Prophylactic platelet transfusions prior to surgery for people with a low platelet count

Lise J Estcourt; Reem Malouf; Carolyn Doree; Marialena Trivella; Sally Hopewell; Janet Birchall

doi:10.1002/14651858.CD012779.pub2

Prophylactic platelet transfusions prior to surgery for people with a low platelet count

Collapse all Expand all

References

References to studies included in this review

Jump to:

excluded studies
ongoing studies
additional references
other published versions

Basu P, Nair T, Farhat S, Shah NJ, Krishnaswamy N. Single use of romiplostim thrombopoietin analogue in thrombocytopenia for liver biopsy in chronic liver disease‐randomized clinical trial. Asian Pacific Digestive Week 2012;27:207‐8. [DOI: dx.doi.org/10.1111/jgh.12006]

Google Scholar

Basu PP, Nair T, Farhat S, James Shah N, Jafri M, Foustin S. Single use of romiplostim thrombopoietin analogue in severe thrombocytopenia for outpatient percutaneous liver biopsy in patients with chronic liver disease‐a randomized double blinded prospective trial. Journal of Hepatology 2012;56:S38. [DOI: dx.doi.org/10.1016/S0168‐8278%2812%2960101‐9]

Basu PP, Nair T, Jafri M, Krishnaswamy NV, Farhat S, Shah NJ, Brown R. Single use of romiplostim thrombopoietin analogue (TPO) in severe thrombocytopenia for outpatient percutaneous liver biopsy in patients with chronic liver disease (CLD) ‐ a randomized double blinded prospective clinical pilot trial. 18th Annual International Congress of the International Liver Transplantation Society, ILTS; 2012 May 15‐19; San Francisco (CA). 2012; Vol. 18:S271. [DOI: dx.doi.org/10.1002/lt.23435]

Google Scholar

Basu PP, Nair T, Krishnaswamy N, James Shah N, Farhat S, Brown R. Single use of romiplostim thrombopoietin analogue (TPO) in severe thrombocytopenia for outpatient percutaneous liver biopsy in patients with chronic liver disease (CLD) ‐ a randomized double blinded prospective clinical pilot trial. 76th Annual Scientific Meeting of the American College of Gastroenterology; 2011 Oct 28‐Nov 2; Washington (DC). 2011, issue 106:S135‐6. [DOI: dx.doi.org/10.1038/ajg.2011.336_5]

Google Scholar

Basu PP, Nair TJ, Krishnaswamy N, Shah NJ, Farhat S. Single use of romiplostim thrombopoietin analogue (TPO) in severe thrombocytopenia for outpatient percutaneous liver biopsy in patients with chronic liver disease (CLD) ‐ a randomized double blinded prospective clinical pilot trial. 62nd Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting; 2011 Nov 4‐8; San Francisco (CA). 2011, issue 54:898A. [DOI: dx.doi.org/10.1002/hep.24666]

Google Scholar

Basu PP, Nair TJ, Krishnaswamy NV, James Shah N, Brown RS. Single use of romiplostim thrombopoietin analogue (TPO) in severe thrombocytopenia for outpatient percutaneous liver biopsy in patients with chronic liver disease (CLD) ‐ a randomized double‐blinded prospective clinical pilot trial. 43rd Nordic Gastroenterology Congress; 2012 Jun 12‐15; Reykjavik Iceland. 2012, issue 47:45‐46. [DOI: dx.doi.org/10.3109/00365521.2012.697267]

Google Scholar

Basu PP, Nair TJ, Krishnaswamy NV, Shah NJ, Brown Jr RS. Single use of romiplostim thrombopoietin analogue (TPO) in severe thrombocytopenia for outpatient percutaneous liver biopsy in patients with chronic liver disease (CLD) ‐ a randomized double blinded prospective clinical pilot trial. 2012 Scientific Session of the Society of American Gastrointestinal and Endoscopic Surgeons; 2012 Mar 7‐10; San Diego (CA). 2012, issue 26:S333. [DOI: dx.doi.org/10.1007/s00464‐012‐2203‐x]

Google Scholar

NCT00816127. Prevention of bleeding in patient with cirrhosis undergoing dental extraction. clinicaltrials.gov/ct2/show/NCT00816127 Date first received: 29 December 2008.

Stanca CM, Montazem AH, Lawal A, Zhang JX, Schiano TD. Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial. Journal of Oral and Maxillofacial Surgery 2010;68(1):138‐43.

Stanca CM, Montazem AH, Zhang JH, Lawal A, Schiano TD. Intranasal desmopressin is effective in preventing bleeding after dental extraction in cirrhotic patients having moderate degrees of coagulopathy. Transfusion 2006;46(4, Suppl 1):568A.

Google Scholar

Veelo DP, Vlaar AP, Dongelmans DA, Binnekade JM, Levi M, Paulus F, et al. Correction of subclinical coagulation disorders before percutaneous dilatational tracheotomy. Blood Transfusion 2012;10:213‐20.

References to studies excluded from this review

Jump to:

included studies
ongoing studies
additional references
other published versions

Abdelfatah M. Management of chronic subdural hematoma in patients with intractable thrombocytopenia. Turkish Neurosurgery Journal 2016;18825(16):1‐5.

Afdhal NH, Giannini EG, Tayyab G, Mohsin A, Lee JW, Andriulli A, et al. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. New England Journal of Medicine 2012;367:716‐24.

Al‐Zaabi M, Clark S, Gomez K, Sekhar M. Assessing risk of bleeding in thrombocytopenic patients requiring platelet transfusion prior to invasive procedures. Haematologica 2014;99(S1):199.

Google Scholar

Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. British Journal of Obstetrics and Gynaecology 1999;106(2):102‐7.

Barrera R, Mina B, Huang Y, Groeger JS. Acute complications of central line placement in profoundly thrombocytopenic cancer patients. Cancer 1996;78:2025‐30.

Cai Y, Liu X, Peng B. Should we routinely transfuse platelet for immune thrombocytopenia patients with platelet count less than 10 × 10⁹/L who underwent laparoscopic splenectomy?. World Journal of Surgery 2014;38:2267‐72.

Chantarangkul V, Primignani M, Lemma L, Clerici M, Jovani M, Rebulla P, et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. 58th Annual Meeting of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis; 2012 Jun 27‐30; Liverpool, UK. 2013, issue 11:73. [DOI: dx.doi.org/10.1111/jth.12443]

Google Scholar

Chen X, Peng B, Cai Y, Zhou J, Wang Y, Wu Z, et al. Laparoscopic splenectomy for patients with immune thrombocytopenia and very low platelet count: is platelet transfusion necessary?. Journal of Surgical Research 2011;170(2):e225‐32.

De Pietri L, Bianchini M, Montalti R, De Maria N, Di Maira T, Begliomini B, et al. Thrombelastography‐guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial. Hepatology 2016;63:566‐73.

Embrey KK, Davis CL, Rey MA, Lumb PD, Gold ME. Perioperative transfusion practices in women versus men. American Association of Nurse Anesthetists Journal 2006;74(5):393‐4.

Google Scholar

EudraCT 2007‐005851‐40. A randomised, double‐blind, placebo‐controlled, multi‐centre study to evaluate the safety and efficacy of eltrombopag to reduce the need for platelet transfusion in thrombocytopenic subjects with chronic liver disease undergoing elective invasive procedures. www.clinicaltrialsregister.eu/ctr‐search/trial/2007‐005851‐40/ES Date first registered: 3 December 2008.

Fayed NA, Abdallah AR, Khalil MK, Marwan IK. Therapeutic rather than prophylactic platelet transfusion policy for severe thrombocytopenia during liver transplantation. Platelets 2014;25(8):576‐86.

Harding SA, Shakoor MA, Grindon AJ. Platelet support for cardiopulmonary bypass surgery. Journal of Thoracic and Cardiovascular Surgery 1975;70(2):350‐3.

Hess R. Results of the pragmatic randomized optimal plasma and platelet ratios trial (PROPPR). British Blood Transfusion Society 2015;109:72.

