Differential In Vitro Inhibition of Thrombin Generation by Anticoagulant Drugs in Plasma from Patients with Cirrhosis

Treatment and prevention of thrombotic complications is frequently required in patients with cirrhosis. However anticoagulant therapy is often withheld from these patients, because of the perceived bleeding diathesis. As a result of the limited clinical experience, the anticoagulant of choice for th...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:PloS one Ročník 9; číslo 2; s. e88390
Hlavní autoři: Potze, Wilma, Arshad, Freeha, Adelmeijer, Jelle, Blokzijl, Hans, van den Berg, Arie P., Meijers, Joost C. M., Porte, Robert J., Lisman, Ton
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 04.02.2014
Public Library of Science (PLoS)
Témata:
Anticoagulants
Anticoagulants - therapeutic use
Benzimidazoles - therapeutic use
beta-Alanine - analogs & derivatives
beta-Alanine - therapeutic use
Bleeding
Blood Coagulation Tests - methods
Care and treatment
Cirrhosis
Complications
Congenital diseases
Dabigatran
Drugs
Female
Gastroenterology
Heparin
Heparin, Low-Molecular-Weight - therapeutic use
Hepatology
Humans
Laboratories
Liver cirrhosis
Liver Cirrhosis - metabolism
Liver diseases
Low molecular weight heparin
Low molecular weights
Male
Medical research
Medicine
Middle Aged
Molecular weight
Morpholines - therapeutic use
Patients
Pharmacokinetics
Pharmacology
Plasma
Polysaccharides - therapeutic use
Rivaroxaban
Surgery
Thiophenes - therapeutic use
Thrombin
Thrombin - metabolism
Thrombosis
Veins & arteries
Weight reduction
ISSN:1932-6203, 1932-6203
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Treatment and prevention of thrombotic complications is frequently required in patients with cirrhosis. However anticoagulant therapy is often withheld from these patients, because of the perceived bleeding diathesis. As a result of the limited clinical experience, the anticoagulant of choice for the various indications is still not known. We evaluated the in vitro effect of clinically approved anticoagulant drugs in plasma from patients with cirrhosis. Thirty patients with cirrhosis and thirty healthy controls were studied. Thrombin generation assays were performed before and after addition of unfractionated heparin, low molecular weight heparin, fondaparinux, dabigatran, and rivaroxaban, to estimate anticoagulant potencies of these drugs. Addition of dabigatran led to a much more pronounced reduction in endogenous thrombin potential in patients compared to controls (72.6% reduction in patients vs. 12.8% reduction in controls, P<0.0001). The enhanced effect of dabigatran was proportional to the severity of disease. In contrast, only a slightly increased anticoagulant response to heparin and low molecular weight heparin and even a reduced response to fondaparinux and rivaroxaban was observed in plasma from cirrhotic patients as compared to control plasma. The anticoagulant potency of clinically approved drugs differs substantially between patients with cirrhosis and healthy individuals. Whereas dabigatran and, to a lesser extent, heparin and low molecular weight heparin are more potent in plasma from patients with cirrhosis, fondaparinux and rivaroxaban showed a decreased anticoagulant effect. These results may imply that in addition to dose adjustments based on altered pharmacokinetics, drug-specific dose adjustments based on altered anticoagulant potency may be required in patients with cirrhosis.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Conceived and designed the experiments: WP FA JA JCMM RP TL. Performed the experiments: WP FA JA. Analyzed the data: WP JA TL. Contributed reagents/materials/analysis tools: HB APvdB. Wrote the paper: WP TL.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0088390