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Hamostaseologie 2020; 40(02): 153-164
DOI: 10.1055/a-1151-9519
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Platelets in Thrombo-Inflammation: Concepts, Mechanisms, and Therapeutic Strategies for Ischemic Stroke

Philipp Burkard
1   Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany
,
Timo Vögtle 
1   Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany
,
Bernhard Nieswandt 
1   Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany
› Author Affiliations
Further Information

Publication History

17 December 2019

18 March 2020

Publication Date:
26 May 2020 (online)

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Abstract

Platelets are anucleate cells known for their essential function in hemostasis and formation of thrombi under pathologic conditions. In recent years, strong evidence emerged demonstrating the critical involvement of platelets in inflammatory processes including acute ischemic stroke (AIS), which is one of the leading causes of death and disability worldwide. Recanalization of the occluded brain artery to reconstitute cerebral blood flow is the primary goal in the treatment of stroke patients. However, despite successful reperfusion many patients show progression of infarct sizes, a phenomenon referred to as ischemia/reperfusion injury (I/RI). Cerebral I/RI involves both thrombotic as well as inflammatory pathways acting in concert to cause tissue damage, defining AIS as a prototypic thrombo-inflammatory disease. Currently used antiplatelet drugs applied to AIS patients eventually increase the risk of partially life-threatening hemorrhages, making more targeted pharmacological intervention necessary. Experimental evidence indicates that inhibition of platelet surface receptors that regulate initial platelet adhesion and activation might be suitable targets in thrombo-inflammatory settings, while inhibitors of platelet aggregation are not. In this review, we will summarize the recent developments in elucidating the role of the main platelet receptors in AIS and discuss their potential as pharmaceutical targets. Furthermore, we will also briefly discuss the important platelet-triggered intrinsic coagulation pathway with the pro-inflammatory kallikrein–kinin system in the context of ischemic stroke.

Zusammenfassung

Thrombozyten sind anukleäre Zellen, die für ihre entscheidende Bedeutung in der Hämostase, aber auch für die Bildung von gefäßverschließenden Thromben unter pathologischen Bedingungen bekannt sind. In den letzten Jahren belegten jedoch einige Studien auch eine wichtige Rolle von Thrombozyten bei inflammatorischen Prozessen. Zu diesen gehört auch der ischämische Schlaganfall (acute ischemic stroke - AIS) - eine der häufigsten Todesursachen und Verursacher von Behinderungen weltweit. Bei dessen Behandlung ist das primäre Ziel die Rekanalisierung des verschlossenen Gefäßes, durch die der Blutfluss wiederhergestellt wird. Dennoch vergrößern sich bei vielen Patienten trotz erfolgreicher Reperfusion des betroffenen Areals die Infarktgebiete weiter. Dieses Phänomen wird Ischämie-Reperfusionsschaden (ischemia / reperfusion injury - I/RI) genannt. Bei dem zerebralen I/RI sind ineinandergreifende pro-thrombotische als auch inflammatorische Mechanismen an der Entstehung von Gewebeschäden beteiligt – AIS gilt daher als Prototyp thrombo-inflammatorischer Erkrankungen. Der Einsatz von gängigen Thrombozytenfunktionshemmern in AIS Patienten führt häufig zu - in Einzelfällen lebensgefährlichen - Blutungen, was die Notwendigkeit einer neuen, zielgerichteteren pharmakologischen Intervention verdeutlicht. Experimentelle Daten zeigen, dass die Inhibition von Thrombozytenrezeptoren, die an der initialen Adhäsion und Aktivierung der Zellen beteiligt sind, möglicherweise gute Angriffspunkte zur Behandlung thrombo-inflammatorischer Erkrankungen darstellen - klassische Thrombozytenaggregationshemmer jedoch nicht. In diesem Übersichtsartikel fassen wir die neuesten Entwicklungen der Forschung über die Funktion der wichtigsten Thrombozytenrezeptoren im AIS zusammen und diskutieren deren Eignung als neue pharmakologische Zielstrukturen. Darüber hinaus diskutieren wir kurz die Rolle der von Thrombozyten induzierten Kontaktaktivierung im AIS, die Startpunkt der intrinsischen Kaogulationskaskade und des inflammatorischen Kallikrein-Kinin-Systems ist.

Keywords

platelet - platelet receptors - stroke - thrombo-inflammation - FXII

Schlüsselwörter

Thrombozyten - Thrombozytenrezeptoren - Schlaganfall - Thrombo-inflammation - FXII
 

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