Control of Bleeding in Cancer

  • Jaime Pereira
Part of the Cancer Treatment and Research book series (CTAR, volume 148)

Clinically significant bleeding occurs in approximately 10% of the patients with advanced cancer [1]. Massive bleeding from the nose, pharynx, lung, or gastrointestinal tract constitutes a major challenge; however, it is difficult to predict who will have a serious bleeding event requiring special management and interventions. Bleeding in patients with cancer may present as a localized bleeding diathesis, more often as a result of local injury by tumor invasion or as a generalized hemorrhagic diathesis caused by thrombocytopenia, platelet dysfunction, coagulation factor deficiencies, presence of inhibitors or increased fibrinolysis. Mild persistent bleeding can be distressing for the patient, family members and caregivers; however, catastrophic massive bleeding may also occur, demanding urgent therapeutic intervention.


International Normalize Ratio Disseminate Intravascular Coagulation Tranexamic Acid Fresh Freeze Plasma Platelet Transfusion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Gagnon B, Mancini I, Pereira J, Bruera E. Palliative management of bleeding events in advanced cancer patients. J Palliat Care 1998;14: 50–54.PubMedGoogle Scholar
  2. 2.
    Prommer E. Management of bleeding in the terminally ill patient. Hematology 2005;10:167–75.PubMedCrossRefGoogle Scholar
  3. 3.
    MacDougall R, Munro AJ, Wilson Janet A. Palliation in head and neck cancer. In: Geoffrey DD, Hanks WC, MacDonald N, editors. Oxford textbook of palliative medicine. 2nd ed. Oxford, England Oxford Medical Publications;1999:677–89.Google Scholar
  4. 4.
    Kvale PA, Selecky PA, Prakash UB. American College of Chest Physicians. Palliative care in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(3 Suppl):368S–403S.PubMedCrossRefGoogle Scholar
  5. 5.
    Zhu LX, Wang GS, Fan ST. Spontaneous rupture of of hepatocellular carcinoma Br J Surg 1996;83:602–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Stalfelt AM, Brodin H, Pettersson S, Eklöf A. The final phase in acute myeloid leukaemia (AML). A study on bleeding, infection and pain. Leuk Res 2003;27:481–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Johnson MJ. Bleeding, clotting and cancer. Clin Oncol 1997;9:294–301.CrossRefGoogle Scholar
  8. 8.
    Avvisati G, Tirindelli MC, Annibali O. Thrombocytopenia and hemorrhagic risk in cancer patients. Crit Rev Hemato Oncol 2003;48:S13–S16.CrossRefGoogle Scholar
  9. 9.
    Heal JM, Blumberg N. Optimizing platelet transfusion therapy. Blood Rev 2004;18:149–65.PubMedCrossRefGoogle Scholar
  10. 10.
    Sallah S, Wan JY, Nguyen NP, et al. Disseminated intravascular coagulation in solid tumors: clinical and pathologic study. Thromb Haemost 2001;86:828–33.PubMedGoogle Scholar
  11. 11.
    Levi M. Disseminated intravascular coagulation. Crit Care Med 2007;35:2191–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Johnson MJ. Problems of anticoagulation within a palliative care setting: an audit of hospice patients taking warfarin. Palliat Med 1997;11:306–12.PubMedCrossRefGoogle Scholar
  13. 13.
    Hutten BA, Prins MH, Gent M, et al. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000;18:3078–83.PubMedGoogle Scholar
  14. 14.
    Peterson DE, Cariello A. Mucosal damage: a major risk factor for severe complications after cytotoxic therapy. Semin Oncol 2004;31:35–44.PubMedCrossRefGoogle Scholar
  15. 15.
    Pihusch M. Bleeding complications after hematopoietic stem cell transplantation. Semin Hematol 2004;41 (Suppl 1):93–100.PubMedCrossRefGoogle Scholar
  16. 16.
    Patsner B. Topical acetone for control of life-threatening vaginal hemorrhage from recurrent gynecologic cancer. Eur J Gynaecol Oncol 1993;14:33–5.PubMedGoogle Scholar
  17. 17.
    Kothari P, Patel SK, O'Malley SJ. Application of cocaine to the nasal mucosa: a novel method. Laryngol Otol 2001;115:650–1Google Scholar
  18. 18.
