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Differential augmentation of the anticoagulant responses by newly developed oral anti‐Xa and Anti‐IIa drugs in patients with liver disease
Author(s) -
Masood Soofia,
VanThiel David,
George Magdalena,
Hoppensteadt Debra,
Fareed Jawed
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb383
Subject(s) - dabigatran , fibrin , rivaroxaban , hemostasis , coagulation , apixaban , pharmacology , anticoagulant , thrombin , clotting time , prothrombin time , chemistry , thrombin time , saline , coagulation testing , medicine , partial thromboplastin time , anesthesia , platelet , warfarin , immunology , atrial fibrillation
The liver plays a central roll in the regulation of hemostasis. Beside synthesis of coagulation factors, the liver is responsible for the metabolism of newly developed anticoagulant drug such as the Rivaroxaban (R), Apixaban (A) and Dabigatran (D). These drugs may have a direct effect by compromising the coagulation process. The purpose of this investigation is to determine the differential effects of R, A and D in liver disease patients (LDP). Citrated plasma samples from LDP (n=10‐20) were supplemented with graded amounts of R, A and D and saline. PT, aPTT, thrombin time (TT), Heptest clotting times and FXIII activity were determined. In addition, thrombin induced fibrinokinetics were measured. These agents produced a concentration dependent increase in the clot based assays with the exception of the Heptest in the range of 0.125‐1 µg/ml. In comparison to saline, the anti‐Xa and anti‐IIa agents produced a sizeable increase in the INR, aPTT and TT. D produced the most pronounced effects on all clotting assays, whereas R and A produced a modest increase. R decreased the Heptest. The fibrinokinetogram revealed mark differences among the different patients indicating the defects in fibrin polymerization. Supplementation of R, A and D resulted in a strong inhibition of fibrin formation which was most pronounced with D. These results clearly demonstrate that (LDP) suffer from a pre‐existing hemostatic imbalance with multiple factor differences.