American Journal of Hematology 5:373-378 (1978)
Matching of Blood Platelets for Transfusion Richard H. Aster The Milwaukee Blood Center, lnc., and the Department of Medicine, The Medical College 0f Wisconsin, Milwaukee Key words: platelets, transfusion, HLA
INTRODUCTION
As almost every practicing physician knows, red cells matched between donor and recipient only for antigens of the ABO system and the D )&I( determinant of the Rh system can usually be transfused indefinitely to a single patient without concern for other red cell alloantigens. Unfortunately, this is not the case with blood platelets: Most patients transfused repeatedly with platelets from random donors become partially or totally refractory to further transfusions as a consequence of alloimmunization. Because of the increasing need for sustained platelet support for patients with aplastic anemia and malignant disorders, clincians now encounter this problem with increasing frequency and have sought ways to circumvent it. It is the intent of this review to summarize current methods of dealing with refractoriness to platelet transfusions in alloimmunzed patients. Because of the large number of recent publications dealing with this subject, the bibliography is, of necessity, selective. NATURE OF THE PLATELET IMMUNOGENS
Studies by Yankee and co-workers [ l ] and by Thorsby et a1 [2] and subsequent reports from other laboratories have clearly shown that serologically defined antigens of the HLA system are the most immunogenic of the various antigens expressed on the platelet surface. Other antigens, possibly platelet-specific,appear to be less important but may also provoke refractoriness in some patients [3-51 . ABO antigens, although expressed on platelets, appear to be of major consequence only under special circumstances [ 6 ] .Other red cell antigens seem not to be present on the platelet surface. Received for publication October 10, 1978; accepted October 23, 1978. Address reprint requests t o Dr. Richard H. Aster, President, Milwaukee Blood Center, Inc., 1701 West Wisconsin Avenue, PO Box 10G, Milwaukee, WI 53233.
0361-8609/78/0504-0373$01.40
0 1978 Alan R. Liss, Inc.
374
Concise Reviews: Aster
PREVENT ION 0 F A L LO IMMUNI ZAT 10N
Theoretically, alloimmunization to platelets could be avoided by supplying perfectly matched platelets from the start to each patient expected to require long-term platelet support. This is not practical, because an almost unlimited number of fully typed donors would be required. Indeed, it has been estimated that more than 100,000 HLA-typed donors from the general population would be needed to supply ten donors matched only for the four antigens of the HLA-A and B loci for the average patient [7]. Moreover, it is not always apparent which patients will require long-term transfusion support. Brand and co-workers [3] have suggested that HLA antigens on granulocytes are more immunogenic than those on platelets and that alloimmunization can be minimized or delayed by rendering platelets relatively free of granulocytes prior to transfusion. This approach is practical and seems worthy of further study. Herzig et a1 have suggested that, even in patients already alloimmunized, removal of granulocytes enhances the effectiveness of transfused platelets through an undefined mechanism [S] . Theoretically, alloimmunization to platelet surface markers could be prevented by injection of alloantibodies or of antigens in a form capable of inducing a measure of immunologic tolerance. These approaches deserve experimental study [9-111.
