Universität zu Köln

Fletcher-Sandersjoo, Alexander ORCID: 0000-0002-3558-3045, Maegele, Marc and Bellander, Bo-Michael ORCID: 0000-0002-0648-2501 (2020). Does Complement-Mediated Hemostatic Disturbance Occur in Traumatic Brain Injury? A Literature Review and Observational Study Protocol. Int. J. Mol. Sci., 21 (5). BASEL: MDPI. ISSN 1422-0067

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Abstract

Despite improvements in medical triage and tertiary care, traumatic brain injury (TBI) remains associated with significant morbidity and mortality. Almost two-thirds of patients with severe TBI develop some form of hemostatic disturbance, which contributes to poor outcome. In addition, the complement system, which is abundant in the healthy brain, undergoes significant intra- and extracranial amplification following TBI. Previously considered to be structurally similar but separate systems, evidence of an interaction between the complement and coagulation systems in non-TBI cohorts has accumulated, with the activation of one system amplifying the activation of the other, independent of their established pathways. However, it is not known whether this interaction exists in TBI. In this review we summarize the available literature on complement activation following TBI, and the crosstalk between the complement and coagulation systems. We demonstrate how the complement system interacts with the coagulation cascade by activating the intrinsic coagulation pathway and by bypassing the initial cascade and directly producing thrombin as well. This crosstalk also effects platelets, where evidence points to a relationship with the complement system on multiple levels, with complement anaphylatoxins being able to induce disproportionate platelet activation and adhesion. The complement system also stimulates thrombosis by inhibiting fibrinolysis and stimulating endothelial cells to release prothrombotic microparticles. These interactions see clinical relevance in several disorders where a deficiency in complement regulation seems to result in a prothrombotic clinical presentation. Finally, based on these observations, we present the outline of an observational cohort study that is currently under preparation and aimed at assessing how complement influences coagulation in patients with isolated TBI.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fletcher-Sandersjoo, Alexander UNSPECIFIED orcid.org/0000-0002-3558-3045 UNSPECIFIED Maegele, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Bellander, Bo-Michael UNSPECIFIED orcid.org/0000-0002-0648-2501 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-342398
DOI:	10.3390/ijms21051596
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	5
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROGRESSIVE HEMORRHAGIC INJURY; TISSUE FACTOR ACTIVITY; ACUTE ISCHEMIC-STROKE; C5A RECEPTOR; FIBRINOLYSIS-SHUTDOWN; PLATELET DYSFUNCTION; INNATE IMMUNITY; CROSS-TALK; COAGULATION; ACTIVATION Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34239