    Adebamowo CA. Topical formalin for management of bleeding malignant ulcers. World J Surg 2000;24:518–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Biswal BM, Lal P, Rath GK, et al. Intrarectal formalin application, an effective treatment for grade III haemorrhagic radiation proctitis. Radiother Oncol 1995;35:212–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Russo P. Urologic emergencies. In: Devita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. Philadelphia, PA: JB Lippincott Co., 1993:2159–60.Google Scholar
  21. 21.
    Dunn CJ, Goa KL. Fibrin sealant: a review of its use in surgery and endoscopy. Drugs 1999;58:863–86.PubMedCrossRefGoogle Scholar
  22. 22.
    Spotnitz WD. Commercial fibrin sealants in surgical care. Am J Surg 2001;182:8S–14S.PubMedCrossRefGoogle Scholar
  23. 23.
    MacGillivray TE. Fibrin sealants and glues. J Card Surg 2003;18:480–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Dickneite G, Metzner H, Pfeifer T, et al. A comparison of fibrin sealants in relation to their in vitro and in vivo properties. Thromb Res 2003;112:73–82.PubMedCrossRefGoogle Scholar
  25. 25.
    Kanaoka Y, Hirai K, Ishiko O, et al. Vesicovaginal fistula treated with fibrin glue. Int J Gynaecol Obstet 2001;73:147–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Brundage MD, Bezjak A, Dixon P, et al. The role of palliative thoracic radiotherapy in non-small cell lung cancer. Can J Oncol 1996;6(Suppl 1):25–32.PubMedGoogle Scholar
  27. 27.
    A Medical Research Council (MRC) randomised trial of palliative radiotherapy with two fractions or a single fraction in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status. Medical Research Council Lung Cancer Working Party. Br J Cancer 1992;65:934–41.Google Scholar
  28. 28.
    Hoskin PJ. Radiotherapy in symptom management. In: Doyle D, Hanks GWC, MacDonald N eds. Oxford Textbook of Palliative Care. Second Edition. New York: Oxford University Press, 1998: 278–80.Google Scholar
  29. 29.
    Biswal BM, Lal P, Rath GK, et al. Hemostatic radiotherapy in carcinoma of the uterine cervix. Int J Gynaecol Obstet 1995;50:281–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Miller CM, O’Neill A, Mortimer PS. Skin problems in palliative care: nursing aspects. In: Doyle D, Hanks GWC, MacDonald N eds. Oxford Textbook of Palliative Care. Second Edition. New York: Oxford University Press, 1993: 395–407.Google Scholar
  31. 31.
    Ferris FD, Bezjak A, Rosenthal SG. The palliative uses of radiation therapy in surgical oncology patients. Surg Oncol Clin N Am 2001;10:185–201.PubMedGoogle Scholar
  32. 32.
    Onsrud M, Hagen B, Strickert T. 10-Gy single-fraction pelvic irradiation for palliation and life prolongation in patients with cancer of the cervix and corpus uteri. Gynecol Oncol 2001;82:167–71.PubMedCrossRefGoogle Scholar
  33. 33.
    Srinivasan V, Brown CH, Turner AG. A comparison of two radiotherapy regimens for the treatment of symptoms from advanced bladder cancer. Clin Oncol (R Coll Radiol) 1994;6:11–3.CrossRefGoogle Scholar
  34. 34.
    Wong R, Thomas G, Cummings B, et al. The role of radiotherapy in the management of pelvic recurrence of rectal cancer. Can J Oncol 1996;6(Suppl 1):39–47.PubMedGoogle Scholar
  35. 35.
    Savides TJ, Jensen DM. Therapeutic endoscopy for nonvariceal gastrointestinal bleeding. Gastroenterol Clin North Am 2000;29:465–87.PubMedCrossRefGoogle Scholar
  36. 36.
    von Ditfurth B, Buhl K, Friedl P. Palliative endoscopic therapy for rectal cancer with neodymium:YAG laser. Eur J Surg Oncol 1990;16:376–9.Google Scholar
  37. 37.
    Sherwood LA, Knowles G, Wilson RG, et al. Retrospective review of laser therapy for palliation of colorectal tumors. Eur J Oncol Nurs 2006;10:30–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Broadley KE, Kurowska A, Dick R, Platts A, Tookman A. The role of embolization in palliative care. Palliat Med 1995;9:331–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Pereira J, Phan T. Management of bleeding in patients with advanced cancer. The Oncologist 2004;9:561–70.PubMedCrossRefGoogle Scholar
  40. 40.
