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Details on Person The contact activation system (CAS) is a plasma protease cas...
| Class:Id | Summation:9651462 |
|---|---|
| _displayName | The contact activation system (CAS) is a plasma protease cas... |
| _timestamp | 2021-08-18 17:47:06 |
| created | [InstanceEdit:9651463] Shamovsky, Veronica, 2019-06-26 |
| literatureReference | [LiteratureReference:9660287] The procoagulant and proinflammatory plasma contact system [LiteratureReference:9660268] The plasma contact system 2.0 [LiteratureReference:9660278] The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities [LiteratureReference:9660277] Contact system revisited: an interface between inflammation, coagulation, and innate immunity [LiteratureReference:9660275] Contact pathway of coagulation and inflammation [LiteratureReference:9660293] The hemostatic role of factor XI [LiteratureReference:9660280] Rare bleeding disorders - bleeding assessment tools, laboratory aspects and phenotype and therapy of FXI deficiency [LiteratureReference:9655780] Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III [LiteratureReference:9660264] Factor XI and XII as antithrombotic targets [LiteratureReference:9655727] Proteolytic properties of single-chain factor XII: a mechanism for triggering contact activation [LiteratureReference:9660279] Human factor XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and ultraviolet difference spectroscopic studies [LiteratureReference:9655734] In vivo roles of factor XII [LiteratureReference:9660272] Hemophilia B: molecular pathogenesis and mutation analysis [LiteratureReference:9660285] Haemophilia A and haemophilia B: molecular insights [LiteratureReference:9651460] HAE Pathophysiology and Underlying Mechanisms [LiteratureReference:9653227] A mechanism for hereditary angioedema with normal C1 inhibitor: an inhibitory regulatory role for the factor XII heavy chain [LiteratureReference:9651482] High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency [LiteratureReference:9653222] Hereditary Angioedema with Normal C1 Inhibitor: Update on Evaluation and Treatment [LiteratureReference:9672885] Nomenclature of genetic variants in hemostasis |
| modified | [InstanceEdit:9653266] Shamovsky, Veronica, 2019-07-11 [InstanceEdit:9653890] Shamovsky, Veronica, 2019-07-15 [InstanceEdit:9657719] Shamovsky, Veronica, 2019-08-09 [InstanceEdit:9660265] Shamovsky, Veronica, 2019-09-09 [InstanceEdit:9671819] Shamovsky, Veronica, 2019-12-20 [InstanceEdit:9672884] Shamovsky, Veronica, 2020-01-03 [InstanceEdit:9674513] Shamovsky, Veronica, 2020-01-13 [InstanceEdit:9687801] Shamovsky, Veronica, 2020-05-12 [InstanceEdit:9751168] Jassal, Bijay, 2021-08-18 |
| text | The contact activation system (CAS) is a plasma protease cascade initiated by factor XII (FXII) that activates the pro-inflammatory kallikrein‐kinin system (KKS) and the pro-coagulant intrinsic coagulation pathway (Renne T 2012; Renne T et al. 2012; Maas C et al. 2011; Schmaier AH 2016; Long AT et al. 2016). The CAS is initiated by the auto‐activation of factor XII (FXII) on charged or neutral surfaces with conversion of plasma prekallikrein (PK) to plasma kallikrein (Samuel M et al. 1992; Ivanov I et al. 2017). These events are followed by reciprocal activation of FXII by kallikrein and amplification of each other's activation. Two branches of the CAS have been identified: (i) the inflammatory branch activates contact factors FXII and PK on the surface of endothelial cells resulting in release of the peptide bradykinin (BK) and (ii) the plasma coagulation branch activates FXII and FXI on the surface of platelets. The CAS is thought to be central to crosstalk between coagulation and inflammation and the underlying cause for various disorders affecting the cardiovascular system (Wu Y 2015; Long AT et al. 2016). Physiologically, a fine balance is normally maintained between blood flow and blood clotting, the dysfunction of which yields either hemorrhage or thrombosis. Defects in the intrinsic pathway coagulation factors (FVIII, FIX, and FXI) are associated with a significant bleeding tendency. The X-linked recessive disorders, hemophilia A (FVIII deficiency) and B (FIX deficiency), are associated with spontaneous and excessive hemorrhage, especially hemarthroses and muscle hematomas (Bowen DJ 2002; Goodeve AC 2015). A deficiency in FXI, which is encoded by a gene on chromosome 4, generally results in a less severe, but still significant, bleeding tendency (James P et al. 2014; Puy C et al. 2016). Although PK and FXIIa are recognized as upstream triggers for the intrinsic coagulation system, the clinical significance of these factors on thrombosis and hemorrhage is not fully understood. The CAS blockade results in prolonged coagulation times in the activated partial thromboplastin time (aPTT) assay. However, the absence of thrombotic and hemostatic abnormalities in individuals with genetic deficiencies of PK or FXII has suggested that the CAS plays a minimal role in physiological coagulation (Müller F et al. 2011). At the same time, excessive formation of bradykinin due to abnormal FXII-dependent KKS activation causes increased vascular permeability at the level of the post capillary venule and results in hereditary angioedema (HAE). HAE initiated by bradykinin is usually associated with SERPING1 (C1-INH) deficiency (Suffritti C et al. 2014). More rarely, HAE occurs in individuals with normal SERPING1 activity, and has been linked to mutations in other proteins, including FXII, plasminogen, and angiopoietin (Cichon S et al. 2006; Magerl M et al. 2017; Zuraw BL 2016; Ivanov I et al. 2019). This Reactome module describes abnormal FXII-dependent KKS activation that leads to an excessive formation of bradykinin causing increased vascular permeability at the level of the post capillary venule and results in hereditary angioedema (HAE). HAE caused by defective function of SERPING1 is also covered here. The module also includes disorders that can cause abnormal bleeding due to a shortage (deficiency) of coagulation factor proteins, which are involved in blood clotting. This module also describes elevation of FIX activity associated with thrombophilia. Genetic variants are named following Human Genome Variation Society (HGVS) nomenclature with sequence numbering starting from the first methionine of the protein as +1.(Goodeve AC et al.2011). |
| (summation) | [Pathway:9651496] OBSOLETE_Defects of contact activation system (CAS) and kallikrein/kinin system (KKS)_REPLACEMENT_9769726_9946127 [Homo sapiens] |
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