MATCHING OF PLATELETS FOR TRANSFUSION
Modern technology has made it possible to obtain large numbers of platelets from a single donor for patients who are refractory to random donor platelets. Initially, platelets from HLA-matched or partially matched family members were used for this purpose [ l ] . In some cases, however, family members are not available. In others, the need to donate repeatedly may place an intolerable burden on a relative. Fortunately, platelets from HLAmatched unrelated donors are frequently effective when transfused to alloimmunized thrombocytopenic patients [ 12-15] ; unfortunately, the HLA system is highly polymorphic, more than sixty antigens having been identified that are inherited at three serologically determined loci designated A, B, and C. Antigens of the A and B loci have been well characterized and can be identified in most individuals. Understanding of the C locus is still incomplete, and it is not possible at present to perform complete HLA-C typing on all subjects. Antigens of a fourth locus, D, and a possible fifth locus, DRW, appear not to be expressed on the platelet surface. The statistical barrier to finding an unrelated donor perfectly matched with a given patient even for antigens of the A and B HLA loci has been mentioned above. We have been studying the immunological aspects of platelet transfusion therapy for about four years, during which time we have evaluated the effectiveness of single donor platelets in more than 2,000 donor-recipient combinations. These investigations are ongoing but have permitted some preliminary conclusions to be made about requirements for donor-recipient platelet matching. Specifically, we have found that: a) satisfactory response is usually achieved when donor and recipient are mismatched for HLA antigens that are similar to each other serologically (cross-reactive) [14, 151(Fig. 1); b) mismatching for antigens of the HLA-C locus is usually of no consequence, presumably because these antigens are weakly expressed on the platelet surface or are of low immunogenicity [16] ; c) precise donor-recipient matching is less critical for patients who are negative for the antigen HLA-A2 than for donors who are positive for that marker [ 171 ; and d) mismatching for certain HLA-B locus antigens that are very weakly expressed on
Concise Reviews: Matching of Blood Platelets
375
1 HR INC L
A
la
BlU
B2U
B1X B2UX B2X
CD
R
B1X B2UX C D B2X
R
24 HR INC L
II-
s
lb
A
B1U
B2U
Fig. 1. Platelet increments in 57 alloimmunized thrombocytopenic patients one hour (Fig. la) and 24 (Fig. l b ) hours after transfusion of platelets from donors of varying degreees of HLA compatibility. Platelets of match grade A were identical for HLA-A and HLA-B antigens with those of the recipients. Platelets of match grades BU lacked one of the antigens present in the recipient, and those of match grade BX differed from the recipient by one or two cross-reactive HLA-A or B antigens. Platelets of match grades C and D differed from the recipient by one or two non-cross-reactive antigens, respectively (“major” mismatch). “R” denotes the response obtained with pooled random platelets (average ?: 1 SD) transfused at least once to each patient. Other horizontal bars denote median response [from reference 141.
376
Concise Reviews: Aster
the platelet surface is acceptable in some donor-recipient pairs [18]. These findings, together with those of others [19] appear to have simplified the process of locating “compatible” platelet donors for individual alloimmunized patients, and it seems reasonable to hope that hemostatically effective platelets can be supplied to most patients by selecting from an HLA-typed panel of only one or two thousand donors. This is a substantial reduction from the 50,000-100,000 donors that would be required for exact matching of the HLA-A and B markers. It should be recognized that even platelets perfectly matched for the serologically defined HLA markers will not be effective in all patients, probably because some become sensitized to platelet-specific alloantigens [3-51. The latter antigens are difficult to type for and are incompletely understood; therefore, further studies are needed to characterize their importance in platelet transfusion therapy. COMPATlBl LlTY TESTING FOR PLATE LET TRANSFUSION
Compatibility testing by the indirect Coombs test is routine for red blood cell transfusions and permits accurate prediction of transfusion response almost without exception. Unfortunately, a test of equal simplicity and reliability is not yet available for platelets. Lyrnphocytotoxicity testing is predictive only in about 75% of cases utilizing unrelated donors [3,20, 211. Other techniques such as serotonin release and platelet aggregation have yielded variable results in different laboratories [20-251 . One of the most promising methods appears to be an indirect immunofluoresecence test that, in conjunction wtih lymphocytotoxicity testing, appears to correlate with the response to transfusion in greater than 90% of instances [3] . Although the desirability of a “perfect” in vitro test for platelet compatibility cannot be denied, such testing presents special problems of a logistical nature for a transfusion service. In the case of red cells, a unit found to be incompatible with a patient can be returned to the refrigerator and reserved for someone else. With platelets, the transfusion service may be faced with the question of whether to discard a platelet preparation laboriously obtained from an apparently matched donor because of a “positive” compatibility test. Fortunately, “mismatched” platelets rarely cause serious reactions when transfused to alloimmunized patients, even though they may be rapidly destroyed and provide little in the way of hemostasis. This is, of course, in marked contrast to the consequences of transfusing mismatched erythrocytes. GENERAL CONSIDERATIONS