    Stroncek DF, Rebulla P. Platelet transfusions. Lancet 2007;370:427–38.PubMedCrossRefGoogle Scholar
  41. 41.
    Schiffer CA, Anderson KC, Bennett CL, et al. for the American Society of Clinical Oncology. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001;19:1519–38.PubMedGoogle Scholar
  42. 42.
    Slichter SL. Evidence-based platelet transfusion guidelines. Hematology Am Soc Hematol Educ Program 2007;2007:172–8.CrossRefGoogle Scholar
  43. 43.
    British Committee for Standards in Haematology, Blood Transfusion Task Force. Guidelines for the use of platelet transfusions. Br J Haematol 2003;122:10–23.CrossRefGoogle Scholar
  44. 44.
    Heaton WA, Rebulla P, Pappalettera M, et al. A comparative analysis of different methods for routine blood component preparation. Transfus Med Rev 1997;11:116–29.PubMedCrossRefGoogle Scholar
  45. 45.
    Chambers LA, Herman JH. Considerations in the selection of a platelet component: apheresis versus whole blood-derived. Transfus Med Rev 1999;1 3: 311–22.CrossRefGoogle Scholar
  46. 46.
    Zumberg MS, del Rosario ML, Nejame CF, et al. A prospective randomized trial of prophylactic platelet transfusion and bleeding incidence in hematopoietic stem cell transplant recipients: 10,000/lL versus 20,000/lL trigger. Biol Blood Marrow Transplant 2002;8:569–76.PubMedCrossRefGoogle Scholar
  47. 47.
    Rebulla P, Finazzi G, Marangoni F, et al. The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. N Engl J Med 1997;337:1870–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Wandt H, Frank M, Ehninger G, et al. Safety and cost effectiveness of a 10 × 109/l trigger for prophylactic platelet transfusions compared to the traditional 20 × 109/l: a prospective comparative trial in 105 patients with acute myeloid leukemia. Blood 1998;91:3601–6PubMedGoogle Scholar
  49. 49.
    Heckman KD, Weiner GJ, Davis CS, et al. Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/lL versus 20,000/lL. J Clin Oncol 1997;15:1143–9.PubMedGoogle Scholar
  50. 50.
    Ancliffe PJ, Machin SJ. Trigger factors for prophylactic platelet transfusion. Blood Rev 1998;12:234–38.CrossRefGoogle Scholar
  51. 51.
    Platelet transfusion therapy. National Institutes of Health Consensus Conference. Transfus Med Rev 1987;1: 195–200.Google Scholar
  52. 52.
    Norfolk DR, Anncliffe PJ, Contreras M. Consensus conference on platelet transfusion. Royal College of Physicians of Edinburgh. 27–28 November 1997. Br J Haematol 1998;101:609–17.PubMedCrossRefGoogle Scholar
  53. 53.
    Lawrence JB, Yomtovian RA, Dillman C, et al. Reliability of automated platelet counts: comparison with manual method and utility for prediction of clinical bleeding. Am J Hematol 1995;48:244–50.PubMedCrossRefGoogle Scholar
  54. 54.
    Slichter SJ, Murphy S, Buchholz D, et al. INTERCEPT platelets and conventional platelets provide comparable hemostatic responses in thrombocytopenic patients: the SPRINT trial. Blood 2002;100:141b.Google Scholar
  55. 55.
    Heddle NM, Cook RJ, Sigouin C, et al. A descriptive analysis of international transfusion practice and bleeding outcomes in patients with acute leukemia. Transfusion 2006;46:903–11.PubMedCrossRefGoogle Scholar
  56. 56.
    Hanson SR, Slichter SJ. Platelet kinetics in patients with bone marrow hypoplasia: evidence for a fixed platelet requirement. Blood 1985;56:1105–9.Google Scholar
  57. 57.
    Ackerman SJ, Klumpp TR, Guzman GI, et al. Economic consequences of alterations in platelet transfusion dose: analysis of a prospective, randomized, double-blind trial. Transfusion 2000;40:1457–62.PubMedCrossRefGoogle Scholar
  58. 58.
