Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Veno-occlusive Hepatic Disease

  • Author: James L Harper, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
 
Updated: Mar 31, 2016
 

Background

Along with graft versus host disease (GVHD) and cytomegalovirus (CMV) infection, veno-occlusive disease (VOD) or Sinusoidal Obstruction Syndrome (SOS), is one of the most frequently encountered serious complications after stem cell transplantation. The reported overall incidence rate of veno-occlusive disease ranges from 5% to more than 60% in children who have undergone stem cell transplantation, and similar rates have been reported in adults.[1, 2, 3, 4, 5, 6, 7]

The causes of veno-occlusive disease are still unclear, but a combination of pretransplant risk factors and transplant-related conditions are believed to trigger a primarily hepatic sinusoidal injury. This can quickly extend to a hepatocytic and panvasculitic disease, which is followed by multiorgan failure that is associated with substantial mortality. The initiating pathophysiological events have prompted this form of liver disease be renamed sinusoidal obstruction syndrome (SOS).

The risk of sinusoidal obstruction syndrome in the pediatric population is not limited to a well-defined group of high-risk patients who have undergone transplantation. The disease frequently occurs outside this group. For example, patients treated for solid tumors (eg, Wilms tumor, neuroblastomas, and rhabdomyosarcomas[8, 9] ) are at risk for developing veno-occlusive disease. SOS has also been described in a patient with Burkitt lymphoma.[10]

Single nucleotide polymorphisms of the donor may also be a factor in the onset of SOS in children receiving an allogeneic transplant.[11]

Next

Pathophysiology

The pathophysiology of sinusoidal obstructive syndrome remains obscure. The primary injury in veno-occlusive disease is most likely a lesion of the sinusoidal endothelial cells of hepatic venules. The first recognizable histologic changes are characterized by widening of the subendothelial zone, red cell extravasation, fibrin deposition, and expression of factor VIII/von Willebrand factor within venule walls, followed by necrosis of the perivenular hepatocytes. Late histological findings include deposits of extracellular matrix, an increased number of stellate cells, and subsequent sinusoidal fibrosis. This process eventually leads to complete venular obliteration, extensive hepatocellular necrosis, and widespread fibrous tissue replacement of normal liver.

The detritus, which consist of endothelial cells, Kupffer cells, and stellate cells, embolize and obstruct downstream sinusoidal flow, characteristically affecting the centrilobular zone 3. Zone 3 is nearest to the central hepatic venules, according to the distance from the afferent arterial supply. Therefore, it receives the least oxygen supply and is given the term centrilobular.

Occluded hepatic venules were not found during autopsy in 25% of patients with even severe veno-occlusive disease. Because involvement of the hepatic veins does not appear to be essential for the development of clinical signs of veno-occlusive disease, a proposal has been made to change the name of the disease to sinusoidal obstruction syndrome.[12, 13]

Numerous studies have demonstrated associations with various hemostatic derangements, such as antithrombin deficiency, protein C deficiency, ADAMTS 13 enzyme deficiency, and elevations of plasminogen activator inhibitor; however, no conclusive evidence of a thrombotic origin to the liver damage has been demonstrated.[14, 15]

Previous
Next

Epidemiology

Frequency

United States

Sinusoidal obstructive syndrome is a rare but significant complication of allogeneic bone marrow transplantation (BMT). Along with GVHD and CMV infection, sinusoidal obstructive syndrome is one of the most common serious complications after stem cell transplantation and is associated with high posttransplantation morbidity and mortality rates. Precise estimates of frequency are difficult because the incidence of veno-occlusive disease varies depending on the preparative regimen, the type of transplantation, and the underlying disease. The reported overall incidence of sinusoidal obstructive syndrome ranges from 5% to more than 60% in children, and similar rates have been reported in adults.[1, 2, 3, 4, 5, 6, 7]

International

The worldwide incidence rate of veno-occlusive disease appears to be similar to that in the United States.

Mortality/Morbidity

Severe disease is associated with significant morbidity and a mortality rate of more than 90%.[16] In children, the mortality rate in patients with veno-occlusive disease 100 days posttransplantation is 38.5%, as opposed to 9% in patients who do not have veno-occlusive disease.[1]

Early identification of high-risk patients with severe disease is of the utmost importance because of the high mortality rates associated with severe veno-occlusive disease.

