Sequestrated thrombolysis: comparative evaluation in vivo

Lysis of a thrombus is a function of the local concentration of thrombolytic enzymes. This study was designed to determine in a porcine model of acute deep vein thrombosis (DVT) whether perithrombic sequestration of small volumes of a concentrated enzyme solution can accelerate the process of thrombolysis.

DVT was induced in both hind limbs using a previously described technique (n = 32). Thirty minutes later the animal was heparinized and unilateral thrombolysis was attempted using 8 mg recombinant tissue plasminogen activator (rt-PA); saline was administered in the opposite leg. For conventional high-volume infusion (CI) (n = 5) rt-PA (0.067 mg/ml) was infused at 1 ml/min. For sequestrated thrombolysis the external iliac vein was endoluminally occluded, and rt-PA (0.25 mg/ml) administered either for proximal injection (ST-P) (n = 5), as a bolus every 3 min through a microcatheter placed via the balloon catheter, or for transthrombic injection (ST-T) (n = 5), as a bolus every 3 min through a Katzen wire in the balloon catheter. At autopsy, the thrombus mass in the iliofemoral veins was measured, and the extent of residual thrombosis in the venous tributaries graded at four sites. From these data a thrombolysis score was calculated.

One pig died before thrombolysis could be performed. Only with ST-T was residual thrombus mass in the test limb normalized to control, residual thrombus index (RTI), consistently less than unity. The median RTI of this group was 0.50 (range 0.39-0.97) compared with 1.22 (0.64-1.38) for ST-P and 0.88 (0.37-1.13) for CI. Compared with contralateral controls, a lower grade of residual thrombosis in tributaries was observed in test limbs at more venous sites with ST-T (8/20; 95% confidence interval 5-13) and ST-P (9/20; confidence interval 5-13) than with CI (2/20; confidence interval 0-5) (p = 0.04). A trend toward lower thrombolysis scores was observed with ST-T (p = 0.08). Systemic fibrinogenolysis was not observed in any of the groups. Changes in coagulation parameters during thrombolysis were similar irrespective of treatment protocol.

"Transthrombic" sequestrated thrombolysis may offer some advantages over conventional selective infusion for the treatment of acute DVT. However further refinements will be necessary before it can be considered an alternative to the latter.