The effects of low-molecular-weight heparin at two different dosages on thrombin generation in cancer patients.

Ludwig Traby; Alexandra Kaider; Rainer Schmid; Alexander Kranz; Peter Quehenberger; Paul A. Kyrle; Sabine Eichinger

doi:10.1160/TH09-12-0863

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2010; 104(01): 92-99
DOI: 10.1160/TH09-12-0863

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

The effects of low-molecular-weight heparin at two different dosages on thrombin generation in cancer patients.

A randomised controlled trial

Ludwig Traby

¹Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

,

Alexandra Kaider

²Core Unit for Medical Statistics and Informatics, Medical University of Vienna, Vienna, Austria

,

Rainer Schmid

³Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria

,

Alexander Kranz

³Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria

,

Peter Quehenberger

⁴Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria

,

Paul A. Kyrle

¹Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

,

Sabine Eichinger

¹Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

› Institutsangaben

Abstract

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Summary

Non-surgical cancer patients are at high thrombotic risk. We hypothesised that the prothrombotic state is reflected by elevated thrombin generation and can be mitigated by increasing the low-molecularweight heparin (LMWH) dose. Non-surgical cancer patients were randomised to enoxaparin 40 or 80 mg. D-dimer, prothrombin fragment F1+2 (F1+2) and peak thrombin (PT) were measured 2, 4, 6 hours (h) after LMWH (day 1) and daily for 4 days. A total of 22 and 27 patients received enoxaparin 40 and 80 mg, respectively. D-dimer and F1+2 moderately decreased after 6 h in both groups. After enoxaparin 80 mg, D-dimer baseline levels [median (quartiles)] decreased from day 1 to 4 [1054.9 (549.5, 2714.0) vs. 613.0 (441.1, 1793.5) ng/ml] (p<0.0001), while no difference was seen after 40 mg. Baseline PT levels [median (quartiles)] were 426.2 nM (347.3, 542.3) (40 mg) and 394.0 nM (357.1, 448.8) (80 mg). After 80 mg, PT significantly decreased to 112.4 nM (68.5, 202.4), 57.1 nM (38.0, 101.2) and 43.6 nM (23.4, 112.8) after 2, 4 and 6 h, which was lower than after 40 mg (p=0.003). After 80 mg, PT decreased from day 1 to 4 [358.6 nM (194.2, 436.6); p=0.06] while no difference was seen after 40 mg. In conclusion, in cancer patients coagulation activation and thrombin generation is substantially increased. Peak thrombin levels are sensitive to the anticoagulant effects of LMWH at different dosages. The prothrombotic state is substantially attenuated by higher LMWH doses.

Keywords

Venous thrombosis - thrombin - cancer - prophylaxis - heparins - LMWH

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Referenzen

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