Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0372544 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2141 (Electronic) Linking ISSN: 00071048 NLM ISO Abbreviation: Br J Haematol Subsets: MEDLINE

Publication: Oxford : Wiley-Blackwell
Original Publication: Oxford : Blackwell Scientific Publications

Blood Coagulation Tests*; Anticoagulants/*blood ; Drug Monitoring/*methods ; Liver Cirrhosis/*blood; Anticoagulants/pharmacology ; Antithrombins/blood ; Antithrombins/pharmacology ; Benzimidazoles/blood ; Benzimidazoles/pharmacology ; Benzimidazoles/therapeutic use ; Blood Coagulation/drug effects ; Dabigatran ; Diagnostic Tests, Routine ; Factor Xa Inhibitors ; False Negative Reactions ; Female ; Fondaparinux ; Heparin/blood ; Heparin/pharmacology ; Heparin/therapeutic use ; Heparin, Low-Molecular-Weight/blood ; Heparin, Low-Molecular-Weight/pharmacology ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; Liver Cirrhosis/complications ; Liver Cirrhosis/drug therapy ; Male ; Middle Aged ; Morpholines/blood ; Morpholines/pharmacology ; Morpholines/therapeutic use ; Polysaccharides/blood ; Polysaccharides/pharmacology ; Polysaccharides/therapeutic use ; Prothrombin/antagonists & inhibitors ; Rivaroxaban ; Sensitivity and Specificity ; Thiophenes/blood ; Thiophenes/pharmacology ; Thiophenes/therapeutic use ; Thrombophilia/blood ; Thrombophilia/etiology ; beta-Alanine/analogs & derivatives ; beta-Alanine/blood ; beta-Alanine/pharmacology ; beta-Alanine/therapeutic use

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.
(© 2013 John Wiley & Sons Ltd.)

Keywords: anti-Xa assay; anticoagulants; antithrombin; cirrhosis; coagulation

0 (Anticoagulants)
0 (Antithrombins)
0 (Benzimidazoles)
0 (Factor Xa Inhibitors)
0 (Heparin, Low-Molecular-Weight)
0 (Morpholines)
0 (Polysaccharides)
0 (Thiophenes)
11P2JDE17B (beta-Alanine)
9001-26-7 (Prothrombin)
9002-04-4 (Factor IIa)
9005-49-6 (Heparin)
9NDF7JZ4M3 (Rivaroxaban)
I0VM4M70GC (Dabigatran)
J177FOW5JL (Fondaparinux)

Date Created: 20131114 Date Completed: 20140121 Latest Revision: 20220318

20221213

10.1111/bjh.12593

24219333