Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction?

Abstract

Patients with cirrhosis can have abnormalities in laboratory tests reflecting changes in primary haemostasis, including bleeding time, platelet function tests, markers of platelet activation, and platelet count. Such changes have been considered particularly relevant in the bleeding complications that occur in cirrhosis. However, several studies have shown that routine diagnostic tests, such as platelet count, bleeding time, PFA-100, thromboelastography are not clinically useful to stratify bleeding risk in patients with cirrhosis. Moreover, treatments used to increase platelet count or to modulate platelet function could potentially do harm. Consequently the optimal management of bleeding complications is still a matter of discussion. Moreover, in the last two decades there has been an increased recognition that not only bleeding but also thrombosis complicates the clinical course of cirrhosis. Thus, we performed a literature search looking at publications studying both qualitative and quantitative aspects of platelet function to verify which primary haemostasis defects occur in cirrhosis. In addition, we evaluated the contribution of qualitative and quantitative aspects of platelet function to the clinical outcome in cirrhosis and their therapeutic management according to the data available in the literature. From the detailed analysis of the literature, it appears clear that primary haemostasis may not be defective in cirrhosis, and a low platelet count should not necessarily be considered as an automatic index of an increased risk of bleeding. Conversely, caution should be observed in patients with severe thrombocytopenia where its correction is advised if bleeding occurs and before invasive diagnostic and therapeutic procedures.

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

“…In these patients, the rate of spontaneous recanalization of portal veins was exceptionally high (70%), compared with only 1/41 in the prospective study by Luca et al [202]. Retrospective studies [43,181,203,205] yielded discordant data but overall indicated poorer survival in patients with stable or progressive PVT, if left untreated [2,4,5]. In addition, PVT in liver transplant candidates correlated with increased mortality after liver transplantation [206].…”

“…The net effect of these changes is a rebalanced hemostasis. However, this hemostatic profile is unstable, and patients can be tipped toward both bleeding and thrombosis under certain conditions [1][2][3][4][5]. Thus, there is growing evidence that proper understanding of the hemostatic pathways in liver disease requires a global perspective which account for the complexity of hemostasis, with dynamic interactions between pro-coagulant and anti-coagulant factors.…”

Coagulopathy in liver disease: Lack of an assessment tool

“…It assesses the risk of thrombosis, but has never been used to assess the risk of bleeding [16] . The measurement of soluble activation markers assesses the presence of products released by platelets (soluble p-selectin, PF-4, beta-TGG, soluble CD40L).…”

“…It is a systematic measurement of the degree of platelet activation, but for several reasons it may lead to artifacts. It helps to predict the risk of thrombosis, but does not predict the risk of bleeding [16] . The platelet adhesion test under flow conditions simulates the in vivo platelet function using standardized reconstituted blood and measures the adhesion of platelets to the subendothelium [17] .…”

Hemostasis, Disorders of Coagulation and Transfusion in Cirrhosis

“…In chronic liver disease, there is a decrease in number of circulating platelets along with thrombocytopathy (platelet dysfunction). This is considered to be multifactorial, which includes pooling of platelets and sequestration in the spleen, presence of antiplatelet glycoprotein IIb-IIIa antibodies in cirrhosis patients, myelosuppression, shorter half-life and rapid turnover secondary to splenic destruction, increased platelet consumption secondary to sustained low grade DIC and lower levels of hepatic thrombopoetin production [9]. Qualitative defects in platelet function also prevail in cirrhosis patients.…”