Further developments in platelet typing, in long-term preservation, and in platelet compatibility testing may permit hemostatically effective platelets to be transfused almost routinely to patients for whom they are indicated. It should be apparent to the reader, however, that matched, single donor platelets stand in marked contrast to erthrocytes in respect to the requirements governing their clinical use. Procurement of matched platelets, even on a modest scale, requires an impressive array oflresources: a) a competent tissuetyping laboratory; b) data-processing capability for information storage and retrieval; c) a large panel of HLA-typed donors willing to contribute platelets on demand (a 2-3 hour process requiring bilateral venipuntures); d) a cytopheresis unit capable of isolating the necessary numbers of platelets from single donors, sometimes at night or on weekends; e) the capability to do pre- and posttransfusion platelet counts to document transfusion effectiveness; and f) close cooperation between the cytopheresis unit, the tissue-typing laboratory, the hospital, and the practicing physician. From this, it should be clear that
Concise Reviews: Matching of Blood Platelets
377
matched platelets cannot in the foreseeable future be made “routinely” available on demand. Rather they must be supplied to patients who meet well-defined criteria after consultation between the agency supplying the platelets, the hospital in which they are transfused, and the physician who requests them. The complexities inherent in the operation of a matched platelet transfusion service are such as to provide a persuasive argument in favor of designating one agency or consortium of agencies to handle this responsibility for an entire metropolitan area, even for very large population centers. ACKNOWLEDGMENTS
This work was supported by grant HL-13629 and Contract 73-2956 from the National Heart, Lung and Blood Institute. REFERENCES 1. Yankee RA, Grumet FC, Rogentine GN: Platelet transfusion therapy. The selection of compatible platelet donors for refractory patients by lymphocyte HLA-typing. N Engl J Med 281: 12081212,1969. 2. Thorsby E, Gelgeson A, Gjemdal T: Repreated platelet transfusions from HLA compatible unrelated and sibling donors. Tissue Antigens 2: 397-404, 1972. 3. Brand A, Van Leeuwen A, Eerniss JG, VanRood JJ: Platelet transfusion therapy. Optimal donor selection with a combination of lymphocytotoxicity and platelet fluorescence tests. Blood 51:781-788,1978. 4. Wu KK, Thompson JS, Koepke JA, Hoak JC, Flink R: Heterogeneity of antibody response t o human platelet transfusion. J Clin Invest 58:432-438, 1976. 5. Bucher U, Deweck A, Spengler H, Pschopp L, Kummer H: Platelet transfusions: Shortened survival of HLA-identical platelets and failure of in vitro detection of anti-platelet antibodies after multiple transfusions. Vox Sang 25: 187-192, 1973. 6. Duquesnoy RJ, Tomasulo PA, Aster RH: Unpublished observations. 7. Opelz 0, Mickey MR, Terasaki PI: Unrelated donors for bone-marrow transplantation and transfusion support: Pool sizes required. Transplant Proc 4:405-409, 1974. 8. Herzig RH, Herzig GP, Bull MI, Dexter JA, Lohrman HP, Stout FG, Yankee RA, Graw RG: Correction of poor platelet transfusion responses with leukocyte-poor HLA matched platelet concentrates. Blood 46:743-750, 1975. 9. Fabre JW, Batchelor GJ: Prevention of blood transfusion-induced immunization against transplantation antigens by treatment of the blood with antibody. Transplantation 20:473-479, 1975. 10. Welch KI, Burgos H, Batchelor JR: The immune response t o allogeneic rat platelets. Ag-B antigens in matrix form lacking Ia. Eur J Immunol7:267-272, 1977. 11. Osborne RM, Grumet FC: Prevention of allosensitization t o transfused platelets. Proceedings of the Fifteenth Congress of the International Society of Blood Transfusion, 1978. 12. Yankee RH, Graff KS, Dowling R, Henderson ES: Selection of unrelated compatible platelet donors by lymphocyte HL-A matching. N Engl J Med 288:760-764,1973. 13. Lohrmann HP, Bull MI, Decter JA, Yankee RA, Graw RG: Platelet transfusions from HL-A compatible unrelated donors to alloimmunized patients. Ann Intern Med 80:9-14, 1974. 14. Duquesnoy RJ, Filip DJ, Rodey GE, Aster RH: Successful transfusion of platelets “mismatched” for HLA antigens to alloimmunized thrombocytopenic patients. Am J Hematol2: 219-226, 1977. 15. Duquesnoy RJ, Testin J, Aster RH: Variable expression of W4 and W6 on platelets. Possible relevance to platelet transfusion therapy of alloimmunized thrombocytopenic patients. Transplant Proc 9:1829-1831, 1977. 16. Duquesnoy RJ, Filip DJ, Tomasulo PA, Aster RH: Role of HLA-C matching in histocompatible platelet transfusion therapy of alloimmunized thrombocytopenic patients. Transplant Proc 9: 1827- 1828,1977. 17. Duquesnoy RJ, Filip DJ, Aster RH: Influence of HLA-A2 on the effectiveness of platelet transfusions in alloimmunized thrombocytopenic patients. Blood 50:407-412, 1977.
