Tissue factor pathway inhibitor release and depletion by sulodexide in humans.


PURPOSE Anticoagulant tissue factor pathway inhibitor (TFPI) is released from its endothelial stores by heparin, which may lead to its untoward depletion. We investigated the effects of sulodexide--a commercially available mixture of heparan and dermatan sulfate, on plasma TFPI release and depletion. MATERIAL AND METHODS An open-label pilot trial of intravenous and/or oral sulodexide effects on plasma immunoreactive total TFPI antigen level was performed in 11 healthy men. The drug was initially administered i.v. at a single dose of 120 mg, thenorally for 12 days (50 mg b.i.d), and again by i.v route after 2 weeks. RESULTS Sulodexide injections induced marked increases in plasma TFPI; they were more pronounced on day 14 than on study initiation (3-fold vs. 2-fold after 10 min) and still evident after 120 min. TFPI levels did not change when measured at 120 min after oral sulodexide administration. The percentage increment in plasma TFPI after 10 min from initial sulodexide injection inversely correlated with baseline TFPI levels (r = - 0.664, P = 0.026). On day 14, the association became strong (r = - 0.970, P < 0.0001) and evident also after 120 min (r = - 0.810, P < 0.002). Baseline TFPI levels decreased over the trial; on day 14 they were lower by 34% than on study initiation (P = 0.001). CONCLUSIONS TFPI release by i.v. sulodexide and its depletion during oral administration of this heparinoid compound constitute novel and likely important hemostatic effects of the drug.

DOI: 10.2478/v10039-009-0009-4

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@article{Borawski2009TissueFP, title={Tissue factor pathway inhibitor release and depletion by sulodexide in humans.}, author={Jacek Borawski and Joanna Goździkiewicz and Miroslaw Dubowski and Krystyna Pawlak and Michał Myśliwiec}, journal={Advances in medical sciences}, year={2009}, volume={54 1}, pages={32-6} }