Effects of aprotinin on plasma coagulation kinetics determined by thrombelastography: role of Factor XI

Nielsen, Vance G.

doi:10.1111/j.1399-6576.2006.00935.x

Cited by 13 publications

(13 citation statements)

References 14 publications

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“…Retrospective meta-analysis Data derived from 859 thrombelastograms that had both a and MRTG values determined with version 4.2 thrombelastography software were obtained from the databases [1][2][3][4][5][6][7][8][9]. The data were primarily obtained from commercially available lots of human plasma that were normal or deficient in various clotting factors to different extents.…”

Section: Methodsmentioning

confidence: 99%

“…Such a comparison would yield clinically useful information, giving clinicians a better grasp of how changes in a secondary to therapeutic interventions actually translate to parametric changes in clot growth velocity. One goal of this study was therefore to determine the effect of changes in a on the MRTG using databases from previously published investigations [1][2][3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…The quantification of coagulation kinetics utilizing thrombelastography typically involves the determination of the time to clot initiation (reaction time, R), the speed of clot propagation [K time, alpha angle a (degrees), maximum rate of thrombus generation (MRTG) (dynes/cm 2 per s)], and final clot strength [maximum amplitude (mm), maximum elastic modulus (dynes/cm 2 )] [1][2][3][4][5][6][7][8][9]. With regard to clot propagation in particular, the comparison of a values has been widely used in both research and clinical settings despite being a nonparametric measure of velocity.…”

Section: Introductionmentioning

confidence: 99%

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Thrombelastographic measures of clot propagation: a comparison of alpha with the maximum rate of thrombus generation

Ellis¹,

Nielsen²,

Marques³

et al. 2007

Blood Coagulation &Amp; Fibrinolysis

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The alpha angle alpha (degrees) is a thrombelastographic measure of clot propagation. A parametric measurement of clot propagation [maximum rate of thrombus generation (MRTG), dynes/cm2 per s], however, has recently been utilized. Thus, the relationship of changes in alpha with changes in MRTG were determined. alpha and MRTG values obtained from 859 thrombelastograms was collected from nine studies. Data were analyzed and the relationship between alpha and MRTG defined with commercially available software. Additional comparisons were made retrospectively from whole-blood and plasma data obtained from 33 normal individuals. Data from the nine studies demonstrated that MRTG increased in an exponential fashion compared with increases in alpha (R2 = 0.88, P < 0.001). Whole-blood alpha values were in the range 66.7-74.7 whereas MRTG values were 5.5-10.8, and plasma alpha values were 65.1-77.9 with corresponding MRTG values of 3.5-12.0. Assessment of clot propagation utilizing MRTG provides a more parametric evaluation than the determination of alpha. While normal alpha values may vary by only 12-20%, MRTG values vary by approximately 200-300%. The MRTG should be progressively utilized to a greater extent in both laboratory and clinical settings to parametrically quantify clot growth kinetics with thrombelastography.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thrombelastographic measures of clot propagation: a comparison of alpha with the maximum rate of thrombus generation

Ellis¹,

Nielsen²,

Marques³

et al. 2007

Blood Coagulation &Amp; Fibrinolysis

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“…Such data has been previously presented, 60 and typical clot growth velocity curves of these conditions following contact activation with celite are depicted in Figure 3. Prekallikrein deficiency is associated with prolongation of time to clot initiation, but does not sig- 60 The hierarchy of both time to initiation of coagulation and/or maximum rate of thrombus generation is as follows: normal plasma (white) Ͼ prekallikrein-deficient plasma (Ͻ1% normal activity, light gray) Ͼ FXI-deficient plasma (Ͻ1% normal activity, gray) Ͼ FXII-deficient plasma (Ͻ1% normal activity, dark gray lines) Ͼ kininogen-deficient plasma (Ͻ1% normal activity, black).…”

Section: Clot Growth Profiles Of Plasma Deficient In Key Contact Protmentioning

confidence: 95%

“…Further, a deficiency of prekallikrein appears to have no important effects on the speed of clot formation, and inhibition of kallikrein by therapeutic (200 KIU/ml) or up to 4-fold therapeutic concentrations of aprotinin only mildly decreases the speed of clot formation. 60 Fortunately, a deficiency in FXII or HMWK has not been associated with clinical bleeding, making inhibition of FXII activity and/or HMWK a potentially important therapeutic goal in patients with MCS. While FXII 59,61 and HMWK 61 activity or activation have been inhibited by utilization of plant proteins and insect venoms, no clinically available pharmaceutical exists at present to inhibit either FXII or HMWK.…”

Section: Clot Growth Profiles Of Plasma Deficient In Key Contact Protmentioning

confidence: 99%

Mechanical Circulatory Device Thrombosis: A New Paradigm Linking Hypercoagulation and Hypofibrinolysis

Nielsen¹,

Kirklin²,

Holman³

et al. 2008

ASAIO Journal

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This review considers the perhaps unappreciated role of contact pathway proteins in the pathogenesis of thrombotic/thromboembolic morbidity associated with mechanical circulatory support. Placement of ventricular assist devices (VADs) has been associated with consumption of circulating contact proteins and persistent generation of activated contact proteins such as Factor XII and high molecular weight kininogen. Importantly, activated contact proteins are absorbed to the surface of VADs via the Vroman effect. Further, hyperfibrinogenemia and persistent platelet activation exist in patients with VADs, likely contributing to speed of clot growth. Using thrombelastographic-based analyses, it has been determined that contact pathway protein activated coagulation results in a thrombus that develops strength at a significantly faster rate that tissue factor initiated coagulation. Further, thrombelastographic analyses that include the addition of tissue-type plasminogen activator have demonstrated that contact protein pathway activation results in thrombin activatable fibrinolysis inhibitor activation to a far greater extent than that observed with tissue factor initiated coagulation, resulting in a thrombus that takes significantly longer to lyse. These observations serve as the rational basis for clinical investigation to determine if regional suppression of thrombin generation with FXII/high molecular weight kininogen inhibition in concert with thrombin-activatable fibrinolysis inhibitor inhibition may decrease mechanical circulatory support-associated thrombotic morbidity.

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Congenital Factor XI Deficiency

Tabatabaei¹,

Dorgalaleh²

2018

Congenital Bleeding Disorders

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Effects of aprotinin on plasma coagulation kinetics determined by thrombelastography: role of Factor XI

Abstract: These data support a role for the inhibition of FXI as the mechanism for aprotinin-mediated delayed contact system clot initiation determined by thrombelastography.

Cited by 13 publications

References 14 publications

Thrombelastographic measures of clot propagation: a comparison of alpha with the maximum rate of thrombus generation

Thrombelastographic measures of clot propagation: a comparison of alpha with the maximum rate of thrombus generation

Mechanical Circulatory Device Thrombosis: A New Paradigm Linking Hypercoagulation and Hypofibrinolysis

Congenital Factor XI Deficiency

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