378
Concise Reviews: Aster
18. Szatkowski N, Duquesnoy RJ, Aster RH: Further studies of the expression of BW4, BW6, and other antigens on the HLA-B locus on human platelets. Transplant Proc (in press). 19. Mittal KK, Ruder A, Green D: Matching of histocompatibility (HL-A) antigens for platelet transfusion. Blood 47 31-41, 1976. 20. Filip DJ, Duquesnoy RJ, Aster RH: Predictive value of cross-matching for transfusion of platelet concentrates to alloimmunized recipients. Am J Hematol 1:471-479, 1976. 21. Gmur J, VonFelten A, Frick P: Platelet support in polysensitized patients: Role of HLA specificities and crossmatch testing for donor selection. Blood 51:903-909, 1978. 22. Cockerman JP, Bowman RP, Conrad ME: Detection of platelet iso-antibodies by the 3Hserotonin platelet release and its clinical application to the problem of platelet matching. J Clin Invest 55:75-83, 1975. 23. Pogliani E, Deliliers GL, Ferrari R, Pozzoli E, Confrancesco E, Praga C: Platelet aggregometry and anti-platelet isoantibodies. Hemostasis 4: 24-25, 1975. 24. Wu KK, HGdk JC, Koepke JA, Thompson JS: Selection of compatible platelet donors. A prospective evaluation of three cross-matching techniques. Transfusion 17:638-643, 1977. 25. Wu KK, Hoak JC, Thompson JS, Koepke JA: Use of platelet aggregometry in selection of compatible platelet donors. N Engl J Med 292:130-133, 1975.
Matching of Blood Platelets for Transfusion Richard H. Aster The Milwaukee Blood Center, lnc., and the Department of Medicine, The Medical College 0f Wisconsin, Milwaukee Key words: platelets, transfusion, HLA
INTRODUCTION
As almost every practicing physician knows, red cells matched between donor and recipient only for antigens of the ABO system and the D )&I( determinant of the Rh system can usually be transfused indefinitely to a single patient without concern for other red cell alloantigens. Unfortunately, this is not the case with blood platelets: Most patients transfused repeatedly with platelets from random donors become partially or totally refractory to further transfusions as a consequence of alloimmunization. Because of the increasing need for sustained platelet support for patients with aplastic anemia and malignant disorders, clincians now encounter this problem with increasing frequency and have sought ways to circumvent it. It is the intent of this review to summarize current methods of dealing with refractoriness to platelet transfusions in alloimmunzed patients. Because of the large number of recent publications dealing with this subject, the bibliography is, of necessity, selective. NATURE OF THE PLATELET IMMUNOGENS
Studies by Yankee and co-workers [ l ] and by Thorsby et a1 [2] and subsequent reports from other laboratories have clearly shown that serologically defined antigens of the HLA system are the most immunogenic of the various antigens expressed on the platelet surface. Other antigens, possibly platelet-specific,appear to be less important but may also provoke refractoriness in some patients [3-51 . ABO antigens, although expressed on platelets, appear to be of major consequence only under special circumstances [ 6 ] .Other red cell antigens seem not to be present on the platelet surface. Received for publication October 10, 1978; accepted October 23, 1978. Address reprint requests t o Dr. Richard H. Aster, President, Milwaukee Blood Center, Inc., 1701 West Wisconsin Avenue, PO Box 10G, Milwaukee, WI 53233.
0361-8609/78/0504-0373$01.40
0 1978 Alan R. Liss, Inc.