The severity of sinusoidal obstructive syndromeis divided into the following 3 categories:

  • Mild disease
    • No adverse effects from sinusoidal obstructive syndrome
    • No treatment necessary
    • Self-limiting
  • Moderate disease
    • No adverse effects from sinusoidal obstructive syndrome
    • Requires treatment (pain medication, diuretics, other supportive care)
  • Severe disease
    • Unresolved signs and symptoms of sinusoidal obstructive syndrome 100 days after stem cell transplantation
    • Death due to complications directly attributable to sinusoidal obstructive syndrome

Severe sinusoidal obstructive syndrome can be more precisely defined based on the presence of multiorgan failure in addition to veno-occlusive disease. Multiorgan failure is characterized by oxygen requirement (with an oxygen saturation of < 90% on room air, ventilator dependence, or both), renal dysfunction (defined as doubling of baseline creatinine levels, dialysis dependence, or both), and/or encephalopathy.[17]

Race

Veno-occlusive disease has no racial predilection.

Sex

Veno-occlusive disease occurs equally in males and females.

Age

Veno-occlusive disease occurs in both children and adults.

Previous
 
 
Contributor Information and Disclosures
Author

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Selim Corbacioglu, MD Professor of Pediatrics, Chair of Pediatric Hematology, Oncology and Stem Cell Transplantation, Children's Hospital Regensburg, University of Regensburg, Germany

Selim Corbacioglu, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Hematology, European Hematology Association, European Society for Blood and Marrow Transplantation

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Jennifer Reikes Willert, MD Associate Clinical Professor, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Section of Stem Cell Transplantation, Stanford University Medical Center, Lucile Packard Children's Hospital

Jennifer Reikes Willert, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society for Blood and Marrow Transplantation, Children's Oncology Group, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Stephan A Grupp, MD, PhD Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, Society for Pediatric Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

References
  1. Barker CC, Butzner JD, Anderson RA, Brant R, Sauve RS. Incidence, survival and risk factors for the development of veno-occlusive disease in pediatric hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2003 Jul. 32(1):79-87. [Medline].

  2. Reiss U, Cowan M, McMillan A, Horn B. Hepatic venoocclusive disease in blood and bone marrow transplantation in children and young adults: incidence, risk factors, and outcome in a cohort of 241 patients. J Pediatr Hematol Oncol. 2002 Dec. 24(9):746-50. [Medline].

  3. Cesaro S, Pillon M, Talenti E, et al. A prospective survey on incidence, risk factors and therapy of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. Haematologica. 2005 Oct. 90(10):1396-404. [Medline]. [Full Text].

  4. Corbacioglu S, Honig M, Lahr G, et al. Stem cell transplantation in children with infantile osteopetrosis is associated with a high incidence of VOD, which could be prevented with defibrotide. Bone Marrow Transplant. 2006 Oct. 38(8):547-53. [Medline].

  5. Coppell JA, Brown SA, Perry DJ. Veno-occlusive disease: cytokines, genetics, and haemostasis. Blood Rev. 2003 Jun. 17(2):63-70. [Medline].

  6. Jones RJ, Lee KS, Beschorner WE, et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation. 1987 Dec. 44(6):778-83. [Medline].

  7. Carreras E, Bertz H, Arcese W, et al. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood. 1998 Nov 15. 92(10):3599-604. [Medline]. [Full Text].

  8. Cecen E, Uysal KM, Ozguven A, Gunes D, Irken G, Olgun N. Veno-occlusive disease in a child with rhabdomyosarcoma after conventional chemotherapy: report of a case and review of the literature. Pediatr Hematol Oncol. 2007 Dec. 24(8):615-21. [Medline].

  9. Cesaro S, Spiller M, Sartori MT, Alaggio R, Peruzzo M, Saggiorato G, et al. Veno-occlusive disease in pediatric patients affected by Wilms tumor. Pediatr Blood Cancer. 2011 Aug. 57(2):258-61. [Medline].

  10. Miyata D, Fukushima T, Matsunaga M, Saito N, Kato Y, Takahashi-Igari M, et al. Fatal pulmonary veno-occlusive disease after chemotherapy for Burkitt's lymphoma. Pediatr Int. 2011 Jun. 53(3):403-5. [Medline].

