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National Clinical Guideline Centre (UK). Blood Transfusion. London: National Institute for Health and Care Excellence (NICE); 2015 Nov. (NICE Guideline, No. 24.)
Platelets are blood cells involved in haemostasis. Platelet concentrates are prepared by blood services from whole blood donations or by apheresis of single donors and are the second most commonly used blood component after red cell transfusion (271,000 adult doses were provided in England in 2013/14).218 Platelet transfusions are used to treat and prevent bleeding in patients with thrombocytopenia or platelet dysfunction. While the majority of platelet transfusions are administered to patients with primary haematological disorders, they are commonly used in other clinical scenarios, such as critical care and major haemorrhage.
There are still several areas of controversy concerning the use of platelet transfusions, including whether a policy of prophylactic platelet transfusion is superior to a policy of no prophylaxis for the prevention of severe thrombocytopenic bleeding, what platelet count threshold should be used to trigger the transfusion of prophylactic platelets, and what is the optimal platelet dose to prevent thrombocytopenic bleeding.
National audits of the use of platelet transfusions have shown considerable non-compliance with BCSH recommendations for platelet count thresholds and platelet dose.290
13.1. Review question: What is the clinical- and cost-effectiveness of different doses of platelet transfusion?
For full details see review protocol in Appendix C.
Table 104PICO characteristics of review question
| Population |
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|---|---|
| Intervention(s) |
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| Comparison(s) |
|
| Outcomes |
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| Study design |
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The GDG was interested to know the most clinical and cost-effective dose for platelet transfusions.
Strata
It was acknowledged that that there are differences between haematology and non-haematology patients, adults and children, and patients who are actively bleeding and not actively bleeding.
The review was thus stratified into broad population groups as follows:
Prophylactic transfusions
- Adults who are haematology patients and not bleeding
- Adults who are non-haematology patients and not bleeding
- Children who are haematology patients and not bleeding
- Children who are non-haematology patients and not bleeding
Therapeutic transfusions
- Adults who are haematology patients and bleeding
- Adults who are non-haematology patients and bleeding
- Children who are haematology patients and bleeding
- Children who are non-haematology patients and bleeding
Outcome- Bleeding
The outcome of bleeding to be assessed in this review was defined as that equivalent to WHO grade 2 and above this grade. WHO defines bleeding as grade 2 if there is mild blood loss.
A modified WHO scale defines grade 2 bleeding as epistaxis or oral bleeding for 30 minutes or more (total duration in the prior 24 hours), haematoma, melena, haemoptysis, purpura of 1-inch diameter or more, retinal haemorrhage without visual impairment or blood in cerebrospinal fluid after non-traumatic lumbar puncture.
For full details and definitions of haematology and non-haematology patients, see review protocol in Appendix C.
13.2. Clinical evidence
We searched for randomised trials comparing the effectiveness of low dose platelet transfusions, medium dose platelet transfusions and high dose platelet transfusions.
No systematic reviews or studies were identified which evaluated dosage in therapeutic platelet transfusions.
One Cochrane review was identified which evaluated the effectiveness of different doses of prophylactic platelet transfusions.98 However, the outcomes and subgroups in this review differed from those outlined in this review's protocol and the analysis has been carried out again taking this into account.
Five studies were included in the review (Heddle 2009,128 Klumpp 1999,170 Sensebe 2005,273 Slichter 2010,282 Tinmouth 2004;303 these are summarised in Table 105 below. Of these, one study was not designed to assess the effect of platelet dose on incidence of haemorrhage or overall survival.170 This study was not analysed as part of this review.
Table 105
Summary of studies included in the review.
All studies were in patients receiving prophylactic platelet transfusions (studies excluded patients who had bleeding greater than WHO grade 2).
There was considerable variation in the reporting of units of platelet dose across the studies. Although doses were classified as low, medium or high in the studies, due to the variation in the dose units reported, there were differences in what the patients actually received in terms of number of platelets.
To standardise the doses and analyse them to their nearest groups, the doses were classified based on the standard dosage of platelets used in clinical practice in the UK. The standard UK dosage of platelets per bag is 2.4×1011 platelets per unit or bag.220 The average body surface area for a man is 1.9 m2 and 1.6 m2 for a woman. The standard dose of platelets in UK clinical practice equates to a platelet dose between the low and medium dose as reported in the Slichter et al. 2010 study (between 1.1×1011 to 2.2×1011 per square metre of body surface area per transfusion).282 Doses reported in other studies were also equated to this standard dose and the classification is presented below (see Table 106).
Table 106
Platelet dose classification.
Evidence from the above studies is summarised in the GRADE clinical evidence summary tables below (Table 107-Table 109). See also the study selection flow chart in Appendix E, study evidence tables in Appendix H, forest plots in Appendix K, GRADE tables in Appendix J and excluded studies list in Appendix P.