374
Concise Reviews: Aster
PREVENT ION 0 F A L LO IMMUNI ZAT 10N
Theoretically, alloimmunization to platelets could be avoided by supplying perfectly matched platelets from the start to each patient expected to require long-term platelet support. This is not practical, because an almost unlimited number of fully typed donors would be required. Indeed, it has been estimated that more than 100,000 HLA-typed donors from the general population would be needed to supply ten donors matched only for the four antigens of the HLA-A and B loci for the average patient [7]. Moreover, it is not always apparent which patients will require long-term transfusion support. Brand and co-workers [3] have suggested that HLA antigens on granulocytes are more immunogenic than those on platelets and that alloimmunization can be minimized or delayed by rendering platelets relatively free of granulocytes prior to transfusion. This approach is practical and seems worthy of further study. Herzig et a1 have suggested that, even in patients already alloimmunized, removal of granulocytes enhances the effectiveness of transfused platelets through an undefined mechanism [S] . Theoretically, alloimmunization to platelet surface markers could be prevented by injection of alloantibodies or of antigens in a form capable of inducing a measure of immunologic tolerance. These approaches deserve experimental study [9-111.
MATCHING OF PLATELETS FOR TRANSFUSION
Modern technology has made it possible to obtain large numbers of platelets from a single donor for patients who are refractory to random donor platelets. Initially, platelets from HLA-matched or partially matched family members were used for this purpose [ l ] . In some cases, however, family members are not available. In others, the need to donate repeatedly may place an intolerable burden on a relative. Fortunately, platelets from HLAmatched unrelated donors are frequently effective when transfused to alloimmunized thrombocytopenic patients [ 12-15] ; unfortunately, the HLA system is highly polymorphic, more than sixty antigens having been identified that are inherited at three serologically determined loci designated A, B, and C. Antigens of the A and B loci have been well characterized and can be identified in most individuals. Understanding of the C locus is still incomplete, and it is not possible at present to perform complete HLA-C typing on all subjects. Antigens of a fourth locus, D, and a possible fifth locus, DRW, appear not to be expressed on the platelet surface. The statistical barrier to finding an unrelated donor perfectly matched with a given patient even for antigens of the A and B HLA loci has been mentioned above. We have been studying the immunological aspects of platelet transfusion therapy for about four years, during which time we have evaluated the effectiveness of single donor platelets in more than 2,000 donor-recipient combinations. These investigations are ongoing but have permitted some preliminary conclusions to be made about requirements for donor-recipient platelet matching. Specifically, we have found that: a) satisfactory response is usually achieved when donor and recipient are mismatched for HLA antigens that are similar to each other serologically (cross-reactive) [14, 151(Fig. 1); b) mismatching for antigens of the HLA-C locus is usually of no consequence, presumably because these antigens are weakly expressed on the platelet surface or are of low immunogenicity [16] ; c) precise donor-recipient matching is less critical for patients who are negative for the antigen HLA-A2 than for donors who are positive for that marker [ 171 ; and d) mismatching for certain HLA-B locus antigens that are very weakly expressed on
Concise Reviews: Matching of Blood Platelets
375
1 HR INC L
A
la
BlU
B2U
B1X B2UX B2X
CD
R
B1X B2UX C D B2X
R
24 HR INC L
II-
s
lb
A
B1U
B2U
Fig. 1. Platelet increments in 57 alloimmunized thrombocytopenic patients one hour (Fig. la) and 24 (Fig. l b ) hours after transfusion of platelets from donors of varying degreees of HLA compatibility. Platelets of match grade A were identical for HLA-A and HLA-B antigens with those of the recipients. Platelets of match grades BU lacked one of the antigens present in the recipient, and those of match grade BX differed from the recipient by one or two cross-reactive HLA-A or B antigens. Platelets of match grades C and D differed from the recipient by one or two non-cross-reactive antigens, respectively (“major” mismatch). “R” denotes the response obtained with pooled random platelets (average ?: 1 SD) transfused at least once to each patient. Other horizontal bars denote median response [from reference 141.