Google Scholar

Hibbert RM, Atwell TD, Lekah A, Patel MD, Carter RE, McDonald JS, et al. Safety of ultrasound‐guided thoracentesis in patients with abnormal preprocedural coagulation parameters. Chest 2013;44(2):456‐63.

Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA 2015;3;313(5):471‐82.

Karkouti K, Callum J, Wijeysundera D, Rao V, Crowther M, Grocott H, et al. Point‐of‐care hemostatic testing in cardiac surgery a stepped‐wedge clustered randomized controlled trial. Circulation 2016;134:1152‐62.

Khair T, El‐Haddad D, Srujal P, Marmagiolis K, Cilingiroglu M, Iliescu G, et al. Triple jeopardy: Heart disease, cancer and thrombocytopenia‐fluoroscopic and echocardiographic guided pericardiocentesis in cancer patients with cardiac tamponade and thrombocytopenia. Catheterization and Cardiovascular Interventions 2015;85:S82‐3. [DOI: dx.doi.org/10.1002/ccd.25910]

Google Scholar

Kultufan, Turan S, Aydinli B, Ayik I, Yagar S, Kazanci D, et al. The role of rotational thromboelastgraphy on decision of blood transfusion in open heart surgery [Acik kalp cerrahisinde tromboelastografinin transfuzyon karari Uzerine etkisi]. Gogus‐Kalp‐Damar Anestezi ve Yogun Bakim Dernegi Dergisi 2006;12(4):154‐9.

Google Scholar

Napolitano G, Iacobellis A, Merla A, Niro G, Valvano MR, Terracciano F, et al. Bleeding after invasive procedures is rare and unpredicted by platelet counts in cirrhotic patients with thrombocytopenia. European Journal of Internal Medicine 2017;38:79‐82.

NCT00521664. A trial comparing a prophylactic with a therapeutic platelet transfusion strategy in two groups. clinicaltrials.gov/ct2/show/NCT00521664 Date first received: 27 August 2007.

NCT00549484. Thrombopoietin levels and platelet transfusion in neonates. clinicaltrials.gov/ct2/show/NCT00549484 Date first received: 24 October 2007.

NCT00678587. Eltrombopagto reduce the need for platelet transfusion in subjects with chronic liver disease and thrombocytopenia undergoing elective invasive procedures (ELEVATE). clinicaltrials.gov/ct2/show/NCT00678587 First submitted 13 May 2008.

NCT01291290. START ‐ early thrombocyte administration to patients with ruptured abdominal aortic aneurism (rAAA). clinicaltrials.gov/ct2/show/NCT01291290 Date first received: 7 February 2011.

NCT01402739. Monocentric pilot study of algorithm‐guided transfusions in cardiac surgery patients for reduction of drainage blood losses. clinicaltrials.gov/ct2/show/NCT01402739 Date first received: 25 July 2011.

NCT01919840. Blood products transfusion in cardiac surgery after the implementation of a coagulation monitoring system at patient bedside: thromboelastometry versus standard transfusion protocol (ROTEM‐2010). clinicaltrials.gov/ct2/show/NCT01919840 Date first received: 12 April 2013.

NCT02042898. Transfusion Requirements In Cardiac Surgery III (TRICS‐III). clinicaltrials.gov/ct2/show/NCT02042898 Date first received: 17 January 2014.

NCT02074436. Prevention of bleeding in hematological malignancies with antifibrinolytic (epsilon aminocaproic acid) (PROBLEMA). clinicaltrials.gov/ct2/show/NCT02074436 Date first received: 26 February 2014.

NCT02200419. POC ‐ Transfusion Algorithm Cardiac Study (TACS). clinicaltrials.gov/ct2/show/NCT02200419 Date first received: 20 June 2014.

NCT02352181. Management of coagulopathy during orthotopic liver transplantation. Comparison between ROTEM‐based management and standard biological assessment. clinicaltrials.gov/ct2/show/NCT02352181 Date first received: 18 December 2014.

NCT02987712. Management of coagulopathy in cirrhotic patients undergoing invasive procedures. clinicaltrials.gov/ct2/show/NCT02987712 Date first received: 6 December 2016.

NCT02990273. The utility of thromboelastography in cirrhotic patients undergoing endoscopic procedures. clinicaltrials.gov/ct2/show/NCT02990273 Date first received: 14 October 2016.

NCT03011827. Transfusion prediction model in orthotopic liver transplantation based on thromboelastometry: prospective validation study. clinicaltrials.gov/ct2/show/NCT03011827 Date first received: 4 January 2017.

NCT03022253. Platelet transfusion for treatment of patent ductus arteriosus in thrombocytopenic preterm neonates. clinicaltrials.gov/ct2/show/NCT03022253 Date first received: 25 June 2016.

Park JM, Oh HJ, Cho YK, Lee B‐I, Cho YS, Choi M‐G. Risk factor analysis of bleeding after endoscopic interventions in patients with chronic thrombocytopenia. Gastrointestinal Endoscopy 2016;83(1):AB205.

Pereboom IT, de Boer MT, Haagsma EB, Hendriks HG, Lisman T, Porte RJ. Platelet transfusion during liver transplantation is associated with increased postoperative mortality due to acute lung injury. Anesthesia and Analgesia 2009;108(4):1083‐91.

Perek B, Stefaniak S, Komosa A, Perek A, Katynska I, Jemielity M. Routine transfusion of platelet concentrates effectively reduces reoperation rate for bleeding and pericardial effusion after elective operations for ascending aortic aneurysm. Platelets 2016;27(8):764‐70.

Perl VJ, Leroux B, Cook MR, Watson J, Fair K, Martin D, et al. Damage‐control resuscitation and emergency laparotomy: findings from the PROPPR study. Journal of Trauma and Acute Care Surgery 2016;80(4):568‐75. [DOI: dx.doi.org/10.1097/TA.0000000000000960]

Pietri L, Bianchini M, Montalti R, Maria N, Maira T, Begliomini B, et al. Thrombelastography (TEG) decreases blood products requirement before invasive procedures in cirrhotic patients with coagulation tests derangement. A randomized controlled trial. Digestive and Liver Disease 2014;46(1):e5‐e6.

Ray CE, Shenoy SS. Patients with thrombocytopenia: outcome of radiologic placement of central venous access devices. Radiology 1997;204(1):97‐9.

Simon TL, Akl B, Murphy W. Controlled trial of platelet concentrates in patients undergoing cardiopulmonary bypass. Transfusion 1982;22(5, S3):423.

Google Scholar

Simon TL, Akl BF, Murphy W. Controlled trial of routine administration of platelet concentrates in cardiopulmonary bypass surgery. Annals of Thoracic Surgery 1984;37(5):359‐64.

Smart L, Wellner M, Gray NA, Michaels A, Kirkpatrick RB, Conteh L, et al. A prospective, randomized clinical trial comparing blood product use, bleeding events, and cost during and after endoscopic procedures in patients with cirrhosis and coagulopathy: rotational thromboelastrometry (ROTEM) versus conventional therapy. Hepatology 2017;66(1):243A‐4A.

Google Scholar

Tanaka KA, Egan K, Szlam F, Ogawa S, Roback JD, Sreeram G, et al. Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion. Transfusion 2014;54(1):109‐18.

Titano JJ, Biederman DM, Marinelli BS, Patel RS, Kim E, Tabori NE, et al. Safety and feasibility of transradial access for visceral interventions in patients with thrombocytopenia. Cardiovascular and Interventional Radiology 2016;39(5):676‐82.

Tripodi A, Primignani M, Chantarangkul V, Lemma L, Jovani M, Rebulla P, et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. Cirrhosis and Liver Failure 2013;33:362‐7.

References to ongoing studies

Jump to:

included studies
excluded studies
additional references
other published versions

NTR5653. Prophylactic platelet transfusion prior to central venous catheter placement in patients with thrombocytopenia [Onderzoek naar de noodzaak van correctie van bloedplaatjestekort voor het plaatsen van een centraal veneuze lijn]. www.trialregister.nl/trialreg/admin/rctview.asp?TC=5653 Date first received: 27 January 2016. [www.trialregister.nl/trialreg/admin/rctview.asp?TC=5653]

NCT02311985. Comparison of three transfusion strategies for central venous catheterization in cirrhotics (POCKET). clinicaltrials.gov/ct2/show/NCT02311985 Date first received: 9 December 2014.

