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Platelet products, where to?
Transfusion Science 22 (2000) 93±97
www.elsevier.com/locate/transci
Platelet products, where to? J.K.M. Duguid a,*, A.C. Newland b a
Department of Haematology, Wrexham Maelor Hospital, Croesnewydd Rd, Wrexham LL13 7TD, UK b Department of Haematology, St Bartholomew's and the Royal London Hospitals, UK Received 13 December 1999; accepted 15 December 1999
1. Introduction There has been a considerable increase in the use of platelet transfusions since the introduction of routine preparation of platelet concentrates within transfusion centres. To take one example, the North London Transfusion Centre has seen an increase in production from 30,000 units in 1975 to 155,000 in 1994, serving a population of 3.5 million [1]. An increase in the use of intensive therapeutic regimes associated with prolonged bone marrow aplasia has been the main reason for this increased usage. Platelet transfusions are now used routinely for patients with a low platelet count or disordered platelet function, who are actively bleeding (therapeutic use) or who are at serious risk of bleeding (prophylactic use). There is little clinical tried-based evidence to justify the increased use of platelet transfusions but clinical experience indicates that platelet transfusions can be eective, however their use is associated with risks and costs [1]. 2. Indications for platelet transfusions Transfusions of platelets can be eective in the prevention and treatment of bleeding in patients who are thrombocytopenic or have dysfunctional platelets. The likelihood of bleeding, relative to a *
Corresponding author.
given platelet count, is to some extent predictable (Table 1) and guidelines exist which include recommendations for optimal platelet transfusion support [2]. Platelet transfusions should be given prophylactically when the platelet count is below 5±10 109 /1 and to support invasive procedures, such as surgery, lumbar puncture or delivery, when the count is less than 50 109 /1. Platelet transfusions should be given therapeutically when serious bleeding occurs in any thrombocytopenic patient, to patients with dysfunctional platelets (acquired or congenital) and to patients in whom active consumption of platelets is known to be occurring.
3. Platelet dose and frequency The dose of platelets transfused should aim to raise the platelet count above 50 109 /1 or alternatively, to reduce or stop bleeding irrespective of platelet count. The recommended standard adult dose varies depending on the reporting group (NIH, BTS, AABB) but such recommendations are only advisory due to the lack of standardisation in platelet production. Usually a dose of 2:5±3:0 1011 platelets is given either as 4±6 single units or a single apheresis pack. Alternatively, a single unit/kilogram body weight can be given. The frequency of platelet transfusions depends on clinical response. Factors such as fever, septicaemia, coagulation abnormalities, concomitant
0955-3886/00/$ - see front matter Ó 2000 Published by Elsevier Science Ltd. All rights reserved. PII: S 0 9 5 5 - 3 8 8 6 ( 0 0 ) 0 0 0 2 7 - 8
94
J.K.M. Duguid, A.C. Newland / Transfusion Science 22 (2000) 93±97
Table 1 The relationship of platelet counts to bleeding in thrombocytopenic patients Platelet count
Likely bleeding problem
> 50 109 =l 10±50 109 =l
Bleeding unlikely Bleeding with trauma, invasive procedures, ulcers Spontaneous bleeding Spontaneous severe bleeding
5±10 109 =l < 5 109 =l
antibiotic therapy or high blast count can all impair a patient's response to platelet transfusion. The development of antibodies to HLA antigens or platelet speci®c antigens also impairs response to transfused platelets. Timing of platelet transfusions, therefore, has to be arranged almost on a personal basis for each patient and may need to be varied according to changing clinical circumstances (Fig. 1). ABO compatible platelets should be used whenever possible. Transfusion of ABO incompatible platelets is associated with a reduction in transfusion increments and often an increased frequency of transfusion is required [3]. The use of group O platelets for group A and B patients should be avoided as problems with passive transfer of donor anti-A and anti-B can arise. Platelet concentrates usually contain some red cell contamination and sensitisation to RhD antigen may occur in RhD negative patients. This is rarely a clinical problem in immunosuppressed patients but may cause problems in the future for pre menopausal women. Current recommendations are that anti-D immunoglobulin, 250iu, should be given to premenopausal RhD negative women if RhD positive platelets are transfused [4]. Platelet recovery also varies according to the length of time platelets have been stored and this can eect clinical response and therefore frequency of transfusion (Fig. 2).
