title: 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 2 months in an observational study. Blood of 64 patients under LMWH administration due to therapeutic (cohort 1 [tinzaparin 90 IE/kg BID, N = 18] and 2 [enoxaparin 100 IE/kg BID; N = 15]) or prophylactic (cohort 3 [tinzaparin 4500 IE; N = 16] and 4 [enoxaparin 4000 IE; 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 7000 IE BID), a-FXa-activity was significantly larger under enoxaparin than under tinzaparin (e.g. median at V2: 0.70 IU/ml vs. 0.33 IU/ml). Also, prophylactic enoxaparin exhibited larger a-FXa-activity than tinzaparin (e.g. median at V2: 0.37 IU/ml vs. 0.22 IU/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 1940 ng/ml) and V2 (median 652 ng/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.
authors.affiliation: Pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology at the Johann Wolfgang Goethe University Frankfurt, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kuczka
authors.forename: K
authors.initials: K
authors.lastname: Baum
authors.forename: B
authors.initials: B
authors.lastname: Picard-Willems
authors.forename: S
authors.initials: S
authors.lastname: Harder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000097:blood* / Q000534:rehabilitation*; D000078222:Tinzaparin
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; C036309:fibrin fragment D; C051928:lipoprotein-associated coagulation inhibitor; D000078222:Tinzaparin