376
Concise Reviews: Aster
the platelet surface is acceptable in some donor-recipient pairs [18]. These findings, together with those of others [19] appear to have simplified the process of locating “compatible” platelet donors for individual alloimmunized patients, and it seems reasonable to hope that hemostatically effective platelets can be supplied to most patients by selecting from an HLA-typed panel of only one or two thousand donors. This is a substantial reduction from the 50,000-100,000 donors that would be required for exact matching of the HLA-A and B markers. It should be recognized that even platelets perfectly matched for the serologically defined HLA markers will not be effective in all patients, probably because some become sensitized to platelet-specific alloantigens [3-51. The latter antigens are difficult to type for and are incompletely understood; therefore, further studies are needed to characterize their importance in platelet transfusion therapy. COMPATlBl LlTY TESTING FOR PLATE LET TRANSFUSION
Compatibility testing by the indirect Coombs test is routine for red blood cell transfusions and permits accurate prediction of transfusion response almost without exception. Unfortunately, a test of equal simplicity and reliability is not yet available for platelets. Lyrnphocytotoxicity testing is predictive only in about 75% of cases utilizing unrelated donors [3,20, 211. Other techniques such as serotonin release and platelet aggregation have yielded variable results in different laboratories [20-251 . One of the most promising methods appears to be an indirect immunofluoresecence test that, in conjunction wtih lymphocytotoxicity testing, appears to correlate with the response to transfusion in greater than 90% of instances [3] . Although the desirability of a “perfect” in vitro test for platelet compatibility cannot be denied, such testing presents special problems of a logistical nature for a transfusion service. In the case of red cells, a unit found to be incompatible with a patient can be returned to the refrigerator and reserved for someone else. With platelets, the transfusion service may be faced with the question of whether to discard a platelet preparation laboriously obtained from an apparently matched donor because of a “positive” compatibility test. Fortunately, “mismatched” platelets rarely cause serious reactions when transfused to alloimmunized patients, even though they may be rapidly destroyed and provide little in the way of hemostasis. This is, of course, in marked contrast to the consequences of transfusing mismatched erythrocytes. GENERAL CONSIDERATIONS
Further developments in platelet typing, in long-term preservation, and in platelet compatibility testing may permit hemostatically effective platelets to be transfused almost routinely to patients for whom they are indicated. It should be apparent to the reader, however, that matched, single donor platelets stand in marked contrast to erthrocytes in respect to the requirements governing their clinical use. Procurement of matched platelets, even on a modest scale, requires an impressive array oflresources: a) a competent tissuetyping laboratory; b) data-processing capability for information storage and retrieval; c) a large panel of HLA-typed donors willing to contribute platelets on demand (a 2-3 hour process requiring bilateral venipuntures); d) a cytopheresis unit capable of isolating the necessary numbers of platelets from single donors, sometimes at night or on weekends; e) the capability to do pre- and posttransfusion platelet counts to document transfusion effectiveness; and f) close cooperation between the cytopheresis unit, the tissue-typing laboratory, the hospital, and the practicing physician. From this, it should be clear that
Concise Reviews: Matching of Blood Platelets
377
matched platelets cannot in the foreseeable future be made “routinely” available on demand. Rather they must be supplied to patients who meet well-defined criteria after consultation between the agency supplying the platelets, the hospital in which they are transfused, and the physician who requests them. The complexities inherent in the operation of a matched platelet transfusion service are such as to provide a persuasive argument in favor of designating one agency or consortium of agencies to handle this responsibility for an entire metropolitan area, even for very large population centers. ACKNOWLEDGMENTS