4. Platelet refractoriness Platelet refractoriness due to allo-antibody production or other non-immune causes can be a major clinical problem and occurs in up to 50% of patients receiving prophylactic platelet transfusion [1]. Fever, infection, bleeding, DIC and spleno-
megaly are all associated with poor platelet recovery and apparent refractoriness. Patient may develop HLA antibodies as a consequence of platelet transfusions or may be already sensitised as a result of previous blood transfusion or pregnancy, this group of patients can be a particular problem to manage. Not all patients with HLA antibodies are refractory to platelet transfusions; problems are more likely to occur in patients with multispeci®c HLA antibodies. Currently, such patients are transfused with HLA matched platelets and satisfactory increments can be obtained but, there is no evidence that this approach is effective in reducing severe bleeding [1]. Patients who develop platelet speci®c antibodies are relatively uncommon but present a greater problem if platelet transfusions are required. Platelet cross matching prior to transfusion is not a routine practice but may be helpful in identifying appropriate platelets for some refractory patients [1,2]. 5. Irradiated platelets Irradiated platelets are used to prevent transfusion acquired graft versus host disease (TA GvHD). This results from the passive transfer of immunologically active donor lymphocytes in platelet concentrates and occurs predominantly in immunocompromised patients. TAGvHD is dicult to diagnose and manage and has a high mortality rate. For this reason certain groups of patients should always receive irradiated blood products including platelets [5]. Consideration is currently being given to increasing these recommendations to include all B cell malignancies as there are an increasing number of reports of TAGvHD in association with these conditions [6]. 6. Leucodepleted platelets The presence of leucocytes in blood components is responsible for many of the complications associated with blood transfusion. Leucodepletion of blood components is therefore being used increasingly in many countries in order to reduce morbidity associated with transfusion, though there is little
J.K.M. Duguid, A.C. Newland / Transfusion Science 22 (2000) 93±97
95
Fig. 1. Response to platelet transfusion in dierent clinical circumstances.
clinical trial base evidence for this. Guidelines for the clinical use of the leucodepleted blood components exist [7]. Within the United Kingdom all blood products will be leucodepleted from November 1999 to minimise the theoretical risk of transmission of the new variant Creutzfeld Jakob Disease. 7. Transfusion transmitted infection The risk of acquiring transfusion transmitted viral infections from platelet transfusions is the
same as for other blood components. Donor selection and routine screening of donations has helped to reduce the risk of acquiring certain viral infections. More sophisticated testing techniques including virus RNA detection are being developed but their routine use for platelets with a limited shelf life could be problematic. The most common infectious risk associated with platelet transfusions is that of bacterial transmission. The symptoms of bacterial infection following platelet transfusion are often masked by the patient's underlying condition and treatment, for this reason it
96
J.K.M. Duguid, A.C. Newland / Transfusion Science 22 (2000) 93±97
Fig. 2. Platelet recovery related to pre-transfusion storage time.
is likely that bacterial infection due to platelet contamination is under reported [6]. Currently routine screening of platelets for bacterial contamination is not undertaken. Experimental procedures for reducing the risk of bacterial transmission by platelets, such as the use of psoralens plus UV light, are under investigation.
