1.Evaluating antithrombotic activity of HY023016 on rat hypercoagulable model.
Chen QF1, Li YZ2, Wang XH1, Su YR1, Cui S1, Miao MX1, Jiang ZZ3, Jiang ML1, Jiang AD1, Chen X1, Xu YG4, Gong GQ5. Eur J Pharmacol. 2016 Apr 13. pii: S0014-2999(16)30238-2. doi: 10.1016/j.ejphar.2016.04.023. [Epub ahead of print]
The generation of thrombus is not considered as an isolated progression without other pathologic processes, which may also enhance procoagulant state. The purpose of this study was to assess whether HY023016, a novel dabigatran prodrug and an oral direct thrombin inhibitor, or dabigatran etexilate, another thrombin inhibitor can improve the state of whole blood hypercoagulability in vitro/vivo. By using whole blood flow cytometry we explored the effects of HY023016 and dabigatran etexilate on thrombin and ADP-induced human platelet-leukocyte aggregation generated in vitro. With the method of continuous infusion of thrombin intravenous, we successfully established a rat hypercoagulable model and evaluated the effect of HY023016 or dabigatran etexilate in vivo. HY023016 was able to inhibit thrombin- or ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates in dose-dependent manner.
2.A real world data of dabigatran etexilate: multicenter registry of oral anticoagulants in nonvalvular atrial fibrillation.
Yavuz B1, Ayturk M2, Ozkan S3, Ozturk M2, Topaloglu C4, Aksoy H5, Şabanoglu C6, Tanalp AC7, Dal K8, Ata N9, Yavuz BB10. J Thromb Thrombolysis. 2016 Apr 16. [Epub ahead of print]
Atrial fibrillation (AF) is a common cardiac arrhythmia. Dabigatran etixalate (DE) is one of the new oral anticoagulant drugs being used in nonvalvular AF (NVAF). There is no adequate real world data in different populations about DE. The aim of this registry was to evaluate the efficacy and safety of DE Consecutive NVAF patients treated with warfarin or both DE doses were enrolled during 18 months study period. The patients were re-evaluated at regular 6-month intervals during the follow-up period. During the follow-up period outcomes were documented according to RELY methodology A total of 555 patients were analyzed. There was no significant difference in ischemic stroke rates (p = 0.73), death rates (p = 0.15) and MI rates (p = 0.56) between groups. The rate of major bleeding was significantly higher in warfarin and dabigatran 150 mg group than dabigatran 110 mg (p < 0.001). Intracranial bleeding rate and relative risk were significantly lower in dabigatran 110 mg group than warfarin group (p = 0.
3.Post-marketing surveillance on the long-term use of dabigatran in Japanese patients with nonvalvular atrial fibrillation: Preliminary report of the J-dabigatran surveillance.
Inoue H1, Uchiyama S2, Atarashi H3, Okumura K4, Koretsune Y5, Yasaka M6, Yamashita T7, Ohnishi M8, Yagi N9, Fukaya T10; J-Dabigatran Surveillance Investigators. J Arrhythm. 2016 Apr;32(2):145-50. doi: 10.1016/j.joa.2015.11.008. Epub 2016 Jan 16.
BACKGROUND/AIM: A post-marketing surveillance (PMS) study is being conducted to investigate the safety and effectiveness of the long-term use of dabigatran etexilate (dabigatran) in Japanese patients with nonvalvular atrial fibrillation (NVAF). Results of an interim analysis of this prospective cohort study including patient characteristics and adverse drug reactions (ADRs) collected up to September 17, 2014 are reported here.
4.Laboratory determination of old and new targeted anticoagulant agents for prevention of bleeding and thrombotic events in cancer patients.
Harenberg J1. Thromb Res. 2016 Apr;140 Suppl 1:S165-7. doi: 10.1016/S0049-3848(16)30117-7.
A two-fold prolongation of activated partial thromboplastin time (APTT) is established as therapeutic range for therapy with unfractionated heparin, hirudin and argatroban. The international normalized ratio (INR) of 2 to 3 is required to maintain anticoagulation in the therapeutic range of vitamin K antagonists. The therapeutic range of anti-factor Xa activity during therapy with low-molecular weight heparins and danaparoid are less well and of direct oral anticoagulants (DOAC) poorly defined. The relation of aPTT and INR values to thrombotic and bleeding events are well established despite a large variation of values in affected patients. The relation of coagulation values of the other anticoagulants to clinical events is open. The value of determination in cancer patients is higher because of the increased risk for thrombotic and bleeding events of this patient group. Several activities are currently undertaken to certify methods for in vitro diagnostic testing for DAOCs.