  11. Elbahlawan L, McArthur J, Quasney MW, Pei D, Srivastava K, Dahmer MK, et al. Association of IL-1ß -511 Polymorphism With Severe Veno-occlusive Disease in Pediatric-matched Allogeneic Hematopoietic Stem Cell Transplantation. J Pediatr Hematol Oncol. 2012 Apr. 34(3):175-9. [Medline].

  12. Shulman HM, Gown AM, Nugent DJ. Hepatic veno-occlusive disease after bone marrow transplantation. Immunohistochemical identification of the material within occluded central venules. Am J Pathol. 1987 Jun. 127(3):549-58. [Medline]. [Full Text].

  13. DeLeve LD, Shulman HM, McDonald GB. Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Semin Liver Dis. 2002 Feb. 22(1):27-42. [Medline].

  14. Pihusch M, Wegner H, Goehring P, et al. Diagnosis of hepatic veno-occlusive disease by plasminogen activator inhibitor-1 plasma antigen levels: a prospective analysis in 350 allogeneic hematopoietic stem cell recipients. Transplantation. 2005 Nov 27. 80(10):1376-82. [Medline].

  15. Matsumoto M, Kawa K, Uemura M, Kato S, Ishizashi H, Isonishi A, et al. Prophylactic fresh frozen plasma may prevent development of hepatic VOD after stem cell transplantation via ADAMTS13-mediated restoration of von Willebrand factor plasma levels. Bone Marrow Transplant. 2007 Aug. 40(3):251-9. [Medline].

  16. McDonald GB, Hinds MS, Fisher LD, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med. 1993 Feb 15. 118(4):255-67. [Medline].

  17. Richardson PG, Elias AD, Krishnan A, et al. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. Blood. 1998 Aug 1. 92(3):737-44. [Medline]. [Full Text].

  18. Hasegawa S, Horibe K, Kawabe T, et al. Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors. Bone Marrow Transplant. 1998 Dec. 22(12):1191-7. [Medline].

  19. Corbacioglu S, Greil J, Peters C, et al. Defibrotide in the treatment of children with veno-occlusive disease (VOD): a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention. Bone Marrow Transplant. 2004 Jan. 33(2):189-95. [Medline].

  20. Carreras E, Granena A, Navasa M, et al. On the reliability of clinical criteria for the diagnosis of hepatic veno-occlusive disease. Ann Hematol. 1993 Feb. 66(2):77-80. [Medline].

  21. Yeager AM, Wagner JE Jr, Graham ML, et al. Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation. Blood. 1992 Nov 1. 80(9):2425-8. [Medline]. [Full Text].

  22. Dix SP, Wingard JR, Mullins RE, et al. Association of busulfan area under the curve with veno-occlusive disease following BMT. Bone Marrow Transplant. 1996 Feb. 17(2):225-30. [Medline].

  23. Slattery JT, Clift RA, Buckner CD, et al. Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation. Blood. 1997 Apr 15. 89(8):3055-60. [Medline]. [Full Text].

  24. Lee JH, Choi SJ, Lee JH. Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic derangements associated with intravenous busulfan vs oral busulfan in adults conditioned with busulfan + cyclophosphamide for allogeneic bone marrow transplantation. Ann Hematol. 2005 May. 84(5):321-30. [Medline].

  25. Nagler A, Labopin M, Berger R, Bunjes D, Campos A, Socié G, et al. Allogeneic hematopoietic SCT for adults AML using i.v. BU in the conditioning regimen: outcomes and risk factors for the occurrence of hepatic sinusoidal obstructive syndrome. Bone Marrow Transplant. 2014 May. 49(5):628-33. [Medline].

  26. Smith LH, Dixon JD, Stringham JR, Eren M, Elokdah H, Crandall DL, et al. Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis. Blood. 2006 Jan 1. 107(1):132-4. [Medline]. [Full Text].

  27. Kulkarni S, Rodriguez M, Lafuente A, et al. Recombinant tissue plasminogen activator (rtPA) for the treatment of hepatic veno-occlusive disease (VOD). Bone Marrow Transplant. 1999 Apr. 23(8):803-7. [Medline].