    Norol F, Bierling P, Roudot-Thoraval F, et al. Platelet transfusion: a dose-response study. Blood 1998;92:1448–53.PubMedGoogle Scholar
  59. 59.
    Sensebe I, Giraudeau B, Bardiaux I, et al. The efficiency of transfusing high doses of platelets in hematologic patients with thrombocytopenia: results of a prospective, randomized, open, blinded end point (PROBE) study. Blood 2005;105:862–64.PubMedCrossRefGoogle Scholar
  60. 60.
    Bishop JF, Mathews JP, Yuen K, et al. The definition of refractoriness to platelet tranasfusions. Transfus Med 1992;2:35–41.PubMedCrossRefGoogle Scholar
  61. 61.
    Rebulla P. Formulae for the definition of refractoriness to platelet transfusions. Transfus med 1993;3:91–3.PubMedCrossRefGoogle Scholar
  62. 62.
    Rebulla P. A mini-review on platelet refractoriness. Haematologica 2005;90:247–53.PubMedGoogle Scholar
  63. 63.
    Trial to Reduce Alloimmunization to Platelets Study Group. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. N Engl J Med 1993;337:1861–70.Google Scholar
  64. 64.
    Legler TJ, Fischer I, Dittmann J, et al. Frequency and causes of refractoriness in multiply transfused patients. Ann Hematol 1997;74:185–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Doughty HA, Murphy MF, Metcalfe P, et al. Relative importance of immune and non-immune causes of platelet refractoriness. Vox Sang 1994;66:200–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Novotny VM, van Doorn R, Witvliet MD, et al. Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of prestorage filtered platelets and red blood cells: a prospective study. Blood 1995;85:1736–41.PubMedGoogle Scholar
  67. 67.
    Bishop JF, Matthews JP, McGrath K, et al. Factors influencing 20-hour increments after platelet transfusion. Transfusion 1991;31:392–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Slichter SJ, Davis K, Enright H, et al. Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Blood 2005;105:4106–14.PubMedCrossRefGoogle Scholar
  69. 69.
    Balduini CL, Salvaneschi L, Klersy C, et al. Factors influencing post-transfusional platelet increment in pediatric patients given hematopoietic stem cell transplantation. Leukemia 2001;15:1885–91.PubMedCrossRefGoogle Scholar
  70. 70.
    Lassauniere JM, Bertolino M, Hunault M, et al. Platelet transfusions in advanced hematological malignancies: a position paper. J Palliat Care 1996;12:38–41.PubMedGoogle Scholar
  71. 71.
    Kicler TS. Transfusion medicine: platelet transfusion therapy, plasma, and plasma concentrates In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, eds. Hemostasis and thrombosis. Basic principles and clinical practice. Fifth Edition, Philadelphia, Lippincott Williams & Wilkins 2006: 1193–1203.Google Scholar
  72. 72.
    Stanworth SJ. The evidence-based use of FFP and cryoprecipitate for abnormalities of coagulation tests and clinical coagulopathy. Hematology Am Soc Hematol Educ Program 2007;2007:179–85.CrossRefGoogle Scholar
  73. 73.
    O'Shaughnessy DF, Atterbury C, Bolton Maggs P, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol 2004;126:11–28.PubMedCrossRefGoogle Scholar
  74. 74.
    Holland LL, Brooks JP. Toward rational fresh frozen plasma transfusion. The effect of plasma transfusion on coagulation test results. Am J Clin Pathol 2006;126:133–39.PubMedCrossRefGoogle Scholar
  75. 75.
    Downes KA, Wilson E, Yomtovian R, et al. Serial measurement of clotting factors in thawed plasma stored for 5 days. Transfusion 2001;41:570.PubMedCrossRefGoogle Scholar
  76. 76.
    Toy P, Popovsky MA, Abraham E, et al. Transfusion-related acute lung injury: definition and review. Crit Care Med 2005;33:721–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Schulman S, Bijsterveld NR. Anticoagulants and their reversal. Transfus Med Rev 2007;21:37–48.PubMedCrossRefGoogle Scholar
  78. 78.
    Ansell J, Hirsh J, Poller L, et al. The pharmacology and management of the vitamin K antagonists: 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(Suppl):204S–233S.PubMedCrossRefGoogle Scholar
  79. 79.
