Coagulation imbalance may not contribute to the development of portal vein thrombosis in patients with cirrhosis

Abstract

Introduction

The relationship between the imbalance in pro- and anti-coagulant factors and portal vein thrombosis (PVT) in individuals with cirrhosis is unclear. The aim of this study was to determine whether the imbalance in pro- and anti-coagulant factors contributes to the development of PVT in cirrhotic patients.

Materials and methods

Blood samples were collected from 30 consecutive cirrhotic patients with PVT and 30 age-, sex-, and Child-Pugh score-matched cirrhotic patients without PVT (controls), and the plasma levels of coagulation factors II, V, VII, VIII, IX, X, XI and XII and of protein C (PC), protein S (PS) and antithrombin (AT) were analyzed. The ratios of pro- vs. anti-coagulant factors were further investigated.

Results

The levels of pro- and anti-coagulant factors were not statistically different between the PVT and control groups. Similar results were obtained when the patients were divided according to Child-Pugh classification. No difference was observed for the ratios of pro- vs. anti-coagulant factors between the two groups but the ratios of factor II-to-PC and factor VII-to-PC which were significantly decreased in the PVT group. Most of the ratios did not reach statistical significance in each Child-Pugh category except the followings: factor VIII-to-PS, factor XII–to-PC and factor XII-to-PS in class A patients; factor II-to-PS, factor VII-to-PC and factor VII-to-PS in class B patients. But the difference might not be so convincing.

Conclusions

PVT in cirrhotic patients may not result from coagulation imbalance.

Introduction

Coagulation is a highly integrated cellular and humoral process that is balanced by two opposing drivers [1]. The pro-coagulant driver is triggered by the complex of factor VII and its specific receptor tissue factor, which in turn activates a series of events in the coagulation cascade, ultimately leading to thrombin generation and fibrin clot formation [2]. The primary anti-coagulant drivers include proteins C (PC), its cofactor protein S (PS) and antithrombin (AT). The ratios of pro- to anti-coagulant factors can be considered indexes of the coagulation imbalance [3].

Patients with liver cirrhosis are characterized by decreased levels of most pro- and anti-coagulant factors, with the exception of factor VIII, which is markedly elevated [4], [5], [6]. For decades, it has been believed that patients with cirrhosis are prone to hypocoagulation and autoanticoagulation, and are thus protected from thrombotic episodes [7]. However, accumulating evidence from both clinical [8], [9], [10], [11] and laboratory studies [3], [12] indicates that patients with cirrhosis have an increased tendency to develop thrombosis. Thus, the prevailing paradigm has been challenged by the concept of rebalanced hemostasis in patients with liver disease [7], [13]. This balance may not be as stable as in healthy individuals, and only slight alterations may tip the balance to either bleeding or thrombosis [7].

Portal vein thrombosis (PVT) is a common complication of liver cirrhosis and is associated with decreased liver function and aggravated portal hypertension [14]. The prevalence of PVT in individuals with liver cirrhosis varies from 10% to 25% [15]. It is generally accepted that decreased portal vein velocity is the primary factor underlying PVT in cirrhosis [16]. The role played by coagulation imbalance in PVT is still unclear. Tripodi et al. hypothesized that hypercoagulability due to high factor VIII combined with low PC is an additional risk factor for PVT, but this has never been demonstrated conclusively [3], [17].

The aim of our study was to investigate the relationship between coagulation imbalance and PVT in patients with liver cirrhosis by comprehensively analyzing the plasma levels of pro- and anti-coagulant factors.