In patients with acute liver failure or chronic liver disease, many changes in the hemostatic system occur. The liver is the site of synthesis of nearly all coagulation factors, both pro- and anticoagulant proteins. A reduced synthesis function of the liver leads to reduced levels of these factors in circulation. In addition, the liver is involved in the clearance of many activated coagulation factors and protein–inhibitor complexes from the circulation, which in turn can lead to activation of the coagulation system if liver function is impaired. Furthermore, the liver is involved in the synthesis and clearance of pro- and antifibrinolytic proteins, which may lead to a shift in the balance of the fibrinolytic system. Also, primary hemostasis might be affected in liver disease because of thrombocytopenia and impaired platelet function, which is frequently encountered in these patients. It is evident that patients with liver disease have frequent bleeding episodes, mainly in the gastrointestinal tract, such as variceal bleeding. It has been a longstanding dogma that patients with liver disease are at a high risk of bleeding caused by these hemostatic changes. However, in recent years, this cause of the bleeding tendency has been questioned because of the concomitant reductions of pro- and anticoagulant factors and pro- and antifibrinolytic factors. More recent studies using more sophisticated coagulation tests showed that thrombin generation is normal in patients with chronic liver failure and that some may even have a prothrombotic phenotype. This led to the development of a model of a rebalanced hemostatic system in these patients, which may have immediate implications for treatment. Hematologists and other clinicians taking care of patients with acute liver failure of chronic liver disease, such as cirrhosis, are still faced with the questions of whether these patients need correction of the changes in hemostasis before interventions such as paracentesis, biopsies, dental care, and surgery. It was generally believed that replacement therapy with frozen plasma or platelet concentrates was indicated. However, based on these new findings, physicians should now be more restrictive in the use of hemostatic agents and blood products in these patients both in liver disease and during liver transplantation. Small volume prohemostatic concentrates such as prothrombin complex concentrate or fibrinogen concentrate may be better suited to prevent or treat bleeding. An emerging challenge is prevention and treatment of thrombosis, including venous thrombosis and portal vein thrombosis, but the optimal treatment regimens have not yet been established.
Acronyms and Abbreviations
ADAMTS13, a disintegrin-like and metalloprotease with thrombospondin domain 13; aPTT, activated partial thromboplastin time; DDAVP, 1-deamino-8-D-arginine vasopressin; DIC, disseminated intravascular coagulation; FFP, fresh-frozen plasma; HAT, hepatic artery thrombosis; HSC, hepatic stellate cell; INR, international normalized ratio; ISI, international sensitivity index; LMWH, low-molecular-weight heparin; MELD, model of end-stage liver disease; PAI-1, plasminogen activator inhibitor 1; PCC, prothrombin complex concentrate; PFA, platelet function analyzer; PT, prothrombin time; PVT, portal vein thrombosis; TAFI, thrombin-activatable fibrinolysis inhibitor; t-PA, tissue-type plasminogen activator; VWF, von Willebrand factor.