8. Conclusion Platelet transfusions are used routinely to prevent or arrest bleeding in patients with thrombocytopenia or dysfunctional platelets. Guidelines exist recommending when and why platelet transfusions should be used [2]. Ideally the platelet
J.K.M. Duguid, A.C. Newland / Transfusion Science 22 (2000) 93±97
count in a thrombocytopenic patient should be raised above 50 109 /l particularly if any interventional procedure is planned. A therapeutic adult dose 2:5±3:0 1011 platelets, either as an apheresis donation or as single donor units, that is ABO compatible is usually given. The dose and frequency of platelet transfusions does however vary according to the patient's clinical state and should be modi®ed to produce the required clinical response. Certain patient groups may become refractory to platelet transfusions and a cause for this should be sought in case the patient has developed allo immune antibodies and requires HLA selected platelets. Patients with a variety of clinical conditions require irradiated platelets to prevent TAGvHD [4], the use of leucodepleted platelets to prevent other complications of platelet transfusion is becoming more widespread [7]. Transmission of bacteria from the transfusion of platelets is an increasingly recognised problem, currently neither routing screening tests, nor preventative measures to minimise this problem are in place. Developmental work is being undertaken on arti®cial platelet substitutes
97
which may help in overcoming some of the problems outlined, however in view of the paucity of clinical trials on the use of platelets it will be dicult to demonstrate any bene®ts from the use of arti®cial platelet substitutes. References [1] Consensus Conference on Platelet Transfusion. Royal College of Physicians Edinburgh. November 1997. [2] BCSH. Guidelines for platelet transfusions. Transfusion Medicine 1992;2:311±8. [3] Carr R, Hutton JL, Jenkins JA, Lucas GF, Amphlett NW. Transfusion of ABO-mismatched platelets leads to early platelet refractoriness. Br J Haematol 1990;75:408±13. [4] BCSH. Guidelines: Recommendations for the use of anti-D immunoglobulin for Rh prophylaxis. Transfusion Medicine 1999;9:93±7. [5] BCSH. Guidelines on gamma irradiation of blood components for the prevention of transfusion-associated graftversus-host disease. Transfusion Medicine 1996;6:261±71. [6] Serious Hazards of Transfusion. Annual Report 1997±98. Serious Hazards of Transfusion Steering Group Manchester M13 9LL. [7] BCSH. Guidelines on the clinical use of leucocyte-depleted blood components. Transfusion Medicine 1998;8:59±71.
www.elsevier.com/locate/transci
Platelet products, where to? J.K.M. Duguid a,*, A.C. Newland b a
Department of Haematology, Wrexham Maelor Hospital, Croesnewydd Rd, Wrexham LL13 7TD, UK b Department of Haematology, St Bartholomew's and the Royal London Hospitals, UK Received 13 December 1999; accepted 15 December 1999
1. Introduction There has been a considerable increase in the use of platelet transfusions since the introduction of routine preparation of platelet concentrates within transfusion centres. To take one example, the North London Transfusion Centre has seen an increase in production from 30,000 units in 1975 to 155,000 in 1994, serving a population of 3.5 million [1]. An increase in the use of intensive therapeutic regimes associated with prolonged bone marrow aplasia has been the main reason for this increased usage. Platelet transfusions are now used routinely for patients with a low platelet count or disordered platelet function, who are actively bleeding (therapeutic use) or who are at serious risk of bleeding (prophylactic use). There is little clinical tried-based evidence to justify the increased use of platelet transfusions but clinical experience indicates that platelet transfusions can be eective, however their use is associated with risks and costs [1]. 2. Indications for platelet transfusions Transfusions of platelets can be eective in the prevention and treatment of bleeding in patients who are thrombocytopenic or have dysfunctional platelets. The likelihood of bleeding, relative to a *
Corresponding author.
given platelet count, is to some extent predictable (Table 1) and guidelines exist which include recommendations for optimal platelet transfusion support [2]. Platelet transfusions should be given prophylactically when the platelet count is below 5±10 109 /1 and to support invasive procedures, such as surgery, lumbar puncture or delivery, when the count is less than 50 109 /1. Platelet transfusions should be given therapeutically when serious bleeding occurs in any thrombocytopenic patient, to patients with dysfunctional platelets (acquired or congenital) and to patients in whom active consumption of platelets is known to be occurring.
