Prothrombotic fibrin network characteristics in patients with acromegaly: a novel mechanism for vascular complications

Objective: There remains increased cardiovascular mortality in patients with acromegaly. This study aims to evaluate whether GH/IGF-1 excess increases vascular disease by adversely affecting fibrin network characteristics. Design: Cross-sectional study in 40 patients with acromegaly (21 males, age 53 ± 13 years) and 40 age/gender-matched controls. Methods: Clot structure was analysed using a validated turbidimetric assay and fibrin networks were visualised by laser scanning confocal microscopy (LSCM). Metabolic profile parameters, body composition, plasma fibrinogen and PAI-1 were also assessed. Results: Twenty-two patients had active acromegaly and 18 were in remission. There was no difference in qualitative patient characteristics between the two groups. Both groups had less favourable body composition and cardiovascular risk profile compared with controls. Despite no difference in clot formation and lysis parameters between the two patient groups, active disease patients had higher fibrinogen and clot maximum absorbance compared with controls, after adjusting for BMI (3.8 ± 0.2 vs 2.6 ± 0.2 mg/mL, P < 0.001; and 0.39 ± 0.02 vs 0.33 ± 0.01 arbitrary units, P = 0.03, respectively). Patients in remission had higher fibrinogen compared with controls following adjustment for BMI (3.3 ± 0.2 vs 2.6 ± 0.2 mg/mL, P = 0.02) but not clot maximum absorbance (0.35 ± 0.03 vs 0.33 ± 0.02 arbitrary units, P = 0.6). LSCM showed increased fibrin network density only in active disease patients, consistent with turbidimetric analysis. In addition to active disease, BMI, fat mass and skinfold thickness were associated with higher clot density and longer lysis time. Conclusions: Patients with active acromegaly have more compact clots, thus conferring increased thrombosis risk. Prothrombotic fibrin networks may represent one mechanism for enhanced vascular risk in active acromegaly