SUN-085 Assessing the Impact of Disease Activity on Clot Formation and Lysis in Patients with Acromegaly

Abstract

Introduction: Data from previous studies suggest increased thrombogenic potential in patients with acromegaly, with higher levels of fibrinogen and a degree of impaired fibrinolysis, which may be contributing to the increased cardiovascular risk associated with acromegaly. However, it remains unclear whether these hemostatic abnormalities reverse in patients with disease remission. Patients and Methods: We conducted a cross-sectional study in 40 patients with acromegaly. The patients were divided into two groups based on the Endocrine Society criteria for disease remission (GH<1mcg/L and IGF-1 within the reference range) at the time of the study. We measured fibrinogen using the Clauss method and also analyzed clot formation and lysis using a validated turbidimetric assay. Results: Twenty-two patients with active acromegaly (Group 1; mean age 51±13 years) and 18 with disease remission (Group 2; mean age 55±13 years) were assessed. There was no difference in the two groups with regards to age, gender distribution, BMI, fat mass (as measured by bioimpedance), skinfold thickness, total cholesterol and HbA1c. Mean GH and IGF-1 values were significantly higher in the group with active acromegaly (2.6±2.4 vs. 0.5±0.5 mcg/L, p<0.001 and 163±105% vs. 73±23% of upper limit of normal, p<0.001 respectively). Mean duration of disease remission in Group 2 was 9.4±6 years. Patients in remission had more prolonged lag time for the initiation of clot formation (571±68 vs. 514±72 sec, p=0.02), however maximum clot optic density was similar in the two groups (Group 1: 0.40±0.12 vs. Group 2: 0.35±0.14 arbitrary units, p=0.26). Additionally, no statistical difference was found in the lysis times in the two groups (mean time from maximum clot formation to 50% lysis was 24.5±18.7 min in Group 1, compared with 34.4±25.3 min in Group 2; p=0.16). Fibrinogen levels were also similar (Group 1: 3.9±1.6 mg/ml vs. Group 2: 3.2±1.5 mg/ml; p=0.2). Duration of active disease was associated with higher fibrinogen levels (coefficient 0.06, p=0.03), while duration of disease remission was associated with longer lag time for clot formation (coefficient 5.0, p=0.015). Disease status was another predictor of lag time for clot formation, with active acromegaly being associated with shorter lag time (coefficient -56.5, p=0.016). Conclusions: We were not able to demonstrate any significant differences in the clot structure properties between patients with active acromegaly and those with disease remission. This may be due to a type II statistical error due to the relatively small sample size or suggest that hemostatic abnormalities described in other studies persist, despite biochemical control of acromegaly. The presence of active disease and the overall duration of this, appear to be associated with increased potential for clot formation in patients with acromegaly.