Thromb Haemostasis
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We tested the hypothesis that activated neutrophil-endothelial cell interaction in DIC can cause endothelial injury contributing to multiple organ dysfunction syndrome (MODS) and a poor outcome after trauma. Fifty-eight severe trauma patients, 29 with DIC and 29 without DIC were studied. Serial levels of soluble L-, P-, and E-selectins, ICAM-1, VCAM-1, thrombomodulin, and neutrophil elastase were measured on days 0-4 after trauma. ⋯ Maximum DIC scores in the DIC group showed good correlations with peak levels of sICAM-1, sVCAM-1, neutrophil elastase, sThrombomodulin, and the number of dysfunctioning organs. Highly activated and sustained inflammation caused by neutrophil-endothelium interaction in DIC gives rise to MODS and poor outcome in patients with severe trauma. These results suggest a close relationship between inflammation and thrombosis in posttrauma DIC.
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Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. ⋯ Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.
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We have recently shown that intravenous immunoglobulin (IVIG) therapy leads to an increased rate of anti-platelet antibody clearance in an animal model of immune thrombocytopenia. The present study was performed to confirm the importance of the FcRn receptor in mediating this effect of IVIG. ⋯ In mice lacking expression of FcRn, IVIG treatment did not increase 7E3 clearance (61.0 +/- 3.6 ml/d/kg vs. 71.5 +/- 4.0 ml/d/kg in controls). Thus, these data support the hypothesis that IVIG increases antibody elimination via saturation of FcRn.