Comparison of Anti-Xa and Activated Partial Thromboplastin Time Monitoring for Heparin Dosing in Patients With Cirrhosis

Abstract

A greater use of blood products among the cirrhotic population may indicate potential bleeding events on therapy. A discrepancy in correlated anti-Xa and aPTT values among patients with cirrhosis may explain the propensity for adverse effects. Further study is required to identify effective heparin anticoagulation monitoring strategies in liver disease.

Anticoagulation in chronic liver disease

“…It is probable that cirrhotics are more sensitive to unfractioned heparin (Potze et al, 2013), and therapeutic doses of this type of heparin also resulted in a significant drop in haemoglobin and platelet counts in cirrhotic patients (Fuentes et al, 2015); the authors of this study conclude that the drop in haemoglobin likely reflected 8 bleeding events during therapy, whilst the drop in platelet count could have represented heparin-induced thrombocytopenia. In contrast, administration of therapeutic doses of LMWH given over prolonged periods (mainly in the context of treating extrahepatic portal vein thrombosis) appears to be safe, with no significantly increased risk of bleeding (even in the presence of advanced fibrosis) when given alone (Amitrano et al, 2010; Francoz et al, 2005, Delagado et al 2012, Maruyama et al, 2012, Werner et al, 2013 or in conjunction with transjugular intrahepatic portosytemic shunt insertion (Senzolo et al, 2012).…”

“…• Increased risk of thrombocytopenia (potentially because of heparin-induced thrombocytopenia) when used in cirrhotic patients (Fuentes et al, 2015).…”

“…Reichert and colleagues did demonstrate that if the INR was greater than 1.5, then the risk of bleeding was increased, but this was only for bleeding classified as of minor severity (Reichert et al, 2014) and stratification by type of anticoagulation has demonstrated that unfractionated heparin results in a higher bleeding risk than low molecular weight heparin in cirrhotic patients (Intagliata et al, 2014). Consistent with this, evaluation of a prophylactic dose of enoxaparin (4000 IU daily) to prevent PVT in patients with Child B/ C cirrhosis resulted in no increased risk of bleeding events in these patients when heparin was given for a period of 48 weeks when compared to a matched control group patients treated with placebo alone (Villa et al, 2012).It is probable that cirrhotics are more sensitive to unfractioned heparin (Potze et al, 2013), and therapeutic doses of this type of heparin also resulted in a significant drop in haemoglobin and platelet counts in cirrhotic patients (Fuentes et al, 2015); the authors of this study conclude that the drop in haemoglobin likely reflected 8 bleeding events during therapy, whilst the drop in platelet count could have represented heparin-induced thrombocytopenia. In contrast, administration of therapeutic doses of LMWH given over prolonged periods (mainly in the context of treating extrahepatic portal vein thrombosis) appears to be safe, with no significantly increased risk of bleeding (even in the presence of advanced fibrosis) when given alone (Amitrano et al, 2010; Francoz et al, 2005, Delagado et al 2012, Maruyama et al, 2012, Werner et al, 2013 or in conjunction with transjugular intrahepatic portosytemic shunt insertion (Senzolo et al, 2012).…”

Portal vein thrombosis in cirrhosis: diagnosis, natural history, and therapeutic challenges

“…Cirrhosis affects coagulation tests, increasing INR and activated partial thromboplastin time (aPTT) and decreasing anti-Xa. Several studies have even documented a correlation between higher INR levels and increased severity of cirrhosis [ 98 - 101 ]. This makes therapeutic drug monitoring difficult to interpret and optimize because INR elevation caused by warfarin cannot be differentiated from progression of the underlying disease.…”

Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review

“…Balance between thrombosis and bleeding in liver disease. ADAMTS13 ADAM metallopeptidase with thrombospondin type 1 motif 13, PAI plasminogen activator inhibitor, TAFI thrombin-activatable fibrinolysis inhibitor, TFPI tissue factor pathway inhibitor Increased baseline INR/aPTT levels in the absence of anticoagulants and decreased antiactivated factor X (anti-Xa) levels after unfractionated/low-molecular weight heparin (UFH/ LMWH) administration have been found in cirrhosis, correlating with the severity of liver disease [18][19][20]. Patients with cirrhosis can be unusually sensitive to the anticoagulant effects of warfarin and this may also be a clue to identifying latent disease [21].…”