Rocha LL, Pessoa CMS, Neto AS, do Prado RR, Silva E, de Almeida MD, et al. Thromboelastometry versus standard coagulation tests versus restrictive protocol to guide blood transfusion prior to central venous catheterization in cirrhosis: study protocol for a randomized controlled trial. Trials 2017;18:85. [DOI: 10.1186/s13063‐017‐1835‐5]

Additional references

Jump to:

included studies
excluded studies
ongoing studies
other published versions

Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, et al. Thrombocytopenia associated with chronic liver disease. Journal of Hepatology 2008;48(6):1000‐7.

British Committee for Standards in Haematology. Guidelines for the use of platelet transfusions. British Journal of Haematology 2003;122(1):10‐23.

Birchall J, Tinegate H, Regan F. Chapter 14 Acute transfusion reactions (ATR). In: Bolton‐Maggs PHB, Poles D, et al. on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group, editor(s). The 2014 Annual SHOT Report. Manchester, UK: SHOT, 2015:106–12.

Google Scholar

Blumberg N, Heal JM, Phillips GL. Platelet transfusions: trigger, dose, benefits and risks. F1000 Medicine Reports 2010;2:1‐5.

Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfusion Medicine Reviews 2012;26(1):1‐13.

Bolton‐Maggs PH, on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2015 Annual SHOT Report. SHOT2016.

Google Scholar

Burrows RF, Kelton JG. Thrombocytopenia at delivery: a prospective survey of 6715 deliveries. American Journal of Obstetrics and Gynecology 1990;162:731‐4.

Cameron B, Rock G, Olberg B, Neurath D. Evaluation of platelet transfusion triggers in a tertiary‐care hospital. Transfusion 2007;47(2):206‐11.

Carless PA, Stokes BJ, Moxey AJ, Henry DA. Desmopressin use for minimising perioperative allogeneic blood transfusion. Cochrane Database of Systematic Reviews 2004, Issue 1. [DOI: 10.1002/14651858.CD001884.pub2]

Chapman C. Transfusion‐related lung injury (TRALI), 2015. www.shotuk.org/wp‐content/uploads/SHOT‐2014‐Annual‐Report_v11‐Web‐Edition.pdf (accessed 26 November 2015).

Veritas Health Innovation. Covidence systematic review software. Melbourne: Veritas Health Innovation, 2016.

Deeks JJ, Higgins JPT, Altman DG. Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Desborough MJ, Smethurst PA, Estcourt LJ, Stanworth SJ. Alternatives to allogeneic platelet transfusion. British Journal of Haematology 2016;175:381‐92.

Desborough MJ, Oakland K, Brierley C, Bennett S, Doree C, Trivella M, et al. Desmopressin use for minimising perioperative blood transfusion. Cochrane Database of Systematic Reviews 2017, Issue 7. [DOI: 10.1002/14651858.CD001884.pub3]

Engele LJ, Straat M, van Rooijen IH, de Vooght KM, Cremer OL, Schultz M, et al. Transfusion of platelets, but not of red blood cells, is independently associated with nosocomial infections in the critically ill. Annals of Intensive Care 2016;6:67. [DOI: 10.1186/s13613‐016‐0173‐1.]

Effective Practice, Organisation of Care (EPOC). EPOC Resources for review authors. Oslo: Norwegian Knowledge Centre for the Health Services 2015. epoc.cochrane.org/epoc–specific–resources–review–authors (accessed prior to 23 August 2018).

Estcourt LJ, Birchall J, Lowe D, Grant‐Casey J, Rowley M, Murphy MF. Platelet transfusions in haematology patients: are we using them appropriately?. Vox Sanguinis 2012;103(4):284‐93.

Estcourt LJ, Desborough M, Hopewell S, Doree C, Stanworth SJ. Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia. Cochrane Database of Systematic Reviews 2015, Issue 12. [DOI: 10.1002/14651858.CD011771.pub2]

Estcourt LJ, Desborough M, Brunskill SJ, Doree C, Hopewell S, Murphy MF, et al. Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders. Cochrane Database of Systematic Reviews 2016, Issue 3. [DOI: 10.1002/14651858.CD009733.pub3]

Estcourt LJ, Ingram C, Doree C, Trivella M, Stanworth SJ. Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia. Cochrane Database of Systematic Reviews 2016, Issue 5. [DOI: 10.1002/14651858.CD011980.pub2]

Estcourt LJ, Birchall J, Allard S, Bassey SJ, Hersey P, Kerr JP, et al. and the British Committee for Standards in Haematology. Guidelines for the use of platelet transfusions. British Journal of Haematology 2017;176:365‐94. [DOI: 10.1111/bjh.14423]

Fabes J, Barker G, Simons G, Curry N, Brunskill SJ, Doree C, et al. Pro‐coagulant haemostatic factors for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database of Systematic Reviews 2013, Issue 7. [DOI: 10.1002/14651858.CD010649]

Fuller AK, Uglik KM, Braine HG, King KE. A comprehensive program to minimize platelet outdating. Transfusion 2011;51:1469‐76. [DOI: 10.1111/j.1537‐2995.2010.03039.x]

Gordon MS, Nemunaitis J, Hoffman R, Paquette RL, Rosenfeld C, Manfreda S, et al. A phase I trial of recombinant human interleukin‐6 in patients with myelodysplastic syndromes and thrombocytopenia. Blood 1995;85:3066‐76.

Greeno E, McCullough J, Weisdorf D. Platelet utilization and the transfusion trigger: a prospective analysis. Transfusion 2007;47:201‐5. [DOI: 10.1111/j.1537‐2995.2007.01089.x]

Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, et al. Anti‐fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD001886.pub4]

Higgins JP, Deeks JJ. Chapter 7: Selecting studies and collecting data. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Higgins JP, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Higgins JP, Deeks JJ, Altman DG. Chapter 16: Special topics in Statistics. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Hui P, Cook DJ, Lim W, Fraser GA, Arnold DM. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest 2011;139(2):271‐8.

Jacobs MR, Smith D, Heaton WA, Zantek ND, Good CE. Detection of bacterial contamination in prestorage culture‐negative apheresis platelets on day of issue with the Pan Genera Detection test. Transfusion 2011;51(12):2573‐82.

Joint Formulary Committee. British National Formulary, 2016. www.medicinescomplete.com/mc/bnf/current. Online. London: BMJ Group and Pharmaceutical Press, (accessed 17 March 2016).

Kaufman RM, Djulbegovic B, Gernsheimer T, Kleinman S, Tinmouth AT, Capocelli KE, et al. Platelet transfusion: a clinical practice guideline from the AABB. Annals of Internal Medicine 2015;162(3):205‐13.

Kurzrock R, Cortes J, Thomas DA, Jeha S, Pilat S, Talpaz M. Pilot study of low‐dose interleukin‐11 in patients with bone marrow failure. Journal of Clinical Oncology 2011;19(21):4165‐72.

Kuter DJ. Milestones in understanding platelet production: a historical overview. British Journal of Haematology 2014;165(2):248‐58.

Leguit RJ, van den Tweel JG. The pathology of bone marrow failure. Histopathology 2010;57(5):655‐70.

Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Journal of Haematology 2009;145(1):24‐33.

McNicol ED, Tzortzopoulou A, Schumann R, Carr DB, Kalra A. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database of Systematic Reviews 2016, Issue 9. [DOI: 10.1002/14651858.CD006883.pub3]

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. Annals of Internal Medicine 2009;151(4):264‐9.

Neunert CE. Current management of immune thrombocytopenia. Hematology 2013;2013:276‐82.

National Institute of Health and Care Excellence. Romiplostim for the treatment of chronic immune (idiopathic) thrombocytopenic purpura, 2011. www.nice.org.uk/guidance/ta221 (accessed prior to 23 August 2018).

