Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis.
There is increasing recognition that thrombotic complications may occur in patients with cirrhosis, and literature on antithrombotic treatment in these patients is rapidly emerging. Due to extensive haemostatic changes in patients with cirrhosis, careful monitoring of anticoagulant therapy may be required. Recent data suggest that plasma levels of low molecular weight heparin (LMWH) are substantially underestimated by the anti-activated factor X (anti-Xa) assay in patients with cirrhosis. We studied the in vitro recovery of antithrombin (AT)-dependent and -independent anticoagulant drugs in plasma from 26 patients with cirrhosis and 30 healthy controls and found substantially reduced anti-Xa levels when AT-dependent anticoagulant drugs were added to the plasma of patients with cirrhosis. LMWH (0·2 U/ml) had the poorest recovery in plasma from patients with cirrhosis (0·13 ± 0·06 U/ml, compared to 0·23 ± 0·03 U/ml in controls, P < 0·0001), followed by unfractionated heparin and fondaparinux. In contrast, the recovery of rivaroxaban and dabigatran was identical between patients and controls. These data suggest that the anti-Xa assay cannot be used to monitor AT-dependent anticoagulant drugs in patients with cirrhosis, as it substantially underestimates drug levels. The direct factor Xa and IIa inhibitors, however, may be monitored through the respective anti-Xa and anti-IIa assays in patients with cirrhosis.
Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Wilma
W
Potze
Freeha
F
Arshad
Jelle
J
Adelmeijer
Hans
H
Blokzijl
Arie P
AP
van den Berg
Robert J
RJ
Porte
Ton
T
Lisman
D000925:Anticoagulants / Q000097:blood* / Q000494:pharmacology; D000991:Antithrombins / Q000097:blood / Q000494:pharmacology; D001562:Benzimidazoles / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D000069604:Dabigatran; D003955:Diagnostic Tests, Routine; D016903:Drug Monitoring / Q000379:methods*; D065427:Factor Xa Inhibitors; D005188:False Negative Reactions; D005260:Female; D000077425:Fondaparinux; D006493:Heparin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D011134:Polysaccharides / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D011516:Prothrombin / Q000037:antagonists & inhibitors; D000069552:Rivaroxaban; D012680:Sensitivity and Specificity; D013876:Thiophenes / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D019851:Thrombophilia / Q000097:blood / Q000209:etiology; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use
D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D009025:Morpholines; D011134:Polysaccharides; D013876:Thiophenes; D015091:beta-Alanine; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D000069552:Rivaroxaban; D000069604:Dabigatran; D000077425:Fondaparinux
anti-Xa assay; anticoagulants; antithrombin; cirrhosis; coagulation