Resistance to activated protein C in patients with venous leg ulcers.

Resistance to activated protein C (APC) Deep-vein thrombosis Postthrombotic syndrome Venous leg ulcer Jürg Hafner, Department of Dermatology, University Hospital of Zurich, CH–8091 Zurich (Switzerland), Tel. +41 1 255 11 11, Fax +41 1 255 44 03 Resistance to activated protein C (APC) is the most frequent cause of inherited thrombophilia [1]. The Leiden Thrombophilia Study detected resistance to APC in 21% of 301 unselected consecutive patients with a first episode of objectively confirmed diagnosis of deep-vein thrombosis (DVT) [2]. Among a matched control group, the incidence of resistance to APC was 5%. This represents a 7-fold increase in the risk of DVT in persons with resistance to APC (odds ratio 6.6, 95% confidence interval 3.6to 12-fold). In contrast, a study from the University Hospital of Geneva detected resistance to APC in only 5.5% of 146 unselected patients with pulmonary embolism, compared to 4.0% of patients with suspicion of pulmonary embolism, in whom the diagnosis could not be confirmed (statistically no difference, p < O.66) [3]. The striking difference might be explained in part by patient selection. Since resistance to APC has practical consequences for the particular individual, it is necessary to identify subgroups of persons in whom systematic screening for resistance to APC would be justified. Patients with venous leg ulcers might represent a subgroup with a high prevalence of resistance to APC. Munkvad and jørgensen [4] reported resistance to APC to be prevalent in 26% of 47 consecutive patients with venous leg ulceration (95% confidence interval 14-41%). To date we could confirm resistance to APC in several patients with venous leg ulcers, especially in those with a positive family history for leg ulcers. Assuming that about two thirds of the patients with venous leg ulceration do have postthrombotic damage of their deep-veins and as a consequence postthrombotic syndrome [5], resistance to APC might be especially prevalent among patients with postthrombotic leg ulceration. This led us to perform a pilot study and to examine 20 consecutive patients presenting for venous leg ulceration. The diagnosis of venous leg ulceration was based on clinical criteria and Doppler ultrasound examination [5]. At the time of blood sampling, none of the patients received heparin or oral anticoagulants. Six patients had a personal history of prior DVT. None of the patients had a family history of thrombophilia. Blood was collected in citrated glass tubes (sodium citrate, 0.11 mol/l), and plasma was prepared by centrifugation (3,000 g for 10 min) and stored at -80 °C. The APC sensitivity ratio was measured with the Coatest APC resistance kit (Cbromogenix,