    Baglin TP, Keeling DM, Watson HG. Guidelines on oral anticoagulation (warfarin): 3rd edition - 2005 update. Br J Haematol 2006;132:277–85.PubMedCrossRefGoogle Scholar
  80. 80.
    Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 1997;90:2515–21.PubMedGoogle Scholar
  81. 81.
    Rodeghiero F, Castaman G. Treatment of von Willebrand disease. Sem Hematol 2005;42:29–35.CrossRefGoogle Scholar
  82. 82.
    Mannucci PM. Hemostatic drugs. N Engl J Med 1998;339:245–53.PubMedCrossRefGoogle Scholar
  83. 83.
    Rodeghiero F, Castaman G, Mannucci PM. Prospective multicenter study on subcutaneous concentrated desmopressin for home treatment of patients with von Willebrand disease and mild or moderate hemophilia A. Thromb Haemost 1996;76:692–96.PubMedGoogle Scholar
  84. 84.
    Mannucci PM. Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 1988;72:1449–55.PubMedGoogle Scholar
  85. 85.
    Federici AB. Acquired von Willebrand syndrome: is it an extremely rare disorder or do we see only the tip of the iceberg? J Thromb Haemost 2008;6:565–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Federici AB, Rand JH, Bucciarelli P, et al. Acquired von Willebrand syndrome: data from an international registry. Thromb Haemost 2000;84:345–9.PubMedGoogle Scholar
  87. 87.
    Castaman G, Di Bonna E, Schiavotto C, et al. Pilot study on the safety and efficacy of desmopressin for the treatment or prevention of bleeding in patients with hematologic malignancies. Haematologica 1997;82:584–87.PubMedGoogle Scholar
  88. 88.
    Stewart D, Marder VJ. Therapy with antifibrinolytic agents. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, eds. Hemostasis and thrombosis. Basic principles and clinical practice. Fifth Edition, Philadelphia, Lippincott Williams & Wilkins 2006: 1173–92.Google Scholar
  89. 89.
    Nesheim M, Wang W, Boffa M, et al. Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thromb Haemost 1997;78:386–91.PubMedGoogle Scholar
  90. 90.
    Dean A, Tuffin P. Fibrinolytic inhibitors for cancer-associated bleeding problems. J Pain Symptom Manage 1997;13:20–4.PubMedCrossRefGoogle Scholar
  91. 91.
    De Boer WA, Koolen MGJ, Roos CM, et al. Tranexamic acid treatment of haemothorax in two patients with malignant mesothelioma. Chest 1991;100:847–48.PubMedCrossRefGoogle Scholar
  92. 92.
    Shpilberg O, Blumenthal R, Soler O, et al. A controlled trial of tranexamic acid therapy for the reduction of bleeding during treatment of acute myeloid leukemia. Leuk Lymphoma 1995;19:141–44.PubMedCrossRefGoogle Scholar
  93. 93.
    Avvisati G, Bulller HR, ten Cate JW, et al. Tranexamic acid for control of haemorrhage in acute promyelocytic leukaemia. Lancet 1989;2:122–24.PubMedCrossRefGoogle Scholar
  94. 94.
    Hashimoto S, Koike T, Tatewaki W, et al. Fatal thromboembolism in acute promyelocytic leukemia during all-trans retinoic acid therapy combined with antifibrinolytic therapy for prophylaxis of hemorrhage. Leukemia 1994;8:1113–15.PubMedGoogle Scholar
  95. 95.
    Woo KS, Tse LK, Woo JL, et al. Massive pulmonary thromboembolism after tranexamic acid antifibrinolytic therapy. Br J Clin Pract1989;43:465–66.PubMedGoogle Scholar
  96. 96.
    Brown JE, Olujohungbe A, Chang J, et al. All-trans retinoic acid (ATRA) and tranexamic acid: a potentially fatal combination in acute promyelocytic leukemia. Br J Haematol 2000;110:1010–12.PubMedCrossRefGoogle Scholar
  97. 97.
    Roberts HR, Monroe DM, White GC. The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood 2004;104: 3858–64.PubMedCrossRefGoogle Scholar
  98. 98.
    Monroe DM, Roberts HR. Mechanism of action of high-dose factor VIIa: points of agreement and disagreement. Arterioscler Thromb Vasc Biol 2003;23:8–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Lusher JM, Roberts HR, Davignon G, et al. A randomized, double-blind comparison of two dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors. rFVIIa Study Group. Haemophilia 1998;4: 790–98PubMedCrossRefGoogle Scholar
  100. 100.
