Anticoagulant Activities of Indobufen, an Antiplatelet Drug

Abstract

Indobufen is a new generation of anti-platelet aggregation drug, but studies were not sufficient on its anticoagulant effects. In the present study, the anticoagulant activity of indobufen was determined by monitoring the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) in rabbit plasma. We evaluated the anticoagulant mechanisms on the content of the platelet factor 3,4 (PF3,4), and the coagulation factor 1, 2, 5, 8, 10 (FI, II, V, VIII, X) in rabbits, as well as the in vivo bleeding time and clotting time in mice. The pharmacodynamic differences between indobufen and warfarin sodium, rivaroxaban, and dabigatran were further studied on thrombus formation and the content of FII and FX in rats. Animal experiments showed that intragastric-administrated indobufen can significantly reduce the APTT, PT, TT, PF3, FI, II, V, VIII, and X plasma contents. Its inhibitory effect on plasma FII was better than thrombin inhibitor dabigatran with effect on FX better than FXa inhibitor rivaroxaban. These results suggest that indobufen has some anticoagulant effects as strong as some conventional anticoagulants. The mechanism may be related to both exogenous and endogenous coagulation system.

Surgical Risk on Patients with Coagulopathies: Guidelines on Hemophiliac Patients for Oro-Maxillofacial Surgery

“…Gill et al evaluated the surgery risks on von Willebrand disease patients, the results in this study indicate that von Willebrand factor and factor VIII concentrate (VWF/FVIII) is safe and effective in the prevention of excessive bleeding [35]. The surgical manoeuvres of these patients may be different, certainly, unlike patients who take antiplatelet drugs, they do not coagulate [36], even with the passage of time and with normal haemostatic manoeuvres, especially in severe cases. These patients may require complex surgeries, especially when there are oral lesions, or abnormalities [36].…”

Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

“…Our previous studies showed that Indobufen had antithrombotic and anticoagulant effects on rats [5]. Therefore, we speculated that Indobufen may be able to treat cerebral ischemia reperfusion injury.…”

“…K3920, Figure 1), with a chemical structure of 2-[p-(1-oxo-2-isoindoline) phenyl] butyrate, is a new generation of antiplatelet aggregation drugs that reversely inhibits platelets, cycoperxygenase and reduces the production of thromboxane A2 (TXA2) [4]. We have previously reported that Indobufen could inhibit the coagulation process and reduce thrombosis [5], so we speculated that Indobufen may also have therapeutic and preventive effects against ischemia/reperfusion (I/R) injury.…”

Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

“…Our previous studies showed that Indobufen had antiplatelet, antithrombotic and anticoagulant effects on rats [11]. Therefore, we speculated that Indobufen may be able to treat cerebral ischemia reperfusion injury.…”

“…K3920, Figure 1), with a chemical structure of 2-[p-(1-oxo-2-isoindoline) phenyl] butyrate, is a new generation of antiplatelet aggregation drugs that reversely inhibits platelets, cycoperxygenase and reduces the production of thromboxane A2 (TXA2) [10]. We previously reported that Indobufen could inhibit blood coagulation process of APTT, PT, TT, platelet factor 3 (PF3), clotting factor I, II, V, IX and X content to reduce thrombosis [11], so we speculated that Indobufen may also have therapeutic and preventive effects against ischemia/reperfusion (I/R) injury. its potential mechanisms may be closely related to inhibition of in ammation/apoptotosis/pyroptosis induced by its platelet inhibition and antithrombotic effects, but research about e cacy of Indobufen in treatment/prevention of cerebral ischemia has not been reported.…”