Abstract
Thrombocytopenia, defined as a platelet count <150,000/μL, is the most common complication of advanced liver disease or cirrhosis with an incidence of up to 75%. A decrease in platelet count can be the first presenting sign and tends to be proportionally related to the severity of hepatic failure. The pathophysiology of thrombocytopenia in liver disease is multifactorial, including (i) splenomegaly and subsequently increased splenic sequestration of circulating platelets, (ii) reduced hepatic synthesis of thrombopoietin with missing stimulation both of megakaryocytopoiesis and thrombocytopoiesis, resulting in diminished platelet production and release from the bone marrow, and (iii) increased platelet destruction or consumption. Among these pathologies, the decrease in thrombopoietin synthesis has been identified as a central mechanism. Two newly licensed oral thrombopoietin mimetics/receptor agonists, avatrombopag and lusutrombopag, are now available for targeted treatment of thrombocytopenia in patients with advanced liver disease, who are undergoing invasive procedures. This review summarizes recent advances in the understanding of defective but at low level rebalanced hemostasis in stable cirrhosis, discusses clinical consequences and persistent controversial issues related to the inherent bleeding risk, and is focused on a risk-adapted management of thrombocytopenia in patients with chronic liver disease, including a restrictive transfusion regimen.
Highlights
Complex disorders of the hemostatic apparatus are present in acute and chronic liver disease, involving combined abnormalities of the megakaryocyte-platelet system, coagulation, and fibrinolysis
Several recent reviews and meta-analyses of studies that compared the effect of three TPO receptor agonists and placebo in patients with chronic liver disease and thrombocytopenia reported on a trend toward increased risk of portal-vein thrombosis upon preprocedural treatment with the TPO receptor agonist (1.6% overall for the drugs vs. 0.6% for placebo) [25,86,87,88]
Hemostatic dysfunction in acute and chronic liver disease and novel therapeutic options to control thrombocytopenia are a prime example for the significant progress that has been made in recent years
Summary
Complex disorders of the hemostatic apparatus are present in acute and chronic liver disease, involving combined abnormalities of the megakaryocyte-platelet system, coagulation, and fibrinolysis. Apart from coagulation defects (international normalized ratio, INR > 1.5) due to reduced hepatocellular synthetic capacity, thrombocytopenia of variable extent is a frequent feature both in acute and chronic liver disease. A decrease in platelet count tends to occur prior to clinical manifestations associated with progressive liver failure and decompensation. Thrombocytopenia can be a sensitive noninvasive biomarker of liver disease and be used as a clinical diagnostic tool. This review covers several aspects of platelet pathology in the context of a defective but at low level rebalanced hemostasis in stable cirrhosis, addresses clinical features and controversial issues, and discusses progress in the management of patients with chronic liver disease and associated risks
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