Unlike other blood components demand for platelet components appears to be increasing in several countries around the world (1). An ageing population, an increase in the incidence of haematological malignancies, and changes to the management of haematological malignancies are likely to be the major reasons for the rise in demand for platelet components. Since 1990, the number of haematopoietic stem cell transplants performed in Europe has risen from 4,200 to over 30,000 annually (2).

People with haematological and oncological disorders are the largest users of platelet components (up to 67%), and platelet transfusions are an important supportive therapy during treatment with chemotherapy or haematopoietic stem cell transplantation (HSCT) (3-7). 

Virtually all the evidence for the use of platelet components is based on studies in this patient group. Much of the remainder are used in cardiac surgery (7-10%) and in intensive care (5-9%). 

 

Prophylactic versus therapeutic-only platelet transfusions

International guidelines recommend that platelets transfusions are given to people with reversible bone marrow failure to reduce the risk of spontaneous bleeding when the platelet count is <10x109/L. A recent Cochrane systematic review in people with haematological malignancies found that overall prophylactic platelet transfusions appeared to reduce the number of bleeding events and days with significant bleeding (8). However, the benefit from prophylactic platelet transfusions differed between treatment groups with patients undergoing autologous HSCT deriving no significant benefit (9). In patients with haematological malignancies bleeding frequently occurs despite prophylactic platelet transfusions, and other risk factors for bleeding such as fever and duration of thrombocytopenia should be considered (10, 11).

In people with chronic bone marrow failure there is little evidence to guide practice, international guidelines which consider these patients recommend either a therapeutic-only strategy (12, 13) or prophylaxis below a count of 5x109/L (14). Recent BCSH Guidelines for the diagnosis and management of adult myelodysplastic syndromes advise a no prophylaxis strategy and include in this group people taking low dose oral chemotherapy or azacitidine (15).

Other patient groups who are significant users of prophylactic platelet transfusions are those in critical care. The optimal platelet transfusion management of these patients , may differ depending upon the underlying clinical diagnosis (16). For example a recent RCT in patients with dengue haemorrhagic fever (87 participants) showed that prophylactic platelet transfusions were ineffective at preventing bleeding but were associated with harm as three anaphylactic reactions occurred in the group receiving prophylactic transfusions (17).

 

Different platelet transfusion doses for prophylactic platelet transfusions

A systematic review identified seven RCTs that compared different platelet transfusion doses in patients with haematological malignancies (18). Five studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no difference in the number of participants with a clinically significant bleeding episode between the low-dose and intermediate-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate quality evidence); or high-dose and intermediate-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate quality evidence). Low dose transfusions decreased the total amount of platelets patients received, but at the expense of a higher number of transfusions episodes. Increasing the dose from an intermediate to a high dose did not increase the transfusion interval in two out of three studies that reported this (median 5 days for both regimens). One study reported on transfusion reactions. This study’s authors suggested that a high-dose platelet transfusion strategy may lead to a higher rate of transfusion-related adverse events (19).

 

Different platelet transfusion thresholds for prophylactic platelet transfusions

A systematic review identified three RCTs that compared different platelet transfusion thresholds in patients with haematological malignancies (20). Two compared a threshold of 20 x 109/L vs. 10 x 109/L, whereas the third compared a threshold of 30 x 109/L vs. 10 x 109/L. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the 10 x 109/L threshold and higher threshold groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence). However, this meta-analysis may not be sufficiently powered to detect a 50% increase in bleeding risk. There has been a suggestion that platelet transfusion thresholds should be lowered below 10 x 109/L, but current platelet count measurement is not accurate enough to support this change (21). No randomised studies in adult patients have assessed the use of other transfusion thresholds, such as platelet mass, absolute immature platelet number or immature platelet fraction. Neonates admitted to the neonatal intensive care unit (NICU) frequently become thrombocytopenic and intracranial haemorrhage (ICH) is a major concern. Guidelines directing neonatal platelet transfusion practice vary considerably, and are generally consensus rather than evidence-based. There has only been one RCT in preterm neonates comparing different platelet count thresholds this found no difference in the incidence of ICH between a liberal platelet transfusion regimen (transfusion when platelet count <150x109/L) versus a more restrictive regimen (platelet count < 50x109/L or clinical concern about bleeding) (22). One small pilot RCT has compared a platelet mass versus platelet count regimen and found no difference in the number of bleeding events (23). There are two ongoing trials assessing different platelet transfusion thresholds (24-25).

