Low-molecular-weight heparin in patients with advanced cirrhosis.
OBJECTIVE
The use of low-molecular-weight heparins (LMWH) in patients with advanced liver diseases is frequently avoided because of the enhanced risk of bleeding complications. However, many patients with impaired liver function are at a high risk of thrombosis or have an indication for therapeutic anticoagulation. Therefore, the aim of this study was to evaluate the pharmacokinetics of LMWH in patients with cirrhosis.


METHODS
Eighty-four consecutive patients with cirrhosis and a clinical indication for prophylactic or therapeutic anticoagulation were included. The LMWH doses were chosen according to current guidelines. Antifactor Xa activity (anti-Xa) was assessed on two consecutive days, 4 h after drug administration. The severity of liver disease was quantified using Child-Turcotte-Pugh score, the MELD score and clinical features and was correlated with the anti-Xa value and the occurrence of complications.


RESULTS
Antifactor Xa activity was negatively correlated with the severity of the liver disease, and a positive correlation was observed between antithrombin-III (AT) levels and anti-Xa value. AT itself was negatively correlated with the severity of liver disease. Seven patients had an episode of variceal bleeding. No patient died during the observation interval and no thromboembolic events occurred.


CONCLUSIONS
Prophylactic use of LMWH in patients with cirrhosis appears to be safe. A decreased anti-Xa value in cirrhotic patients and a negative correlation with liver function challenge the unconditional use of anti-Xa assays in LMWH monitoring in cirrhotic patients and reveals a potential limitation of anti-Xa analysis in these patients. Low levels of AT, because of reduced hepatic synthesis, are the most likely cause of this phenomenon.
Department of Gastroenterology and Hepatology, University-Hospital Essen, Essen, Germany.
Lars P
LP
Bechmann
Matthias
M
Sichau
Marc
M
Wichert
Guido
G
Gerken
Knut
K
Kröger
Philip
P
Hilgard
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D016903:Drug Monitoring / Q000379:methods; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004932:Esophageal and Gastric Varices / Q000097:blood / Q000209:etiology*; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D005858:Germany; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D055815:Young Adult
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D000990:Antithrombin III; D015951:Factor Xa