The effect of aspirin on haemostatic activity in the treatment of chronic venous leg ulceration

An increased rate of venous ulcer healing with the use of oral enteric-coated aspirin (300 mg) daily has been reported. Whether the effect of aspirin in this condition is related to its action on the haemostatic mechanism is unclear, and therefore this study aimed to assess the effect of aspirin on some haemostatic parameters in patients with chronic venous leg ulcers. A double-blind, randomized, placebo-controlled, parallel-group study of haemostatic activity and the effect of aspirin was implemented over a 4-month period. Twenty patients with venous leg ulcers, and 20 age- and sex-matched controls were studied. Patients received enteric-coated aspirin (300 mg) or placebo (one tablet) daily for 4 months, in addition to standardized local compressive bandaging (Setopress). Assessments made at recruitment, and at 2 and 4 months, included measurement of total ulcer surface area, haematological and biochemical screening, measurement of coagulation times, coagulation factor VIII:C (FVIII:C) and von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) levels. Procoagulant activity was assessed by a computer-assisted technique, to determine the rate of thrombin production in vitro. Patients with venous ulcers had increased levels of fibrinogen (P <0.01), FVIII:C (P <0.05), vWF (P <0.05) and PAI-1 antigen (P <0.01) compared with controls. Shortening of the coagulation rate, shown by a reduction of the time to generate 50% maximal thrombin activity in seconds (T₅₀), was seen in patients, in comparison with control subjects (P <0.05). T₅₀ was longer in patients receiving aspirin than those receiving placebo, reflecting prolongation of coagulation rate in the aspirin-treated group. In addition, an increased rate of ulcer healing occurred in subjects receiving aspirin compared with the placebo-treated group (P <0.01, P <0.02 at 2 and 4 months, respectively). No significant change in fibrinogen, FVIII:C, vWF or PAI-1 levels occurred in either group during the 4-month period.