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Thromb Haemost 1994; 72(01): 028-032
DOI: 10.1055/s-0038-1648806
Original Article
Schattauer GmbH Stuttgart

Factor Vila and other Haemostatic Variables following Bone Marrow Transplantation

P Collins
1   The Department of Haematology, The Royal London Hospital, London, UK
,
A Roderick
1   The Department of Haematology, The Royal London Hospital, London, UK
,
D O’Brien
2   Haemostasis Research Group, Clinical Research Council, Northwick Park Hospital, Harrow, Middlesex, UK
,
E Tuddenham
2   Haemostasis Research Group, Clinical Research Council, Northwick Park Hospital, Harrow, Middlesex, UK
,
A O’Driscoll
3   Department of Haematology, University College Hospital, London, UK
,
R Chopra
3   Department of Haematology, University College Hospital, London, UK
,
A Goldstone
3   Department of Haematology, University College Hospital, London, UK
,
A Newland
1   The Department of Haematology, The Royal London Hospital, London, UK
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 10. Dezember 1993

Accepted after resubmission 17. März 1994

Publikationsdatum:
12. Juli 2018 (online)

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Summary

Hepatic venocclusive disease causes considerable morbidity and mortality following bone marrow transplantation. There are two hypotheses regarding the aetiology of this syndrome; firstly that changes in plasma coagulation factors and natural anticoagulants lead to a prothrombotic state and secondly that endothelial cell activation stimulates intravascular deposition of fibrin. We have investigated these mechanisms by measuring the changes in proteins C and S and factors VII and X in the post transplant period and by using the plasma concentration of factor Vila as an in vivo marker of potential endothelial cell tissue factor expression. Protein C fell in both allograft and autograft patients but more so in the allografts. Similar results were found for factors VII and X. These changes were predominantly due to hepatic dysfunction induced by the chemo-radiotherapy. Factor Vila levels were unchanged in both the allograft and autograft patients. We conclude that there is no convincing evidence for a procoagulant state following BMT as there are both anticoagulant and procoagulant changes. The absence of any changes in factor Vila levels suggests that tissue factor was not exposed to the general circulation following BMT but does not exclude focal expression at the sites of thrombosis.

 

