Selective thrombolysis in acute deep vein thrombosis: Evaluation of adjuvant therapy in vivo

Purpose: To evaluate in a porcine model of acute deep vein thrombosis (DVT) the efficacy of dalteparin and antithrombin with respect to heparin for lo cal adjuvant therapy during selective thrombolysis, and the utility of nitr oglycerin and iloprost as heparin supplements. Methods: DVT was induced in both hind limbs using a previously described te chnique (n = 20). Thirty minutes later, the animal was heparinized (2500 IU IV), and bilateral sequestrated thrombolysis was performed using 8 mg alte plase: both external iliac veins were endoluminally occluded with Swan-Ganz catheters, and a multi-sideport infusion wire coaxially introduced through each catheter and advanced into the ipsilateral popliteal vein. In the con trol limbs, tissue plasminogen activator (tPA) 8 mg was injected as 0.8-ml boluses at 3-min intervals for 2 hr as a 0.25-mg/ml solution containing hep arin 50 IU/ml (n = 20). On the contralateral side, heparin was substituted with either dalteparin 50 IU/ml(n = 5) or antithrombin 12.5 IU/ml(n = 5), o r supplemented with either nitroglycerin 0.075 mg/ml (n = 5) or iloprost (1 50 ng/ml) (n = 5), Blood samples were taken at predetermined intervals to m easure the activated partial thromboplastin time (aPTT), prothrombin time ( PT), and fibrinogen concentration. At autopsy, the thrombus mass in the ili ofemoral veins was measured, and the extent of residual thrombosis in the v enous tributaries graded at four sites. Results: Bilateral thrombolysis was successfully completed in all animals. The median thrombus mass in the iliofemoral veins after thrombolysis was 0. 48 g (range 0.06-1.58 g), 0.95 g (0.59-1.29 g), 0.74 g (0.52-0.96 g), and 0 .29 g (0.0-0.77 g) for dalteparin, antithrombin, iloprost, and nitroglyceri n respectively, as compared with 0.53 g (0.18-0.88 g) (p = 0.69), 0.97 g (0 .46-1.15 g) (p = 0.69), 0.53 g (0.48-1.10 g) (p = 0.69), and 0.18 g (0.13-1 .04 g) (p = 0.5) for the respective controls. Likewise, the severity of res idual thrombosis in the venous tributaries was not affected by the constitu ents of adjuvant therapy. Nitroglycerin induced a small drop in blood press ure, which was transient. The temporal change in aPTT was similar in all fo ur groups. Invariably PT progressively shortened during thrombolysis (p = 0 .0001); this effect was somewhat blunted with antithrombin. Fibrinogen leve ls demonstrated a time-dependent increase (p = 0.004) that was not influenc ed by the adjuvant therapy used. Conclusions: Dalteparin or antithrombin demonstrated no appreciable advanta ge over heparin as local adjuvant therapy for selective venous thrombolysis . Supplementation of heparin with iloprost or nitroglycerin also had virtua lly no effect on thrombolytic efficacy.