Integrin αIIbβ₃ plays a pivotal role in platelet aggregation. Three αIIbβ₃ antagonists have been approved by the Food and Drug Administration (FDA) for the treatment of cardiovascular diseases. Unfortunately, all of these three drugs can cause the side effect of severe bleeding. Therefore, developing a new αIIbβ₃ antagonist with low bleeding was needed. In the present study, we screened compounds by using a fibrinogen/integrin αIIbβ₃ enzyme-linked immunosorbent assay (ELISA), and a novel αIIbβ₃ antagonist ANTP266 was attained. The antithrombotic effects of ANTP266 were estimated by using two animal models, the bleeding risk was estimated by using a mice tail cutting assay, and the plasma half-life time was tested by LC-MS/MS. The results showed that ANTP266 potently decreased thrombosis formation, while not prolonging bleeding time at its effective dosage. The bleeding of ANTP266 reduced rapidly as time went on from 5 to 60 min, but tirofiban produced high bleeding continuously. The plasma half-life of ANTP266 in rats was 10.8 min. Taken together, ANTP266 is an effective antithrombotic agent with a low bleeding risk. The shorter bleeding time benefits from its short plasma half-life. ANTP266 could be a candidate for developing the αIIbβ₃ antagonist of rapid elimination for a patient undergoing percutaneous coronary intervention.

In its severest forms, decompression sickness (DCS) may extend systemically and/or induce severe neurological deficits, including paralysis or even death. It seems that the sterile and ischemic inflammatory phenomena are consecutive to the reaction of the bubbles with the organism and that the blood platelet activation plays a determinant role in the development of DCS. According to the hypotheses commonly put forward, the bubbles could either activate the platelets by direct contact or be the cause of abrasion of the vascular epithelium, which would expose the basal plate glycogen and then prompt the platelets to activate. The purpose of this study is to confirm anti-platelet drugs specific to GPIIb/IIIa integrin could prevent DCS, using a rat model. There is a significant difference concerning the incidence of the drug on the clinical status of the rats (p = 0.016), with a better clinical outcome for rats treated with tirofiban (TIR) compared with the control rats (p = 0.027), even if the three anti-GPIIb/IIIa agents used have limited respiratory distress. TIR limited the decrease in platelet counts following the hyperbaric exposure. TIR help to prevent from DCS. TIR is specific to GPIIb/IIIa whereas eptifibatide and abciximab could inhibit αVβ3 and αMβ2 involved in communication with the immune system. While inhibiting GPIIb/IIIa could highlight a platelet-dependent inflammatory pathway that improves DCS outcomes, we wonder whether inhibiting the αVβ3 and αMβ2 communications is not a wrong approach for limiting mortality in DCS.

Thrombocytopenia is defined as a condition where the platelet count is below the lower limit of normal (<150 G/L), and it is categorized as mild (100-149 G/L), moderate (50-99 G/L), and severe (<50 G/L). We present here a 79-year-old man who developed severe thrombocytopenia with a platelet count of 6 G/L, less than 24 hours after intravenous tirofiban infusion that was given to the patient during a percutaneous transluminal coronary angioplasty procedure with placement of 3 drug-eluting stents. The patient's baseline platelet count was 233 G/L before the procedure. Based on the timeline of events during hospitalization and laboratory evidence, it was highly likely that the patient's thrombocytopenia was the result of tirofiban-induced immune thrombocytopenia, a type of drug-induced immune thrombocytopenia (DITP) which occurs due to drug-dependent antibody-mediated platelet destruction. Anticoagulant-mediated artefactual pseudothrombocytopenia was ruled out as no platelet clumping was seen on the peripheral blood smears. The treatment of DITP includes discontinuation of the causative drug; monitoring of platelet count recovery; or treatment of severe thrombocytopenia with glucocorticoids, IVIG, or platelet transfusions depending on the clinical presentation. The most likely causative agent of this patient's thrombocytopenia-tirofiban-was discontinued, and the patient did not develop any signs of bleeding during the remainder of his hospital stay. His platelet count gradually improved to 24 G/L, and he was discharged on the sixth hospital day.

Venomous and hematophagous animals use their venom or saliva for survival, to obtain food, and for self-defense. Venom and saliva from these animals are cocktails of bioactive molecules primarily composed of proteins and peptides. These molecules are called toxins because they cause unwanted consequences on prey. They exhibit unique, diverse, and specific biological activities that perturb normal physiological processes of their prey and host. However, the potential of toxins as inspirations for the development of therapeutic agents or pharmacological tools has also long been recognized. In addition to their small size, the exquisite selectivity and structural stability of toxins make them attractive as starting molecule in the development of therapeutic and diagnostic agents. Drug discovery and development from venomous and hematophagous animals against cardiovascular diseases have been particularly successful. Some of the notable success include antihypertensive (captopril and enalapril) and antiplatelet agents (tirofiban and eptifibatide), as well as anticoagulants (lepirudin and bivalirudin). Highlighted in this review are many venom or saliva-derived cardiovascular-active proteins and peptides of therapeutic interest, including those that are currently in preclinical stages and those that have been approved by FDA and currently in the market. The authors attempt to summarize their structure, function, mechanism of action, and development with respect to cardiovascular diseases.

The redundant mechanisms involved in blood coagulation are crucial for rapid hemostasis. Yet they also create challenges in blood processing in medical devices and lab-on-a-chip systems. In this work, we investigate the effects of both shear stress and hypothermic blood storage on thrombus formation in microfluidic processing. For fresh blood, thrombosis occurs only at high shear, and the glycoprotein IIb/IIIa inhibitor tirofiban is highly effective in preventing thrombus formation. Blood storage generally activates platelets and primes them towards thrombosis via multiple mechanisms. Thrombus formation of stored blood at low shear can be adequately inhibited by glycoprotein IIb/IIIa inhibitors. At high shear, von Willebrand factor-mediated thrombosis contributes significantly and requires additional treatments with thiol-containing antioxidants-such as N acetylcysteine and reduced glutathione-that interfere with von Willebrand factor polymerization. We further demonstrate the effectiveness of these anti-thrombotic strategies in microfluidic devices made of cyclic olefin copolymer, a popular material used in the healthcare industry. This work identifies effective anti-thrombotic strategies that are applicable in a wide range of blood- and organ-on-a-chip applications.