Extended coagulation profiles of healthy baboons and of baboons rejecting GT-KO pig heart grafts

Academic Article

Abstract

  • Introduction: Derangements of coagulation, e.g. thrombotic microangiopathy (TM) and disseminated intravascular coagulation (DIC), limit the success of pig-to-baboon organ transplantation. Studies have investigated the coagulation profile in baboons post-xenotransplantation (XTx), but an extended coagulation profile of healthy baboons pre-XTx has not been reported. Methods: Blood was drawn from nine healthy male baboons (approximate age 5 yr, mean weight 15 kg) that had not undergone any prior surgical or therapeutic procedures. An extended coagulation profile, consisting of markers of thrombin activation, fibrinolysis, endothelial activation, the protein C pathway, and overall reactive state, was investigated by a reference coagulation laboratory, using tests for human plasma. The mean value ± SD was calculated for 18 parameters (analytes); values outside of the mean ± 2 SD were excluded. Three baboons subsequently underwent transplantation with hearts from GT-KO pigs, and received either no therapy (B24603), CVF (B25003), or CVF + leflunomide (B24903), and their extended coagulation parameters were followed. Results: For 14 of the 18 analytes, the human reference range reflected the coagulation status of healthy baboons. Exceptions included thrombin/antithrombin complex and fibrinopeptide A, which were elevated compared with the human reference range, while plasminogen activity was lower. The human assay failed to detect baboon plasminogen activator inhibitor-1. Immediately after GT-KO pig heart transplantation, the untreated B24603 demonstrated a coagulation profile consistent with its postoperative clinical status; DIC was not apparent, and the heart was electively excised within 2.5 h. In B25003 and B24903, that rejected their grafts on days 8 and 12, respectively, the coagulation profile showed evidence of DIC, particularly in B24903, which was clinically coagulopathic by this time. Conclusions: (i) The human reference range of extended coagulation parameters forms a basis for studies in baboons, with a few exceptions. (ii) Antibody-mediated rejection of GT-KO pig hearts in baboons can be associated with laboratory and clinical evidence of DIC. © 2006 Blackwell Munksgaard.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Ezzelarab M; Cortese-Hassett A; Cooper DKC; Yazer MH
  • Start Page

  • 522
  • End Page

  • 528
  • Volume

  • 13
  • Issue

  • 6