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Antifibrinolytics (lysine analogues) for the prevention of bleeding in patients with haematological disorders

  1. Douglas Wardrop1,
  2. Lise J Estcourt2,*,
  3. Susan J Brunskill3,
  4. Carolyn Doree3,
  5. Marialena Trivella4,
  6. Simon Stanworth2,
  7. Michael F Murphy5

Editorial Group: Cochrane Haematological Malignancies Group

Published Online: 29 JUL 2013

Assessed as up-to-date: 10 JAN 2013

DOI: 10.1002/14651858.CD009733.pub2


How to Cite

Wardrop D, Estcourt LJ, Brunskill SJ, Doree C, Trivella M, Stanworth S, Murphy MF. Antifibrinolytics (lysine analogues) for the prevention of bleeding in patients with haematological disorders. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD009733. DOI: 10.1002/14651858.CD009733.pub2.

Author Information

  1. 1

    Haematology, Oxford Cancer and Haematology Centre, Oxford, Oxfordshire, UK

  2. 2

    NHS Blood and Transplant, Haematology/Transfusion Medicine, Oxford, UK

  3. 3

    NHS Blood and Transplant, Systematic Review Initiative, Oxford, Oxon, UK

  4. 4

    University of Oxford, Centre for Statistics in Medicine, Oxford, UK

  5. 5

    John Radcliffe Hospital, NHS Blood and Transplant, Oxford, UK

*Lise J Estcourt, Haematology/Transfusion Medicine, NHS Blood and Transplant, Level 2, John Radcliffe Hospital, Headington, Oxford, OX3 9BQ, UK. lise.estcourt@nhsbt.nhs.uk. lestcourt@doctors.org.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 29 JUL 2013

