Identification of the Factor XII Contact Activation Site Enables Sensitive Coagulation Diagnostics
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Human Factor XII Purified, Human Kallikrein Purified, and Human Prekallikrein Purified from Molecular Innovations were used in the following study:
Identification of the Factor XII Contact Activation Site Enables Sensitive Coagulation Diagnostics
Marco Heestermans, Clément Naudin, Reiner K. Mailer, Sandra Konrath, Kristin Klaetschke, Anne Jämsä, Maike Frye, Carsten Deppermann, Giordano Pula, Piotr Kuta, Manuel A. Friese, Mathias Gelderblom, Albert Sickmann, Roger J. S. Preston, Jerzy-Roch Nofer, Stefan Rose-John, Lynn M. Butler, Ophira Salomon, Evi X. Stavrou, and Thomas Renné
Nature Communications
September 22, 2021
Blood coagulation is an essential part of stopping bleeding at the site of vascular injuries. However, uncontrolled coagulation, or thrombosis, is one of the leading causes of morbidity and mortality in Western countries.
Activated partial thromboplastin time (aPTT) coagulation tests are used to monitor the integrity of intrinsic coagulation pathways and are performed billions of times globally each year. This test relies on factor XII (FXII) contact activation – the process of surface activation of FXII that initiates blood coagulation - that is triggered by particles like white clay material kaolin, micronized silica, or ellagic acid and can be captured and measured by the aPTT assay. Unfortunately, the surface properties of said FXII activating particles haven’t been fully characterized, so there are difficulties in standardizing aPTT-based diagnostic procedures.
In this study, researchers screened recombinant FXII mutants and identified residual peptides that were essential for FXII surface binding and activation. These residual peptides raised antibodies and triggered controllable contact activation in solution that leads to thrombin generation via intrinsic coagulation pathways. The methodology of using antibody-activated aPTT screening allows for more standardization in particulate aPTT reagents along with more sensitive monitoring of various coagulation factors.
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