Long term administration of LMWH - pharmacodynamic parameters under therapeutic or prophylactic regimen of enoxaparin or tinzaparin in neurological rehabilitation patients

Abstract We investigated anti-FXa- and anti-FIIa-activity, thrombin generation (ETP), tissue factor pathway inhibitor (TFPI) - and D-dimer in patients exhibiting high bleeding risk in early neurological rehabilitation over 2months in an observational study. Blood of 64 patients under LMWH administration due to therapeutic (cohort 1 [tinzaparin 90IE/kg BID, N=18] and 2 [enoxaparin 100IE/kg BID; N=15]) or prophylactic (cohort 3 [tinzaparin 4500IE; N=16] and 4 [enoxaparin 4000IE; N=15]) indication was drawn before and 4h after injection on day 7 (V1) and 2 months (follow up [V2]). Although the dose in cohort 1 and 2 was similar (median 7000IE BID), a-FXa-activity was significantly larger under enoxaparin than under tinzaparin (e.g. median at V2: 0.70IU/ml vs. 0.33IU/ml). Also, prophylactic enoxaparin exhibited larger a-FXa-activity than tinzaparin (e.g. median at V2: 0.37IU/ml vs. 0.22IU/ml). The a-FXa/a-FIIa-ratio in plasma samples at 4h p.a. was about 4 (tinzaparin) and 8 (enoxaparin), respectively. No differences were seen for TFPI and ETP between cohort 1 and 2 or between cohort 3 and 4. D-dimer levels decreased significantly between V1 (e.g. cohort 4 median 1940ng/ml) and V2 (median 652ng/ml). Minimal bleeding events occurred in 6 patients (2 under tinzaparin, 4 under enoxaparin) and were associated with significantly higher anti-FXa-activity. In conclusion, although marked differences between tinzaparin and enoxaparin based on anti-FXa-activity were seen, markers of in vivo biological activity such as TFPI and D-dimer were not different. Furthermore, BID tinzaparin is a feasible option for therapeutic anticoagulation in patients with high bleeding risk.