    Lusher J. Acute hemarthroses: the benefits of early versus late treatment with rfVIIa. Blood Coagul Fibrinolysis 2000;11: S45–S49.PubMedCrossRefGoogle Scholar
  101. 101.
    Abshire T, Kenet G. Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost 2004;2:899–909.PubMedCrossRefGoogle Scholar
  102. 102.
    Poon MC, D'Oiron R, Von Depka M, et al. Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann's thrombasthenia: results of an international survey. J Thromb Haemost 2004;2:1096–1103.PubMedCrossRefGoogle Scholar
  103. 103.
    Almeida AM, Khair K, Hann I, Liesner R. The use of recombinant factor VIIa in children with inherited platelet function disorders. Br J Haematol 2003;121:477–81.PubMedCrossRefGoogle Scholar
  104. 104.
    Goodnough LT. Experiences with recombinant human factor VIIa in patients with thrombocytopenia. Semin Hematol 2004;41:25–29.PubMedCrossRefGoogle Scholar
  105. 105.
    Salomon O, Zivelin A, Livnat T, et al. Prevalence, causes, and characterization of factor XI inhibitors in patients with inherited factor XI deficiency. Blood 2003;101:4783–88.PubMedCrossRefGoogle Scholar
  106. 106.
    Aldouri M. The use of recombinant factor VIIa in controlling surgical bleeding in non-haemophiliac patients. Pathophysiol Haemost Thromb 2002;32(suppl 1):41–46.PubMedCrossRefGoogle Scholar
  107. 107.
    Hay CR, Negrier C, Ludlam C. The treatment of bleeding in acquired hemophilia with recombinant factor VIIa: a multicenter study. Thromb Haemost 1997;78:1463–67.PubMedGoogle Scholar
  108. 108.
    Lusher JM, Roberts HR, Davignon G, et al. A randomized, double-blind comparison of two dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors. rFVIIa Study Group. Haemophilia 1998;4:790–8PubMedCrossRefGoogle Scholar
  109. 109.
    Shapiro A, Gilchrist GS, Hoots WK, et al. Prospective randomized trial of two doses of rFVIIa (Novoseven) in hemophilic patients with inhibitors undergoing surgery. J Thromb Haemost 1998;80:773–8.Google Scholar
  110. 110.
    Hedner U. Dosing with recombinant factor viia based on current evidence. Semin Hematol 2004;41:35–39.PubMedCrossRefGoogle Scholar
  111. 111.
    Kenet G, Lubetsky A, Luboshitz J, et al. A new approach to treatment of bleeding episodes in young hemophilia patients: a single bolus megadose of recombinant activated factor VII (NovoSeven). J Thromb Haemost 2003;1:450–5.PubMedCrossRefGoogle Scholar
  112. 112.
    O'Connell KA, Wood JJ, Wise RP, et al. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA 2006;295:293–8.PubMedCrossRefGoogle Scholar
  113. 113.
    Aledort LM. Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus FVIII inhibitor bypass activity. J Thromb Haemost 2004;2:1700–8.PubMedCrossRefGoogle Scholar
  114. 114.
    Mayer SA, Brun NC, Begtrup K, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005;352:777–85.PubMedCrossRefGoogle Scholar
  115. 115.
    Deveras RA, Kessler CM. Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa concentrate. Ann Intern Med 2002;137:884–8.PubMedGoogle Scholar
  116. 116.
    Turecek PL, Varadi K, Gritsch H, et al. FEIBA: Mode of action. Haemophilia 2004;10(suppl 2):3–9.PubMedCrossRefGoogle Scholar
  117. 117.
    Luu H, Ewenstein B. FEIBA® safety profile in multiple modes of clinical and home-therapy application. Haemophilia 2004;10(suppl 2):10–16.PubMedCrossRefGoogle Scholar
  118. 118.
    Ehrlich HJ, Henzl MJ, Gompertz ED. Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of thrombotic adverse events. haemophilia 2002;8:83–90.PubMedCrossRefGoogle Scholar
  119. 119.
    Astermark J, Donfield SM, DiMichele DM, et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. Blood 2007;109:546–51.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Hematology-Oncology, School of MedicinePontificia Universidad Católica de ChileSantiago

Personalised recommendations