Acute intraprocedural thrombosis during an arterial ductal stenting successfully managed by eptifibatide.

Acute stent thrombosis may complicate neonatal arterial duct stenting for reduced pulmonary blood flow. Thrombolytic agents recanalise the clot but may cause bleeding around the vascular sheaths and other sites. Since early thrombus is platelet mediated, intravenous platelet glycoprotein inhibitor like eptifibatide is likely to be effective, but rarely utilised in neonates. Ductal stent thrombosis treated with eptifibatide is reported.

Platycodin D inhibits platelet function and thrombus formation through inducing internalization of platelet glycoprotein receptors.

BACKGROUND: Platycodin D (PD) is one of the major bioactive components of the roots of Platycodon grandiflorum and possesses multiple biological and pharmacological properties, such as antiviral, anti-inflammatory, and anti-cancer activities. However, whether it affects platelet function remains unclear. This study aims to evaluate the role of PD in platelet function and thrombus formation. METHODS: Platelets were treated with PD followed by measuring platelet aggregation, activation, spreading, clot retraction, expression of glycoprotein receptors. Moreover, mice platelets were treated with PD and infused into wild-type mice for analysis of in vivo hemostasis and arterial thrombosis. RESULTS: Platycodin D treatment significantly inhibited platelet aggregation in response to collagen, ADP, arachidonic acid and epinephrine, reduced platelet P-selectin expression, integrin αIIbß3 activation, spreading on fibrinogen as well as clot retraction, accompanied with decreased phosphorylation of Syk and PLCγ2 in collagen-related peptide or thrombin-stimulated platelets. Moreover, PD-treated mice platelets presented significantly impaired in vivo hemostasis and arterial thrombus formation. Interestingly, PD induced internalization of glycoprotein receptors αIIbß3, GPIbα and GPVI. However, GM6001, cytochalasin D, BAPTA-AM and wortmannin did not prevent PD-induced internalization of receptors. CONCLUSIONS: Our study demonstrates that PD inhibits platelet aggregation, activation and impairs hemostasis and arterial thrombosis, suggesting it might be a potent anti-thrombotic drug.

Antiplatelet drugs: mechanisms and risks of bleeding following cardiac operations.

Preoperative antiplatelet drug use is common in patients undergoing coronary artery bypass grafting (CABG). The impact of these drugs on bleeding and blood transfusion varies. We hypothesize that review of available evidence regarding drug-related bleeding risk, underlying mechanisms of platelet dysfunction, and variations in patient response to antiplatelet drugs will aid surgeons as they assess preoperative risk and attempt to limit perioperative bleeding. The purpose of this review is to (1) examine the role that antiplatelet drugs play in excessive postoperative blood transfusion, (2) identify possible mechanisms to explain patient response to antiplatelet drugs, and (3) formulate a strategy to limit excessive blood product usage in these patients. We reviewed available published evidence regarding bleeding risk in patients taking preoperative antiplatelet drugs. In addition, we summarized our previous research into mechanisms of antiplatelet drug-related platelet dysfunction. Aspirin users have a slight but significant increase in blood product usage after CABG (0.5 U of nonautologous blood per treated patient). Platelet adenosine diphosphate (ADP) receptor inhibitors are more potent antiplatelet drugs than aspirin but have a half-life similar to aspirin, around 5 to 10 days. The American Heart Association/American College of Cardiology and the Society of Thoracic Surgeons guidelines recommend discontinuation, if possible, of ADP inhibitors 5 to 7 days before operation because of excessive bleeding risk, whereas aspirin should be continued during the entire perioperative period in most patients. Individual variability in response to aspirin and other antiplatelet drugs is common with both hyper- and hyporesponsiveness seen in 5 to 25% of patients. Use of preoperative antiplatelet drugs is a risk factor for increased perioperative bleeding and blood transfusion. Point-of-care tests can identify patients at high risk for perioperative bleeding and blood transfusion, although these tests have limitations. Available evidence suggests that multiple blood conservation techniques benefit high-risk patients taking antiplatelet drugs before operation. Guidelines for patients who take aspirin and/or thienopyridines before cardiac procedures include some or all of the following: (1) preoperative identification of high-risk patients using point-of-care testing; (2) withdrawal of aspirin or other antiplatelet drugs for a few days and delay of operation in patients at high risk for bleeding if clinical circumstances permit; (3) selective perioperative use of evidence-based blood conservation interventions (e.g., short-course erythropoietin, off-pump procedures, and use of intraoperative blood conservation techniques), especially in high-risk patients; and (4) platelet transfusions if clinical bleeding occurs.

Bad Science: Cause and Consequence.

Scientific progress is dependent on accumulation of quality data with appropriate data analysis. Unfortunately, there are a troubling number of accounts describing an inability to replicate published work. Some explanations are lack of access to proprietary reagents and equipment, or lack of expertise and know how. However, it is clear that there are many publications that are fatally flawed, and it is difficult to ascertain which ones they are, but there are clues. Many articles are improperly controlled, resulting in false-positive or -negative results. Reagents and procedures are used without verifying their specificity. There is also confirmation bias, a tendency to seek and find conclusions that we like, which is exacerbated by faithful acceptance by readers of the publication record without assessment of merit. These and other issues have slowed progress, resulted in waste of scarce funds, and even put patients at risk when clinical decisions are made according to flawed data. Solving these and related problems requires recognition of the problem and better training. We also need to take personal responsibility for not only our own work, but also for the accuracy of information in the scientific domain.

Genetic variations of orosomucoid genes associated with serum alpha-1-acid glycoprotein level and the pharmacokinetics of paclitaxel in Japanese cancer patients.

Alpha-1-acid glycoprotein (AGP) encoded by orosomucoid genes (ORM1 and ORM2) is an acute-phase response protein and functions as a drug-binding protein that affects pharmacokinetics (PK)/pharmacodynamics of binding drugs. To explore the effects of genetic variations of ORMs and a role of AGP on paclitaxel (PTX) therapy, we analyzed the duplication and genetic variations/haplotypes of ORMs in 165 Japanese cancer patients and then investigated their associations with serum AGP levels and the PK parameters of PTX. No effects of ORM duplications on serum AGP levels at baseline or PK of PTX were observed, but close associations of ORM1 -559T > A with the increases of AGP levels and area under the curve (AUC) of PTX metabolites were detected. In addition, a significant correlation between the serum AGP level and the AUCs of PTX metabolites was observed, suggesting that AGP may function as a carrier of PTX from the blood into the liver via putative receptors. This study provided useful information on the possible clinical importance of ORM genetic polymorphisms and a novel role of AGP in PTX therapy.