Potential role of blood biomarkers in the management of nontraumatic intracerebral hemorrhage

Cerebrovasc Dis. 2014;38(6):395-409. doi: 10.1159/000366470. Epub 2014 Dec 3.

Abstract

Background: Intracerebral hemorrhage (ICH), a subtype of stroke associated with high mortality and disability, accounts for 13% of all strokes. Basic and clinical research has contributed to our understanding of the complex pathophysiology of neuronal injury in ICH. Outcome rates, however, remain stable, and questions regarding acute management of ICH remain unanswered. Newer research is aiming at matching measured levels of serum proteins, enzymes, or cells to different stages of brain damage, suggesting that blood biomarkers may assist in acute diagnosis, therapeutic decisions, and prognostication. This paper provides an overview on the most promising blood biomarkers and their potential role in the diagnosis and management of spontaneous ICH.

Summary: Information was collected from studies, reviews, and guidelines listed in PubMed up to November 2013 on blood biomarkers of nontraumatic ICH in humans. We describe the potential role and limitations of GFAP, S100B/RAGE, and ApoC-III as diagnostic biomarkers, β-​Amyloid as a biomarker for etiological classification, and 27 biomarkers for prognosis of mortality and functional outcome. Within the group of prognostic markers we discuss markers involved in coagulation processes (e.g., D-Dimers), neuroendocrine markers (e.g., copeptin), systemic metabolic markers (e.g., blood glucose levels), markers of inflammation (e.g., IL-6), as well as growth factors (e.g., VEGF), and others (e.g., glutamate). Some of those blood biomarkers are agents of pathologic processes associated with hemorrhagic stroke but also other diseases, whereas others play more distinct pathophysiological roles and help in understanding the basic mechanisms of brain damage and/or recovery in ICH.

Key messages: Numerous blood biomarkers are associated with different pathophysiological pathways in ICH, and some of them promise to be useful in the management of ICH, eventually contributing additional information to current tools for diagnosis, therapy monitoring, risk stratification, or intervention. Up to date, however, no blood biomarker of ICH has been studied sufficiently to find its way into clinical routine yet; well-designed, large-scale, clinical studies addressing relevant clinical questions are needed. We suggest that the effectiveness of biomarker research in ICH might be improved by international cooperation and shared resources for large validation studies, such as provided by the consortium on stroke biomarker research (http://stroke-biomarkers.​com/page.php?title=Resources).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid beta-Peptides / blood
  • Apolipoprotein C-III / blood
  • Biomarkers / blood*
  • Cerebral Hemorrhage / blood*
  • Cerebral Hemorrhage / diagnosis
  • Cytokines / blood
  • Fibrin Fibrinogen Degradation Products
  • Glial Fibrillary Acidic Protein / blood
  • Glycopeptides / blood
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Prognosis
  • Receptor for Advanced Glycation End Products / blood
  • Receptor for Advanced Glycation End Products / chemistry
  • S100 Calcium Binding Protein beta Subunit / blood

Substances

  • AGER protein, human
  • Amyloid beta-Peptides
  • Apolipoprotein C-III
  • Biomarkers
  • Cytokines
  • Fibrin Fibrinogen Degradation Products
  • Glial Fibrillary Acidic Protein
  • Glycopeptides
  • Intercellular Signaling Peptides and Proteins
  • Receptor for Advanced Glycation End Products
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • copeptins
  • fibrin fragment D