Temporary interruption of the inferior vena cava (IVC) with a retrievable filter should be considered in patients with objectively verified proximal deep vein thrombosis (DVT) of the legs who have a temporary contraindication to therapeutic anticoagulation, or in patients who experience severe complications from anticoagulation. The risk of the temporary filter being left in place permanently must be considered. Use of a retrievable filter in conjunction with therapeutic anticoagulation during the early phase of therapy for acute DVT in patients whose cardiopulmonary reserve is limited (ie, those with pre-existing pulmonary hypertension) may be a future indication for this intervention. Interruption of the superior vena cava with a retrievable filter has been performed in a small number of cases, but there are insufficient data to guide risk:benefit analysis for this procedure. Thrombolysis, either systemic or local, results in a higher rate of thrombus resolution than anticoagulation alone. However, the long-term benefit of thrombolysis in preventing or improving the post-thrombotic syndrome remains unproven. Due to the substantial risk and cost of thrombolytic therapy, it should not be performed in the routine treatment of DVT. Thrombolytic therapy, in the absence of contraindication, should be considered in highly symptomatic, massive iliofemoral DVT. Catheter-directed thrombolytic therapy has shown promise in case series, but its role remains to be elucidated in randomized trials.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to evaluate a small-molecule PAI-1 inhibitor (PAI-039; tiplaxtinin) in a rodent stenosis model of venous thrombosis in a two-phase experiment. Phase 1 determined the efficacy of tiplaxtinin against Lovenox (LOV), while phase 2 determined the dose-dependent efficacy. For both phases, drug treatment began 24 hours after surgically induced venous thrombosis and continued for four days. Phase 1 animals (n = 24) receiving low-dose (LD; 1 mg/kg oral gavage) PAI-1 inhibitor demonstrated a 52% decrease in thrombus weight (TW) versus controls (p < 0.05) with significant reductions in active plasma PAI-1, while the high-dose (HD; 10 mg/kg oral gavage) group demonstrated a 23% reduction in TW versus controls. Animals treated subcutaneously with LOV (3 mg/kg) showed a 39% decrease in TW versus controls (p < 0.05). Coagulation tests (aPTT and TCT) were significantly different in LOV compared to PAI-1 inhibitor groups. PAI-039 treatment was also associated with significantly increased return of inferior vena cava blood flow four days post-thrombosis versus controls (p < 0.05). In phase 2 (n = 30), TW was reduced from the 0.5 mg/kg to 5 mg/kg experimental groups, with the 10 mg/kg group demonstrating a paradoxical increase. The 5 mg/kg group showed statistically significant decreases in TW versus controls after four treatment days (p < 0.05). This is the first study to demonstrate dose related effects of PAI-039 on increasing thrombus resolution and inferior vena cava blood flow without adverse effects on anti-coagulation in a rat stenosis model of venous thrombosis.
Thrombosis and Haemostasis 04/2008; 99(4):749-58. DOI:10.1160/TH07-11-0669 · 4.98 Impact Factor
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