The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Abstract

Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

The efficacy of low molecular weight heparin in severe acute pancreatitis: A systematic review and meta‐analysis of randomized controlled trials

“…Although the role of coagulation dysfunction in SAP pathogenesis has not been well understood, it is known that coagulation dysfunction is one of the common complications in SAP. Emerging evidence showed that coagulation dysfunction and inflammation could promote progression of SAP . Proinflammatory cytokines, particularly interleukin‐6, together with impaired endothelial cells could activate the coagulation process in local or systemic inflammatory state, inducing a hypercoagulable state .…”

“…In the meta-analysis, since the mean length of hospital stay were shorter in both 7-day and 14-day LMWH treatment subgroups than those of the conventional treatment subgroups, 7-day LMWH treatment is recommended because of an reduced risk of bleeding, while the course of treatment could be prolonged to 14 days when the SAP patients have high risk of embolization.Although the role of coagulation dysfunction in SAP pathogenesis has not been well understood, it is known that coagulation dysfunction is one of the common complications in SAP. Emerging evidence showed that coagulation dysfunction and inflammation could promote progression of SAP 31. Proinflammatory cytokines, particularly interleukin-6, together with impaired endothelial cells could activate F I G U R E 5 Forest plot of meta-analyses of A, acute physiology and chronic health evaluation (APACHE) II score and B, computed tomography severity index in low molecular weight heparin treatment group and conventional treatment group.…”

Higher Thrombin-Antithrombin III Complex Levels May Indicate Severe Acute Pancreatitis

“…An ideal prognostic marker is needed to show the severity of the disease in the early period and as a guide to treatment. Studies have suggested that parameters associated with coagulation disorder and inflammation, thought to play a significant role in the pathogenesis of the disease, can be used for his purpose [10, 18-20, 30, 31]. …”

“…Coagulation disorders may develop in association with the severity of AP [6-10]. However, the pathogenesis of coagulation disorder in patients with AP is uncertain.…”

“…However, the pathogenesis of coagulation disorder in patients with AP is uncertain. Increased cytokine release, inflammation and resulting endothelial injury are thought to lead to thrombin formation and hypercoagulability [10-12]. Thrombin and antithrombin III that form as a result of activation of the coagulation system constitute the TAT complex.…”