Semin Thromb Hemost 2007; 33(4): 427-434
DOI: 10.1055/s-2007-976178
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Management of Bleeding Complications of Hematologic Malignancies

David Green1
  • 1Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine of Northwestern University, Chicago, Illinois
Further Information

Publication History

Publication Date:
24 May 2007 (online)

ABSTRACT

Persons with hematologic malignancies bleed for a variety of reasons, including alterations in platelet function and numbers, clotting factor deficiencies, circulating anticoagulants, and defects in vascular integrity. The management of bleeding begins with a full characterization of the hemostatic defect. Vitamin K deficiency always should be considered and excluded by clinical history and laboratory tests. Localized bleeding is treated by packing, topical hemostatic agents, dressings, vessel ligation, laser beam coagulation, or embolization. Platelet transfusions are administered for hemorrhage secondary to severe platelet dysfunction or thrombocytopenia, but usually are not indicated if there is no bleeding, even though platelets may be as low as 10,000/μL. Bleeding due to thrombocytopenia that is refractory to random-donor platelets may respond to cross-matched compatible platelets, or to recombinant factor VIIa (rFVIIa). Fresh frozen plasma is indicated infrequently; bleeding due to coagulopathies is better managed with cryoprecipitate if fibrinogen is low, or with clotting factor concentrates appropriate for the specific clotting factors found to be deficient. rFVIIa or activated prothrombin complex concentrate usually controls hemorrhage due to autoantibodies directed against factor VIII, and acquired von Willebrand's disease may be responsive to desmopressin or intravenous gamma globulin infusion. Antifibrinolytic agents often enhance other hemostatic therapies, but should be withheld if there is genitourinary bleeding or evidence of disseminated intravascular coagulation. Finally, plasmapheresis and immunoadsorption to remove paraproteins may be helpful when other measures fail to curb bleeding.

