Thrombin generation in morbid obesity: significant reduction after weight loss

Background: Patients with morbid obesity (MO; body mass index > 40 kg m-2) suffer from an increased risk of cardiovascular disease, stroke, venous thromboembolism and all-cause mortality. Objectives: Because weight loss by bariatric surgery reduces cardiovascular and all-cause mortality, we hypothesized that the plasmatic clotting system might be involved in cardiovascular risk. Patients/Methods: Thirty-six MO patients [mean age 42 (+/- 13) years; 29 female) were investigated before and 2 years after bariatric surgery. Thrombin generation was measured with a commercially available assay (Technothrombin-TGA,Technoclone). Metabolic parameters and parameters of the hemostatic system, such as tissue factor (TF), TF pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1) and prothrombinfragment 1.2 (F1.2), were determined. To investigate associations of changing parameters, deltas were calculated. Results: Metabolic parameters improved with a mean weight loss of 41 (+/- 19) kg. Postoperatively, the lag phase was significantly extended compared with preoperative values [median (25th-75th percentile), 7 (4-12) vs. 12 (7-19) min, P = 0.005]. Peak thrombin decreased after weight loss from 345 (232-455) to 282 (111-388) nm (P = 0.015) and the area under the curve from 3962 (3432-5023) to 3227 (2202-4030) nm thrombin (P < 0.001). TF, PAI-1 and F1.2 significantly decreased after weight loss. Analyses of the deltas showed a significant correlation between peak thrombin and total cholesterol (r = 0.50), triglycerides (r = 0.46) and HbA1c (r = 0.55). Moreover, an inverse correlation was found between insulin resistance and the lag phase (r = -0.46). Conclusion: Thrombin generation, a marker of the overall coagulation potential, decreased significantly with weight reduction. This might, at least in part, explain the decreased risk of cardiovascular disease after bariatric surgery.