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: K Kuczka, K Baum, B Picard-Willems, S Harder
• Journal: Thrombosis research (Thromb Res) Vol. 124 Issue 5 Pg. 625-30 (Nov 2009) ISSN: 1879-2472 [Electronic] United States
• PMID: 19625075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Enoxaparin
• Fibrin Fibrinogen Degradation Products
• Fibrinolytic Agents
• Heparin, Low-Molecular-Weight
• Lipoproteins
• fibrin fragment D
• lipoprotein-associated coagulation inhibitor
• Tinzaparin

Topics

• Adult
• Aged
• Aged, 80 and over
• Anticoagulants (administration & dosage)
• Drug Administration Schedule
• Enoxaparin (administration & dosage)
• Female
• Fibrin Fibrinogen Degradation Products (metabolism)
• Fibrinolytic Agents (administration & dosage)
• Hemorrhage (chemically induced, drug therapy, prevention & control)
• Heparin, Low-Molecular-Weight (administration & dosage)
• Humans
• Lipoproteins (metabolism)
• Male
• Middle Aged
• Nervous System Diseases (blood, rehabilitation)
• Tinzaparin