In vitro comparison of dabigatran, unfractionated heparin, and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves.
BACKGROUND
Lifelong oral anticoagulation (OAC) therapy is required for the prevention of thromboembolic events after implantation of an artificial heart valve. Thromboembolism and anticoagulant-related bleedings account for approximately 75% of all complications experienced by heart valve recipients (2-9% of patients per year). The present study investigated the efficacy of dabigatran, a new direct thrombin inhibitor for oral use, as compared to unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in preventing thrombus formation on mechanical heart valves in vitro.


METHODS
Blood (230 ml) from healthy young male volunteers was anticoagulated either by dabigatran (1 micromol/l), UFH (150 IU), or LMWH (100 IU). Mechanical heart valve prostheses were placed in an in vitro thrombosis tester and exposed to the anticoagulated blood samples under continuous circulation at a rate of 75 beats per minute.


RESULTS
In whole blood with no anticoagulant, the apparatus completely clotted in 15-20 minutes. When blood was treated with dabigatran, the mean thrombus weight was 164+/-55 mg, in the UFH group 159+/-69 mg, and in the LMWH group 182+/-82 mg (p-value: 0.704). Electron microscopy showed no significant difference in thrombus formation in any group.


CONCLUSIONS
Dabigatran was as effective as UFH and LMWH in preventing thrombus formation on mechanical heart valves in our in vitro investigation. Thus, we hypothesize that dabigatran etexilate might potentially be a useful and competitive orally administered alternative to UFH and LMWH for recipients of alloplastic heart valve prostheses.
Maegdefessel
Lars
L
Department of Medicine III at the University Hospital Haale (Saale), Martin-Luther-University Halle-Wittenberg, Germany. maegdefessel@stanford.edu
Linde
Torsten
T
Krapiec
Franziska
F
Hamilton
Kathrin
K
Steinseifer
Ulrich
U
van Ryn
Joanne
J
Raaz
Uwe
U
Buerke
Michael
M
Werdan
Karl
K
Schlitt
Axel
A
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D000069604:Dabigatran; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011474:Prosthesis Design; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors
D000925:Anticoagulants; D001562:Benzimidazoles; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D011725:Pyridines; D006493:Heparin; D000069604:Dabigatran