title: Early thrombin generation and impaired fibrinolysis after SCT associate with acute GVHD.
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.
authors.affiliation: Coagulation Disorders, Helsinki University Central Hospital, Helsinki, Finland. anne.pinomaki@hus.fi
authors.forename: A
authors.initials: A
authors.lastname: Pinomäki
authors.forename: L
authors.initials: L
authors.lastname: Volin
authors.forename: L
authors.initials: L
authors.lastname: Joutsi-Korhonen
authors.forename: J O
authors.initials: JO
authors.lastname: Virtanen
authors.forename: M
authors.initials: M
authors.lastname: Lemponen
authors.forename: T
authors.initials: T
authors.lastname: Ruutu
authors.forename: R
authors.initials: R
authors.lastname: Lassila
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005342:Fibrinolysis; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014185:Transplantation, Isogeneic; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D013917:Thrombin; D010959:Tissue Plasminogen Activator