Role of contact factors on the procoagulant activity of ribonucleic acid (RNA) in different animal species

• Grant number: 09/54620-4
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2010
• End date: April 30, 2012
• Field of knowledge: Biological Sciences - Physiology - Compared Physiology
• Principal Investigator: Benedito Carlos Prezoto
• Grantee: Benedito Carlos Prezoto
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Under physiological conditions, the contact phase proteins appears to be dispensable for normal haemostasis. However, data from animal models strongly suggest that these proteins play a decisive role in pathological thrombus formation. The physiological role, physiological activator and mechanism of activation of factor XII (FII) are obscure so far. Recently, Kannemeier et al provided evidences in vitro and in vivo that extracellular nucleic acids, in particular RNA, serve to promote the activation of contact phase proteins, mainly FXII. This hypothesis is very important, since these authors believe that extracellular nucleic acids can activate blood coagulation mechanism and promote hypercoagulable state or thromboembolic complications in tumor patients. In spite of having an efficient haemostasis, with a bleeding time of less than 60 s, avian species seem to present a natural "Hageman factor deficiency disease", since no FXII-like activity or FXII-related gene can be detected in plasma or genoma, respectively. In previous studies using thrombelastographic assay with chicken whole blood, thrombocyte-rich and thrombocyte-poor plasma samples, we observed one thrombocyte-dependent and plasma FXII-independent clotting mechanism. We propose the thrombelastographic assay with chicken whole blood and thrombocyte-poor plasma samples, to test one possible RNA-dependent increase on thrombin (and fibrin) generation. This assay can be considered as one suitable test to refute or confirm the hypothesis proposed by Kannemeier et al, that extracellular nucleic acids, in particular RNA, serve to promote the activation of plasma FXII. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PREZOTO, BENEDITO C.; OGUIURA, NANCY. Factor XII-Deficient Chicken Plasma as a Useful Target for Screening of Pro- and Anticoagulant Animal Venom Toxins. TOXINS, v. 12, n. 2, FEB 2020. (09/54620-4)

PREZOTO, B. C.; ABUD, L. L.; BORGES, F. G.; CARNEIRO, S. M.; ARANHA, T. E. D. O.; LEWIS, BS; FLUGELMAN, MY; HALON, DA. Polyphosphate released from activated thrombocytes triggers the intrinsic pathway of coagulation in the absence of factor XII in chickens. CORONARY ARTERY DISEASE: 2011 UPDATE: FROM PREVENTION TO INTERVENTION, v. N/A, p. 6-pg., 2011-01-01. (09/54620-4)