13.2.1. Clinical evidence summary (summary GRADE profiles)
Table 107
Clinical evidence summary- Low dose versus medium dose.
Table 108
Clinical evidence summary- High dose versus medium dose.
Table 109
Clinical evidence summary-Low dose versus high dose.
13.2.2. Clinical evidence (data not reported in analysable format)
Table 110
Number of platelet transfused.
13.3. Economic evidence
Published literature
No relevant economic evaluations were identified.
One economic evaluation relating to this review question was identified but was excluded due to a combination of limited applicability and methodological limitations.259 This is summarised in Appendix Q, with reasons for exclusion given.
See also the economic article selection flow chart in Appendix F.
Unit costs
Relevant unit costs are provided in Appendix N to aid consideration of cost-effectiveness.
13.4. Evidence statements
Clinical
Low platelet dose versus medium platelet dose
Three RCTs compared low dose platelet transfusions with medium dose platelet transfusions. The evidence showed that there was no important difference between low platelet dose and medium platelet dose with respect to number of patients with bleeding (WHO Grade 2 and above). The evidence suggested that mortality and serious adverse events were higher in patients receiving low dose platelet transfusion and that there was no difference between the low dose and medium dose with respect to infections but there was considerable uncertainty. The evidence ranged from moderate to very low quality.
No evidence was identified for the critical outcome quality of life and important outcomes such as number of patients needing platelet transfusions, number of platelet units transfused and length of stay in hospital.
High platelet dose versus medium platelet dose
Two RCTs compared high dose with medium dose for platelet transfusion. The evidence showed that there was no important difference between the groups for the outcome number of patients with bleeding (WHO Grade 2 and above). The evidence suggested that mortality, infections, and serious adverse events were higher in patients receiving high dose platelet transfusion, but there was considerable uncertainty. The quality of the evidence ranged from moderate to very low quality.
No evidence was identified for the critical outcome quality of life, and important outcomes such as number of patients needing platelet transfusions, number of platelet units transfused and length of stay in hospital.
Low platelet dose versus high platelet dose
One RCT compared low dose with high dose for platelet transfusion. The evidence suggested that mortality was higher and infections were fewer in patients receiving low dose platelet transfusion, however there was considerable uncertainty. The evidence suggested that there was no important difference between the groups for the outcomes number of patients with bleeding and serious adverse events, but there was considerable uncertainty. The evidence ranged from low to very low quality.
No evidence was identified for the critical outcome quality of life, and important outcomes such as number of patients needing platelet transfusions, number of platelet units transfused and length of stay in hospital.
Economic
No relevant economic evaluations were identified.
13.5. Recommendations and link to evidence
| Recommendations |
|
|---|---|
| Relative values of different outcomes | The GDG considered all-cause mortality at 30 days, bleeding (the number of patients with bleeding that was WHO grade 2 and above or equivalent), infections (for example, pneumonia), quality of life and serious adverse events as the critical outcomes for decision making. Other important outcomes included the number of patients needing platelet transfusions, the number of platelet units transfused and length of stay in hospital. |
| Trade off between clinical benefits and harms | The GDG noted that one unit of platelets in England and North Wales is equivalent to a dose midway between the low and medium doses described in the clinical evidence reviewed. Evidence from three RCTs comparing low dose with medium dose for platelet transfusion suggested benefit for patients receiving low dose platelet transfusion with respect to mortality and serious adverse events; but there was considerable uncertainty. The evidence showed that there was no important difference in effects between low platelet dose and medium platelet dose for the outcomes number of patients with bleeding and infections, but there was some uncertainty. No evidence was identified for the critical outcome quality of life and important outcomes such as number of patients needing platelet transfusions, number of platelet units transfused and length of stay in hospital. Evidence from two RCTs comparing high dose with medium dose for platelet transfusion suggested benefit for medium dose with respect to mortality, infections, and serious adverse events, but there was considerable uncertainty in the effect estimates. The evidence showed that there was no important difference in effects between the groups for the outcome number of patients with bleeding. No evidence was identified for the critical outcome quality of life, and important outcomes such as number of patients needing platelet transfusions, number of platelet units transfused and length of stay in hospital. Evidence from one RCT comparing low dose with high dose for platelet transfusion suggested benefit for high dose with respect to mortality, however there was some uncertainty. The evidence suggested that there were fewer infections in patients receiving low dose platelet transfusion, but there was some uncertainty. The evidence suggested that there was no important difference in effects between the groups for the outcomes number of patients with bleeding and serious adverse events, but there was some uncertainty. The evidence was generally of very low quality. No evidence was identified for the critical outcome quality of life, and important outcomes such as number of patients needing platelet transfusions, number of platelet units transfused and length of stay in hospital. Based on the lack of evidence of benefit for medium and high dose over single dose platelets, the potential for harm from increased donor exposure and the additional costs, the GDG recommended a single dose of platelets per transfusion. It was agreed that limiting the dosage of platelets to a single dose in a transfusion would help save resources and minimise exposure to donor blood. The GDG agreed that in general the same recommendations should apply for children as for adults in the absence of evidence that children should be treated differently from adults. |