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Avvisati 1989 {published data only}
  • Avvisati G, ten Cate JW, Buller HR, Mandelli F. Tranexamic acid for control of haemorrhage in acute promyelocytic leukaemia. Lancet 1989;2(8655):122-4.
Fricke 1991 {published data only}
Gallardo 1983 {published data only}
  • Gallardo RL, Gardner FH. Antifibrinolytic therapy for bleeding control during remission induction for acute leukemia. Blood 1983;62:202a.
Shpilberg 1995 {published data only}
  • Shpilberg O, Blumenthal R, Sofer O, Eldor A, Ben-Bassat I. A controlled trial of tranexamic acid (TA) treatment for reduction of bleeding during acute myeloid leukemia (AML) induction and consolidation. Blood 1993;82:547a.
  • Shpilberg O, Blumenthal R, Sofer O, Katz Y, Chetrit A, Ramot B, et al. A controlled trial of tranexamic acid therapy for the reduction of bleeding during treatment of acute myeloid leukemia. Leukemia and Lymphoma 1995;19:141-4.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Amar 2003 {published data only}
  • Amar D, Grant FM, Zhang H, Boland PJ, Leung DH, Healey JA. Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery. Anesthesiology 2003;98:337-42.
Bartholomew 1989 {published data only}
  • Bartholomew J, Salgia R, Bell W. Control of bleeding in patients with immune and non-immune thrombocytopenia with aminocaproic acid. Archives of Internal Medicine 1989;149:1959-61.
Bates 2011 {published data only}
  • Bates JS, Buie LW, Woodis CB. Management of menorrhagia associated with chemotherapy-induced thrombocytopenia in women with hematologic malignancy. Pharmacotherapy 2011;11:1092-110.
Bedirhan 2001 {published data only}
  • Bedirhan MA, Turna A, Yagan N, Tasci O. Aprotinin reduces postoperative bleeding and the need for blood products in thoracic surgery: results of a randomized double-blind study. European Journal of Cardio-thoracic Surgery 2001;20:1122-7.
Ben-Bassat 1990 {published data only}
  • Ben-Bassat I, Douer D, Ramot B. Tranexamic acid therapy in acute myeloid leukemia: possible reduction of platelet transfusions. European Journal of Haematology 1990;45:86-9.
Breen 2012 {published data only}
Brown 2002 {published data only}
Byams 2007 {published data only}
  • Byams VR, Dowling NF, Heit JA, Kouides PA, Philipp CS, Stein SF, et al. Quality of life (QOL) evaluation in women with menorrhagia and abnormal hemostasis testing participating in a cross-over study of intranasal desmopressin and oral tranexamic acid. Journal of Thrombosis and Hemostasis 2007;5(2):P-S-189.
Cattan 1963 {published data only}
  • Cattan A, Schwarzenberg L, Schneider M, Amiel J-L, Mathé G. Trial of epsilon-amino-caproic acid in patients with a bleeding disorder, in particular thrombocytopenic disorders [Essai de traitement par l'acide epsilon-amino-caproique de patients atteints de syndrome hémorragiques, en particulier de syndromes liés a une thrombocytopénie]. La Presse Medicale 1963;71(43):2037-8.
Celebi 2006 {published data only}
  • Celebi N, Celebioglu B, Selcuk M, Canbay O, Karagoz AH, Aypar U. The role of antifibrinolytic agents in gynecologic cancer surgery. Saudi Medical Journal 2006;27(5):637-41.
Chakrabarti 1998 {published data only}
  • Chakrabarti S. Low dose bolus aminocaproic acid: an alternative to platelet transfusion in thrombocytopenia. European Journal of Haematology 1998;60:313-4.
Dean 1997 {published data only}
Fossa 1978 {published data only}
  • Fossa SD, Solheim OO, Fossa JJ. Cyklokapron (tranexamic acid) in the treatment of patients with advanced neoplasms. Tsdssk Nor Laegeforen 1978;98(28):1368-70.
Gardner 1980 {published data only}
  • Gardner FH, Helmer RE. Aminocaproic acid: use in control of hemorrhage in patients with amegakaryocytic thrombocytopenia. JAMA 1980;243(1):35-7.
Garewal 1985 {published data only}
  • Garewal HS, Durie BGM. Anti-fibrinolytic therapy with aminocaproic acid for the control of bleeding in thrombocytopenic patients. Scandinavian Journal of Haematology 1985;35:497-500.
Jeserschek 2003 {published data only}
  • Jeserschek R, Clar H, Aigner C, Rehak P, Primus B, Windhager R. Reduction of blood loss using high-dose aprotinin in major orthopaedic surgery. Journal of Bone and Joint Surgery 2003;85(2):174-7.
Kalmadi 2006 {published data only}
Katzel 1998 {published data only}
  • Katzel R, Keuper H, Wiedemann B, Brethner L, Viogt B. The effects of intraoperative aprotinin on perioperative haemostasis and fibrinolysis and their effects on blood loss and transfusion requirements in lung surgery [Effekte der intraoperativen Aprotininapplikation auf perioperative Haemostase und Fibrinolyseveraenderungen und ihre Auswirkungen auf Blutverlust und Transfusionsbedarf bei lungenchirurgischen Eingriffen]. Infusionstherapie und Transfusionsmedizin 1998;25:236-45.
Levy 2005 {published data only}
  • Levy JH. Novel concepts in treatment and prevention of bleeding. IARS Review Course Lectures. International Anesthesia Research Society, 2005:43-7.
Marti-Carvajal 2011 {published data only}
McConnell 2011 {published data only}
  • McConnell JS, Shewale S, Munro NA, Shah K, Deakin AH, Kinninmonth AWG. Reduction of blood loss in primary hip arthroplasty with tranexamic acid or fibrin spray. Acta Orthopaedica 2011;82(6):660-3.
McConnell 2012 {published data only}
  • McConnell JS, Shewale S, Munro NA, Shah K, Deakin AH, Kinninmonth AWG. Reducing blood loss in primary knee arthroplasty: a prospective randomised controlled trial of tranexamic acid and fibrin spray. Knee 2012;19(4):295-8.
Mevio 1983 {published data only}
  • Mevio E, Santarelli P. Tranexamic acid in prevention of oropharyngeal radiomucositis [L'acido tranexamico nella prevenzione delle radiomucositi a livello oro-faringeo]. La Radiologia Medica 1983;69:325-8.
Movafegh 2011 {published data only}
