Publications

Keywords: Venous thromboembolism, ischemic stroke, anticoagulant treatment, antiplatelet therapy, thrombolysis.

Acute coronary syndromes are the clinical presentations of complex biochemical events which in most cases culminate in intracoronary thrombosis. A central role in the process of intravascular thrombosis is played by thrombin, a glycosylated trypsin-like serine protease with multiple action in vascular biology [l]. In patients with acute coronary syndromes thrombin is generated by the exposure of tissue factor after fissuring or rupture of a coronary plaque. Tissue factor leads to thrombin generation through the activation of the coagulation factors VII and IX and the prothrombinase complex. Once generated, thrombin initiates a positive feed-back autocatalytic loop by directly activating factors V and VIII, thus amplifying its generation by about lOOO-fold. At substrate level, other than activating factors V and VIII, thrombin cleaves fibrinogen to fibrin and activates factor XIII which results in formation of stable, cross-linked fibrin clot. Thrombin binds to a specific receptor on the platelet surface initiating a number of intracellular processes, including ADP and thromboxane A, release and expression of GP IIb/IIIa receptors, which result in platelet aggregation. Thrombin receptors have been cloned from human platelets and vascular smooth muscle cells [2,3]. The activation of thrombin receptor on vascular smooth muscle cells is followed by most of the multiple cellular effects of thrombin, mainly by smooth muscle cell mitogenesis and migration. High concentrations of thrombin are present at the time and the site of mechanical injury or PTCA and persist throughout the period of vascular formation. The restenosis process appears to be triggered by the formation of a “neointima”

Circulatory disease accounts for fifteen million deaths each year, of which stroke accounts for four and a half million- with an estimated nine million stroke survivors annually. The overall incidence rate of stroke is 2 to 2.5 per thousand adults with an approximate prevalence of 5 per thousand and an estimated 5-year risk of stroke recurrence of 15 to 40 percent. Conventional risk factors for stroke include: increasing age, hypertension, diabetes mellitus, smoking, increased body mass index, ischemic heart disease, heart failure, atrial fibrillation and lack of physical activity. Age is the strongest risk factor for both ischemic and haemorrhagic stroke with its incidence doubling for each successive decade after the age of fifty-five years. However, there is a substantial portion of patients with significant cerebrovascular disease who do not have any of these stroke risk-factors, leading to the speculation that there are other factors that have not been identified yet So as to improve diagnosis and treatment strategies, as well as to reduce the related public health burden, it could be helpful to successfully identify its extremely complex genetic determinants (polygenic, multiple genes play a role).Pharmacogenetics is the field of pharmacology that deals with the influence of genetic variation on drug response by correlating gene expression and gene variants with the efficacy or toxicity of drugs. The principle drugs in stroke medicine are antithrombotics. The aim of this paper was to review the most commonly used drugs for stroke such as rtPA in the acute phase as well as antiplatelets and wafarin for secondary prophylaxis.

The epidemiology of venous thromboembolism (VTE) after cancer surgery is based on clinical trials on VTE prophylaxis that used venography to screen deep vein thrombosis (DVT). However, the clinical relevance of asymptomatic venography-detected DVT is unclear, and the population of these clinical trials is not necessarily representative of the overall cancer surgery population.The aim of this study was to evaluate the incidence of clinically overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and to identify risk factors for VTE.@RISTOS was a prospective observational study in patients undergoing general, urologic, or gynecologic surgery. Patients were assessed for clinically overt VTE occurring up to 30 +/- 5 days after surgery or more if the hospital stay was longer than 35 days. All outcome events were evaluated by an independent Adjudication Committee.A total of 2373 patients were included in the study: 1238 (52%) undergoing general, 685 (29%) urologic, and 450 (19%) gynecologic surgery. In-hospital prophylaxis was given in 81.6% and postdischarge prophylaxis in 30.7% of the patients. Fifty patients (2.1%) were adjudicated as affected by clinically overt VTE (DVT, 0.42%; nonfatal pulmonary embolism, 0.88%; death 0.80%). The incidence of VTE was 2.83% in general surgery, 2.0% in gynecologic surgery, and 0.87% in urologic surgery. Forty percent of the events occurred later than 21 days from surgery. The overall death rate was 1.72%; in 46.3% of the cases, death was caused by VTE. In a multivariable analysis, 5 risk factors were identified: age above 60 years (2.63, 95% confidence interval, 1.21-5.71), previous VTE (5.98, 2.13-16.80), advanced cancer (2.68, 1.37-5.24), anesthesia lasting more than 2 hours (4.50, 1.06-19.04), and bed rest longer than 3 days (4.37, 2.45-7.78).VTE remains a common complication of cancer surgery, with a remarkable proportion of events occurring late after surgery. In patients undergoing cancer surgery, VTE is the most common cause of death at 30 days after surgery.

The current recommended treatment of venous thromboembolism (VTE) consists of an initial treatment with heparin (either subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin) relayed with a longterm treatment with oral anticoagulants (INR 2.0 3.0) given for at least three months [1]. The majority of the studies on the long-term treatment of VTE included patients with deep vein thrombosis (DVT). Based on the assumption that DVT and pulmonary embolism (PE) are two manifestations of the same disease, information available for patients with DVT are commonly translated to patients with PE. Recently, several differences regarding the risk for recurrent VTE in patients with DVT and PE have been reported. In particular, it has been shown that patients with PE are at slightly higher risk of dying from recurrent PE than are patients with DVT [2-3]. For this reason, more prolonged anticoagulation has been proposed for patients with PE, but this choice is not evidence based. Need for Shortand Long-Term Anticoagulant Treatment