  • References

  • 1 McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence and predisposing factors. Hepatology 1984; 4: 116-123
    CrossrefPubMedGoogle Scholar
  • 2 McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. The clinical course of 53 patients with venocclusive disease of the liver after marrow transplantation. Transplantation 1985; 39: 603-608
    CrossrefPubMedGoogle Scholar
  • 3 Dulley FL, Kanfer EJ, Applebaum FR, Amos D, Hill RS, Buckner CD, Shulman HM, McDonald GB, Thomas ED. Venocclusive disease of the liver after chemoradiotherapy and autologous bone marrow transplantation. Transplantation 1987; 43: 870-873
    CrossrefPubMedGoogle Scholar
  • 4 Shulman HM, McDonald GB, Matthews DE, Doney KC, Kopecky KJ, Gauvreau JM, Thomas ED. An analysis of hepatic venocclusive disease and centrilobular hepatic degeneration following bone marrow transplantation. Gastroenterology 1980; 79: 1178-1191
    PubMedGoogle Scholar
  • 5 Faioni EM, Krachmalnicoff A, Bearman SI, Federici AB, Decarli A, Gianni AM, McDonald GB, Mannucci PM. Naturally occurring anticoagulants and bone marrow transplantation: plasma protein C predicts the development of venocclusive disease of the liver. Blood 1993; 81: 3458-3462
    PubMedGoogle Scholar
  • 6 Gordon B, Haire W, Kessinger A, Duggan M, Armitage J. High frequency of antithrombin III and protein C deficiency following autologous bone marrow transplantation for lymphoma. Bone Marrow Transplantation 1991; 8: 497-502
    PubMedGoogle Scholar
  • 7 Harper PL, Jarvis J, Jennings I, Luddington R, Marcus RE. Changes in the natural anticoagulants following bone marrow transplantation. Bone marrow transplantation 1990; 5: 39-42
    PubMedGoogle Scholar
  • 8 Scrobohaci ML, Drouet L, Monem-Mansi A, Devergie A, Baudin B, D’Agay MF, Gluckman E. Liver veno-occlusive disease after bone marrow transplantation changes in coagulation parameters and endothelial markers. Thromb Res 1991; 63: 509-519
    CrossrefPubMedGoogle Scholar
  • 9 Allen JR, Carstens LA, Katagiri GJ. Hepatic veins of monkeys with veno-occlusive disease. Arch Pathol 1969; 87: 279-289
    PubMedGoogle Scholar
  • 10 Collins P, Gutteridge C, O’Driscoll A, Blair S, Jones L, Aitcheson R, Kelsey S, Chopra R, Goldstone A, Newland A. Von Willebrand factor as a marker of endothelial cell activation following bone marrow transplantation. Bone Marrow Transplantation 1992; 10: 499-506
    PubMedGoogle Scholar
  • 11 Colucci M, Balconi G, Lorenzet R, Locati PD. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-1896
    CrossrefPubMedGoogle Scholar
  • 12 Bevilacqua MP, Pober JS, Majeau GR, Cotran RS, Gimbrone MA. Interleukin 1 (IL1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med 1984; 160: 618-623
    CrossrefPubMedGoogle Scholar
  • 13 Nawroth PP, Handley DA, Esmon CT, Stem DM. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci USA 1986; 83: 3460-3461
    CrossrefPubMedGoogle Scholar
  • 14 Moore KL, Esmon CT, Esmon NL. Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture. Blood 1989; 73: 159-165
    PubMedGoogle Scholar
  • 15 Gelehrter TD, Sznycer-Laszuk R. Thrombin induction of plasminogen activator-inhibitor in cultured human endothelial cells. J Clin Invest 1986; 77: 165-169
    CrossrefPubMedGoogle Scholar
  • 16 O’Brien DP. The molecular biology and biochemistry of tissue factor. In: Clinical Haematology, The molecular biology of coagulation 1989: 801-820 Ed EGD Tuddenham, Bailliere Tindall:
  • 17 Collins P, Wilkie M, Razak K, Abbott S, Harley S, Zaidi M, Blake D, Cunningham J, Newland A. Cyclosporin A and cremaphor modulate von Willebrand factor release from cultured human endothelial cells. Transplantation 1993; 56: 1218-1223
    CrossrefPubMedGoogle Scholar
  • 18 Carlsen E, Flatmark A, Prydz H. Cytokine induced procoagulant activity in monocytes and endothelial cells. Further enhancement by cyclosporin. Transplantation 1988; 46: 575-580
    CrossrefPubMedGoogle Scholar
  • 19 Drake TA, Cheng J, Chang A, Taylor F. Expression of tissue factor, thrombomodulin and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993; 142: 1458-1470
    PubMedGoogle Scholar
  • 20 Morrissey JH, Macik BG, Neuenschwander PF, Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. Blood 1993; 81: 734-714
    PubMedGoogle Scholar
  • 21 Holler E, Kolb HJ, Moller A, Kempeni J, Liesenfeld S, Pechumer H, Lehmacher W, Ruckdeschel G, Gleixner B, Riedner C, Ledderose G, Brehm G, Mittermuller J, Wilmanns W. Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. Blood 1990; 75: 1011-1016
    PubMedGoogle Scholar
  • 22 Rao L, Rapaport S. Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation. Blood 1987; 69: 645-651
    PubMedGoogle Scholar
  • 24 Rogers JS, Murgo AJ, Fontana JA, Raich PC. Chemotherapy for breast cancer decreases in plasma protein C and protein S. J Clin Oncology 1988; 6: 276-281
    CrossrefPubMedGoogle Scholar