Post-translational carboxylation of preprothrombin

Johnson, B. Connor

doi:10.1007/978-94-009-8027-3_6

Cited by 5 publications

(5 citation statements)

References 369 publications

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“…As a further possible mechanism, decreased carboxylation of coagulation factors II, VII, IX, and X could alter the accessibility of the respective binding sites to different extents for each drug. 19 An eventual inhibition promiscuity for FII and FX described for some inhibitors 20 should also be taken into consideration as a possible reason. Feedback mechanisms between FII, FVII, FIX, and FX could also play a role in generating the differences between the effects of oral anticoagulation on the actions of each DTI.…”

Section: Discussionmentioning

confidence: 99%

Monitoring of Anticoagulant Effects of Direct Thrombin Inhibitors

Fenyvesi¹,

Jörg²,

Harenberg³

2002

Semin Thromb Hemost

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Monitoring of direct thrombin inhibitors with the activated partial thromboplastin time (aPTT) is limited by poor linearity and reproducibility. Recently, direct prothrombin activation methods have been developed for coagulation analysis: ecarin clotting time (ECT) and prothrombinase-induced clotting time (PiCT). Laboratory monitoring of the direct thrombin inhibitors lepirudin, argatroban, and melagatran was analyzed and compared with monitoring unfractionated heparin (UFH). Plasma samples of six healthy donors were spiked with lepirudin and argatroban extending to 3000 ng/mL, melagatran extending to 1000 ng/mL, and UFH up to 0.48 IU/mL. Clotting times of aPTT (two reagents), ECT, PiCT, and prothrombin time were determined in a KC 10, a micro instrument. At 3000 ng/mL ECT values were 339.1 +/- 25.0 seconds with lepirudin and 457.5 +/- 29.5 seconds with argatroban. ECT was 586.0 +/- 38.2 seconds with 1000 ng/mL melagatran. The PiCT method provided clotting times of 137.0 +/- 8.4 seconds with UFH, 128.0 +/- 23.4 seconds with lepirudin, and 151 +/- 23.9 seconds with argatroban, and 153.5 +/- 9.9 seconds with melagatran, with the concentrations mentioned. ECT is more sensitive to therapeutic drug concentration ranges than aPTT (prolongations of 3-7 versus 2-3). PiCT yields comparable results with direct thrombin inhibitors and UFH. This method could therefore be suitable for monitoring both drug groups.

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Section: Discussionmentioning

confidence: 99%

Monitoring of Anticoagulant Effects of Direct Thrombin Inhibitors

Fenyvesi¹,

Jörg²,

Harenberg³

2002

Semin Thromb Hemost

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“…As a further possible mechanism, decreased carboxylation of coagulation factors II, VII, IX and X could alter the accessibility of the respective binding sites to different extents for each drug during therapy with vitamin K antagonists [20]. An eventual inhibition promiscuity for FII and FX described for some inhibitors [21] should also be taken into consideration as a possible reason.…”

Section: Discussionmentioning

confidence: 99%

Effect of Phenprocoumon on Monitoring of Lepirudin, Argatroban, Melagatran and Unfractionated Heparin with the PiCT Method

Fenyvesi

Jörg

Harenberg

2002

Pathophysiol Haemos Thromb

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Prothrombinase-induced clotting time (PiCT) is a clotting-time test for heparins and direct thrombin inhibitors to reduce drawbacks of aPTT. Effects of the direct thrombin inhibitors lepirudin, argatroban, melagatran and of unfractionated heparin (UFH) were investigated in normal and oral anticoagulant plasma samples. Lepirudin showed potentiating interferences with phenprocoumon effects. Melagatran, argatroban and UFH delivered distinct linear additive effects in both plasma sample groups. PiCT ratio reduces differences between both groups with UFH, and argatroban inhibitor-receptor-binding mode plays a role in interaction patterns.

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“…This can be seen from a lack of an increase of clotting times with increasing concentrations of the inhibitor in VKAP. In contrast, the bivalent inhibitor lepirudin, the interaction of the anionic binding site seems not to be involved into the reduced gammacarboxylation of factor II during vitamin K therapy [27]. In this respect, the two ECT methods were similar.…”

Section: Discussionmentioning

confidence: 84%