Recent Insights Into the Regulation of Coagulation and Thrombosis

Li, Xian; Sim, Martha M.S.; Wood, Jeremy P.

doi:10.1161/atvbaha.120.312674

Cited by 23 publications

(20 citation statements)

References 51 publications

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“…The coagulation process is accomplished by consecutive activity of several plasmatic serine proteases, which always circulate as zymogen precursors and, once activated, provide complex feedback loops to trigger other coagulation or anticoagulation factors ( 1 , 9 ). Serine proteases (serine endopeptidases) are defined as proteolytic enzymes with a serine residue in their active site; they usually have a multidomain structure containing β-barrel regions and multiple surface loops surrounding the active site ( 10 ).…”

Section: Coagulation and Related Proteasesmentioning

confidence: 99%

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Platelet Membrane Receptor Proteolysis: Implications for Platelet Function

Heemskerk

Baaten

2021

Front. Cardiovasc. Med.

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The activities of adhesion and signaling receptors in platelets are controlled by several mechanisms. An important way of regulation is provided by proteolytic cleavage of several of these receptors, leading to either a gain or a loss of platelet function. The proteases involved are of different origins and types: (i) present as precursor in plasma, (ii) secreted into the plasma by activated platelets or other blood cells, or (iii) intracellularly activated and cleaving cytosolic receptor domains. We provide a comprehensive overview of the proteases acting on the platelet membrane. We describe how these are activated, which are their target proteins, and how their proteolytic activity modulates platelet functions. The review focuses on coagulation-related proteases, plasmin, matrix metalloproteinases, ADAM(TS) isoforms, cathepsins, caspases, and calpains. We also describe how the proteolytic activities are determined by different platelet populations in a thrombus and conversely how proteolysis contributes to the formation of such populations.

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Section: Coagulation and Related Proteasesmentioning

confidence: 99%

“…In the extrinsic coagulation process triggered by tissue factor, the protease factor Xa is produced from its zymogen factor X by factor VII/VIIa ( 1 , 9 ). Cleavage into factor Xa is greatly enhanced in the presence of phosphatidylserine-exposing membranes, such as present on procoagulant platelets ( 12 , 13 ).…”

Section: Coagulation and Related Proteasesmentioning

confidence: 99%

Platelet Membrane Receptor Proteolysis: Implications for Platelet Function

Heemskerk

Baaten

2021

Front. Cardiovasc. Med.

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“…Atrial brillation (AF) is the most common arrhythmia, which associated with increased risk of mortality and disability after stroke. The large infarcts characteristically associated with AF re ect the larger size of stasis thrombi that form in the low shear environment of the left atrium [1,2]. 30-day mortality of AF-related stroke was more than 24%, another 35% patients had severe disability [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Plasma D-Dimer Level is Associated with Clinical Outcomes in Patients with Atrial Fibrillation Related Acute Ischemic Stroke after Pneumonia

et al. 2020

Preprint

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Objectives: Pneumonia is related to poor prognosis in acute ischemic stroke (AIS), and its risk might be higher in atrial fibrillation (AF) related AIS with elevated plasma D-dimer. The aim of our study was to investigate the prognostic value of D-dimer for predicting clinical outcome of AF-related AIS with pneumonia. Method: AF-related AIS patients with pneumonia were prospectively enrolled. Receiver operating characteristic (ROC) curve was used to determine the optimal D-dimer point for 3-month mortality and death/severe disability. The associations between the D-dimer and 3-month mortality and death/severe disability were assessed by multivariable logistic regression analysis. Results: A total of 415 patients were enrolled in this study. ROC curve analysis showed that the optimal cut point of D-dimer for 3-month death/severe disability and mortality were D-dimer≥2.35mg/l and D-dimer≥3.35mg/l, respectively. Multivariable logistic regression analysis showed that D-dimer≥2.35mg/l(OR 5.95, 95% CI: 3.09-11.45, P＜0.001), higher NIHISS score(OR:1.53, 95% CI: 1.38–1.68, P＜0.001) were associated with increased risk of 3-month death/severe disability), and anticoagulant was associated with decreased risk of death/severe disability (OR:0.16, 95% CI: 0.07-0.35, P＜0.001). Higher NIHISS score(OR:1.56, 95% CI: 1. .37–1.77, P＜0.001), higher age(OR 1.06, 95% CI: 1.01–1.11, P=0.019), D-dimer≥3.35mg/l (OR 7.85, 95% CI: 3.21-19.21, P=0.001)were associated with increased risk of 3-month mortality.Conclusions: AF-related AIS patients with concurrent high D-dimer and pneumonia increased risk of 3-month mortality and death/severe disability, plasma D-dimer may have predictive value in outcome after AF-related AIS with pneumonia.

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“…Yet Xase and prothrombinase complexes are extremely specific for their respective substrates, raising the question of how they discriminate among all the possible substrates present in blood plasma. Several advances have been made in recent years to better understand these structure-function relationships (1,2). Whereas a number of structures of coagulation factor serine protease domains are available that provide insights into the enzymatic mechanisms of zymogen activation, how this process works in the context of the full-length enzymes and larger molecular assemblies is less well-understood and experimentally more difficult to tackle.…”

mentioning

confidence: 99%

Exosites expedite blood coagulation

Oliva

Dreveny

Emsley

2020

Journal of Biological Chemistry

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A careful balance between active-site and exosite contributions is critically important for the specificity of many proteases, but this balance is not yet defined for some of the serine proteases that serve as coagulation factors. Basavaraj and Krishnaswamy have closed an important gap in our knowledge of coagulation factor X activation by the intrinsic Xase complex by showing that exosite binding plays a critical role in this process, which they describe as a “dock and lock.” This finding not only significantly enhances our understanding of this step in the coagulation cascade and highlights parallels with the prothrombinase complex, but will also provide a novel rationale for inhibitor development in the future.

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Recent Insights Into the Regulation of Coagulation and Thrombosis

Cited by 23 publications

References 51 publications

Platelet Membrane Receptor Proteolysis: Implications for Platelet Function

Platelet Membrane Receptor Proteolysis: Implications for Platelet Function

Plasma D-Dimer Level is Associated with Clinical Outcomes in Patients with Atrial Fibrillation Related Acute Ischemic Stroke after Pneumonia

Exosites expedite blood coagulation

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