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Graft-Versus-Host Disease

Early thrombin generation and impaired fibrinolysis after SCT associate with acute GVHD

Bone Marrow Transplantation volume 45, pages 730–737 (2010)Cite this article

Abstract

The evolution of coagulation and fibrinolysis has not been thoroughly evaluated in allogeneic SCT. In this pilot study, we characterized the adaptive mechanisms of coagulation and fibrinolysis during allogeneic SCT and 3-month follow-up and studied possible associations with outcome, including acute GVHD. Thirty patients underwent SCT for a haematological malignancy after myeloablative conditioning. Nineteen patients received the transplant from an HLA-identical sibling and 11 from an unrelated donor. GVHD prophylaxis consisted of CYA and MTX, with methylprednisolone in sibling transplants. Serial coagulation and fibrinolytic activity markers were assessed, including prothrombin fragments 1+2 (F1+2), thrombin time, D-dimer, tissue-type plasminogen-activator (tPA) and plasminogen-activator inhibitor (PAI-1). Early during conditioning therapy, F1+2 and D-dimer increased threefold indicating thrombin generation and fibrin turnover. TPA activity peaked before engraftment, concurring with diminished PAI-1. At 10 days after transplantation shortened thrombin time (<15 s), F1+2 exceeding 0.7 nmol/L and PAI-1 3.0 IU/mL were associated with the development of GVHD. In conclusion, early maladaptation, that is, upregulated thrombin generation and inhibition of fibrinolysis, occurred in one-third of the SCT patients associating with the development of GVHD, a finding suggesting an interplay between coagulation and immunology during SCT.

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Acknowledgements

We thank Professor Seppo Sarna for his expertise and help in the statistical analysis, and laboratory technician Ellen Saarela for her help in the laboratory analyses.

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Authors and Affiliations

  1. Coagulation Disorders, Helsinki University Central Hospital, Helsinki, Finland

    A Pinomäki & R Lassila

  2. Division of Haematology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

    L Volin & T Ruutu

  3. Coagulation Disorders, Clinical Chemistry and Haematology, HUSLAB Laboratory Services, Helsinki, Finland

    L Joutsi-Korhonen, M Lemponen & R Lassila

  4. Department of Virology, HUSLAB Laboratory Services and Haartman Institute, University of Helsinki, Helsinki, Finland

    J O Virtanen

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  1. A Pinomäki
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  6. T Ruutu
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Correspondence to A Pinomäki.

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Pinomäki, A., Volin, L., Joutsi-Korhonen, L. et al. Early thrombin generation and impaired fibrinolysis after SCT associate with acute GVHD. Bone Marrow Transplant 45, 730–737 (2010). https://doi.org/10.1038/bmt.2009.227

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