola, Pierre, Bostl, Pietr0, and Zangaglia, Onorio: Complement Fixation Test Due to the I n t e r a c t i o n of Specific A~tiplatelet Serum and tIeterologous Platelet Antigen, J. Lab. & Clan. Med. 45: 725, 1955.