National Institute of Health and Care Excellence. Eltrombopag for treating chronic immune (idiopathic) thrombocytopenic purpura (review of technology appraisal 205). www.nice.org.uk/guidance/ta293/documents/thrombocytopenic‐purpura‐eltrombopag‐rev‐ta205‐final‐appraisal‐determination3 (accessed prior to 23 August 2018).

National Institute for Health and Care Excellence. Blood transfusion. www.nice.org.uk/guidance/ng24 (accessed 10 November 2016).

Nisha S, Amita D, Uma S, Tripathi AK, Pushplata S. Prevalence and characterization of thrombocytopenia in pregnancy in Indian women. Indian Journal of Hematology and Blood Transfusion 2012;28(2):77‐81.

Pacheco LD, Berkowitz RL, Moise KJ, Bussel JB, McFarland JG, Saade GR. Fetal and neonatal alloimmune thrombocytopenia: a management algorithm based on risk stratification. Obstetrics and Gynecology 2011;118(5):1157‐63.

Parmar M, Torri V, Stewart L. Extracting summary statistics to perform meta‐analyses of the published literature for survival endpoints. Statistics in Medicine 1998;17(24):2815‐34.

Pendry K, Davies T. An audit of use and wastage in the north west of England and North Wales: where have all the platelets gone?. Blood and Transplant Matters 2011;34:17‐9.

Google Scholar

Perdigão JP, de Almeida PC, Rocha TD, Mota MR, Soares EC, Alves AP, et al. Postoperative bleeding after dental extraction in liver pretransplant patients. Journal of Oral and Maxillofacial Surgery 2012;70:e177‐84.

Provan D, Stasi R, Newland AC, Blanchette VS, Bolton‐Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010;115(2):168‐86.

Reeves BC, Deeks JJ, Higgins JP, Wells GA. Chapter 13: Including non‐randomised studies. In: Higgins JP, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Sainio S, Kekomäki R, Riikonen S, Teramo K. Maternal thrombocytopenia at term: a population‐based study. Acta Obstetricia et Gynecologica Scandinavica 2000;79:744‐9.

Schünemann HJ, Oxman AD, Higgins JP, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and 'Summary of findings' tables. In: Higgins JP, Green S editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Schünemann HJ, Oxman AD, Vist GE, Higgins JP, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C. Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database of Systematic Reviews 2012, Issue 3. [DOI: 10.1002/14651858.CD005011.pub4]

Slichter SJ. Evidence‐based platelet transfusion guidelines. Hematology 2007;1520:172‐8.

Spiess BD, Royston D, Levy JH, Fitch J, Dietrich W, Body S, et al. Platelet transfusions during coronary artery bypass graft surgery are associated with serious adverse outcomes. Transfusion 2004;44(8):1143‐8.

Stanworth SJ, Walsh TS, Prescott RJ, Lee RJ, Watson DM, Wyncoll DLA. Thrombocytopenia and platelet transfusion in UK critical care: a multicenter observational study. Transfusion 2013;53(5):1050‐8.

Sterne JA, Egger M, Moher D. Chapter 10: Addressing reporting biases. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook cochrane.org.

Sterne JA, Hernán MA, Reeves C, Savović J, Berkman ND, Viswanathan M, et al. ROBINS‐I: a tool for assessing risk of bias in non‐randomised studies of interventions. BMJ 2016;355:i4919.

Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time‐to‐event data into meta‐analysis. Trials 2007;8:16. [DOI: 10.1186/1745‐6215‐8‐16]

Tsimberidou AM, Giles FJ, Khouri I, Bueso‐Ramos C, Pilat S, Thomas DA, et al. Low‐dose interleukin‐11 in patients with bone marrow failure: update of the M. D. Anderson Cancer Center Experience. Annals of Oncology 2005;16(1):139‐45.

Vlaar AP, Juffermans NP. Transfusion‐related acute lung injury: a clinical review. Lancet 2013;382(9896):984‐94.

Weinzierl EP, Arber DA. The differential diagnosis and bone marrow evaluation of new‐onset pancytopenia. American Journal of Clinical Pathology 2013;139(1):9‐29.

Whitaker BI. National blood collection and utilization survey report. Washington, DC: U.S. Department of Health and Human Services; 2013. www.hhs.gov/ash/bloodsafety/2011‐nbcus.pdf (accessed 1 December 2016).

Zeng Y, Duan X, Xu J, Ni X. TPO receptor agonist for chronic idiopathic thrombocytopenic purpura. Cochrane Database of Systematic Reviews 2011, Issue 7. [DOI: 10.1002/14651858.CD008235.pub2]

References to other published versions of this review

Jump to:

included studies
excluded studies
ongoing studies
additional references

Estcourt LJ, Malouf R, Doree C, Trivella M, Hopewell S, Birchall J. Prophylactic platelet transfusions prior to surgery for people with a low platelet count. Cochrane Database of Systematic Reviews 2017, Issue 9. [DOI: 10.1002/14651858.CD012779]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Jump to:

excluded studies
ongoing studies

Basu 2012

Methods	Study design: randomised, double‐blind, parallel‐group controlled trial Setting and country: outpatient university hospital, USA Number of centres: 1 Study duration (start to end): unclear Follow‐up duration: 4 weeks Power calculation: unclear Publication type: abstract
Participants	Inclusion criteria: CLD with thrombocytopenia Exclusion criteria: ITP, drug‐induced thrombocytopenia, HIV, hepatocellular carcinoma, haemangioma, autoimmune thrombocytopenia, use of steroids, MDS Number screened: unclear Number randomised: 65 Number analysed: unclear Number excluded: unclear Baseline characteristics Number of participants: 18 in the platelet transfusion group, 23 in the romiplostim group, 24 in the eltrombopag group Age (years): mean 56 Gender (male/female): 43/22 Platelet count (× 10⁹/L): mean 77 Creatinine (mg/L): not reported Total bilirubin (mg/dL): not reported ALT: not reported Albumin: not reported INR: not reported PT: not reported Primary diagnosis: hepatitis C 37/65 (57%); hepatitis B 7 (15.5%), alcoholic cirrhosis 10 (15%); non‐alcoholic steatohepatitis 3 (5%), primary biliary cirrhosis 6 (9%) Antiplatelet agents: not reported Anticoagulants: exclusion criterion Coagulopathy: not reported
Interventions	Procedure: liver biopsy Platelet transfusion (n = 18) Dose: 7 units of platelets Frequency: once at night for the morning liver biopsy Administration route: IV Romiplostim (n = 23) Dose: 500 μg Frequency: given once 2 weeks before the liver biopsy Administration route: subcutaneous Eltrombopag (n = 24) Dose: 57 mg/day Frequency: for 2 weeks before the liver biopsy Administration route: by mouth
Outcomes	Review outcomes Bleeding and haematoma Other outcomes adverse effects of the eltrombopag and romiplostim: nausea, vomiting, dry mouth, headache, insomnia, irritability, local skin rash, shortness of breath, myalgia, arthralgia, erythema in postbiopsy and postinjection site cost effectiveness
Notes	Trial registration: none found Sources of funding: not reported Conflicts of interest: unclear Ethical approval: unclear
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Published as an abstract, no information available
Allocation concealment (selection bias)	Unclear risk	Published as an abstract, no information available
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind trial
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind trial
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Published as an abstract, no information available
Selective reporting (reporting bias)	Unclear risk	Published as an abstract, no information available
Other bias	Unclear risk	Published as an abstract, no information available

