T BATT1, R PRASAD1, L LINCZ2, R PATEL3, M SHASTRI3, N LIOUFAS4, AG SMITH1, MD JOSE 3,4
1Haematology Department, Royal Hobart Hospital, Tasmania; 2Hunter Haematology Research Group, Calvary Mater Newcastle Hospital, Waratah, NSW; 3Nephrology Department, Royal Hobart Hospital, Tasmania; 4School of Medicine, University of Tasmania.
Aims: To investigate anti-Xa levels, thrombin generation, enoxaparin fragments and clinical effectiveness of enoxaparin given for haemodialysis.
Background: Low molecular weight heparins (LMWH) are used during haemodialysis to prevent clotting of the dialysis circuit with dosing regimens based on weight or clinical effectiveness, without routine measurement of anticoagulation effect. Individual oligosaccharide fragments of LMWH may have specific biological activity.
Methods: Prospective observational repeated measures study using currently prescribed enoxaparin, measuring anti-Xa levels, thrombin generation and enoxaparin fragments. Bleeding and thrombosis outcomes were recorded. Anti-Xa >0.5U/ml was considered adequate.
Results: 16 subjects during 31 dialysis sessions (mean 276 minutes) completed the study. Enoxaparin dose varied widely (mean 49 mg, range 0.22 – 1.24 mg/kg). There were no serious bleeding events, nor significant difference in bleeding times between doses. No therapeutic bioaccumulation of enoxaparin was detected. A dose of 20 mg was inadequate to reach an anti-Xa level of >0.5 U/ml, and did not suppress thrombin generation to below 50%. Four sessions recorded clots in the dialyser, 3 of which were using 20mg. Doses of 40 and 60 mg did suppress thrombin generation at 2 hours, but only a dose of 80 mg maintained this for the duration of dialysis. Modelling of our data suggests anti-Xa levels of >0.53 U/ml suppresses thrombin generation to 15%. Enoxaparin fragment (dp8-dp16) levels were highly variable between patients but remained relatively stable over the study period. Dp6 was only detected in patients receiving ≥40mg and was quickly cleared after 4 h.
Conclusion: A dose of 80 mg of enoxaparin was required to achieve adequate anti-Xa levels throughout the dialysis session. Enoxaparin fragments are numerous and cleared at different rates.