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The haemostatic system in acromegaly: a single-centre case-control study
E Campello1, M Marobin1, M Barbot2
1Thrombotic and Haemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, via Giustiniani 2, Padua, Italy.
Insights
Acromegaly patients exhibit hypercoagulability due to elevated fibrinogen, factor VIII, and thrombin generation. This pro-thrombotic state is more pronounced in the chronic phase of the disease.
Area of Science:
- Endocrinology
- Hematology
- Cardiovascular Medicine
Background:
- Acromegaly, a disorder caused by excess growth hormone, is associated with increased cardiovascular mortality.
- The role of hemostatic balance and hypercoagulability in acromegaly pathogenesis remains incompletely understood.
Purpose of the Study:
- To globally assess the coagulation profile in acromegaly patients.
- To investigate the presence of hypercoagulability using traditional and global coagulation assays.
Main Methods:
- Enrolled consecutive acromegaly outpatients and matched healthy controls.
- Measured thromboelastometry, impedance aggregometry, coagulation factors, thrombin generation, and microvesicles.
Main Results:
- Acromegaly patients showed higher fibrinogen, factor VIII, endogenous thrombin potential (ETP), and thrombin peak compared to controls.
- Increased endothelial-derived microvesicles were observed in acromegaly patients.
- Untreated acromegaly patients had lower ETP than treated patients.
Conclusions:
- Hypercoagulability in acromegaly is primarily driven by elevated fibrinogen, factor VIII, and thrombin generation.
- The pro-thrombotic state in acromegaly appears linked to the chronic nature of the disease.
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.
