Inhibition of clot formation process by treatment with the lowmolecular-weight heparin nadroparin in patients with carotid artery disease undergoing angioplasty and stenting - A thromboelastography study on whole blood

Abstract

Low-molecular-weight heparins (LMWHs) have become the corner stone of antithrombotic treatment but their administration protocol needs to be optimized for certain groups of patients. In this paper, we studied the influence of nadroparin treatment on clot formation process assessed by thromboelastography in patients with carotid artery disease undergoing angioplasty and stenting. Standard thromboelastography assays (in-TEM^® and ex-TEM^® ) and minimal TF-triggered thromboelastography assay in citrated whole blood were performed in normal volunteers (n=20), in patients with carotid artery disease receiving only antiplatelet treatment (n=30), and in patients undergoing angioplasty receiving nadroparin 5750 anti-Xa IU s.c. twice daily (n=60). Blood samples were collected four hours after a second injection of nadroparin. In a subgroup of LMWH-patients (n=18) blood samples were also obtained prior to first injection of LMWH. Antiplatelet treatment had no effect on any parameter of the thromboelastographic pattern. Nadroparin treatment resulted in significant prolongation of clotting time (CT) and clot formation time (CFT) and significantly reduced α-angle in minimal TF-triggered thromboelastography and 30–38% of nadroparin treated patients had thromboelastographic parameters beyond the normal maximum limit. In-TEM test revealed a significant prolongation of clotting time while ex-TEM was not modified, and 20 to 30% of the patients had thromboelastographic parameters beyond the normal maximum limit. Anti factor-Xa activity in platelet-poor plasma (PPP) was also measured, and statistical analysis showed that prolongation of CFT of minimal TF-triggered TEM was significantly correlated to the levels of anti-Xa activity in patients’ plasma (p=0.04; r² =0.7). There was no statistical correlation for any other parameter in all tests. In conclusion, the present study shows that nadroparin treatment in patients with carotid artery disease undergoing endovascular procedures induces significant modification of the thrombus kinetics assessed by minimal TF-triggered whole blood thromboelastography. The clinical relevance of these findings has to be evaluated in future studies.