This work was supported by grant HL-13629 and Contract 73-2956 from the National Heart, Lung and Blood Institute. REFERENCES 1. Yankee RA, Grumet FC, Rogentine GN: Platelet transfusion therapy. The selection of compatible platelet donors for refractory patients by lymphocyte HLA-typing. N Engl J Med 281: 12081212,1969. 2. Thorsby E, Gelgeson A, Gjemdal T: Repreated platelet transfusions from HLA compatible unrelated and sibling donors. Tissue Antigens 2: 397-404, 1972. 3. Brand A, Van Leeuwen A, Eerniss JG, VanRood JJ: Platelet transfusion therapy. Optimal donor selection with a combination of lymphocytotoxicity and platelet fluorescence tests. Blood 51:781-788,1978. 4. Wu KK, Thompson JS, Koepke JA, Hoak JC, Flink R: Heterogeneity of antibody response t o human platelet transfusion. J Clin Invest 58:432-438, 1976. 5. Bucher U, Deweck A, Spengler H, Pschopp L, Kummer H: Platelet transfusions: Shortened survival of HLA-identical platelets and failure of in vitro detection of anti-platelet antibodies after multiple transfusions. Vox Sang 25: 187-192, 1973. 6. Duquesnoy RJ, Tomasulo PA, Aster RH: Unpublished observations. 7. Opelz 0, Mickey MR, Terasaki PI: Unrelated donors for bone-marrow transplantation and transfusion support: Pool sizes required. Transplant Proc 4:405-409, 1974. 8. Herzig RH, Herzig GP, Bull MI, Dexter JA, Lohrman HP, Stout FG, Yankee RA, Graw RG: Correction of poor platelet transfusion responses with leukocyte-poor HLA matched platelet concentrates. Blood 46:743-750, 1975. 9. Fabre JW, Batchelor GJ: Prevention of blood transfusion-induced immunization against transplantation antigens by treatment of the blood with antibody. Transplantation 20:473-479, 1975. 10. Welch KI, Burgos H, Batchelor JR: The immune response t o allogeneic rat platelets. Ag-B antigens in matrix form lacking Ia. Eur J Immunol7:267-272, 1977. 11. Osborne RM, Grumet FC: Prevention of allosensitization t o transfused platelets. Proceedings of the Fifteenth Congress of the International Society of Blood Transfusion, 1978. 12. Yankee RH, Graff KS, Dowling R, Henderson ES: Selection of unrelated compatible platelet donors by lymphocyte HL-A matching. N Engl J Med 288:760-764,1973. 13. Lohrmann HP, Bull MI, Decter JA, Yankee RA, Graw RG: Platelet transfusions from HL-A compatible unrelated donors to alloimmunized patients. Ann Intern Med 80:9-14, 1974. 14. Duquesnoy RJ, Filip DJ, Rodey GE, Aster RH: Successful transfusion of platelets “mismatched” for HLA antigens to alloimmunized thrombocytopenic patients. Am J Hematol2: 219-226, 1977. 15. Duquesnoy RJ, Testin J, Aster RH: Variable expression of W4 and W6 on platelets. Possible relevance to platelet transfusion therapy of alloimmunized thrombocytopenic patients. Transplant Proc 9:1829-1831, 1977. 16. Duquesnoy RJ, Filip DJ, Tomasulo PA, Aster RH: Role of HLA-C matching in histocompatible platelet transfusion therapy of alloimmunized thrombocytopenic patients. Transplant Proc 9: 1827- 1828,1977. 17. Duquesnoy RJ, Filip DJ, Aster RH: Influence of HLA-A2 on the effectiveness of platelet transfusions in alloimmunized thrombocytopenic patients. Blood 50:407-412, 1977.
378
Concise Reviews: Aster
18. Szatkowski N, Duquesnoy RJ, Aster RH: Further studies of the expression of BW4, BW6, and other antigens on the HLA-B locus on human platelets. Transplant Proc (in press). 19. Mittal KK, Ruder A, Green D: Matching of histocompatibility (HL-A) antigens for platelet transfusion. Blood 47 31-41, 1976. 20. Filip DJ, Duquesnoy RJ, Aster RH: Predictive value of cross-matching for transfusion of platelet concentrates to alloimmunized recipients. Am J Hematol 1:471-479, 1976. 21. Gmur J, VonFelten A, Frick P: Platelet support in polysensitized patients: Role of HLA specificities and crossmatch testing for donor selection. Blood 51:903-909, 1978. 22. Cockerman JP, Bowman RP, Conrad ME: Detection of platelet iso-antibodies by the 3Hserotonin platelet release and its clinical application to the problem of platelet matching. J Clin Invest 55:75-83, 1975. 23. Pogliani E, Deliliers GL, Ferrari R, Pozzoli E, Confrancesco E, Praga C: Platelet aggregometry and anti-platelet isoantibodies. Hemostasis 4: 24-25, 1975. 24. Wu KK, HGdk JC, Koepke JA, Thompson JS: Selection of compatible platelet donors. A prospective evaluation of three cross-matching techniques. Transfusion 17:638-643, 1977. 25. Wu KK, Hoak JC, Thompson JS, Koepke JA: Use of platelet aggregometry in selection of compatible platelet donors. N Engl J Med 292:130-133, 1975.
