Summary.  Background:  Both established oral anticoagulants such as warfarin and newer agents such as dabigatran etexilate (DE) effectively prevent thromboembolic disease, but may provoke bleeding. Limited clinical data exist linking oral anticoagulant reversal and bleeding tendency, as opposed to surrogate laboratory markers. Objective:  To quantify bleeding in warfarin‐anticoagulated and DE‐anticoagulated mice by tail transection with or without pretreatment with potential reversal agents: prothrombin complex concentrate (PCC); activated PCC (APCC); recombinant factor VIIa (rFVIIa); or murine fresh‐frozen plasma (FFP). Methods:  CD1 mice were given warfarin or DE by gavage, and the effects on in vitro coagulation assays, volume of blood loss and the bleeding time following tail transection injury were evaluated with different reversal agents. Results:  PCC (14.3 IU kg−1), but not rFVIIa (3 mg kg−1) or FFP (12 mL kg−1), normalized blood loss and bleeding time in mice with warfarin‐induced elevations of mean prothrombin time at two intensities (prothrombin time ratios of either 4.3 or 24). Neither separate nor combined PCC and/or rFVIIa treatment nor APCC (100 U kg−1) treatment significantly reduced blood loss in mice anticoagulated with 60 mg kg−1 DE 75 min prior to tail transection. Both combined PCC plus rFVIIa treatment and APCC treatment significantly reduced bleeding time in the DE‐treated mice. Conclusions:  Our data suggest that PCC treatment prevents excess bleeding much more effectively in warfarin‐induced coagulopathy than in DE‐induced coagulopathy.

Toll-like receptors (TLRs) trigger the innate immune system by responding to specific components of microorganisms. MyD88 and TRIF are Toll/interleukin (IL)-1 (TIR)-domain containing adapters, which play essential roles in TLR-mediated signalling via the MyD88-dependant and -independent pathways, respectively. Genes encoding several TLRs have been identified in the chicken genome, however, elements of their signalling pathways have not been well characterized. Here we describe the cloning of chicken MyD88 and TRIF orthologs, and examine the spatial and temporal expression of these genes. The chicken MyD88 cDNA was shown to have an open reading frame (ORF) of 1104 bp, encoding a predicted protein sequence of 368 aa, 8 aa short of a previously published coding sequence due to a premature stop codon. MyD88 gene expression was detected in each tissue tested except in muscle. The chicken TRIF cDNA possessed an ORF of 2205 bp, encoding a predicted protein sequence of 735 aa, which shared 37.3% similarity and 28.9% identity to human TRIF protein sequence. TRIF was ubiquitously expressed in all tissues.

No abstract

Cytokine gene expression in the chicken spleen during embryogenesis and the early posthatch period was investigated in the present study. The constitutive expression of interleukin-4, interleukin-10, interleukin-18, and interferon-gamma genes was detectable as early as embryonic day 12. Expression of cytokine genes was higher in the spleen of posthatch chickens compared with chick embryos. There was a gradual increase in expression of all the cytokine genes in the spleen, which peaked by d 7 posthatch. This expression pattern coincided with the completion of T-cell colonization and structural development of the spleen during the early posthatch period. It is therefore possible that the cytokines examined in the present study are involved in the maturation of colonized T cells and in shaping the spleen microenvironment.

The content of Fg, but not FVIII, determined the efficacy of plasma transfusion in coagulopathic mice.