Enhanced anticoagulant activity of enoxaparin in patients with ESRD as measured by thrombin generation time.
BACKGROUND
Patients with renal dysfunction who undergo systemic anticoagulation with enoxaparin are at increased risk for bleeding. Although there is decreased renal clearance of enoxaparin in this population, the clinical utility of monitoring antifactor Xa activity is controversial because it is weakly correlated to bleeding. The goal of this study was to investigate the role of other novel anticoagulation markers, such as thrombin generation time, platelet contractile force, and clot elastic modulus, while controlling for antifactor Xa activity in patients with and without renal dysfunction.


METHODS
Thirty anticoagulant- and antiplatelet-naive subjects completed this trial (10 controls, 10 patients with chronic kidney disease, and 10 patients with end-stage renal disease [ESRD]). Blood samples were obtained and spiked ex vivo with increasing concentrations of enoxaparin antifactor Xa activity (0.25, 0.5, 1.0, and 3.0 IU/mL). Thrombin generation time, platelet contractile force, and clot elastic modulus were measured in each group at each antifactor Xa activity concentration.


RESULTS
Subjects with ESRD had an approximately 50% greater anticoagulant effect, determined by thrombin generation time prolongation, than controls at antifactor Xa activity concentrations of 0.5 to 3.0 IU/mL. This may explain why subjects with ESRD with seemingly therapeutic antifactor Xa levels still experience adverse bleeding. There were no intergroup differences in platelet function, determined by platelet contractile force and clot elastic modulus.


CONCLUSIONS
Antifactor Xa poorly predicts the degree of anticoagulation in patients with ESRD administered low-molecular-weight heparin (LMWH). Thrombin generation time may be a clinically useful anticoagulation monitoring tool to monitor LMWH therapy, especially in patients with renal dysfunction. Additional randomized prospective studies are needed to corroborate these findings.
Brophy
Donald F
DF
Department of Pharmacy Practice, Virginia Commonwealth University/Medical College of Virginia, Richmond, VA, USA. dbrophy@vcu.edu
Martin
Erika J
EJ
Gehr
Todd W B
TW
Carr
Marcus E
ME
D000328:Adult; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002908:Chronic Disease; D017984:Enoxaparin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D005260:Female; D006474:Hemorrhagic Disorders / Q000139:chemically induced; D006801:Humans; D007674:Kidney Diseases / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests; D011446:Prospective Studies; D013917:Thrombin / Q000096:biosynthesis*
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D013917:Thrombin