Laboratory Analysis of Blood Samples from Patients Treated with Tinzaparin

Tinzaparin at two dosages, 175 anti-Xa U/kg subcutaneously administered for 7 days, followed by warfarin, and 175 anti-Xa U/kg subcutaneously given for 90 days was compared with continuous intravenous unfractionated heparin (UFH) for 5 days, followed by warfarin for 3 months, were tested in the treatment of patients with proximal deep vein thrombosis. Several laboratory assays were used to monitor the effects of tinzaparin and UFH. The tinzaparin only study arm produced a 4- to 6-second prolongation of the activated partial thromboplastin time (aPTT). However, in the anti-Xa chromogenic assay and the Heptest assays, there was a prolongation after the administration of all three agents. In the two groups treated for 7 days, the anti-Xa and Heptest values returned to baseline after cessation of therapy. In the patients treated with tinzaparin for 90 days, the anti-Xa and Heptest remained elevated throughout the treatment period. The anti-IIa (anti-thrombin) results were considerably lower values in the tinzaparin-treated groups. Tissue factor pathway inhibitor (TFPI) antigen levels were elevated 2- to 2.5-fold in all three groups. In addition, the thrombin/antithrombin (TAT) complexes were also measured. After treatment, the TAT levels decreased over time. Tinzaparin was more effective in decreasing these levels. These results suggest that both Heptest and anti-Xa assays can be used to monitor patients receiving tinzaparin. TAT may be a useful test in monitoring the resolution of the clots. However, additional clinical validation is required to demonstrate the relevance of these parameters with the clinical outcome.

KEYWORDS

Deep vein thrombosis - tinzaparin - heparin - monitoring - anticoagulants - thrombin/antithrombin complex (TAT) - tissue factor pathway inhibitor (TFPI)

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