  28. Bearman SI, Lee JL, Baron AE, McDonald GB. Treatment of hepatic venocclusive disease with recombinant human tissue plasminogen activator and heparin in 42 marrow transplant patients. Blood. 1997 Mar 1. 89(5):1501-6. [Medline]. [Full Text].

  29. Bajwa RP, Cant AJ, Abinun M, et al. Recombinant tissue plasminogen activator for treatment of hepatic veno-occlusive disease following bone marrow transplantation in children: effectiveness and a scoring system for initiating treatment. Bone Marrow Transplant. 2003 Apr. 31(7):591-7. [Medline].

  30. Baglin TP, Harper P, Marcus RE. Veno-occlusive disease of the liver complicating ABMT successfully treated with recombinant tissue plasminogen activator (rt-PA). Bone Marrow Transplant. 1990 Jun. 5(6):439-41. [Medline].

  31. Yakushijin K, Okamura A, Ono K, et al. [Defibrotide therapy for patients with sinusoidal obstruction syndrome after hematopoietic stem cell transplantation]. Rinsho Ketsueki. 2009 Jan. 50(1):3-8. [Medline].

  32. Guglielmelli T, Bringhen S, Palumbo A. Update on the use of defibrotide. Expert Opin Biol Ther. 2012 Mar. 12(3):353-61. [Medline].

  33. Richardson PG, Soiffer RJ, Antin JH, Uno H, Jin Z, Kurtzberg J, et al. Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial. Biol Blood Marrow Transplant. 2010 Jul. 16(7):1005-17. [Medline]. [Full Text].

  34. Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM, et al. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016 Jan 29. [Medline]. [Full Text].

  35. Falanga A, Marchetti M, Vignoli A, et al. Defibrotide (DF) modulates tissue factor expression by microvascular endothelial cells. Blood. 1999. 94:146a.

  36. Falanga A, Marchetti M, Vignoli A, et al. Impact of defibrotide on the fibrinolytic and procoagulant properties of endothelial cells from macro- and micro-vessles. Blood. 2000. 96:53a.

  37. Falanga A, Vignoli A, Marchetti M, Barbui T. Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells. Leukemia. 2003 Aug. 17(8):1636-42. [Medline].

  38. Eissner G, Multhoff G, Gerbitz A, et al. Fludarabine induces apoptosis, activation, and allogenicity in human endothelial and epithelial cells: protective effect of defibrotide. Blood. 2002 Jul 1. 100(1):334-40. [Medline]. [Full Text].

  39. Palmer KJ, Goa KL. Defibrotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in vascular disorders. Drugs. 1993 Feb. 45(2):259-94. [Medline].

  40. Chopra R, Eaton JD, Grassi A, et al. Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study. Br J Haematol. 2000 Dec. 111(4):1122-9. [Medline].

  41. Richardson PG, Soiffer R, Antin JH, et al. Defibrotide (DF) appears effective and safe in a Phase II, randomized study of patients with severe veno-occlusive disease (VOD) and multisystem organ failure (MOF) post stem cell transplantation (SCT). Blood. 2002. 100:112a.

  42. Richardson PG, Murakami C, Jin Z, et al. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood. 2002 Dec 15. 100(13):4337-43. [Medline]. [Full Text].

  43. Chueh HW, Sung KW, Lee SH, Yoo KH, Koo HH, Kim JY, et al. Iron chelation treatment with deferasirox prior to high-dose chemotherapy and autologous stem cell transplantation may reduce the risk of hepatic veno-occlusive disease in children with high-risk solid tumors. Pediatr Blood Cancer. 2012 Mar. 58(3):441-7. [Medline].

  44. Bearman SI, Hinds MS, Wolford JL, et al. A pilot study of continuous infusion heparin for the prevention of hepatic veno-occlusive disease after bone marrow transplantation. Bone Marrow Transplant. 1990 Jun. 5(6):407-11. [Medline].

  45. Attal M, Huguet F, Rubie H, et al. Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial. Blood. 1992 Jun 1. 79(11):2834-40. [Medline]. [Full Text].

  46. Rosenthal J, Sender L, Secola R, et al. Phase II trial of heparin prophylaxis for veno-occlusive disease of the liver in children undergoing bone marrow transplantation. Bone Marrow Transplant. 1996 Jul. 18(1):185-91. [Medline].