3. Platelet dose and frequency The dose of platelets transfused should aim to raise the platelet count above 50 109 /1 or alternatively, to reduce or stop bleeding irrespective of platelet count. The recommended standard adult dose varies depending on the reporting group (NIH, BTS, AABB) but such recommendations are only advisory due to the lack of standardisation in platelet production. Usually a dose of 2:5±3:0 1011 platelets is given either as 4±6 single units or a single apheresis pack. Alternatively, a single unit/kilogram body weight can be given. The frequency of platelet transfusions depends on clinical response. Factors such as fever, septicaemia, coagulation abnormalities, concomitant
0955-3886/00/$ - see front matter Ó 2000 Published by Elsevier Science Ltd. All rights reserved. PII: S 0 9 5 5 - 3 8 8 6 ( 0 0 ) 0 0 0 2 7 - 8
94
J.K.M. Duguid, A.C. Newland / Transfusion Science 22 (2000) 93±97
Table 1 The relationship of platelet counts to bleeding in thrombocytopenic patients Platelet count
Likely bleeding problem
> 50 109 =l 10±50 109 =l
Bleeding unlikely Bleeding with trauma, invasive procedures, ulcers Spontaneous bleeding Spontaneous severe bleeding
5±10 109 =l < 5 109 =l
antibiotic therapy or high blast count can all impair a patient's response to platelet transfusion. The development of antibodies to HLA antigens or platelet speci®c antigens also impairs response to transfused platelets. Timing of platelet transfusions, therefore, has to be arranged almost on a personal basis for each patient and may need to be varied according to changing clinical circumstances (Fig. 1). ABO compatible platelets should be used whenever possible. Transfusion of ABO incompatible platelets is associated with a reduction in transfusion increments and often an increased frequency of transfusion is required [3]. The use of group O platelets for group A and B patients should be avoided as problems with passive transfer of donor anti-A and anti-B can arise. Platelet concentrates usually contain some red cell contamination and sensitisation to RhD antigen may occur in RhD negative patients. This is rarely a clinical problem in immunosuppressed patients but may cause problems in the future for pre menopausal women. Current recommendations are that anti-D immunoglobulin, 250iu, should be given to premenopausal RhD negative women if RhD positive platelets are transfused [4]. Platelet recovery also varies according to the length of time platelets have been stored and this can eect clinical response and therefore frequency of transfusion (Fig. 2).
4. Platelet refractoriness Platelet refractoriness due to allo-antibody production or other non-immune causes can be a major clinical problem and occurs in up to 50% of patients receiving prophylactic platelet transfusion [1]. Fever, infection, bleeding, DIC and spleno-
megaly are all associated with poor platelet recovery and apparent refractoriness. Patient may develop HLA antibodies as a consequence of platelet transfusions or may be already sensitised as a result of previous blood transfusion or pregnancy, this group of patients can be a particular problem to manage. Not all patients with HLA antibodies are refractory to platelet transfusions; problems are more likely to occur in patients with multispeci®c HLA antibodies. Currently, such patients are transfused with HLA matched platelets and satisfactory increments can be obtained but, there is no evidence that this approach is effective in reducing severe bleeding [1]. Patients who develop platelet speci®c antibodies are relatively uncommon but present a greater problem if platelet transfusions are required. Platelet cross matching prior to transfusion is not a routine practice but may be helpful in identifying appropriate platelets for some refractory patients [1,2]. 5. Irradiated platelets Irradiated platelets are used to prevent transfusion acquired graft versus host disease (TA GvHD). This results from the passive transfer of immunologically active donor lymphocytes in platelet concentrates and occurs predominantly in immunocompromised patients. TAGvHD is dicult to diagnose and manage and has a high mortality rate. For this reason certain groups of patients should always receive irradiated blood products including platelets [5]. Consideration is currently being given to increasing these recommendations to include all B cell malignancies as there are an increasing number of reports of TAGvHD in association with these conditions [6]. 6. Leucodepleted platelets The presence of leucocytes in blood components is responsible for many of the complications associated with blood transfusion. Leucodepletion of blood components is therefore being used increasingly in many countries in order to reduce morbidity associated with transfusion, though there is little
J.K.M. Duguid, A.C. Newland / Transfusion Science 22 (2000) 93±97
95
Fig. 1. Response to platelet transfusion in dierent clinical circumstances.