 

Therapeutic platelet transfusions

There is little evidence for the effectiveness of platelet transfusions or the optimal dose when a person with thrombocytopenia is actively bleeding. Current recommendations are based on consensus guidelines from around the world and are dealt with in [ISBT section on major haemorrhage].

 

Key recommendations based on the evidence from RCTs

  • Give prophylactic platelet transfusions (platelet transfusions to patients who do not have clinically significant bleeding [WHO grade 0 or 1] and do not require a procedure) to patients with reversible bone marrow failure receiving intensive chemotherapy or undergoing allogeneic HSCT to maintain a platelet count at or above 10x 10x9/L
  • Do not give high dose platelet transfusions routinely for prophylactic platelet transfusions
 
References
  1. Estcourt L. Why has demand for platelet components increased? A review. Transfusion Medicine. 2014;24(5):260-8.
  2. Passweg JR, Baldomero H, Gratwohl A, Bregni M, Cesaro S, Dreger P, et al. The EBMT activity survey: 1990-2010. Bone Marrow Transplant. 2012;47(7):906-23.
  3. Cameron B, Rock G, Olberg B, Neurath D. Evaluation of platelet transfusion triggers in a tertiary-care hospital. Transfusion. 2007;47(2):206-11.
  4. Greeno E, McCullough J, Weisdorf D. Platelet utilization and the transfusion trigger: a prospective analysis. Transfusion. 2007;47(2):201-5.
  5. Jones A, Birchall J, Roberts P, Davies L, Webb M, Cooke SJ, et al. A survey of where and why platelets are used in hospitals in the South West region of England. Transfusion Medicine. 2013;23(Supplement 2):PO34.
  6. Pendry K, Davies T. An audit of the use and wastage in the North West of England and North Wales - where have all the platelets gone? Blood and Transfusion Matters. 2011;34:17-9.
  7. Charlton A, Wallis J, Robertson J, Watson D, Iqbal A, Tinegate H. Where did platelets go in 2012? A survey of platelet transfusion practice in the north of England. Transfusion Medicine. 2014;24:213-8.
  8. Crighton G, Estcourt L, Wood E, Stanworth S, Trivella M, Doree C, et al. A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation. Cochrane Database of Systematic Reviews. 2015;2015(9).
  9. Stanworth S, Estcourt LJ, Llewelyn C, Murphy MF, Wood EM, for the TOPPS study investigators. Impact of prophylactic platelet transfusions on bleeding events in patients with hematologic malignancies: a sub-group analysis of a randomized trial. Transfusion. 2014;54(10):2385–93.
  10. Stanworth SJ, Hudson CL, Estcourt LJ, Johnson RJ, Wood EM. Risk of bleeding and use of platelet transfusions in patients with hematological malignancies: recurrent event analysis. Haematologica. 2015.
  11. Webert K, Cook RJ, Sigouin CS, Rebulla P, Heddle NM. The risk of bleeding in thrombocytopenic patients with acute myeloid leukemia. Haematologica. 2006;91(11):1530-7.
  12. Kaufman RM, Djulbegovic B, Gernsheimer T, Kleinman S, Tinmouth AT, Capocelli KE, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Intern Med. 2015;162(3):205-13.
  13. Liumbruno G, Bennardello F, Lattanzio A, Piccoli P, Rossetti G. Recommendations for the transfusion of plasma and platelets. Blood Transfus. 2009;7(2):132-50.
  14. Executive Committee of the German Medical Association on the recommendation of the Scientific Advisory Board. Cross-sectional guidelines for therapy with blood components and plasma derivatives. 2014.
  15. Killick S, Carter C, Culligan D, Dalley C, Das-Gupta E, Drummond M, et al. Guidelines for the diagnosis and management of adult myelodysplastic syndromes. British Journal of Haematology. 2014;164(4):503-25.
