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Long-term central venous catheters (CVCs) have considerably improved the management of cancer patients because they facilitate chemotherapy, transfusions, parenteral nutrition, and blood sampling. However, the use of long-term CVCs, especially for chemotherapy, has been associated with the occurrence of upper-limb deep venous thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related to CVCs has been reported to vary between 0.3% and 28.3%. The incidence of CVC-related UL-DVT screened by venography reportedly varies between 27% and 66%. The incidence of clinically overt pulmonary embolism (PE) in patients with CVC-related UL-DVT ranges from 15% to 25%, but an autopsy-proven PE rate of up to 50% has been reported. Vessel injury caused by the procedure of CVC insertion, venous stasis caused by the indwelling CVC, and cancer-related hypercoagulability are the main pathogenetic factors for CVC-related venous thromboembolism (VTE). Several studies have assessed the benefit of the prophylaxis of UL-DVT after CVC insertion in cancer patients. According to the results of these studies, prophylaxis with low molecular weight heparin or a low fixed dose of warfarin has been recently proposed. However, the limitations of the experimental design of the prophylactic studies do not allow definitive recommendations. The recommended therapy for UL-DVT associated with CVC is based on anticoagulant therapy with or without catheter removal. This review focuses on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of VTE in cancer patients with long-term CVC.

The effects of the new monobactam antibiotic aztreonam on platelet function and blood coagulation were evaluated both in vitro and ex vivo. In the in vitro studies carried out on platelets from 6 healthy volunteers, therapeutic concentrations of aztreonam had no effect on platelet function. Aztreonam inhibited platelet aggregation only at concentrations far in excess of those clinically achievable. In the ex vivo studies carried out in 11 patients with aztreonam-sensitive infections, aztreonam, 1 g t.i.d. intravenously, did not produce any effect on platelet function and blood coagulation. We conclude that therapeutic doses of aztreonam appear not to affect haemostasis.

The aim of this study was to compare the ability of heparin and recombinant hirudin (r-hirudin) in preventing accretion of new fibrin on thrombi during and after treatment with tissue-type plasminogen activator (t-PA) and in enhancing t-PA induced fibrinolysis in a rabbit jugular vein thrombosis model. Heparin and r-hirudin were infused at doses capable of doubling aPTT. In the fibrin accretion inhibition experiments t-PA was infused over 3 h at a dose of 0.2 mg/kg along with saline or heparin, 0.75 mg/kg or r-hirudin, 1.25 mg/kg. In rabbits treated with t-PA plus saline, heparin or r-hirudin, an accumulation of 125I-fibrinogen on the thrombi of 52.5 +/- 5.1 micrograms, 49.5 +/- 5.6 micrograms and 23.5 +/- 3.5 micrograms was observed, respectively, the difference between r-hirudin and both saline and heparin being statistically significant (p less than 0.01). The inhibition of fibrin accretion on the thrombi induced by r-hirudin persists for at least 9 h after the end of the infusion. By that time r-hirudin has been cleared from the circulation and aPTT has returned to the baseline level for at least 8 h. t-PA, 0.2, 0.4, and 1 mg/kg, infused with saline produced 34 +/- 6%, 52 +/- 5% and 79 +/- 8% lysis of pre-formed thrombi, respectively. The same doses of t-PA infused with heparin, 0.75 mg/kg, produced 32 +/- 3%, 54 +/- 5% and 78 +/- 6% fibrinolysis, respectively and infused with r-hirudin, 1.25 mg/kg, 38 +/- 3%, 57 +/- 5% and 82 +/- 8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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”

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

Antithrombotic drugs represent one of the leading pharmacological category used in clinical practice, especially in cardiovascular setting. Their demonstrated antithrombotic efficacy has been fundamental in the improvement of the management of many diseases related to athero-thrombotic or thromboembolic risk in prevention and treatment of cardiovascular events. Nonetheless, they are also associated with a not negligible haemorrhagic risk. Among these risks, intracranial bleeding represents the most feared, and should be kept in mind, prevented when possible and adequately managed when occurs. In this article the intracranial haemorrhagic risk associated to drugs vitamin K antagonists and new oral anticoagulants is reviewed.