Stanca 2010

Methods	Study design: randomised, open‐label, parallel‐controlled trial Setting and country: dental clinic, Mount Sinai Hospital, USA Number of centres: 1 Study duration (start to end): study enrolment occurred between October 2005 and May 2007 Follow‐up duration: 24 hours after surgery Study power calculation: no Publication type: full
Participants	Inclusion criteria: adults with biopsy‐confirmed liver cirrhosis or clinical/radiological evidence of cirrhosis, requiring dental extraction, having a platelet count of 30 × 10⁹/L to 50 × 10⁹/L, INR of 2.0 to 3.0, or a combination of these Exclusion criteria: presence of other bleeding disorders besides cirrhosis such as renal dysfunction (creatinine 2.0 mg/dL) or HIV, receipt of blood transfusion within 2 weeks before the study, recent acute decompensation of liver cirrhosis, malignancy excluding hepatocellular carcinoma in the absence of portal vein thrombosis, treatment with antiplatelet medications (aspirin, non‐steroidal anti‐inflammatory drugs or clopidogrel) within 10 days before the extraction and documented allergy to desmopressin Pretreatment: no difference between groups with regard to the age, gender, the severity of liver disease as reflected by MELD score, number of teeth removed and percentage of surgical extractions Number screened: 43 enrolled. 2 participants assigned to the blood transfusion group withdrew their consent for the study; 1 participant wanted to be assigned to the desmopressin group, and the other participant changed his mind about having the dental extraction done at that time. 5 participants, 4 in the desmopressin group and 1 in the transfusion group, had blood drawn after being enrolled in the study but before their surgical procedure that resulted in laboratory values outside of the study parameters. These 5 participants underwent the surgical procedure but were not included in the analysis. Number excluded: 5 participants underwent the surgical procedure but were not included in the analysis. Baseline characteristics Platelet transfusion group Number of participants: 19 Age (years): mean 50 (range 28 to 65) Gender (male/female): 13/6 Platelet count (× 10⁹/L): mean 45 (range 22 to 103), 11 out of 19 participants had low platelets Creatinine (mg/dL): mean 0.8 (range 0.5 to 1.8) Total bilirubin (mg/dL): mean 2.7 (range 1.5 to 24.9) ALT (IU/L): mean 46 (range 17 to 188) Albumin (g/dL): mean 2.5 (range 1.4 to 3.5) INR: mean 2.1 (range 1.4 to 2.9) PT: not reported Procedure: dental extraction: simple 10; surgical 7; unknown 2 Primary diagnosis: liver cirrhosis Antiplatelet agents: exclusion criterion Anticoagulants: exclusion criteria included the presence of other bleeding disorders Coagulopathy: exclusion criteria included the presence of other bleeding disorders Platelet dysfunction: exclusion criteria included the presence of other bleeding disorders Alternatives to platelet transfusions group Number of participants: 17 Age (years): mean 51 (range 34 to 63) Gender (male/female): 12/5 Platelet count (× 10⁹/L): mean 48 (range 30 to 147), 11 out of 17 participants had low platelets Creatinine (mg/dL): mean 0.9 (range 0.5 to 1.9) Total bilirubin (mg/dL): mean 2.7 (range 1.1 to 15.4) ALT (IU/L): mean 30 (range 13 to 491) Albumin (g/dL): mean 2.7 (range 1.9 to 4.1) INR: mean 2.0 (range 1.0 to 3.0) PT: NR Procedure: dental extraction: simple 9; surgical 7; unknown 1 Primary diagnosis: liver cirrhosis Antiplatelet agents: exclusion criterion Anticoagulants: exclusion criteria included the presence of other bleeding disorders Coagulopathy: exclusion criteria included the presence of other bleeding disorders Platelet dysfunction: exclusion criteria included the presence of other bleeding disorders
Interventions	Surgical procedure: dental extraction Platelet transfusion Dose: FFP 10 mL/kg for INR of 2.0 to 3.0 or 1 unit of single donor platelets if the platelet count was in the range of 30,000/L to 50,000/L (or both) Frequency: additional transfusions if bleeding post procedure Administration route: IV Alternatives to platelet transfusions Dose: desmopressin acetate, nasal spray, 1.5 mg/mL; 25 doses in 1 container) provided by CSL Behring, Kankakee, IL Frequency: both nostrils, prior to surgery and after surgery if bleeding or evening after procedure if bleeding Administration route: intranasal
Outcomes	Primary outcome: necessity of rescue blood transfusion in participants who received desmopressin or blood transfusion prior to dental extraction (time frame: 48 hours) Secondary outcomes: number of participants with major procedure‐related bleeding within 7 days of surgery number of participants with minor procedure‐related bleeding within 7 days of surgery number of platelet transfusions per participant and number of platelet components per participant number of red cell transfusions per participant and number of red cell components per participant serious adverse events cost
Notes	Trial registration number:NCT00816127 Source of funding: Icahn School of Medicine at Mount Sinai, New York City, NY Conflicts of interest: unclear Ethical approval: yes, "The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in the approval by the Mount Sinai Institutional Review Board."
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "randomization list was generated by one member of the biomathematics team using computer software for randomization."
Allocation concealment (selection bias)	Low risk	Quote: "same member of the biomathematics team, not involved in patient enrollment, prepared sealed white randomization envelopes prelabeled with an ID number. The content of the envelope (patient's assignment to the DDAVP [desmopressin] or blood transfusion group) matched the information in the randomization plan for that particular ID number (DDAVP or blood transfusion group). The content of the envelope was not accessible to the research coordinator who enrolled patients or to any member of the team at the time of enrollment." Judgement comment: sealed white envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label design, no blinding
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	In all, 43 participants were enrolled in the study and randomised: 21 in desmopressin group and 22 in transfusion group. 36 participants (17 in desmopressin group and 19 in transfusion group) completed the study procedures. 2 participants assigned to the blood transfusion group withdrew their consent for the study; 1 participant wanted to be assigned to the desmopressin group, and the other participant changed his mind about having the dental extraction done at that time. 5 participants, 4 in desmopressin group and 1 in transfusion group, had blood drawn after being enrolled in the study but before their surgical procedure that resulted in laboratory values outside of the study parameters. These 5 participants underwent the surgical procedure but were not included in the analysis. None of these participants experienced bleeding after the procedure. 7 participants randomised were not included in the analysis. 3 in transfusion arm and 4 in desmopressin arm. This is a relative large (up to 19%) number of participants randomised who were not included in the analysis.
Selective reporting (reporting bias)	Unclear risk	Only outcome listed on clinical trials.gov was: "Necessity of rescue blood transfusion in patients who received DDAVP [desmopressin] or blood transfusion prior to dental extraction." No other secondary outcomes listed. This outcome was reported. However, no protocol to assess if other outcomes was planned.
Other bias	Low risk	No other biases found

