Endothelial fibrinolytic reactivity and the risk of deep venous thrombosis after spinal cord injury

Deep vein thrombosis (DVT) is a frequent event in patients with spinal cord injury, even with prophylactic anticoagulant therapy. Lower limb paralysis is a known major risk factor for venous thrombosis, supposedly due to the venostasis in relation with total immobility. The main goal of this study was to evaluate the endothelial response to anoxia to determine whether recovery of fibrinolytic potential occurs in patients subjected to forced bedrest because of a spinal cord injury and whether this recovery is related to the incidence and/or evolution of DVT. We evaluated vascular endothelium reactivity in the lower limbs no longer submitted to the hydrostatic pressure of the erected position in 15 patients with paraplegia or tetraplegia and in 10 normal volunteers after venous occlusion produced by the application of 10 cm Hg pressure to the lower limb for 15 min comparatively to the upper limb used as reference. Among the 15 patients, 10 whose spinal cord injury had occurred 1 to 6 months earlier were still receiving prophylactic anticoagulant therapy, whereas the five other patients were not receiving prophylactic anticoagulants because the injury dated back 6 months or more. After venostasis, tissue plasminogen activator (tPA) increased significantly in both patients and controls in the upper limb (tPA levels twofold and threefold respectively in controls and patients) but showed no significant changes in the lower limb; prolonged immobility did not allow recovery in the lower limbs of a level of fibrinolytic responsiveness identical to that in the upper limbs. The plasminogen activator inhibitor (PAI(1)) remained unchanged after anoxia, although wide interindividual variations were seen. Natural coagulation inhibitors and circulating blood stigmates of hypercoagulability were measured. None of the patients had abnormally low levels of coagulation inhibitors tie, antithrombin III, protein C and protein S levels were normal). Seventy-five per cent of patients (prophylactically anticoagulated or not) had very high levels of fibrin degradation products (D. Dimer levels sevenfold to eightfold those of the controls), but all patients had normal levels of thrombin-antithrombin complexes and prothrombin fragments 1 + 2. The permanence of the thrombotic process characterized by an increase in D. Dimer levels without recovery of fibrinolytic potential suggests a proposal for the patients an indefinite antithrombotic treatment at curative doses.