Thrombin-activatable fibrinolysis inhibitor influences disease severity in humans and mice with pneumococcal meningitis

Journal of Thrombosis and Haemostasis : JTH
B B Mook-KanamoriDiederik van de Beek

Abstract

Mortality and morbidity in patients with bacterial meningitis result from the proinflammatory response and dysregulation of coagulation and fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is activated by free thrombin or thrombin in complex with thrombomodulin, and plays an antifibrinolytic role during fibrin clot degradation, but also has an anti-inflammatory role by inactivating proinflammatory mediators, such as complement activation products. To assess the role of TAFI in pneumococcal meningitis. We performed a prospective nationwide genetic association study in patients with bacterial meningitis, determined TAFI and complement levels in cerebrospinal fluid (CSF), and assessed the function of TAFI in a pneumococcal meningitis mouse model by using Cpb2 (TAFI) knockout mice. Polymorphisms (reference sequences: rs1926447 and rs3742264) in the CPB2 gene, coding for TAFI, were related to the development of systemic complications in patients with pneumococcal meningitis. Higher protein levels of TAFI in CSF were significantly associated with CSF complement levels (C3a, iC3b, and C5b-9) and with more systemic complications in patients with bacterial meningitis. The risk allele of rs1926447 (TT) was associated with...Continue Reading

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Citations

Mar 24, 2016·Acta Neuropathologica Communications·Joo-Yeon Engelen-LeeDiederik van de Beek
Dec 15, 2015·The Lancet Infectious Diseases·Merijn W BijlsmaDiederik van de Beek
Dec 5, 2017·Annals of Intensive Care·Xavier DelabrancheFerhat Meziani
Apr 19, 2017·The Journal of International Medical Research·Yanbing LiangLiao Pinhu
Sep 9, 2018·Journal of Neuroinflammation·Merel M KoopmansDiederik van de Beek
Sep 15, 2019·BMC Medical Genomics·Anne T KloekDiederik van de Beek
Apr 30, 2020·Journal of Clinical Medicine·Jan Tilmann VollrathBorna Relja
May 1, 2021·Biomolecules·Nathan A ShlobinChaim G Pick

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