Antifactor Xa activity correlates to thrombin generation time, platelet contractile force and clot elastic modulus following ex vivo enoxaparin exposure in patients with and without renal dysfunction.
Antifactor Xa activity is the gold standard monitoring parameter for low molecular weight heparin (LMWH) derivatives. It is frequently measured in high-risk populations, such as patients with renal dysfunction. Despite antifactor Xa monitoring, however, bleeding in renal dysfunction patients receiving LMWH remains a problem. This study determined the relationship between antifactor Xa activity and three novel coagulation monitoring parameters: thrombin generation time (TGT), platelet contractile force (PCF) and clot elastic modulus (CEM). This study also assessed the effect of renal dysfunction on these relationships. This was an ex vivo pharmacodynamic study of the relationship between antifactor Xa activity and TGT, PCF and CEM in subjects both with and without renal dysfunction. Thirty subjects completed this study (10 controls, 10 chronic kidney disease subjects, and 10 end-stage renal disease subjects receiving hemodialysis). Blood samples obtained from participants were spiked with increasing enoxaparin concentrations (0.25, 0.5, 1.0 and 3.0 IU mL(-1)). Samples were analyzed for TGT, PCF and CEM. The relationship between antifactor Xa activity and TGT, PCF and CEM was determined by Pearson's correlation. The effect of renal dysfunction on the relationship between antifactor Xa activity and TGT, PCF and CEM was determined by analysis of covariance. There is strong correlation between antifactor Xa activity and TGT, CEM and PCF. The presence of renal dysfunction significantly prolongs the TGT, and decreases the CEM relative to controls. These results suggest that patients with renal dysfunction have a greater pharmacodynamic response to LMWH, independent of the pharmacokinetics of LMWH.
Department of Pharmacy, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia, USA. dbrophy@bcu.edu
D F
DF
Brophy
E J
EJ
Martin
A M
AM
Best
T W B
TW
Gehr
M E
ME
Carr
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000494:pharmacology*; D015951:Factor Xa / Q000096:biosynthesis*; D065427:Factor Xa Inhibitors; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D013917:Thrombin / Q000096:biosynthesis / Q000378:metabolism*; D013918:Thrombin Time; D013997:Time Factors
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D013917:Thrombin; D015951:Factor Xa