clinical trial base evidence for this. Guidelines for the clinical use of the leucodepleted blood components exist [7]. Within the United Kingdom all blood products will be leucodepleted from November 1999 to minimise the theoretical risk of transmission of the new variant Creutzfeld Jakob Disease. 7. Transfusion transmitted infection The risk of acquiring transfusion transmitted viral infections from platelet transfusions is the
same as for other blood components. Donor selection and routine screening of donations has helped to reduce the risk of acquiring certain viral infections. More sophisticated testing techniques including virus RNA detection are being developed but their routine use for platelets with a limited shelf life could be problematic. The most common infectious risk associated with platelet transfusions is that of bacterial transmission. The symptoms of bacterial infection following platelet transfusion are often masked by the patient's underlying condition and treatment, for this reason it
96
J.K.M. Duguid, A.C. Newland / Transfusion Science 22 (2000) 93±97
Fig. 2. Platelet recovery related to pre-transfusion storage time.
is likely that bacterial infection due to platelet contamination is under reported [6]. Currently routine screening of platelets for bacterial contamination is not undertaken. Experimental procedures for reducing the risk of bacterial transmission by platelets, such as the use of psoralens plus UV light, are under investigation.
8. Conclusion Platelet transfusions are used routinely to prevent or arrest bleeding in patients with thrombocytopenia or dysfunctional platelets. Guidelines exist recommending when and why platelet transfusions should be used [2]. Ideally the platelet
J.K.M. Duguid, A.C. Newland / Transfusion Science 22 (2000) 93±97
count in a thrombocytopenic patient should be raised above 50 109 /l particularly if any interventional procedure is planned. A therapeutic adult dose 2:5±3:0 1011 platelets, either as an apheresis donation or as single donor units, that is ABO compatible is usually given. The dose and frequency of platelet transfusions does however vary according to the patient's clinical state and should be modi®ed to produce the required clinical response. Certain patient groups may become refractory to platelet transfusions and a cause for this should be sought in case the patient has developed allo immune antibodies and requires HLA selected platelets. Patients with a variety of clinical conditions require irradiated platelets to prevent TAGvHD [4], the use of leucodepleted platelets to prevent other complications of platelet transfusion is becoming more widespread [7]. Transmission of bacteria from the transfusion of platelets is an increasingly recognised problem, currently neither routing screening tests, nor preventative measures to minimise this problem are in place. Developmental work is being undertaken on arti®cial platelet substitutes
97
which may help in overcoming some of the problems outlined, however in view of the paucity of clinical trials on the use of platelets it will be dicult to demonstrate any bene®ts from the use of arti®cial platelet substitutes. References [1] Consensus Conference on Platelet Transfusion. Royal College of Physicians Edinburgh. November 1997. [2] BCSH. Guidelines for platelet transfusions. Transfusion Medicine 1992;2:311±8. [3] Carr R, Hutton JL, Jenkins JA, Lucas GF, Amphlett NW. Transfusion of ABO-mismatched platelets leads to early platelet refractoriness. Br J Haematol 1990;75:408±13. [4] BCSH. Guidelines: Recommendations for the use of anti-D immunoglobulin for Rh prophylaxis. Transfusion Medicine 1999;9:93±7. [5] BCSH. Guidelines on gamma irradiation of blood components for the prevention of transfusion-associated graftversus-host disease. Transfusion Medicine 1996;6:261±71. [6] Serious Hazards of Transfusion. Annual Report 1997±98. Serious Hazards of Transfusion Steering Group Manchester M13 9LL. [7] BCSH. Guidelines on the clinical use of leucocyte-depleted blood components. Transfusion Medicine 1998;8:59±71.