Abnormal plasma fibrin clot characteristics are associated with worse clinical outcome in patients with peripheral arterial disease and thromboangiitis obliterans

Background: A role of blood coagulation in the pathogenesis of peripheral arterial disease (PAD) and Buerger's disease, or thromboangiitis obliterans (TAO), remains unclear.

Objective: To test the hypothesis that PAD and TAO are associated with prothrombotic phenotype of a fibrin clot.

Patients and methods: Ex vivo plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated in 106 patients with PAD and 20 patients with TAO and compared with the respective control groups matched for age, sex, and cardiovascular risk factors. The progression of PAD and TAO were evaluated during follow-up of 3-7.5 years. PAD patients were characterized by lower clot permeability (-18.8%, p=0.005), shorter lag phase (-35.3%, p<0.001), higher maximum clot absorbancy (+22.4%, p<0.001), prolonged clot lysis time (+30.6%, p=0.003), and lower rate of D-dimer release from clots in the presence of recombinant tissue plasminogen activator (-16.5%, p=0.009), but twofold lower maximum D-dimer levels released from clots during lysis (p<0.001) than the controls. Similar, but more pronounced abnormalities were observed in TAO patients versus controls (all p<0.01). Seventeen PAD (16%) and 3 (15%) TAO patients were lost to follow-up. The progression observed in 47 (52.8%) PAD patients and 10 (59%) TAO patients was associated with lower clot permeability (-14.6%, p=0.009, and -17.5%, p=0.02) and prolonged clot lysis (+11.3%, p=0.004, and +12.4%, p=0.03, respectively).

Conclusions: Unfavorably altered fibrin clot properties are observed in both PAD and TAO. Denser fibrin clots with reduced susceptibility to lysis might characterize the progression of both diseases during long-term follow-up.