Thrombocytopenia in chronic liver disease

Abstract

Thrombocytopenia is a common haematological disorder in patients with chronic liver disease. It is multifactorial and severity of liver disease is the most influential factor. As a result of the increased risk of bleeding, thrombocytopenia may impact upon medical procedures, such as surgery or liver biopsy. The pathophysiology of thrombocytopenia in chronic liver disease has long been associated with the hypothesis of hypersplenism, where portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen. Other mechanisms of importance include bone marrow suppression by toxic substances, such as alcohol or viral infection, and immunological removal of platelets from the circulation. However, insufficient platelet recovery after relief of portal hypertension by shunt procedures or minor and transient recovery after splenic artery embolization have caused many to question the importance and relative contribution of this mechanism to thrombocytopenia. The discovery of the cytokine thrombopoietin has led to the elucidation of a central mechanism. Thrombopoietin is predominantly produced by the liver and is reduced when liver cell mass is severely damaged. This leads to reduced thrombopoiesis in the bone marrow and consequently to thrombocytopenia in the peripheral blood of patients with advanced-stage liver disease. Restoration of adequate thrombopoietin production post-liver transplantation leads to prompt restoration of platelet production. A number of new treatments that substitute thrombopoietin activity are available or in development.

Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma

“…However, the cellular and molecular mechanisms remain unclear; it might well be that thrombocytosis "just" reflects cancer-driven systemic inflammation. In cirrhotic patients with a high prevalence of hepatic dysfunction, portal hypertension, and splenomegaly/hypersplenism, the pathophysiology of thrombocytopenia is more complex per se [38,39].…”

Immature platelet fraction values predict recovery of platelet counts following liver transplantation

“…TPO, an important regulator in platelet production [23][24][25], is known to be mainly produced in the liver [26]. Inadequate hepatic TPO production causes low platelet production by the bone marrow, and has been shown to be an important causative factor in the development of thrombocytopenia in advanced cirrhosis of the liver [27][28][29][30]. In the current study, liver function tests (such as total bilirubin) normalized or improved following liver transplantation.…”

Thrombocytopenia in Liver Transplant

“…There is no absolute threshold of platelet count for performing any of those procedures but if platelets are <75,000/mm 3 , the risk of bleeding seems to be higher [4].…”

“…Splenectomy prior to transplantation has been proposed as a therapeutic option to increase platelet count but this approach remains controversial because splenic pooling is not so significant as it was first described and the removal of the spleen does not always lead to substantial and persistent increase in thrombocytes. On the other hand, elimination of the spleen increases the risk of septic complications and portal thrombosis [4].…”

“…This explains why with a reduction in platelet number TPO level in liver disease would not be elevated, as production is lower. TPO level is inappropriate to platelet level and as a consequence the bone marrow stimulation to produce thrombocytes would not be adequate [2,4].…”