Rodger MA et al. – Dalteparin and tinzaparin significantly accumulate in hemodialysis (HD) patients at therapeutic doses. “Bridging therapy” with low–molecular–weight heparins at therapeutic doses in HD patients who require temporary interruption of warfarin therapy has the potential for complications and is of uncertain benefit.Methods
- Open-label randomized controlled trial.
- HD patients undergoing periprocedure bridging anticoagulation.
- After warfarin therapy was discontinued, participants were randomly assigned to either 3 daily doses of tinzaparin (175 IU/kg) or dalteparin (200 IU/kg), with 2 intervening HD treatments between the first dose of study drug and their procedure.
- The primary outcome was predialysis anti-Xa levels 20 to 24 hours after the third LMWH dose (therapeutic target, <0.2 IU/mL).
- Secondary outcomes included thromboembolic events and major bleeding.
- Of 29 eligible and consenting patients, 17 patients received tinzaparin and 12 patients received dalteparin.
- Mean predialysis anti-Xa level 20-24 hours after the third LMWH dose was 0.37 ± 0.23 (SD) IU/mL for tinzaparin and 0.62 ± 0.41 IU/mL for dalteparin (P = 0.1), indicating clinically important accumulation for both drugs.
- No invasive procedures were canceled due to study drug accumulation.
- 4 patients experienced serious adverse events (1 major bleed after traumatic arteriovenous fistula puncture in the tinzaparin arm, 2 non–ST-elevation myocardial infarctions [1 in each group], and 1 upper-extremity deep venous thrombosis [dalteparin group]).