  16. Lieberman L, Sholapur NS, Bercovitz RS, Heddle N, Stanworth S, Arnold DM. Platelet transfusions in critically ill patients with thrombocytopenia: An evidence-based review. Blood. 2013.
  17. Assir MZK, Kamran U, Ahmad HI, Bashir S, Mansoor H, Anees SB, et al. Effectiveness of platelet transfusion in dengue fever: A randomized controlled trial. Transfusion Medicine and Hemotherapy. 2013;40(5):362-8.
  18. Estcourt L, Stanworth S, Doree C, Trivella M, Hopewell S, Blanco P, et al. Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation (Review). Cochrane Database of Systematic Reviews. 2015;2015(10):CD010984.
  19. Kaufman RM, Assmann SF, Triulzi DJ, Strauss RG, Ness P, Granger S, et al. Transfusion-related adverse events in the Platelet Dose study. Transfusion. 2015;55(1):144-53.
  20. Estcourt LJ, Stanworth SJ, Doree C, Hopewell S, Trivella M, Murphy M. Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation. Cochrane Database of Systematic Reviews. 2015;2015(11):CD010983.
  21. Lozano M, Mahon A, van der Meer PF, Stanworth S, Cid J, Devine D, et al. Counting platelets at transfusion threshold levels: impact on the decision to transfuse. A BEST Collaborative - UK NEQAS(H) International Exercise. Vox Sanguinis. 2014;106(4):330-6.
  22. Andrew M, Vegh P, Caco C, Kirpalani H, Jefferies A, Ohlsson A, et al. A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants. J Pediatr. 1993;123(2):285-91.
  23. Zisk JL, Mackley A, Clearly G, Chang E, Christensen RD, Paul DA. Transfusing neonates based on platelet count vs. platelet mass: A randomized feasibility-pilot study. Platelets. 2014;25(7):513-6.
  24. Kumar A. Platelet transfusion based on platelet mass or count Scientific title: A randomized controlled trial of Platelet Transfusion Based on Platelet Mass versus Platelet count in severely thrombocytopenic neonates: Clinical Trials Registry. CTRI/2013/02/003405]. Available from: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=5392 
  25. Willoughby K. A randomised controlled trial to compare two different platelet count thresholds for prophylactic platelet transfusion to preterm neonates ISRCTN87736839.
  26. Kumar A, Mhaskar R, Grossman BJ, Kaufman RM, Tobian AA, Kleinman S, et al. Platelet transfusion: a systematic review of the clinical evidence. Transfusion. 2015;55(5):1116-27.
  27. Estcourt LJ, Desborough M, Hopewell S, Doree C, Stanworth S. Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia. Cochrane database of systematic reviews (Online). 2015;2015(12):CD011771.
  28. Estcourt LJ, Ingram C, Hopewell S, Trivella M, Doree C. Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia (Protocol). Cochrane database of systematic reviews (Online). 2015;2015(12):CD011980.
  29. NCT02311985. Comparison of three transfusion strategies for central venous catheterization in cirrhotics (POCKET).
  30. NICE. Blood transfusion NG24. In: National Institute for Health and Clinical Excellence, editor. 2015.

Relevant Guidelines

  1. National Institute for Health and Care ExcellenceNICE2015
  2. AABB platelet transfusion guidelinesAABB2015
  3. The National Blood Authority’s Patient Blood Management GuidelinesNational Blood Authority Australia2010-2012
  4. The Board of the German Medical Association GuidelinesExecutive Committee of the German Medical Association on the recommendation of the Scientific Advisory Board2014

Available training and e-learning resources

  1. Learn blood transfusion NHS2016
  2. AABB AABB2016
  3. Transfusion handbook Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee2014

Additional Reading

  1. Transfusion Evidence Library

 

The author

Lise Estcourt

Lise Estcourt

Associate Medical Director Research, Development and Quality Improvement for Transfusion, NHS Blood and Transplant, Oxford, UK