  • Movafegh A, Eslamian L, Dorabadi A. Effects of intravenous tranexamic acid administration on blood loss during and after cesarian delivery. International Journal of Gynecology and Obstetrics 2011;115:224-6.
Rickles 2007 {published data only}
  • Rickles FR, Falanga A, Montesinos P, Sanz MA, Brenner B, Barbui T. Bleeding and thrombosis in acute leukemia: what does the future of therapy look like?. Thrombosis Research 2007;120(2):99-106.
Sanz 2010 {published data only}
  • Sanz MA, Montesinos P. Open issues on bleeding and thrombosis in acute promyelocytic leukemia. Thrombosis Research 2010;125(2):51-4.
Schwartz 1986 {published data only}
  • Schwartz BS, Williams EC, Conlan MG, Mosher DF. Epsilon-aminocaproic acid in the treatment of patients with acute promyelocytic leukaemia and acquired alpha-2-plasmin inhibitor deficiency. Annals of Internal Medicine 1986;105:873-7.
Wassenaar 2008 {published data only}
  • Wassenaar T, Black J, Kahl B, Schwartz B, Longo W, Mosher D, et al. Acute promyelocytic leukemia and acquired alpha-2-plasmin inhibitor deficiency: a retrospective look at the use of epsilon-aminocaproic acid (Amicar) in 30 patients. Hematological Oncology 2008;26:241-6.
Yang 2001 {published data only}
  • Yang H, Zheng S, Shi C. Clinical study on the efficacy of tranexamic acid in reducing postpartum blood loss: a randomized, comparative, multicenter trial. Chinese Journal of Obstetrics and Gynecology 2001;36(10):590-2.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
BCSH 2003
Bolton-Maggs 2012
  • Bolton-Maggs PHB (editor) and Cohen H on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2011 Annual SHOT Report. Serious Hazards of Transfusion (SHOT), 2012.
Cameron 2007
Deeks 2011
  • Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Faught 1998
  • Faught C, Wells P, Fergusson D, Laupacis A. Adverse effects of methods for minimizing perioperative allogeneic transfusion: a critical review of the literature. Transfusion Medicine Reviews 1998;12(3):206-25.
Fergusson 2008
  • Fergusson DA, Hebert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. New England Journal of Medicine 2008;358(22):2319-31.
Franchini 2010
  • Franchini M, Dario Di Minno MN, Coppola A. Disseminated intravascular coagulation in hematologic malignancies. Seminars in Thrombosis and Haemostasis 2010;36(4):388-403.
Friedmann 2002
  • Friedmann AM, Sengul H, Lehmann H, Schwartz C, Goodman S. Do basic laboratory tests or clinical observations predict bleeding in thrombocytopenic oncology patients? A reevaluation of prophylactic platelet transfusions. Transfusion Medicine Reviews 2002;16(1):34-45.
Greeno 2007
Guerriero 2011
  • Guerriero C, Cairns J, Perel P, Shakur H, Roberts I. Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. PLoS One 2011;6(5):e18987.
Gurusamy 2011
  • Gurusamy KS, Pissanou T, Pikhart H, Vaughan J, Burroughs AK, Davidson BR. Methods to decrease blood loss and transfusion requirements for liver transplantation. Cochrane Database of Systematic Reviews 2011, Issue 12. [DOI: 10.1002/14651858.CD009052.pub2]
Heddle 2009
  • Heddle NM, Webbert K. Chapter 6: Investigation of acute transfusion reactions. In: Murphy MF, Pamphilion DH editor(s). Practical Transfusion Medicine. 3rd Edition. Blackwell, 2009:63-89.
Henry 2011
  • 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 2011a
  • Higgins JPT, Deeks JJ (editors). Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Higgins 2011b
  • Higgins JPT, Deeks JJ, Altman DG (editors). Chapter 16: Special topics in Statistics. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Higgins 2011c
  • Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Ker 2012
  • Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 2012;344:e3054. [PUBMED: 22611164]
Khorana 2006
Lefebvre 2011
  • Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Llewelyn 2009
Lozano 2013
  • Lozano M, Sweeney JD. Avoiding platelet transfusions. In: Sweeney J, Lozano M editor(s). Platelet Transfusion Therapy. Bethesda, Maryland: AABB Press, 2013:567-89.
Martin 2011
  • Martin K, Gertler R, Sterner A, MacGuill M, Schreiber C, Horer J, et al. Comparison of blood-sparing efficacy of epsilon-aminocaproic acid and tranexamic acid in newborns undergoing cardiac surgery. The Thoracic and Cardiovascular Surgeon 2011;59(5):276-80.
Martin-Hirsch 2010
Novikova 2011
Okamoto 1997
Pendry 2011
  • 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.
Pogue 1997
Popovsky 1985
Prentice 1980
  • Prentice CR. Basis of antifibrinolytic therapy. Journal of Clinical Pathology Supplement 1980;14:35-40.
Roberts 2011
  • Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011;377(9771):1096-101, 1101.e1-2.
Roos 2008
  • Roos YB, Rinkel GJE, Vermeulen M, Algra A, van Gijn J. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database of Systematic Reviews 2003, Issue 2. [DOI: 10.1002/14651858.CD001245]
Sawamura 2009
  • Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T, et al. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thrombosis Research 2009;124(5):608-13.
Schünemann 2011
  • Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and 'Summary of findings' tables. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Shakur 2010
  • Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010;376(9734):23-32.
Slichter 2005
  • Slichter SJ, Davis K, Enright H, Braine H, Gernsheimer T, Kao KJ, et al. Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Blood 2005;105(10):4106-14.
Slichter 2010
  • Slichter SJ, Kaufman RM, Assmann SF, McCullough J, Triulzi DJ, Strauss RG, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. New England Journal of Medicine 2010;362(7):600-13.
Sterne 2011
  • Sterne JAC, Egger M, Moher D (editors). Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Intervention. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
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