STUDIES ON THE MEDICAL TREATMENT OF DEEP VEIN THROMBOSIS
Authors: Schulman Sam 
Published: August 2010

The aim of these studies was to investigate different regimens of thrombolytic therapy and oral anticoagulation, and to evaluate the effects of streptokinase (SK), heparin and warfarin in the treatment of deep vein thrombosis (DVT).

Low‐dose SK, although controlled according to the fibrinogen levels, did not provide improved thrombolysis compared to conventional high‐dose SK, and more postthrombotic changes were registered after an average of 3 years. Furthermore, serious hemorrhagic side‐effects occurred, which makes this regimen inexpedient.

Various regimens of local venous infusion of SK were tried, and with a dose of 4,000 IU/h for 72 h in combination with heparin a thrombolytic effect was achieved, albeit not greater than usually observed with conventional SK. Systemic hypofibrinogenemia and hemorrhage were not avoided. A hitherto not described side‐effect with bullous dermatitis was reported.

Venographic severity of calf vein thrombosis displayed a statistically significant correlation to long‐term hemodynamic changes, as assessed with foot volumetry, after an average of 5 years. This correlation was stronger for the size of the thrombus after initial treatment than for the size at diagnosis. Thus it seems important to treat calf vein thrombosis with heparin in order to limit the extent of the thrombus, thereby reducing long‐term sequelae.

During heparin treatment, an average reduction of the thrombi of 17% was observed. This reduction was significantly correlated to a short duration of symptoms but not to parameters of heparin therapy or fibrinolytic components. However, patients with substantial thrombolysis had high plasmin‐α2‐antiplasmin (PAP) levels, and those with high tissue plasminogen activator (t‐PA) inhibitor levels and remarkably also those with high t‐PA antigen levels, had no lysis. The concentration of t‐PA antigen showed a significant increase during heparin infusion, whereas that of PAP and t‐PA inhibitor was not influenced.

By applying more intensive initial oral anticoagulation, stable therapeutic prothrombin time (PT)‐levels were achieved one day earlier and the duration of heparin infusion could be equally reduced compared to the conventional regimen (4.4–5 days vs 5.4–6 days). The activity of coagulation factors II, VII, IX and X had dropped to the same level with both regimens the day heparin was discontinued, thromboembolic complications did not occur and no difference in bleeding was observed.

The effectiveness of oral anticoagulation after DVT was studied in 596 patients treated for a total of 4450 months. Thromboembolic complications (n=36) during long‐term prophylaxis with oral anticoagulants following DVT occurred throughout the entire therapeutic range in patients with cancer, but never below a PT‐level of 27% as assessed with Simplastin A (International Normalized Ratio (INR) > 1.9) among those without neoplastic disease. This confirmed that the limit of the therapeutic range, determined by the risk of thromboembolic complications, should be set at a Simplastin A‐level of approx 25% (INR = 2.0) in prophylaxis of venous thrombosis.

In a randomized comparison of our routine duration of oral anticoagulation and 50% reduction thereof, with stratification according to the nature of risk factors, no differences in thromboembolic complications could be detected. Experiences from this study will be used in a larger trial to establish the optimal duration of treatment.