Veelo 2012

Methods	Study design: parallel‐group, open‐label, RCT Setting and country: ICU University hospital, the Netherlands Number of centres: 1 Study duration (start to end): July 2007 to October 2009 Follow‐up duration: Not reported Power calculation: yes, "Although a sample size of 152 patients was considered necessary to find a difference of 15% in bleeding between groups, the study was prematurely terminated." Publication type: full
Participants	Inclusion criteria: participants planned for bedside PDT with mild coagulation disorders defined as PT 14.7–20.0 seconds or platelet counts 40–100 × 10⁹/L or active treatment with aspirin at any dose, or a combination of these Exclusion criteria: aged < 18 years; need for surgical tracheotomy; contraindications to transfusion of blood products and use of clopidogrel. Participant would also be excluded from participation if the attending physician insisted on the need for transfusion of FFP or platelets (or both) before the procedure. Number screened: 355 Number randomised: 72 Number analysed: 64, 4 in each arm did not undergo PDT Number excluded: 283 (refused consent 27, surgical procedure 53, clopidogrel 13, PT > 20 seconds, 11, normal coagulation 179) Baseline characteristics Platelet transfusion group Number of participants: 35 Age (years): median 64 (IQR 56–72) Gender (male/female): 22/13 Platelet count (× 10⁹/L): median 81 (IQR 63–85), low platelet count 13 Creatinine: not reported Total bilirubin: not reported ALT: not reported Albumin: not reported INR: not reported PT (secs): mean 16.0 (SD 1.2) Primary diagnosis: 9 acute renal failure, 2 chronic renal failure, 7 sepsis, 5 massive transfusion, 2 haematological malignancy, 0 liver cirrhosis Antiplatelet agents: 11 (aspirin) Anticoagulants: exclusion criterion Coagulopathy: 8 had > 1 coagulation disorder present Platelet dysfunction: not reported No platelet transfusion group Number of participants: 37 Age (years): median 68 (IQR 60–76) Gender (male/female): 16/21 Platelet count (× 10⁹/L): median 56 (IQR 47–70), low platelet count 10 Creatinine: not reported Total bilirubin: not reported ALT: not reported Albumin: not reported INR: not reported PT (secs): mean 16.6 (SD 1.1) Primary diagnosis: 3 acute renal failure, 2 chronic renal failure, 9 sepsis, 5 massive transfusion, 3 haematological malignancy, 0 liver cirrhosis Antiplatelet agents: 12 participants were on aspirin Anticoagulants: excluded criterion Coagulopathy: 7 had > 1 coagulation disorder present Platelet dysfunction: not reported
Interventions	Procedure: PDT Platelet transfusion group Dose: participants with a prolonged PT (normal values 11.0–14.7 seconds) assigned to the "correction group" received 1 or 2 units of FFP (1 unit contained 300 mL of FFP: if the PT was between 14.7 and 18.0 seconds the participant received 1 unit of FFP; if the PT was between 18.0 and 20.0 seconds the participant received 2 units of FFP). Participants with a low platelet count or active use of aspirin (or both) assigned to the correction group received 5 units of platelet concentrates prepared from 5 pooled buffy coats. Frequency: before procedure Administration route: IV No platelet transfusion group Dose: participants assigned to the "no correction" group received neither plasma nor platelets. However, FFP or platelets (or both) were made available for immediate transfusion in case bleeding occurred during or after PDT
Outcomes	Primary outcomes Volume of blood loss during PDT Intensity of intra‐tracheal bleeding Time until no blood is visible in tracheal aspirates Secondary outcome Amount of blood products used during and after tracheotomy Review outcomes reported by the trial All‐cause mortality within 30 days of surgery Major bleeding within 7 days of surgery Minor bleeding within 7 days of surgery Number of participants received platelet transfusions Number of participants received red blood cells transfusions Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery Serious adverse effects
Notes	Trial registration number: Current Controlled Trials ISRCTN31808827 Source of funding: Academic Medical Centre (AMC) (The Netherlands), Department of Intensive Care Conflicts of interest: authors declared no conflicts of interest Ethical approval: yes. "The study was approved by the local ethics committee."
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "computer‐generated randomisation scheme was used."
Allocation concealment (selection bias)	Low risk	Quote: "Each assignment ("correction" or "no correction") was recorded on a piece of paper folded three times and enclosed in a consecutively numbered, opaque, sealed envelope."
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label design RCT
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label design RCT
Incomplete outcome data (attrition bias) All outcomes	Low risk	CONSORT flow diagram clearly reported. All participants who underwent the procedure were included in the analysis. 4 in each arm did not undergo the procedure.
Selective reporting (reporting bias)	High risk	No protocol available, but registered ISRCTN31808827. Primary outcome measures: volume of blood loss during PDT2; intensity of intratracheal bleeding; time until no blood is visible in tracheal aspirates. All these were all reported in the published paper. Secondary outcome measures: amount of blood products used during and after tracheotomy – not clearly reported in the published paper
Other bias	Unclear risk	Trial stopped early due to increase resistance to recruitment and low rate of bleeding in either arm of the study. Quote: "Although a sample size of 152 patients was considered necessary to find a difference of 15% in bleeding between groups, the study was prematurely terminated."

ALT: alanine transaminase; CLD: chronic liver disease; FFP: fresh frozen plasma; ICU: intensive care unit; INR: international normalised ratio; IQR: interquartile range; ITP: immune thrombocytopenia; IV: intravenous; MDS: myelodysplastic syndrome; MELD: Model for End‐Stage Liver Disease; n: number of participants; PDT: percutaneous dilational tracheotomy; PT: prothrombin time; RCT: randomised controlled trial; SD: standard deviation.

Characteristics of excluded studies [ordered by study ID]

Jump to:

included studies
ongoing studies

Study	Reason for exclusion
Abdelfatah 2016	Wrong study design, observational retrospective cohort
Afdhal 2012	Wrong intervention, no platelet transfusions
Al‐Zaabi 2014	Wrong study design, single‐centre observational cohort
Backos 1999	Wrong participant population, not receiving surgery or a procedure
Barrera 1996	Wrong study design, observational retrospective cohort
Cai 2014	Wrong study design, single‐centre observational cohort
Chantarangkul 2013	Wrong study design, single‐centre observational cohort
Chen 2011	Wrong study design, single‐centre observational cohort
De Pietri 2016	wrong intervention, thrombelastography‐guided blood product use
Embrey 2006	Wrong study design, observational retrospective cohort
EudraCT 2007‐005851‐40	Wrong intervention, no platelet transfusions
Fayed 2014	Wrong study design, observational cohort
Harding 1975	Wrong participant population (not thrombocytopenic prior to surgery)
Hess 2015	Wrong participant population (bleeding)
Hibbert 2013	Wrong study design, observational cohort
Holcomb 2015	Wrong participant population (bleeding)
Karkouti 2016	Wrong intervention, thrombelastography‐guided blood product use
Khair 2015	Wrong study design, case series
Kultufan 2006	Wrong intervention, thrombelastography‐guided blood product use
Napolitano 2017	Wrong study design, case series
NCT00521664	Wrong participant population, not receiving surgery or a procedure
NCT00549484	Wrong study setting, measuring thrombopoietin levels
NCT00678587	Wrong intervention, no platelet transfusions
NCT01291290	Wrong participant population (bleeding)
NCT01402739	Wrong participant population (not thrombocytopenic prior to surgery)
NCT01919840	Wrong intervention, thrombelastography‐guided blood product use
NCT02042898	Wrong intervention, no platelet transfusions
NCT02074436	Wrong participant population, not receiving surgery or a procedure
NCT02200419	Wrong study design, observational study
NCT02352181	Wrong intervention, thrombelastography‐guided blood product use
NCT02987712	Wrong study design, single‐centre non‐randomised study
NCT02990273	Wrong intervention, thrombelastography‐guided blood product use
NCT03011827	Wrong study design, observational cohort study
NCT03022253	Wrong participant population, not receiving surgery or a procedure
Park 2016	Wrong study design, observational cohort
Pereboom 2009	Wrong study design, case series
Perek 2016	Wrong study design, retrospective cohort
Perl 2016	Wrong intervention, blood transfusion ratios in trauma (PROPPR study)
Pietri 2014	Wrong intervention, thrombelastography‐guided blood product use
Ray 1997	Wrong study design, observational cohort
Simon 1982	Wrong participant population (not thrombocytopenic prior to surgery)
Simon 1984	Wrong participant population (not thrombocytopenic prior to surgery)
Smart 2017	Wrong intervention, thrombelastography‐guided blood product use
Tanaka 2014	Wrong participant population (not thrombocytopenic prior to surgery)
Titano 2016	Wrong intervention, no platelet transfusions
Tripodi 2013	Wrong study design, observational cohort study

Characteristics of ongoing studies [ordered by study ID]

Jump to:

included studies
excluded studies

NTR5653

Trial name or title	Prophylactic platelet transfusion prior to central venous catheter placement in patients with thrombocytopenia
Methods	Study design: parallel‐group, single‐blind, randomised controlled trial Country: the Netherlands Number of centres: multicentre Planned starting date: February 2016 Planned completion date: October 2019 Follow‐up points: directly after CVC insertion, 1 hour, 24 hours
Participants	Target number of participants: 462 Inclusion criteria: Aged > 18 years Need for CVC placement at the clinician's discretion Platelet count 10–50 × 10⁹/L INR < 1.5 Informed consent Exclusion criteria: Use of therapeutic anticoagulant therapy, except single antiplatelet therapy Contraindication for platelet transfusion, such as thrombotic thrombocytopenic purpura, or congenital IgA deficiency Previous randomisation in the current trial People with a history of congenital or acquired coagulation factor deficiency or bleeding diathesis
Interventions	Intervention arm: 1 unit of platelets Control arm: no platelets or placebo treatment
Outcomes	Primary outcome: A procedure‐related relevant bleeding, occurring within 24 hours after the procedure. A WHO grade 2–4 bleed up to 24 hours from randomisation was defined as relevant bleeding. Secondary outcomes: WHO grade 1 bleeding within 24 hours of CVC placement Adjusted WHO bleeding score, HEmorrhage MEasurement (HEME)‐bleeding score Allergic transfusion reaction within 24 hours Onset of acute lung injury within 48 hours Length of hospital stay Number of RBC and platelet transfusions within 24 hours Costs
Starting date	February 2016
Contact information	APJ Vlaar
Notes	Trial registration date: January 2016

