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Hamostaseologie 2021; 41(06): 489-501
DOI: 10.1055/a-1528-0499
Review Article

Mechanism, Functions, and Diagnostic Relevance of FXII Activation by Foreign Surfaces

Sandra Konrath
1   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Reiner K. Mailer
1   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Thomas Renné
1   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
› Author Affiliations Funding/Acknowledgment T.R. acknowledges the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) for grants A11/SFB 877, B8/SFB 841, and P6/KFO 306.
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Abstract

Factor XII (FXII) is a serine protease zymogen produced by hepatocytes and secreted into plasma. The highly glycosylated coagulation protein consists of six domains and a proline-rich region that regulate activation and function. Activation of FXII results from a conformational change induced by binding (“contact”) with negatively charged surfaces. The activated serine protease FXIIa drives both the proinflammatory kallikrein–kinin pathway and the procoagulant intrinsic coagulation cascade, respectively. Deficiency in FXII is associated with a prolonged activated partial thromboplastin time (aPTT) but not with an increased bleeding tendency. However, genetic or pharmacological deficiency impairs both arterial and venous thrombosis in experimental models. This review summarizes current knowledge of FXII structure, mechanisms of FXII contact activation, and the importance of FXII for diagnostic coagulation testing and thrombosis.

Zusammenfassung

Faktor XII (FXII) ist das Zymogen der Serinprotease FXIIa, wird von Hepatozyten produziert und ins Plasma sekretiert. Das Plasmaprotein besteht aus sechs Domänen sowie einer Prolin-reichen Region und ist stark glykosyliert. Die Aktivierung von FXII erfolgt durch eine Konformationsänderung, die durch die Bindung (den „Kontakt“) mit negativ geladenen Oberflächen hervorgerufen wird. In der Folge aktiviert FXIIa sowohl das proinflammatorische Kallikrein-Kinin-System, welches Bradykinin produziert, als auch die intrinsische Gerinnungskaskade. Eine FXII-Defizienz oder Dysfunktionalität ist mit einer verzögerten aktivierten partiellen Thromboplastinzeit (aPTT) assoziiert, nicht aber mit einer erhöhten Blutungsneigung. Dennoch zeigen experimentelle Modelle, dass FXII essentiell für die Bildung arterieller und venöser, Gefäß-verschließender Thrombosen ist. Diese Übersichtsarbeit fasst das aktuelle Wissen über die Struktur von FXII, den Mechanismus der FXII-Kontaktaktivierung und die Bedeutung von FXII für diagnostische Gerinnungstests zusammen.

Keywords

contact system - blood coagulation - polyphosphate - inflammation - factor XII

Schlüsselwörter

Kontaktphasesystem - Blutgerinnung - Polyphosphat - Entzündung - Faktor XII


Publication History

Received: 17 January 2021

Accepted: 11 June 2021

Article published online:
30 September 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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