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Helen Philippou
University of Leeds
ThrombinFibrinogenFibrinBiochemistryMedicine
82Publications
27H-index
2,644Citations
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Publications 83
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Pathogenic thrombus formation accounts for the aetiology of many serious conditions including myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. Despite the development of ...
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#1Boris A. Anokhin (University of Louisville)H-Index: 2
#2William L. Dean (University of Louisville)H-Index: 31
Last. Muriel C. Maurer (University of Louisville)H-Index: 12
view all 7 authors...
: Factor XIIIA (FXIIIA) is a transglutaminase that cross-links intra- and extracellular protein substrates. FXIIIA is expressed as an inactive zymogen, and during blood coagulation, it is activated by removal of an activation peptide by the protease thrombin. No such proteolytic FXIIIA activation is known to occur in other tissues or the intracellular form of FXIIIA. For those locations, FXIIIA is assumed instead to undergo activation by Ca2+ ions. Previously, we demonstrated a monomeric state f...
2 CitationsSource
#1Sneha SinghH-Index: 5
#2Johannes Dodt (Paul Ehrlich Institute)H-Index: 12
Last. Arijit BiswasH-Index: 29
view all 9 authors...
The dimeric FXIII-A2, a pro-transglutaminase is the catalytic part of the heterotetrameric coagulation FXIII-A2B2 complex that upon activation by calcium binding/thrombin cleavage covalently cross-links preformed fibrin clots protecting them from premature fibrinolysis. Our study characterizes the recently disclosed three calcium binding sites of FXIII-A concerning evolution, mutual crosstalk, thermodynamic activation profile, substrate binding, and interaction with other similarly charged ions....
3 CitationsSource
#1Ahsan A KhanH-Index: 1
#2Eduard Shantsila (University of Birmingham)H-Index: 34
Last. Gregory Y.H. LipH-Index: 143
view all 6 authors...
Introduction Atrial fibrillation (AF) and coronary artery disease (CAD) are two common cardiovascular conditions associated with increased morbidity and mortality. Both conditions bring a risk of thrombosis and thus antithrombotic therapy is indicated. Despite recognised treatment, stroke and myocardial infarctions still occur. Accordingly, the identification of patients whose haemostasis remains unimpaired by treatment is valuable. Purpose To investigate differences in plasma clot properties in...
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#1Ahsan A KhanH-Index: 1
#2Eduard Shantsila (University of Birmingham)H-Index: 34
Last. Gregory Y.H. LipH-Index: 143
view all 6 authors...
Introduction Atrial fibrillation (AF) is associated with an increased risk of stroke and thromboembolism. Despite best clinical care, patients on anticoagulation therapy still suffer from thrombosis and remain at risk of haemorrhage with devastating consequences. The assessment of different oral anticoagulants to identify the effects on plasma clots may help in identifying reasons for this. Aim To study how different oral anticoagulants affect plasma clot properties in patients with AF. Methods ...
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#1Ahsan A KhanH-Index: 1
#2Eduard Shantsila (University of Birmingham)H-Index: 34
Last. Gregory Y.H. LipH-Index: 143
view all 6 authors...
Introduction Anticoagulation use in atrial fibrillation (AF) is common, but concurrent chronic kidney disease (CKD) reduces its efficacy and potentiates the risk of bleeding. Patients with AF have a higher incidence of renal impairment and the latter predisposes to incident AF. The co-existence of both conditions leads to a higher risk for thromboembolic-related adverse events but also a paradoxical increased haemorrhagic risk with devastating consequences for the individual. Assessing the effec...
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#1Helen Philippou (University of Leeds)H-Index: 27
In this issue of Blood , Ivanov et al 1 have identified that the N-terminal noncatalytic heavy chain of factor XII (FXII) plays an important role in the regulation of activation of the contact pathway of coagulation by the reciprocal activation of FXII and prekallikrein (PK). This mechanism provides insights into the clinical manifestation of an edema outbreak in patients with a rare form of hereditary angioedema (HAE).
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#1Sneha SinghH-Index: 5
#2Johannes Dodt (Paul Ehrlich Institute)H-Index: 12
Last. Arijit BiswasH-Index: 29
view all 9 authors...
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#1Fraser L. MacraeH-Index: 7
#2Cédric DuvalH-Index: 11
Last. Robert A. S. Ariëns (University of Leeds)H-Index: 43
view all 16 authors...
Hemostasis requires conversion of fibrinogen to fibrin fibers that generate a characteristic network, interact with blood cells, and initiate tissue repair. The fibrin network is porous and highly permeable, but the spatial arrangement of the external clot face is unknown. Here we show that fibrin transitioned to the blood-air interface through Langmuir film formation, producing a protective film confining clots in human and mouse models. We demonstrated that only fibrin is required for formatio...
14 CitationsSource
#1Emma Hethershaw (University of Leeds)H-Index: 3
#2Penelope J. Adamson (University of Leeds)H-Index: 3
Last. Helen Philippou (University of Leeds)H-Index: 27
view all 10 authors...
Background; Factor XIII (FXIII) is composed of an activation peptide segment, a β‐sandwich domain, a catalytic core, and finally β‐barrels 1 and 2. FXIII is activated following cleavage of its A‐subunits by thrombin. The resultant transglutaminase activity leads to increased resistance of fibrin clots to fibrinolysis. Objectives; To assess the functional roles of β‐barrels 1 and 2 in FXIII, we expressed and characterised the full‐length FXIII‐A subunit (FXIII‐A) and variants truncated to residue...
1 CitationsSource
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