Rocha 2017

Trial name or title	Point‐of‐care versus standard coagulation tests versus restrictive strategy to guide transfusion in chronic liver failure patients requiring central venous line: prospective randomized trial (POCKET)
Methods	Allocation: randomised Endpoint classification: safety/efficacy study Intervention model: parallel assignment (3 arms) Masking: double‐blind (participant, caregiver) Primary purpose: treatment
Participants	Inclusion criteria: adults (aged ≥ 18 years) with chronic liver failure (cirrhosis or chronic liver graft dysfunction or both) admitted to ICU and requiring insertion of a central line. Exclusion criteria: acute liver failure use of therapeutic doses of oral or parenteral anticoagulants (unfractionated heparin or low molecular weight heparin or oral anticoagulants) use of oral or parenteral platelet aggregation inhibitors people with von Willebrand disease over‐the‐guidewire CVC changing people previously included in this study protocol during the same hospital stay
Interventions	Arm 1: coagulogram‐based protocol Arm based on standard coagulation tests protocol to guide blood transfusion before central venous catheterisation. The possible components to be used include fresh frozen plasma, platelets (random or apheresis), cryoprecipitate (or a combination of these), based on INR), PTT, platelet count, fibrinogen (or a combination of these). INR > 1.5 or PTT > 50 seconds, fresh frozen plasma is administered (dose: 10 mL/kg) Platelets < 50 × 10⁹/L, platelet transfusion is administered (random or apheresis) Fibrinogen < 1.5g/L, cryoprecipitate is administered Arm 2: thromboelastometry‐based protocol The interventions for this protocol included transfusion of fresh frozen plasma, platelets (random or aphaeresis) cryoprecipitate (or a combination of these), based on rotational thromboelastometry. Coagulation time (extrinsically activated) < 80 seconds and A10 (extrinsically activated) > 40 mm, then no blood transfusion is performed Coagulation time (extrinsically activated) > 80 seconds then fresh frozen plasma is administered (dose: 10 mL/kg) A10 (extrinsically activated) < 40 mm or A10 (fibrinogen polymerisation) > 10 mm platelet transfusion is administered (random or apheresis) A10 (extrinsically activated) < 40 mm or A10 (fibrinogen polymerisation) < 10 mm cryoprecipitate is administered Arm 3: restrictive strategy The interventions for this protocol include transfusion of fresh frozen plasma or platelets (random or aphaeresis), or both, based on INR and platelet count. INR > 5, fresh frozen plasma is administered (dose: 10 mL/kg) Platelets < 25 × 10⁹/L, platelet transfusion is administered (random or apheresis)
Outcomes	Primary outcome: proportion of participants receiving a blood component transfusion, i.e. fresh frozen plasma, platelets, cryoprecipitate (or a combination of these) before central venous catheterisation (on day of randomisation) Secondary outcomes: incidence of haemorrhagic complications associated with central venous catheterisation procedure (up to 24 hours) incidence of acute immunological and non‐immunological adverse effects of blood transfusion (up to 24 hours) cost assessments (laboratory and blood transfusion) between the 3 strategies (up to 24 hours) length of stay in ICU (up to 90 days) length of stay in hospital (up to 180 days) mortality rate (up to 28 days)
Starting date	September 2014
Contact information	Leonardo L Rocha, MD +55‐11‐21511500, [email protected] Thiago D Correa, MD, PhD +55‐11‐21511500, [email protected]
Notes	Estimated enrolment: 165 Estimated study completion date: January 2019 Estimated primary completion date: December 2018 (final data collection date for primary outcome measure) Trial registration: NCT02311985 Location of trial: Hospital Israelita Albert Einstein, Sao Paulo, Brazil

CVC: central venous catheter; ICU: intensive care unit; IgA: immunoglobulin A; INR: international normalised ratio; PTT: partial thromboplastin time; RBC: red blood cell; WHO: World Health Organization.

Data and analyses

Open in table viewer

Comparison 1. Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality within 30 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.1 Comparison 1 Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery, Outcome 1 All‐cause mortality within 30 days of surgery.
2 Number of participants with major procedure‐related bleeding within 7 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.2 Comparison 1 Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery, Outcome 2 Number of participants with major procedure‐related bleeding within 7 days of surgery.
3 Number of participants with minor procedure‐related bleeding within 7 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.3 Comparison 1 Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery, Outcome 3 Number of participants with minor procedure‐related bleeding within 7 days of surgery.
4 Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.4 Comparison 1 Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery, Outcome 4 Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery.

Open in table viewer

Comparison 2. Prophylactic platelet transfusion prior to surgery versus alternative treatments

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of participants with minor procedure‐related bleeding within 7 days of surgery Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.1 Comparison 2 Prophylactic platelet transfusion prior to surgery versus alternative treatments, Outcome 1 Number of participants with minor procedure‐related bleeding within 7 days of surgery.
1.1 Desmopressin vs platelet transfusion	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Thrombopoietin mimetics vs platelet transfusion	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.2 Comparison 2 Prophylactic platelet transfusion prior to surgery versus alternative treatments, Outcome 2 Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery.
2.1 Desmopressin vs platelet transfusion	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Serious adverse events (transfusion related adverse effects within 24 hours of the transfusion) Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.3 Comparison 2 Prophylactic platelet transfusion prior to surgery versus alternative treatments, Outcome 3 Serious adverse events (transfusion related adverse effects within 24 hours of the transfusion).
3.1 Desmopressin vs platelet transfusion	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Figure 1

Study flow diagram.

Navigate to figure in ReviewOpen in new tab

Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Navigate to figure in ReviewOpen in new tab

Analysis 1.1

Comparison 1 Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery, Outcome 1 All‐cause mortality within 30 days of surgery.

Navigate to figure in ReviewOpen in new tab

Analysis 1.2

Comparison 1 Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery, Outcome 2 Number of participants with major procedure‐related bleeding within 7 days of surgery.

Navigate to figure in ReviewOpen in new tab

Analysis 1.3

Comparison 1 Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery, Outcome 3 Number of participants with minor procedure‐related bleeding within 7 days of surgery.

Navigate to figure in ReviewOpen in new tab

Analysis 1.4

Comparison 1 Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery, Outcome 4 Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery.

Navigate to figure in ReviewOpen in new tab

Analysis 2.1

Comparison 2 Prophylactic platelet transfusion prior to surgery versus alternative treatments, Outcome 1 Number of participants with minor procedure‐related bleeding within 7 days of surgery.

Navigate to figure in ReviewOpen in new tab

Analysis 2.2

Comparison 2 Prophylactic platelet transfusion prior to surgery versus alternative treatments, Outcome 2 Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery.

Navigate to figure in ReviewOpen in new tab

Analysis 2.3

Comparison 2 Prophylactic platelet transfusion prior to surgery versus alternative treatments, Outcome 3 Serious adverse events (transfusion related adverse effects within 24 hours of the transfusion).

