Increased anticoagulant response to low molecular weight heparin in plasma from patients with advanced cirrhosis.
J Thromb Haemost. 2012 Jun 19;
Authors: Marco S, Isabel RK, Valeria R, Claudia R, Sabrina G, P C, Patrizia Z, Teresa SM, Paolo S
Introduction: cirrhotic patients may present thrombotic complications that warrant anticoagulant therapy. However, the efficacy of low molecular weight heparin (LMWH) in this clinical setting is still unclear. Aims/methods: to evaluate the in vitro effect of LMWH on thrombin generation (TG) in cirrhotic patients at different stages of liver disease. Thirty cirrhotics (10 Child-A, 10 Child-B, 10 Child-C), 10 subjects with inherited type 1 antithrombin (AT) defect, and 10 healthy controls were studied. TG was determined at baseline and with anti-Xa levels after the addition of enoxaparin at 0.35U anti-Xa/mL and 0.7U anti-Xa/mL. Endogenous thrombin potential (ETP) ratio at 0.35U anti-Xa/mL and 0.7U anti-Xa/mL were obtained by dividing ETP with LMWH by ETP at baseline. Results: Mean AT levels in all cirrhotic subgroups and in patients with AT deficiency were significantly lower than in controls. The 0.35ETP ratio was significantly lower in cirrhotics than in controls (0.26ÃÂ±0.1 vs 0.48ÃÂ±0.1, p<.001) and the reduction paralleled the severity of liver disease, despite the concomitant decrease in AT and anti-Xa activity. AT-deficient subjects showed a significantly increased 0.35ETP ratio compared to both cirrhotics and controls (0.69ÃÂ±1 vs 0.26ÃÂ±0.1, p<.001, and vs 0.48ÃÂ±0.1, p=.04 respectively). LMWH at 0.7U anti-Xa/mL completely inhibited TG in 9/30 cirrhosis patients with more advanced liver disease (Child B and C), while complete TG abolition was seen in only 1/10 controls. Conclusions: cirrhotic patients show an increased response to LMWH, which correlates with the severity of liver disease, despite reduced AT and anti-Xa activity levels. Thrombin generation may be a useful tool to monitor the response to LMWH in cirrhotic patients. ÃÂ© 2012 International Society on Thrombosis and Haemostasis.
PMID: 22712870 [PubMed - as supplied by publisher]