| Economic considerations | No relevant economic evaluations comparing different doses of platelets for transfusion were identified. The cost of platelets transfusion was considered by the GDG. Allogeneic platelets cost £208.09 per unit in England and North Wales.219 It was noted that this cost does not include all costs associated with a transfusion such as staff time, disposables, storage, wastage and laboratory tests. One US study (Riley 2012)259 was identified which reported that the additional costs associated with platelet transfusion were £56 per transfusion. The GDG discussed this estimate and felt that it may underestimate the additional costs of platelet transfusion. As part of the health economic model developed in this guideline, the additional cost associated with transfusion was estimated to be £70 per first unit transfused. Of note this estimate does not include costs associated with hospital stay or with the management of transfusion-related complications. Furthermore, these costs do not include consideration of the additional laboratory and clinical workload of taking or testing additional samples. Higher doses (more units) will be associated with higher costs. Based on this and the clinical evidence considerations, the GDG recommended a single unit of platelets per transfusion. |
| Quality of evidence | The quality of evidence was moderate for the critical outcome of number of patients who had bleeding above WHO grade 2 or equivalent for low dose compared with medium dose and high dose compared with medium dose. The quality of evidence was low for the same outcome when low dose was compared with high dose. The quality of evidence was very low for other critical outcomes (all-cause mortality at 30 days, infections, serious adverse events) for all comparisons in the review. There was no specific evidence available for children. |
| Other considerations | An adult dose (or unit) of platelets is prepared either by pooling platelets from the buffy coats of 4 whole blood donations or by apheresis of a single donor; the platelet content is approximately 3 × 1011/unit and the volume is approximately 300ml for a unit of pooled buffy coat platelets and 200ml for a unit of apheresis platelets. The recommendation applies to adults and children requiring platelet transfusions. The GDG noted that the dose range for children is usually 10-20ml/kg up to the maximum adult dose. The GDG considered dosing of platelets in platelet function disorders, such as thrombocytopenia, and agreed that higher doses e.g. a dose of 2 adult units may be considered in the presence of bleeding or as prophylaxis in advance of major surgery. Haematology departments could consider giving larger doses of platelets to outpatients with chronic thrombocytopenia to extend the interval between transfusions and minimise the number of attendances for platelet transfusions. The GDG agreed that higher doses e.g. a dose of 2 adult units may be considered in the presence of severe thrombocytopenia and /or platelet dysfunction and bleeding in a critical site (see recommendation 28) or about to undergo major surgery. Some patients may have poor response to platelet transfusion and this should be investigated and managed appropriately. Although no evidence was identified in non-haematology patients, the GDG was confident in extrapolating the evidence to this population and the recommendation applies to both haematology and non-haematology patients. |
| Recommendations |
|
|---|---|
| Relative values of different outcomes | The GDG considered all-cause mortality at 30 days, bleeding (the number of patients with bleeding that was WHO grade 2 and above or equivalent), infections (for example, pneumonia), quality of life and serious adverse events as the critical outcomes for decision making. Other important outcomes included the number of patients needing platelet transfusions, the number of platelet units transfused and length of stay in hospital. |
| Trade off between clinical benefits and harms | The GDG noted that one unit of platelets in England and North Wales is equivalent to a dose midway between the low and medium doses described in the clinical evidence reviewed. No clinical evidence was identified for any specific group who require higher doses of platelet transfusion. The GDG considered specific requirements for patients who had severe thrombocytopenia and bleeding in a critical site and agreed that higher doses of platelet transfusions may be needed to provide timely and effective haemostasis. Based on the above rationale and economic considerations, the GDG recommended that higher doses of platelet transfusions, whilst not the standard treatment, may be considered in patients with severe thrombocytopenia and bleeding from a critical site. The GDG agreed that in general the same recommendations should apply for children as for adults in the absence of specific evidence that children should be treated differently from adults, while acknowledging that the precise volume of platelets transfused to children will partly take into account optimal utilisation of the platelet unit in order to minimise wastage and donor exposure (see Other considerations). |
