Evaluation of the thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK) with the factor Xa inhibitor 1,5-dansyl-L-glutamyl-L-glycyl-L-arginine chloromethylketone (GGACK) as anticoagulants for critical care clinical chemistry specimens

Lyon, Martha E.; Drobot, Duane; Harding, Sheila Rutledge; Lyon, Andrew W.

doi:10.1016/s0009-8981(98)00176-4

Clinica Chimica Acta

1999

DOI: 10.1016/s0009-8981(98)00176-4

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Evaluation of the thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK) with the factor Xa inhibitor 1,5-dansyl-L-glutamyl-L-glycyl-L-arginine chloromethylketone (GGACK) as anticoagulants for critical care clinical chemistry specimens

Martha E. Lyon

Duane Drobot

Sheila Rutledge Harding

et al.

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Cited by 4 publications

(7 citation statements)

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“…However, sodium citrate chelates extracellular calcium, creating an artificial milieu that does not represent the in vivo situation. An alternative in vitro anticoagulant is D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone (PPACK), which acts by inhibiting thrombin, thereby maintaining physiologic extracellular calcium levels [3].…”

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The importance of anticoagulant agents in measuring platelet aggregation in patients treated with clopidogrel and aspirin

Bouman¹,

Werkum²,

Hackeng

et al. 2008

Journal of Thrombosis and Haemostasis

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“…This material (rTF/95) was established as the 3rd IS for Thromboplastin, Human, Recombinant, Plain by the WHO Expert Committee on Biological Standardization in 1996 after a multicentre calibration study [3]. It consists of ampoules containing freeze-dried recombinant tissue factor and of ampoules containing reconstitution fluid which contains …”

mentioning

confidence: 99%

The importance of anticoagulant agents in measuring platelet aggregation in patients treated with clopidogrel and aspirin

Bouman¹,

Werkum²,

Hackeng

et al. 2008

Journal of Thrombosis and Haemostasis

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“…This could result in an underestimation or overestimation of the true inhibitory effects of P2Y12 receptor antagonists in vivo. Other anticoagulants, such as hirudin and D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), prevent coagulation of blood by direct inhibition of thrombin, thereby maintaining physiologic calcium levels [4]. This approach might therefore mimic the in vivo situation of platelet function more precisely than anticoagulation with citrate.…”

mentioning

confidence: 99%

“…The SRA uses washed platelets, and the PAT uses citrated plateletrich plasma. This is the main reason why the SRA is more sensitive and specific than the PAT, and is therefore considered to be the reference method for HIT laboratory diagnosis [4]. Although ELISA-based assays are standardized and widely available, platelet activation assays have a higher diagnostic specificity [4].…”

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confidence: 99%

“…This is the main reason why the SRA is more sensitive and specific than the PAT, and is therefore considered to be the reference method for HIT laboratory diagnosis [4]. Although ELISA-based assays are standardized and widely available, platelet activation assays have a higher diagnostic specificity [4]. The combination of ELISA with a functional test improves the accuracy of HIT diagnosis [5,6].…”

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Comparison between hirudin and citrate in monitoring the inhibitory effects of P2Y12 receptor antagonists with different platelet function tests

Pittens¹,

Bouman²,

Werkum³

et al. 2009

Journal of Thrombosis and Haemostasis

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To cite this article: Pittens CACM, Bouman HJ, van Werkum JW, ten Berg JM, Hackeng CM. Comparison between hirudin and citrate in monitoring the inhibitory effects of P2Y12 receptor antagonists with different platelet function tests. J Thromb Haemost 2009; 7: 1929-32. Dual treatment with aspirin and clopidogrel is currently the therapy of choice in the prevention of recurrent cardiovascular events following coronary stent implantation. However, not all patients benefit equally from this antiplatelet regimen, as inadequate suppression of platelet aggregation by clopidogrel and/or aspirin -also referred to as Ôhigh on-treatment platelet reactivityÕ or Ôantiplatelet therapy resistanceÕ -is associated with worsened clinical outcome. The prevalence of this phenomenon varies widely, and is highly dependent on the type of platelet function test and the type of anticoagulant that is being used [1,2].ÔClassicÕ light transmission aggregometry (LTA), using ADP as agonist, is considered to be the reference standard platelet function test for determining the effectiveness of clopidogrel. Its use in daily practice is, however, not viable, owing to important limitations [3]. To overcome these limitations, various wholeblood platelet function assays designed to evaluate the efficacy of P2Y12 receptor antagonism have been introduced to the commercial market.Trisodium citrate dihydrate is the preferred anticoagulant agent for platelet function testing, as it has been in use for more than 40 years. However, measurements in citrate do not resemble physiologic conditions, as citrate inhibits coagulation by chelating calcium. This could result in an underestimation or overestimation of the true inhibitory effects of P2Y12 receptor antagonists in vivo. Other anticoagulants, such as hirudin and D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), prevent coagulation of blood by direct inhibition of thrombin, thereby maintaining physiologic calcium levels [4]. This approach might therefore mimic the in vivo situation of platelet function more precisely than anticoagulation with citrate. Previous studies on this issue have demonstrated a generally higher magnitude of ADP-induced platelet aggregation in blood anticoagulated with citrate than in blood anticoagulated with PPACK or hirudin when measured with classic LTA [5][6][7].The manufacturers of the multiple-electrode aggregometry (MEA) assay strongly recommend the use of hirudin instead of citrate as an anticoagulant agent. Two recent publications reported a reduced area under the MEA curve, which indicates a lower magnitude of platelet aggregation, when platelet function was measured in citrated blood than when it was measured in hirudin-anticoagulated blood [8,9]. This finding is opposite to the results obtained with classic LTA when measurements are made in citrate vs. PPACK (or hirudin) [5,7]. For the whole-blood assays determining the efficacy of P2Y12 receptor antagonists, no information regarding the effects of anticoagulants other than citrate on the test performan...

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FVII Dependent Coagulation Activation in Citrated Plasma by Polymer Hydrogels

et al. 2010

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Polymer hydrogels containing positively charged functional groups were used to investigate the critical material and biological components of FVII activation and subsequent fibrin formation in citrated plasma. A FVIIa ELISA confirmed the ability of the polymer to induce FVII activation and provided insight into the material parameters which were influential in this activation. Experiments utilizing coagulation factor depleted and inhibited plasmas indicated that FVII, FX, FII, and FI are all vital to the process outlining the general mechanism of fibrin formation from the onset of FVII activation. Dynamic mechanical analysis and swelling experiments were used to establish a critical correlation between polymer microstructure and FVII activation.

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Evaluation of the thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK) with the factor Xa inhibitor 1,5-dansyl-L-glutamyl-L-glycyl-L-arginine chloromethylketone (GGACK) as anticoagulants for critical care clinical chemistry specimens

Cited by 4 publications

References 19 publications

The importance of anticoagulant agents in measuring platelet aggregation in patients treated with clopidogrel and aspirin

The importance of anticoagulant agents in measuring platelet aggregation in patients treated with clopidogrel and aspirin

Comparison between hirudin and citrate in monitoring the inhibitory effects of P2Y12 receptor antagonists with different platelet function tests

FVII Dependent Coagulation Activation in Citrated Plasma by Polymer Hydrogels

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