Acute stent thrombosis after early withdrawal of platelet glycoprotein IIb/IIIa antagonists: Potential rebound prothrombotic effect?

We report on two cases of acute coronary stent thrombosis after early withdrawal of different competitive inhibitors of the platelet glycoprotein IIb/IIIa receptor, eptifibatide and tirofiban. Differences in pharmacokinetics between different types of glycoprotein IIb/IIIa receptor blockers and a potential rebound prothrombotic effect with the use of these antiplatelet drugs are reviewed.     

Antithrombotic therapy in the elderly

Antithrombotic therapy represents the mainstay of treatment for prevention of recurrent ischemic events in patients with atherothrombotic disease processes. Although the benefits of antithrombotic pharmacotherapy in the elderly are well established, the elderly are generally more vulnerable to the adverse effects of antithrombotic drugs. Such higher vulnerability may be related to distinct pharmacokinetic and pharmacodynamic responses in the late age of life, during which drug-drug interactions due to polypharmacy further enhance the risk of adverse effects associated with the use of antithrombotic agents. Given that the prevalence of atherothrombotic disease, as well as diseases with thromboembolic potential, increases exponentially with age and that the elderly population is in continuous growth, understanding strategies of antithrombotic management in these patients is of key importance. The present paper provides an overview of the current available evidence on the use of antithrombotic therapy in elderly patients with the primary focus on treatment of coronary artery disease.     

Use of flashlamp-pumped pulsed dye laser in the treatment of superficial vascular malformations and ulcerated hemangiomas

A retrospective study of 502 patients treated with tunable flashlamp pulsed dye laser for superficial vascular malformations (433), ulcerated hemangiomas (65) and postinvolutional redness (4) is presented. Patients were treated in the period from June 1997 to March 2006, with follow-up ranging from six months to four years. The age of the patients ranged from three months to 80 years. Correlation between clinical response and patients' age, location of lesion and number of treatments were evaluated in groups of superficial vascular malformations, whereas healing rates of the ulceration were assessed in a series of hemangiomas. The result were judged to be excellent in 51%, good in 39%, fair in 7% and poor in 3% of patients with vascular malformations. Excellent ultimate outcome confirmed the clinical efficacy of the use of the pulsed dye laser in the treatment of dermal vascular malformations, which also appears to have good prospects in the management of hemangioma complication.     

Antiplatelet therapy: thrombin receptor antagonists

Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease. Multiple pathways contribute to platelet activation. Aspirin, an irreversible inhibitor of thromboxane A2 synthesis, in combination with clopidogrel, an inhibitor of P2Y(12) adenosine diphosphate platelet receptors, represent the current standard-of-care of antiplatelet therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. Although these agents have demonstrated significant clinical benefit, the increased risk of bleeding and the recurrence of thrombotic events represent substantial limitations. Thrombin is one of the most important platelet activators. The inhibition of protease-activated receptor 1 showed a good safety profile in preclinical studies. In fact, phase II studies with vorapaxar (SCH530348) and atopaxar (E5555) showed no increase of bleeding events in addition to the current standard-of-care of antiplatelet therapy. Although the results of phase III trials for both drugs are awaited, this family is a promising new addition to the current clinical practice for patients with atherothrombotic disease, not only as an alternative, but also as additional therapy.     

Personality organization, five-factor model, and mental health

Otto Kernberg has developed a model of personality and psychological functioning centered on the concept of personality organization. The purpose of this study is to empirically examine the relationships between this model, the five-factor model, and mental health. The Personality Organization Diagnostic Form (Diguer et al., The Personality Organization Diagnostic Form-II (PODF-II), 2001), the NEO Five-Factor Inventory (Costa and McCrae, Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) Professional Manual. 1992a), and the Health-Sickness Rating Scale (Luborsky, Arch Gen Psychiatry. 1962;7:407-417) were used to assess these constructs. Results show that personality organization and personality factors are distinct but interrelated constructs and that both contribute in similar proportion to mental health. Results also suggest that the integration of personality organization and factors can provide clinicians and researchers with an enriched understanding of psychological functioning.     

Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions. Clopidogrel, in combination with aspirin, is currently the antiplatelet treatment of choice for prevention of stent thrombosis, and clinical trials have shown that, in high-risk patients, prolonged dual antiplatelet treatment is more effective than aspirin alone in preventing major cardiovascular events. However, despite the use of clopidogrel, a considerable number of patients continue to have cardiovascular events. Numerous in vitro studies have shown that individual responsiveness to clopidogrel is not uniform in all patients and is subject to inter- and intraindividual variability. Notably, there is a growing degree of evidence that recurrence of ischemic complications may be attributed to poor response to clopidogrel. The mechanisms leading to poor clopidogrel effects are not fully elucidated and are likely multifactorial. Although the gold standard definition to assess antiplatelet drug response has not been fully established, there is sufficient evidence to support that persistence of enhanced platelet reactivity despite the use of clopidogrel is a clinically relevant entity. This paper reviews the impact of individual response variability to clopidogrel on clinical outcomes and current and future directions for its management.