| Economic considerations | No relevant economic evaluations comparing different doses of platelets for transfusion were identified. The cost of platelet transfusion was considered by the GDG. Allogeneic platelets cost £208.09 per unit in England and North Wales.219 It was noted that this cost does not include all costs associated with a transfusion such as staff time, disposables, storage, wastage and laboratory tests. One US study (Riley 2012)259 was identified which reported that the additional costs associated with platelet transfusion were £56 per transfusion. The GDG discussed this estimate and felt that it may underestimate the additional costs associated with platelet transfusion. As part of the health economic model developed in this guideline, the additional cost associated with transfusion was estimated to be £70 per first unit transfused. Of note this estimate does not include costs associated with hospital stay or with the management of transfusion-related complications. Furthermore, these costs do not include consideration of the additional laboratory and clinical workload of taking or testing additional samples. In patients with severe thrombocytopenia and bleeding in a critical site the GDG made a consensus recommendation to consider transfusing more than one unit per transfusion. The GDG considered that the cost of transfusing additional units in these patients was outweighed by the savings as a result of preventing further bleeding and complications. |
| Quality of evidence | No studies were identified which met the review protocol criteria. The recommendation for consideration of higher doses of platelet transfusion for severely thrombocytopenic patients and patients who were bleeding from critical sites was based on the consensus expert opinion of the GDG members. Although there was no specific evidence available for the paediatric population, the GDG agreed that the same recommendations should apply for children as for adults. |
| Other considerations | The protocol for the clinical evidence review set to evaluate the evidence for both haematology and non-haematology populations. Although no evidence was identified in non-haematology patients, the GDG was confident in extrapolating the evidence to this population and the recommendation is applicable to both haematology and non-haematology patients. The GDG noted that the dose range for children is usually 10-20ml/kg up to the maximum adult dose, taking into account aspects including maximal utilisation of the platelet unit and the volume clinically appropriate to transfuse to the patient. The GDG considered dosing of platelets in platelet function disorders and agreed that higher doses may be required in these cases. Tests for platelet dysfunction and coagulopathies may be carried out as adjuncts to measuring platelet count and are helpful in diagnosis and management. The GDG also considered that some patients may have poor response to platelet transfusion and this should be investigated and managed appropriately. The GDG discussed specific considerations with respect to investigations and platelet dosing in patients receiving antiplatelet drugs and patients who have coexisting coagulopathies. |
| Recommendations |
|
|---|---|
| Relative values of different outcomes | The GDG considered all-cause mortality at 30 days, bleeding (the number of patients with bleeding that was WHO grade 2 and above or equivalent), infections (for example, pneumonia), quality of life and serious adverse events as the critical outcomes for decision making. Other important outcomes included the number of patients needing platelet transfusions, the number of platelet units transfused and length of stay in hospital. |
| Trade off between clinical benefits and harms | No clinical evidence was identified for monitoring of platelet counts after each transfusion. The recommendation was based on the consensus expert opinion of the GDG members. It was agreed that there would be minimal discomfort or harms for patients to be reassessed and it was beneficial to check platelet counts after each transfusion to determine the effectiveness of transfusions and potentially avoid further unnecessary transfusions. Based on the above rationale and economic considerations, the GDG recommended checking platelet counts after each transfusion. There was no specific evidence available for the paediatric population. The GDG agreed that the same recommendations should apply for children as for adults in order to assess the effectiveness of platelet transfusion. |
| Economic considerations | The GDG highlighted that the cost of clinically reassessing and checking platelet count was negligible and would be offset by savings as a result of transfusing fewer units of platelets. |
| Quality of evidence | No studies were identified which met the review protocol criteria. The recommendation for the assessment of platelet counts after each platelet transfusion was based on the consensus expert opinion of the GDG members. |
| Other considerations | The GDG discussed the importance of monitoring and recommended assessment of platelet count after each platelet transfusion to evaluate response to platelet therapy and guide a further course of treatment. Traditionally this assessment is carried out at 1 hour and 24 hours post-transfusion but the initial assessment of the effectiveness of the transfusion can be achieved by sampling 10 minutes after the transfusion. Although no evidence was identified in non-haematology patients, the GDG was confident in extrapolating the evidence to this population and the recommendation is applicable to both haematology and non-haematology patients. Tests for platelet dysfunction and coagulopathies may be carried out as adjuncts to measuring platelet count and are helpful in diagnosis and management. The GDG highlighted the importance of availability of point of care testing to provide evidence for the urgent need for platelet transfusion in clinical settings such as critical care and major surgery. The GDG also considered that some patients may have poor response to platelet transfusion and this should be investigated and managed appropriately. The GDG noted that it was important to check platelet counts after administration of each platelet dose and the recommendation applies to all patients receiving platelet transfusions. |
- Platelet: doses - Blood TransfusionPlatelet: doses - Blood Transfusion
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