Regulatory mechanisms of the plasma contact system

Maas, Coen; Renné, Thomas

doi:10.1016/j.thromres.2012.02.039

Cited by 48 publications

(35 citation statements)

References 56 publications

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“…These coagulation factors spontaneously activate in the presence of negatively charged surfaces, which [as previously reviewed in Ref. (1, 2)] can be non-natural (e.g., kaolin) or cell-derived (e.g., polyphosphate). Surface-binding of FXII is accompanied by a conformational shift (3).…”

Section: Introductionmentioning

confidence: 99%

Processing of Factor XII during Inflammatory Reactions

2016

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The contact system was originally identified as an obsolete part of the coagulation system, but it has been repeatedly implicated in inflammatory states, such as infection, as well as in allergic- and chronic inflammatory disease. Under these conditions, there is surprisingly little evidence that factor XII (FXII) acts as a coagulation factor, and its activity appears to be mainly directed toward activation of the kallikrein–kinin system. The contact system factors interact with pathogens as well as cells of the (innate) immune system on several levels. Among others, these cells may provide negatively charged surfaces that contribute to contact activation as well as release enzymes that feed into this system. Furthermore, cellular receptors have been identified that bind contact factors at sites of inflammation. Based on the accumulated evidence, we propose a model for enzymatic crosstalk between inflammatory cells and the plasma contact system. During these reactions, FXII is enzymatically cleaved by non-contact system enzymes. This generates unactivated FXII fragments that can subsequently be rapidly activated in the fluid phase. The resulting enzyme lacks procoagulant properties, but retains its pro-inflammatory characteristic as a prekallikrein activator.

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Section: Introductionmentioning

confidence: 99%

Processing of Factor XII during Inflammatory Reactions

2016

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“…Transcription of FXII may be influenced by female hormones, owing to an estrogenreceptive element in the promoter region of F12 [3]. FXII is activated by negatively charged surfaces, and perhaps by platelet-derived polyphosphates, which act as a scaffold on which FXII and cofactors can colocalize [4][5][6]. Activation of FXII and subsequently prekallikrein (PK) can lead to several distinct phenomena, including clot propagation, clot structure, bradykinin formation, complement activation, neutrophil aggregation, and promotion of fibrinolysis through activation of plasminogen [2,[7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Antigen levels of coagulation factor XII, coagulation factor XI and prekallikrein, and the risk of myocardial infarction and ischemic stroke in young women

Siegerink

Rosendaal

Algra

2014

Journal of Thrombosis and Haemostasis

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To cite this article: Siegerink B, Rosendaal FR, Algra A. Antigen levels of coagulation factor XII, coagulation factor XI and prekallikrein, and the risk of myocardial infarction and ischemic stroke, in young women. J Thromb Haemost 2014; 12: 606-13.Summary. Background: High levels of activated proteininhibitor complexes of the intrinsic coagulation proteins are associated with ischemic stroke (IS) but not with myocardial infarction (MI). This study was aimed at determining whether the antigen levels of coagulation factors (factor XII, FXII, and FXI and prekallikrein (PK) are associated with MI and IS, and whether this association is independent of levels of activated protein-inhibitor complexes. Patients and Methods: The RATIO study included young women (< 50 years) with MI (N = 205) and IS (N = 175), and 638 healthy controls. Antigen levels of FXII, FXI and PK were measured and expressed as percentages of of those in pooled normal plasmas. Odds ratios (ORs) and corresponding 99% confidence intervals (CIs) were calculated for high levels (i.e. ≥ 90th percentile of controls) as measures of rate ratios. Results: After adjustment for potential confounders, high levels of FXII antigen were not associated with MI risk or IS risk (OR MI 1.18, 99% CI 0.51-2.74; OR IS 1.03, 9% CI 0.41-2.55). High levels of FXI antigen were slightly associated with an increase in MI risk (OR MI 1.55, 9% CI 0.74-3.21), whereas there was a substantial association with IS risk (OR IS 2.65, 9% CI 1.27-5.56). PK antigen was slightly associated with MI risk but not with IS risk (OR MI 1.54, 9% CI 0.67-3.52; OR IS 0.90, 9% CI 0.35-2.33). All associations remained similar after adjustment for levels of protein-inhibitor complexes. Conclusion: Increased levels of FXI antigen were associated with an increase in IS risk, whereas they showed only a marginal association with MI risk. FXII antigen and PK antigen levels were not substantially associated with MI risk and IS risk.

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“…Therefore, in patients with high risk of recurrence indefinite treatment may be warranted if the anticipated [20,21]. These proteins become activated when blood comes into contact with negatively charged surfaces and initiate procoagulant and pro-inflammatory reactions via the intrinsic pathway and the kallikrein-kinin system [22]. Contact factors are not required for thrombin generation and clot formation.…”

Section: Duration Of Anticoagulationmentioning

confidence: 99%

Highlights of the American Society of Hematology Meeting 2014: Hemostaseology

Feistritzer

Mosheimer

2015

memo

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In patients suffering from venous thromboembolism, the subsequent anticoagulation treatment significantly reduces the risk of recurrence of further thromboembolic events. However, all available treatment options put the patients at risk of potential life-threatening bleeding complications. Consequently, during the 56th Annual Meeting 2014 of the American Society of Hematology in San Francisco researchers focused on optimizing the use of the current available anticoagulants. Therefore, in the Choosing Wisely ® campaign the expert committee recommended to treat patients suffering from their first venous thromboembolism in the setting of major transient risk factors for (not longer than) 3 months. In addition, a French national multicenter trial showed that-if indefinite anticoagulation is not indicated-extended treatment after spontaneous thromboembolism does not reduce the risk of recurrence after stopping the anticoagulation therapy. In patients with cancer-associated thromboembolism, a multicenter study demonstrated the superiority of low molecular heparins over vitamin K antagonist. Finally, a novel, promising target for dissecting hemostasis and antithrombotic effects might be the plasma contact system. Downregulation of factor XI levels in patients undergoing elective knee arthroplasty was an effective method for prevention of postoperative venous thrombosis without increasing the risk of bleeding.

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Regulatory mechanisms of the plasma contact system

Cited by 48 publications

References 56 publications

Processing of Factor XII during Inflammatory Reactions

Processing of Factor XII during Inflammatory Reactions

Antigen levels of coagulation factor XII, coagulation factor XI and prekallikrein, and the risk of myocardial infarction and ischemic stroke in young women

Highlights of the American Society of Hematology Meeting 2014: Hemostaseology

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