Navigate to figure in ReviewOpen in new tab

Summary of findings for the main comparison. Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery

Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery
Patient or population: people with a low platelet count Setting: surgery Intervention: platelet transfusion Comparison: no platelet transfusion
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with no platelet transfusion	Risk with platelet transfusion
All‐cause mortality within 30 days of surgery	Study population		RR 0.78 (0.41 to 1.45)	72 (1 RCT)	⊕⊝⊝⊝ Very low^a,b	—
	405 per 1000	316 per 1000 (166 to 588)
Mortality secondary to bleeding within 30 days of surgery – not reported	—	—	—	—	—	—
Mortality secondary to thromboembolism within 30 days of surgery – not reported	—	—	—	—	—	—
Mortality secondary to infection within 30 days of surgery – not reported	—	—	—	—	—	—
Number of participants with major bleeding within 7 days of surgery (surgical site bleeding requiring a second intervention or reoperation or surgical site bleeding that causes a haematoma or haemarthrosis of sufficient size to delay mobilisation or wound healing)	Study population		RR 1.60 (0.29 to 8.92)	64 (1 RCT)	⊕⊝⊝⊝ Very low^b,c	—
	61 per 1000	97 per 1000 (18 to 541)
The number of participants with minor procedure‐related bleeding within 7 days of surgery	Study population		RR 1.29 (0.90 to 1.85)	64 (1 RCT)	⊕⊝⊝⊝ Very low^a,c,d	—
	576 per 1000	743 per 1000 (518 to 1000)
Serious adverse events (surgery‐related adverse effects within 30 days)	No events occurred in either study arm			64 (1 RCT)	⊕⊝⊝⊝ Very low^a,c,d	—
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aOnly adults in the intensive care unit were included in this trial (downgraded one level for indirectness). ^bThe confidence intervals included a serious risk of harm or benefit (downgraded two levels for imprecision). ^cThis is a subjective outcome and the trial was unblinded (downgraded one level for risk of bias). ^dThe confidence intervals included a risk of harm or benefit (downgraded one level for imprecision).

Summary of findings for the main comparison. Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery

Navigate to table in Review

Summary of findings 2. Prophylactic platelet transfusion prior to surgery versus alternative treatments

Prophylactic platelet transfusion prior to surgery versus alternative treatments
Patient or population: people with a low platelet count Setting: surgery Intervention: platelet transfusion Comparison: desmopressin
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with desmopressin	Risk with platelet transfusion
All‐cause mortality within 30 days of surgery – not reported	—	—	—	—	—	—
Mortality secondary to bleeding within 30 days of surgery – not reported	—	—	—	—	—	—
Mortality secondary to thromboembolism within 30 days of surgery – not reported	—	—	—	—	—	—
Mortality secondary to infection within 30 days of surgery – not reported	—	—	—	—	—	—
Number of participants with major bleeding within 7 days of surgery (bleeding that required ≥ 2 units of whole blood/red blood cells within 24 hours of the bleeding)	No events in either study arm			36 (1 RCT)	⊕⊝⊝⊝ Very low^a,b,c	—
Number of participants with minor procedure‐related bleeding within 7 days of surgery	Study population		RR 0.89 (0.06 to 13.23)	36 (1 RCT)	⊕⊝⊝⊝ Very low^a,b,c	—
	59 per 1000	52 per 1000 (4 to 778)
Serious adverse events (transfusion‐related adverse effects within 24 hours of the transfusion)	Study population		RR 2.70 (0.12 to 62.17)	36 (1 RCT)	⊕⊝⊝⊝ Very low^a,b,c	—
	0 per 1000	0 per 1000 (0 to 0)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aOpen‐label trial (downgraded one level for risk of bias). ^bStudy only included adults with chronic liver disease (downgraded one level for indirectness). ^cConfidence intervals included a serious risk or benefit or treatment (downgraded one level for imprecision, as already downgraded one level for indirectness and risk of bias).

Summary of findings 2. Prophylactic platelet transfusion prior to surgery versus alternative treatments

Navigate to table in Review

Summary of findings 3. Different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery

Different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery
Patient or population: people with a low platelet count Setting: surgery Intervention: platelet transfusion Comparison: TPO mimetic
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with TPO mimetic	Risk with platelet transfusion	Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
All‐cause mortality within 30 days of surgery – not reported	—	—	—	—	—	—
Mortality secondary to bleeding within 30 days of surgery – not reported	—	—	—	—	—	—
Mortality secondary to thromboembolism within 30 days of surgery – not reported	—	—	—	—	—	—
Mortality secondary to infection within 30 days of surgery – not reported	—	—	—	—	—	—
Number of participants with major bleeding within 7 days of surgery	No bleeding in any of the study arms			65 (1 RCT)	⊕⊝⊝⊝ Very low^a,b	—
Number of participants with minor procedure‐related bleeding within 7 days of surgery	No bleeding occurred in any of the study arms			65 (1 RCT)	⊕⊝⊝⊝ Very low^a,b	—
Serious adverse events – not reported	—	—	—	—	—	—
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; TPO: thrombopoietin.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aStudy only included adults with chronic liver disease (downgraded one level for indirectness). ^bNo events occurred (downgraded two levels for imprecision).

Summary of findings 3. Different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery

Navigate to table in Review

Comparison 1. Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality within 30 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

2 Number of participants with major procedure‐related bleeding within 7 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

3 Number of participants with minor procedure‐related bleeding within 7 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

4 Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Comparison 1. Prophylactic platelet transfusion prior to surgery versus no prophylactic platelet transfusion prior to surgery

Navigate to table in Review

Comparison 2. Prophylactic platelet transfusion prior to surgery versus alternative treatments

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of participants with minor procedure‐related bleeding within 7 days of surgery Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

1.1 Desmopressin vs platelet transfusion	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Thrombopoietin mimetics vs platelet transfusion	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Proportion of participants requiring additional interventions to stop bleeding within 7 days of surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

2.1 Desmopressin vs platelet transfusion	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Serious adverse events (transfusion related adverse effects within 24 hours of the transfusion) Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

3.1 Desmopressin vs platelet transfusion	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Prophylactic platelet transfusion prior to surgery versus alternative treatments

Navigate to table in Review

	Cochrane Review language Select your preferred language for Cochrane Reviews and other content. Sections without translation will be in English.

	Website language Select your preferred language for the Cochrane Library website.

Cochrane Review language

Website language

References

References to studies included in this review

Basu 2012 {published data only}

Stanca 2010 {published data only}

Veelo 2012 {published data only}

References to studies excluded from this review

Abdelfatah 2016 {published data only}

Afdhal 2012 {published data only}

Al‐Zaabi 2014 {published data only}

Backos 1999 {published data only}

Barrera 1996 {published data only}

Cai 2014 {published data only}

Chantarangkul 2013 {published data only}

Chen 2011 {published data only}

De Pietri 2016 {published data only}

Embrey 2006 {published data only}

EudraCT 2007‐005851‐40 {published data only}

Fayed 2014 {published data only}

Harding 1975 {published data only}

Hess 2015 {published data only}

Hibbert 2013 {published data only}

Holcomb 2015 {published data only}

Karkouti 2016 {published data only}

Khair 2015 {published data only}

Kultufan 2006 {published data only}

Napolitano 2017 {published data only}

NCT00521664 {published data only}

NCT00549484 {published data only}

NCT00678587 {published data only}

NCT01291290 {published data only}

NCT01402739 {published data only}

NCT01919840 {published data only}

NCT02042898 {published data only}

NCT02074436 {published data only}

NCT02200419 {published data only}

NCT02352181 {published data only}

NCT02987712 {published data only}

NCT02990273 {published data only}

NCT03011827 {published data only}

NCT03022253 {published data only}

Park 2016 {published data only}

Pereboom 2009 {published data only}

Perek 2016 {published data only}

Perl 2016 {published data only}

Pietri 2014 {published data only}

Ray 1997 {published data only}

Simon 1982 {published data only}

Simon 1984 {published data only}

Smart 2017 {published data only}

Tanaka 2014 {published data only}

Titano 2016 {published data only}

Tripodi 2013 {published data only}

References to ongoing studies

NTR5653 {published data only}

Rocha 2017 {published data only}

Additional references

Afdhal 2008

BCSH 2003

Birchall 2015

Blumberg 2010

Bolliger 2012

Bolton‐Maggs 2016

Burrows 1990

Cameron 2007

Carless 2004

Chapman 2015

Covidence 2016 [Computer program]

Deeks 2011

Desborough 2016

Desborough 2017

Engele 2016

EPOC 2015

Estcourt 2012

Estcourt 2015

Estcourt 2016a

Estcourt 2016b

Estcourt 2017a

Fabes 2013