The haemostatic system in acromegaly: a single-centre case-control study.

PURPOSE: Although the mortality from acromegaly is due in most cases to an increased cardiovascular risk, no study has globally evaluated the haemostatic balance in acromegaly to ascertain the presence of hypercoagulability. We endeavoured to assess the overall coagulation profile in patients with acromegaly using both traditional and global coagulation assays. METHODS: Consecutive outpatients with a diagnosis of acromegaly were enrolled and matched with healthy subjects. Whole blood thromboelastometry and impedance aggregometry, procoagulant, anticoagulant and fibrinolytic factors, as well as thrombin-generation assay and circulating endothelium-derived microvesicles were measured. RESULTS: Forty patients (M/F 14/26, median age 59 years) with either new diagnosis (naïve, 14 cases) or treated acromegaly (26 cases) were enrolled in this study. Median time from diagnosis was 11 years. Levels of factor VIII and fibrinogen were significantly higher in acromegalic patients vs. controls (p = 0.029 and < 0.003, respectively). Overall, thromboelastometry parameters showed a faster coagulation formation with a more stable clot. Acromegaly patients showed significantly higher endogenous thrombin potential [ETP] and thrombin peak compared to controls (p = 0.016 and p < 0.001, respectively). ETP remained significantly higher (p < 0.001) when thrombomodulin was added. Endothelial-derived microvesicles were significantly higher in acromegaly patients than controls (52 [40.5-67] MVs/µL and 30 [18-80] MVs/µL, p = 0.03). Patients with untreated (naïve) acromegaly showed significantly reduced ETP with and without thrombomodulin vs. patients with treated acromegaly (p = 0.01). CONCLUSION: Hypercoagulability in acromegaly is mainly due to higher levels of fibrinogen, factor VIII and thrombin generation, and appears to be more linked to the chronic phase of the disease.

Circulating microparticles in carriers of prothrombin G20210A mutation.

Factor V Leiden (FVL) and prothrombin gene mutation G20210A (PTM) are the two most common genetic polymorphisms known to predispose carriers to venous thromboembolism (VTE). A recent study in FVL carriers showed that circulating levels of microparticles (MP) may contribute to their thrombogenic profile. To further elucidate the prothrombotic state linked to genetic thrombophilia, we extended this study to carriers of PTM. The plasma level of annexin V-MP, endothelial-MP (EMP), platelet-MP (PMP), tissue factor-bearing MP (TF+) and the MP procoagulant activity (PPL) was measured in 124 carriers of PTM (105 heterozygous and 19 homozygous) and in 120 age- and gender-matched healthy individuals. Heterozygous and homozygous carriers of PTM showed significantly increased levels of annexin V-MP (2930 [1440-4646] MP/µl and 3064 [2412-4906] MP/µl, respectively) and significantly shorter PPL clotting time (54 [46-67] sec and 55 [46-64] sec) compared to controls (1728 [782-2122] MP/µl and 71 [61-75] sec, respectively; p<0.01). Similarly, heterozygous and homozygous subjects presented with significantly higher levels of EMP, PMP and TF+ than controls (p<0.05). PTM carriers with a VTE history had significantly higher MP numbers and activity than controls. No significant difference was seen between carriers with and without a VTE history. We conclude that the higher levels of circulating MP found in PTM carriers may play a role in the development of VTE possibly by increasing thrombin generation. Further studies are needed to better define the role of MP as triggering factors for the thrombotic complications characterizing mild genetic thrombophilic defects.