  47. Song JS, Seo JJ, Moon HN, Ghim T, Im HJ. Prophylactic low-dose heparin or prostaglandin E1 may prevent severe veno-occlusive disease of the liver after allogeneic hematopoietic stem cell transplantation in Korean children. J Korean Med Sci. 2006 Oct. 21(5):897-903. [Medline]. [Full Text].

  48. Gluckman E, Jolivet I, Scrobohaci ML, et al. Use of prostaglandin E1 for prevention of liver veno-occlusive disease in leukaemic patients treated by allogeneic bone marrow transplantation. Br J Haematol. 1990 Mar. 74(3):277-81. [Medline].

  49. Schlegel PG, Haber HP, Beck J, et al. Hepatic veno-occlusive disease in pediatric stem cell recipients: successful treatment with continuous infusion of prostaglandin E1 and low-dose heparin. Ann Hematol. 1998 Jan. 76(1):37-41. [Medline].

  50. Park SH, Lee MH, Lee H, et al. A randomized trial of heparin plus ursodiol vs. heparin alone to prevent hepatic veno-occlusive disease after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2002 Jan. 29(2):137-43. [Medline].

  51. Ibrahim RB, Peres E, Dansey R, Abidi MH, Abella EM, Klein J. Anti-thrombin III in the management of hematopoietic stem-cell transplantation-associated toxicity. Ann Pharmacother. 2004 Jun. 38(6):1053-9. [Medline].

  52. Haussmann U, Fischer J, Eber S, Scherer F, Seger R, Gungor T. Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy. Haematologica. 2006 Jun. 91(6):795-800. [Medline]. [Full Text].

  53. Cheuk DK, Chiang AK, Ha SY, Chan GC. Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation. Cochrane Database Syst Rev. 2015 May 27. 5:CD009311. [Medline].

  54. [Guideline] Children's Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. Sections 92-106: hematopoetic cell transplant. 2006 Mar. [Full Text].

  55. Bartelink IH, Bredius RG, Ververs TT, et al. Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2008 Jan. 14(1):88-98. [Medline].

  56. Cefalo MG, Maurizi P, Arlotta A, Scalzone M, Attinà G, Ruggiero A, et al. Hepatic veno-occlusive disease: a chemotherapy-related toxicity in children with malignancies. Paediatr Drugs. 2010 Oct 1. 12(5):277-84. [Medline].

  57. Jevtic D, Zecevic Z, Veljkovic D, Dopsaj V, Radojicic Z, Elezovic I. Veno-occlusive disease in pediatric patients after hematopoietic stem cell transplantation: relevance of activated coagulation and fibrinolysis markers and natural anticoagulants. J Pediatr Hematol Oncol. 2011 Apr. 33(3):227-34. [Medline].

  58. Kasow KA, Stewart CF, Barfield RC, Wright NL, Li C, Srivastava DK, et al. A phase I/II study of CY and topotecan in patients with high-risk malignancies undergoing autologous hematopoietic cell transplantation: the St Jude long-term follow-up. Bone Marrow Transplant. 2012 Mar 19. [Medline].

  59. Lee SH, Yoo KH, Sung KW, Koo HH, Kwon YJ, Kwon MM, et al. Hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation: incidence, risk factors, and outcome. Bone Marrow Transplant. 2010 Aug. 45(8):1287-93. [Medline].

  60. Meresse V, Hartmann O, Vassal G, et al. Risk factors for hepatic veno-occlusive disease after high-dose busulfan-containing regimens followed by autologous bone marrow transplantation: a study in 136 children. Bone Marrow Transplant. 1992 Aug. 10(2):135-41. [Medline].

  61. Sartori MT, Cesaro S, Peruzzo M, Messina C, Saggiorato G, Calore E, et al. Contribution of fibrinolytic tests to the differential diagnosis of veno-occlusive disease complicating pediatric hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2012 May. 58(5):791-7. [Medline].

  62. Yamada N, Urahashi T, Ihara Y, Sanada Y, Wakiya T, Okada N, et al. Veno-occlusive disease/sinusoidal obstruction syndrome associated with potential antibody-mediated rejection after pediatric living donor liver transplantation: a case report. Transplant Proc. 2012 Apr. 44(3):810-3. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.