Inflammatory bowel disease: epidemiology, pathology and risk factors for hypercoagulability

Abstract

Hypercoagulability observed in patients with inflammatory bowel diseases (IBD) may lead to thromboembolic events (TE), which affect the venous and arterial systems alike and are an important factor in patients' morbidity and mortality. The risk of TE in IBD patients has been demonstrated to be approximately three-fold higher as compared to the general population. The pathogenesis of thrombosis in IBD patients is multifactorial and not fully explained. The most commonly listed factors include genetic and immune abnormalities, disequilibrium between procoagulant and anticoagulant factors, although recently, the role of endothelial damage as an IBD-triggering factor is underlined. Several studies report that the levels of some coagulation enzymes, including fibrinogen, factors V, VII, VIII, active factor XI, tissue factor, prothrombin fragment 1 + 2 and the thrombin-antithrombin complex, are altered in IBD patients. It has been demonstrated that there is a significant decrease of tissue plasminogen activator level, a marked increase of plasminogen activator inhibitor type 1 and thrombin-activable fibrinolysis inhibitor, a significantly lower level of antithrombin III and tissue factor pathway inhibitor. IBD patients have been also observed to produce an increased amount of various anticoagulant antibodies. Hyperhomocysteinemia, which is a potential risk factor for TE was also observed in some IBD patients. Further studies are necessary to assess the role of coagulation abnormalities in IBD etiology and to determine indications for thromboprophylactic treatment in patients at high risk of developing TE.

Keywords: Crohn’s disease; Hypercoagulation; Risk factors; Thrombosis; Ulcerative colitis.

Figure 1

Coagulation cascade model. ↑/↓: Changes in coagulation factors, in patients with inflammatory bowel diseases.

Figure 2

The elements of the fibrinolytic system. tPA: Tissue-type plasminogen activator; uPA: Urokinase plasminogen activator; PAI-1: Plasminogen activator inhibitor type 1; TAFI: Thrombin activatable fibrinolysis inhibitor; FDP: Fibrin degradation products; FgDP: Fibrinogen degradation products. ↑/↓: Changes in coagulation factors, in patients with inflammatory bowel diseases.

Figure 3

Plasma coagulation inhibitors. AT III: Antithrombin III; TF: Tissue factor; TFPI: TF pathway inhibitor; PS: Protein S; APC: Activated protein C. ↓: Changes in plasma coagulation inhibitors, in patients with inflammatory bowel diseases.

Figure 4

Protein C system. PC: Protein C; APC: Activated protein C; S: Protein S; TM: Thrombomodulin; PAT-1: Plasminogen activator inhibitor 1; EPCR: Endothelial cell PC receptor; C4bBP: C4b-binding protein; Va: V active; Vi: V inactive; VIIIa: VIII active; VIIIi: VIII inactive. ↑/↓: Changes in protein C system, in patients with inflammatory bowel diseases.