Reductions in plasmin inhibitor and fibrinogen predict the improved fibrin clot lysis 6 months after obesity surgery

Abstract

Summary Prothrombotic and metabolic variables are decreased after obesity surgery, and fibrin clot lysis is increased. It is unknown how fibrinolytic variables are affected, and whether fibrinolytic and metabolic changes predict the enhanced clot lysis. Study aims were to determine fibrinolytic biomarkers before and 6 months after Roux‐en‐Y gastric bypass (RYGB) and to identify predictors of the RYGB‐induced increase in clot lysis. Women (n = 42) and men (n = 18) with obesity underwent RYGB, and factor XIII (FXIII), thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen and plasmin inhibitor (PI) were measured before and 6 months after surgery. Regression analyses identified determinants of the RYGB‐induced increase in clot lysis among changes in fibrinogen and in fibrinolytic and metabolic variables. Results showed that after RYGB, FXIII, TAFI, plasminogen and PI were reduced (P < .0005). Reductions in PI (β = −0.59) and fibrinogen (β = −0.35), together with age (β = −0.22) and male sex (β = 0.22), predicted the enhanced clot lysis with the model explaining 56% (P < .0005). Predictors of the reduction in PI were reductions in cholesterol (β = 0.37) and glucose (β = 0.29), together with male sex (β = −0.28), whereas reductions in fibrinogen were predicted by lowering of interleukin‐6 (IL‐6) (β = 0.32). In conclusion, fibrinolytic variables were reduced 6 months after RYGB. Targeting PI and fibrinogen, by reducing metabolic variables such as glucose, cholesterol and IL‐6, has a profibrinolytic effect in obesity.

Changes in fibrin clot properties in patients after Roux-en-Y gastric bypass surgery

“…Notably, a further substudy by Pedersen et al. [ 21 ] specifically linked a reduction in PI and fibrinogen 6 months after bariatric surgery to improved lysis. Therefore, it is conceivable that lysis times did not change due to the unaltered fibrinogen (and potentially PI) concentration.…”

“…These studies showed that RYGB led to an improvement in clot lysis 6, 12, and 24 months after surgery [ 19 , 20 ]. A later substudy showed that the enhanced clot lysis 6 months after surgery was predicted by reductions in circulating fibrinogen and plasmin inhibitor (PI) [ 21 ]. It is noted, however, that the factors influencing fibrin clot structure and fibrinolysis are complex.…”

Imbalanced Coagulation in the Airway of Type-2 High Asthma with Comorbid Obesity

“…In addition to improved asthma control, bariatric surgery corrects inflammatory cytokine and adipokine profiles. Circulating levels of leptin, TNF-α, IL-6 and C-reactive protein (CRP), an indirect inhibitor of tPA through augmentation of IL-1β and TNF-α, 94 significantly decrease 3-to-12 months following bariatric surgery, [95][96][97][98][99][100] with a concomitant increase seen in circulating adiponectin levels. [95][96][97] Serum levels of Type-2 cytokines IL-13 and chitinase-3-like protein 1 (YKL-40) are also shown to decrease following bariatric surgery.…”

“…Bariatric surgery induces improvement in coagulation through normalized anti-coagulant and anti-fibrinolytic mediators. 22,[63][64][65][66]97,99,100,105 Batist et al reported increased systemic anti-thrombin III associated with bariatric surgery-stimulated weight loss. 63,105 Moreover, circulating PC/APC levels decreased 1 year following bariatric surgery due to reduced thrombomodulin and thrombin potential.…”

“…63,105 Moreover, circulating PC/APC levels decreased 1 year following bariatric surgery due to reduced thrombomodulin and thrombin potential. [64][65][66] Bariatric surgery also promoted a significant reduction in systemic PAI-1 as early as 3-months post-operative, 22,65,97,99,100 reducing the inhibition of tPA and uPA, leading to improved fibrinolysis. Indeed, epigenetic mechanisms may provide a link between bariatric surgery and improved coagulation profiles in patients with obesity.…”