REFERENCES

  • 1 Elting L S, Martin C G, Kurtin D J et al.. The bleeding risk index: a clinical prediction rule to guide the prophylactic use of platelet transfusions in patients with lymphoma or solid tumors.  Cancer. 2002;  94 3252-3262
  • 2 Ey F S, Goodnight S H. Bleeding disorders in cancer.  Semin Oncol. 1990;  17 187-197
  • 3 Tallman M, Abutalib S A, Altman J K. The double hazard of thrombophilia and bleeding in acute promyelocytic leukemia.  Semin Thromb Hemost. 2007;  33 330-338
  • 4 Federici A B. Acquired von Willebrand Syndrome: an underdiagnosed and misdiagnosed bleeding complication in patients with lymphoproliferative and myeloproliferative disorders.  Semin Hematol. 2006;  43(suppl 1) S48-S58
  • 5 Pereira J, Phan T. Management of bleeding in patients with advanced cancer.  Oncologist. 2004;  9 561-570
  • 6 Schiffer C A, Anderson K C, Bennett C L et al.. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.  J Clin Oncol. 2001;  19 1519-1538
  • 7 Slichter S J, Davis K, Enright H et al.. Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients.  Blood. 2005;  105 4106-4114
  • 8 Brubaker D B, Marcus C, Holmes E. Intravascular and total body platelet equilibrium in healthy volunteers and in thrombocytopenic patients transfused with single donor platelets.  Am J Hematol. 1998;  58 165-176
  • 9 Downes K A, Wilson E, Yomtovian R, Sarode R. Serial measurement of clotting factor in thawed plasma stored for 5 days.  Transfusion. 2001;  41 570
  • 10 Gill J C, Endres-Brooks J, Bauer P J, Marks W J, Montgomery R R. The effect of ABO blood group on the diagnosis of von Willebrand disease.  Blood. 1987;  69 1691-1695
  • 11 Sallah S, Nguyen N P, Abdallah J M, Hanrahan L R. Acquired hemophilia in patients with hematologic malignancies.  Arch Pathol Lab Med. 2000;  124 730-734
  • 12 Budde U, Dent J A, Berkowitz S D et al.. Subunit composition of plasma von Willebrand factor in patients with the myeloproliferative syndrome.  Blood. 1986;  68 1213-1217
  • 13 Gabriel D A, Li X, Monroe III D M, Roberts H R. Recombinant human factor VIIa (rFVIIa) can activate factor FIX on activated platelets.  J Thromb Haemost. 2004;  2 1816-1822
  • 14 Hoffman M, Monroe III D M, Roberts H R. Activated factor VII activates factors IX and X on the surface of activated platelets: thoughts on the mechanism of action of high-dose activated factor VII.  Blood Coagul Fibrinolysis. 1998;  1(suppl) S21-S25
  • 15 Hay C R, Negrier C, Ludlam C. The treatment of bleeding in acquired hemophilia with recombinant factor VIIa: a multicenter study.  Thromb Haemost. 1997;  78 1463-1467
  • 16 Poon M-C. Management of thrombocytopenic bleeding: is there a role for recombinant coagulation factor VIIa?.  Curr Hematol Rep. 2003;  2 139-147
  • 17 Richardson P. Hemostatic complications of hematopoietic stem cell transplantation: from hemorrhage to microangiopathies and VOD.  Pathophysiol Haemost Thromb. 2003;  33(suppl 1) 50-53
  • 18 O'Connell K A, Wood J J, Wise R P, Lozier J N, Braun M M. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa.  JAMA. 2006;  295 293-298
  • 19 Aledort L M. Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity.  J Thromb Haemost. 2004;  2 1700-1708
  • 20 Mayer S A, Brun N C, Begtrup K et al.. Recombinant activated factor VII for acute intracerebral hemorrhage.  N Engl J Med. 2005;  352 777-785
  • 21 Turecek P L, Varadi K, Gritsch H, Schwarz H P. FEIBA: mode of action.  Haemophilia. 2004;  10(suppl 2) 3-9
  • 22 Luu H, Ewenstein B. FEIBA® safety profile in multiple modes of clinical and hone-therapy application.  Haemophilia. 2004;  10(suppl 2) 10-16
  • 23 Negrier C, Goudemand J, Sultan Y et al.. Multicenter retrospective study on the utilization of FEIBA in France in patients with factor VIII and factor IX inhibitors.  Thromb Haemost. 1997;  77 1113-1119
  • 24 Ehrlich H J, Henzl M J, Gomperts E D. Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of thrombotic adverse events.  Haemophilia. 2002;  8 83-90
  • 25 Berntorp E, Donfield S, Waters J et al.. The FEIBA® NovoSeven® Comparative Study (FENOC)-a randomized evaluation of by-passing agents in hemophilia complicated by inhibitors.  Blood. 2005;  106 98a (abst)
  • 26 Federici A B, Stabile F, Castaman G, Canciani M T, Mannucci P M. Treatment of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: comparison of three different therapeutic approaches.  Blood. 1998;  92 2707-2711
  • 27 Kazatchkine M D, Kaveri S V. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin.  N Engl J Med. 2001;  345 747-755
  • 28 Glick R, Green D, Ts'ao C, Witt W, Yu A, Raimondi A. High dose epsilon-aminocaproic acid prolongs the bleeding time and increases rebleeding and intraoperative hemorrhage in patients with subarachnoid hemorrhage.  Neurosurgery. 1981;  9 398-401
  • 29 Brown J E, 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 1010-1012
  • 30 Federici A B, Rand J H, Bucciarelli P et al.. Subcommittee on von Willebrand factor: acquired von Willebrand syndrome: data from an international registry.  Thromb Haemost. 2000;  84 345-349
  • 31 Pineda A A, Vamvakas E C. Applications of therapeutic apheresis in patients with malignant disease.  Oncologist. 1997;  2 94-103
  • 32 Snyder H W, Cochran S K, Balint J P et al.. Experience with protein A-immunoadsorption in treatment-resistant adult immune thrombocytopenic purpura.  Blood. 1992;  79 2237-2245
  • 33 Dzik W H, Duncan L M. Case 35-1994-A 55-year-old woman with a skin rash and hemiparesis after staphylococcal protein A column therapy.  N Engl J Med. 1994;  331 792-800

David GreenM.D. Ph.D. 

676 North St. Clair Street

Suite 850, Chicago, IL 60611

Email: d-green@northwestern.edu

    >