Tissue factor-dependent coagulation activation by heme: A thromboelastometry study

Author(s)

de Souza, Gleice Regina ; Hounkpe, Bidossessi Wilfried ; Luz Fiusa, Maiara Marx ; Colella, Marina Pereira ; Annichino-Bizzacchi, Joyce M. ; Traina, Fabiola ; Costa, Fernando Ferreira ; De Paula, Erich Vinicius

• Document type: Journal article
• Source: PLoS One; v. 12, n. 4 APR 24 2017.
• Web of Science Citations: 1

Abstract

Heme has been characterized as potent trigger of inflammation. In hemostasis, although heme has been shown to both induce and inhibit different compartments of hemostasis, its net effect on the hemostatic balance, and the biological relevance of these effects remain to be determined. Herein we evaluated the effect of heme on hemostasis using a global assay able to generate clinically relevant data in several other complex hemostatic diseases. Citrated whole blood samples from healthy participants were stimulated by heme or vehicle and incubated for 4h at 37 degrees C. Rotational thromboelastometry was immediately performed. The participation of tissue factor in coagulation activation was evaluated using inhibitory antibody. Heme was able of inducing ex vivo coagulation activation in whole blood, affecting predominantly parameters associated with the initial phases of clot formation. This activation effect was at least partially dependent on hematopoietic tissue factor, since the effects of heme were partially abrogated by the inhibition of human tissue factor. In conclusion, using a global hemostasis assay, our study confirmed that heme is able to activate coagulation in whole blood, in a tissue factor-dependent way. These findings could explain the disturbance in hemostatic balance observed in conditions associated with the release of heme such as sickle cell disease. (AU)

• FAPESP's process: 15/24666-3 - Investigation of new pathophysiological mechanisms of hypercoagulability in Sickle Cell Disease
• Grantee: Bidossessi Wilfried Hounkpe
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/09319-0 - Exploration of new mechanisms of epithelial barrier brekdown in acute gastrintestinal graft-versus-host-disease associated with alterations in "tight junctions"
• Grantee: Erich Vinicius de Paula
• Support Opportunities: Regular Research Grants