The function of factor XI in tissue factor-initiated thrombin generation

Butenas, Saulius; Dee, Josh; Mann, Kenneth G.

doi:10.1046/j.1538-7836.2003.00431.x

Cited by 50 publications

(30 citation statements)

References 54 publications

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“…28 Inhibitory monoclonal anti-TF (αTF-5; prevents binding of TF to FVIIa), anti-FXIa (αFXI-2; inhibits FIX activation by FXIa) and anti-FIXa (αFIX-91; inhibits FX activation by FIXa) antibodies were produced and characterized in-house. 29, 30 The fluorogenic substrate used was benzyloxycarbonyl-Gly-Gly-Arg-7-amido-4methylcoumarin• HCl (Z-GGR-AMC) (Bachem, Torrance, CA). TF, FIXa and FXIa activity in plasma was calculated from calibration curves developed with human FIXa, human FXIa and relipidated TF 1–263 26 (all from Haematologic Technologies, Inc., Essex Junction, VT).…”

Section: Methodsmentioning

confidence: 99%

Correlation between factor (F)XIa, FIXa and tissue factor and trauma severity

Prior

Cohen

Conroy

et al. 2017

Journal of Trauma and Acute Care Surgery

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BACKGROUND It has been observed that trauma patients often display elevated procoagulant activity that could be caused, in part, by tissue factor (TF). We previously observed that trauma patients with thermal, blunt and penetrating injuries have active FIXa and FXIa in their plasma. In the current study we evaluated the effect of injury severity, with or without accompanying shock, on the frequency and concentration of TF, FIXa and FXIa in plasma from trauma patients. METHODS Eighty trauma patients were enrolled and divided equally into 4 groups based on their injury severity score (ISS) and base deficit (BD): Group 1: Non-severe injury, no shock Group 2: Non-severe injury, with shock Group 3: Severe injury, no shock Group 4: Severe injury, with shock Blood was collected at a 0 time-point (first blood draw upon arrival at hospital) and citrate plasma was prepared, frozen and stored at −80C. FXIa, FIXa and TF activity assays were based on a response of thrombin generation to corresponding monoclonal inhibitory antibodies. RESULTS The frequency and median concentrations of TF were relatively low in non-severe injury groups (17.5 % and 0 pM respectively) but were higher in those with severe injury (65% and 0.5 pM, respectively). While FXIa was observed in 91% of samples and was high across all 4 groups, median concentrations were highest (by approximately 4-fold) in groups with shock. FIXa was observed in 80% of plasma samples and concentrations varied in a relatively narrow range between all 4 groups. No endogenous activity was observed in plasma from healthy individuals. CONCLUSIONS 1) Frequency and concentration of TF is higher in patients with a higher trauma severity; 2) Concentration of FXIa is higher in patients with shock; 3) For the first time reported, the vast majority of plasma samples from trauma patients contain active FIXa and FXIa. LEVEL of EVIDENCE Diagnostic Tests or Criteria, level I. Diagnostic Tests.

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Section: Methodsmentioning

confidence: 99%

Correlation between factor (F)XIa, FIXa and tissue factor and trauma severity

Prior

Cohen

Conroy

et al. 2017

Journal of Trauma and Acute Care Surgery

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“…Three models of blood coagulation developed in our laboratory were used for this evaluation: numerical coagulation simulations [26,27], synthetic coagulation proteome [28][29][30] and contact pathway-inhibited whole blood [31,32].…”

Section: Introductionmentioning

confidence: 99%

Influence of bivalirudin on tissue factor-triggered coagulation

Butenas

Orfeo

Brummel‐Ziedins

et al. 2007

Blood Coagulation &Amp; Fibrinolysis

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Bivalirudin, a synthetic analog of the carboxy-terminus of hirudin, is a reversible thrombin inhibitor used during coronary balloon angioplasty. The objective of this study was to evaluate the influence of bivalirudin on thrombin generation. Three in-vitro models (numerical simulations, synthetic coagulation proteome and whole blood) of contact pathway-independent blood coagulation triggered with tissue factor were used in this study. Increasing concentrations of bivalirudin prolong the initiation phase of thrombin generation in a concentration-dependent manner. At subpharmacologic bivalirudin concentrations (0.5-2 micromol/l), total thrombin generation was significantly increased. At a pharmacologic concentration (5 micromol/l), bivalirudin suppressed thrombin generation in the synthetic coagulation proteome; in numerical simulations and contact pathway-inhibited whole blood, no thrombin generation was detected over 1200-2000 s and platelet activation was inhibited by 80%. The addition of a pharmacologic concentration (9 micromol/l) of a naturally occurring protease inhibitor aprotinin in the presence of at least 0.5 micromol/l bivalirudin provided limited enhancement of the bivalirudin inhibitory effect. In conclusion, bivalirudin at pharmacologic concentrations is an efficient inhibitor of thrombin generation, platelet activation and clot formation, which acts not as a modulator but as an 'on-off' switch of blood coagulation.

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“…It activates FXI, which is an alternative way to generate FIXa. 1,2 Thrombin also activates FXIII, as well as various cofactors, cleaves fibrinogen, and stimulates platelets via cleavage of protease activated receptors (PARs). Platelets accelerate the activation of the coagulation cascade by binding FXI via the receptor glycoprotein Ib-IX-V and by providing a thrombogenic surface for the assembly of the prothrombinase complex (FVa:FXa).…”

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confidence: 99%