Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Gütl, K.
Monitoring of Anticoagulation in Cirrhosis
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2015. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Baumann-Durchschein Franziska
- Fickert Peter
- Altmetrics:
- Abstract:
- Background: Cirrhosis has been accepted a hypocoagulable status with a hemostasis-related bleeding tendency for a long period of time. Routine coagulation tests including prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (aPTT) are frequently abnormal and are thus confirming the hypothesis of auto-anticoagulation in cirrhosis. In these days, the concept of rebalanced hemostasis as resulting from a concomitant decrease in both endogenous pro- and anticoagulant forces has already been established. Accordingly, patients with cirrhosis are at high risk for both hemorrhagic episodes as well as thrombotic disorders and may thus require anticoagulant treatment, either therapeutic or prophylactic. Traditional coagulation tests were found to be inadequate for the assessment of bleeding risk or monitoring of anticoagulation in cirrhosis as they reflect the diminishment of endogenous procoagulants only. Hence, there is increasing interest in evaluating coagulation tests with regard to their eligibility to truly reflect the hemostatic status in cirrhosis. Furthermore, the question of the ideal anticoagulant in cirrhosis still remains unresolved. Aims: To evaluate the in vitro anticoagulant response to various anticoagulant drugs in plasma from patients with cirrhosis and healthy controls by determination of anti-activated factor X activity (anti-Xa activity) and endogenous thrombin potential (ETP). Materials and methods: 77 patients with an established diagnosis of cirrhosis (34 Child-Pugh A, 29 Child-Pugh B, 14 Child-Pugh C) and 22 healthy subjects were studied. Both measure of anti-Xa levels and thrombin generation were performed after addition of anticoagulant drugs (enoxaparin, fondaparinux, danaparoid) from platelet-poor plasma (PPP); thrombin generation was determined at baseline additionally. Results: Drug potency of enoxaparin was underestimated by anti-Xa measure in patients with cirrhosis as determination of thrombin generation explored increased response to enoxaparin in advanced cirrhosis. In case of fondaparinux, drug potency was not differing between patients and controls, but was significantly reduced in thrombin generation testing as compared with anti-Xa measurement. When using danaparoid, both anti-Xa levels and ETP reduction were diminished in cirrhosis compared to controls. In addition, severity of disease as expressed by Child-Pugh classes was correlating inversely with anti-Xa levels and antithrombin (AT) plasma activity levels. Conclusion: Our study demonstrates different potency of various anticoagulant drugs in patients with cirrhosis compared to healthy individuals. Anti-Xa assays should not be used to monitor treatment with enoxaparin and fondaparinux since anti-Xa levels do not correlate well with their pharmacological potency. In contrast, danaparoid has shown reduced anticoagulant response in patients with cirrhosis, but both anti-Xa measure and thrombin generation tests may be eligible for monitoring of anticoagulation. Based on these results, dose adjustment may be required in order to avoid either excessive or decremented anticoagulant effects.