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ABSTRACT: Hospitalization for acute medical illnesses confers an eight-fold increased risk of venous thromboembolic (VTE) disorders that persists for up to three months and is even higher after discharge than during in-hospital stay [1]. However, in spite of strong evidence in favor of thromboprophylaxis [2-4], several observation studies from various countries found that less than 50% of admitted medical patients at risk receive prophylaxis against VTE [5-8]. This article is protected by copyright. All rights reserved.
Journal of Thrombosis and Haemostasis 04/2013; · 5.73 Impact Factor
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ABSTRACT: Hepatic cirrhosis is characterized by complex abnormalities of the fibrinolytic system. Little is known about the possible association between these alterations and thrombosis. The aim of this study was to evaluate the fibrinolytic profile in cirrhotic individuals with and without portal vein thrombosis (PVT). We measured thrombin activatable fibrinolysis inhibitor (TAFI), total amount of activated TAFI (TAFIa/ai), plasminogen activator inhibitor (PAI-1), plasminogen and fibrinogen plasma levels in 66 cirrhotic patients (33 with and 33 without PVT) and in 66 healthy volunteers. TAFI plasma levels (median [range]) were significantly lower in cirrhotic individuals (5.6 μg/ml [1.7-11.7]) than in controls (10.1 μg/ml [6.6-14.2], p < 0.0001), while TAFIa/ai levels were significantly higher in cases (18.3 ng/ml [0.3-35.4]) than in controls (15.9 ng/ml [7.4-41], p = 0.02). Cirrhotic patients with PVT had higher TAFI (6.6 μg/ml [2.9-10.1]), TAFIa/ai (19.2 ng/ml [11.6-35.4]) and PAI-1 (33.1 ng/ml [27.6-56.3]) plasma levels than those without PVT (3.9 μg/ml [1.7-11.7], p = 0.001; 15.6 ng/ml [10.3-33.9], p = 0.037; 15.9 ng/ml [2.5-29.1], p = 0.004. The fibrinolytic profile in cirrhotic individuals with PVT is characterized by higher levels of TAFI, TAFIa/ai and PAI-1 than in those without PVT. These alterations identify a hypofibrinolytic condition that may increase the risk of developing a thrombotic event.
Internal and Emergency Medicine 03/2013; · 2.06 Impact Factor
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Clinical and Applied Thrombosis/Hemostasis 06/2012; 18(3):331-3. · 1.33 Impact Factor
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Liver Transplantation 03/2011; 17(3):347-8. · 3.39 Impact Factor
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ABSTRACT: Antithrombin (AT), in the presence of heparin, is able to inhibit the catalytic activity of factor VIIa bound to tissue factor (TF) on cell surfaces. The clinical meaning of FVIIa-AT complexes plasma levels is unknown. It was the objective of this study to evaluate FVIIa-AT complexes in subjects with thrombosis. Factor VIIa-AT complexes plasma levels in 154 patients consecutively referred to our Department with arterial or venous thrombosis and in a group of 154 healthy subjects, were measured. Moreover, FVIIa-AT complexes were determined in: i) n = 53 subjects belonging to 10 families with inherited factor VII deficiency; ii) n = 58 subjects belonging to seven families with AT deficiency; iii) n = 49 patients undergoing oral anticoagulant therapy (OAT). Factor VIIa-AT levels were determined by a specific ELISA kit (R&D, Diagnostica Stago, Gennevilliers, France). Factor VIIa-AT complexes mean plasma levels were lower in patients with either acute arterial (136 +/- 40 pM) or venous (142 +/- 53 pM) thrombosis than subjects with previous thrombosis (arterial 164 +/- 33 pM and venous 172 +/- 61 pM, respectively) and than healthy controls (156 +/- 63 pM). Differences between acute and previous thrombosis, were statistically significant (p < 0.05). Subjects with inherited and acquired (under OAT) factor VII deficiency had statistically significant lower FVIIa-AT complexes plasma levels (80 +/- 23 pM and 55 +/- 22 pM, respectively) than controls (150 +/- 51 pM, p < 0.0001 and 156 +/- 63 pM, p < 0.00001, respectively). Factor VIIa-AT complexes are positively correlated with plasma factor VII/VIIa levels. Further investigations are needed to verify the possible role of higher FVIIa-AT complex plasma levels in predicting hypercoagulable states and thrombosis.
Thrombosis and Haemostasis 06/2010; 103(6):1188-92. · 5.04 Impact Factor
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ABSTRACT: The association between venous thromboembolism (VTE) and antibodies anti-Protein C (PC)/Protein S (PS) is still uncertain. We performed a case-control study to determine the risk of VTE related to the presence of these auto-antibodies considered independently of the presence of lupus anticoagulant (LAC) or anti-cardiolipin antibodies (ACA). One hundred thirty-five patients with idiopathic VTE and 164 healthy subjects were enrolled. Anti-PC and anti-PS antibodies (both IgG and IgM) were assessed using commercially available ELISA kits. Among cases there was a higher prevalence of elevated anti-PC IgM antibodies than in controls (OR 2.44, 95%CI 1.00-5.94). The presence of anti-PC IgG and anti-PS IgG and IgM antibodies was also higher in cases than in controls, but the difference was not statistically significant. Only five patients had both anti-PC or anti-PS antibodies and LAC or ACA. We performed a stepwise multivariate logistic regression analysis showing that anti-PC IgM>958 percentile was a significant predictor of VTE after adjustment for LAC or ACA (OR 2.52, 95%CI 1.01-6.24)). Larger prospective studies are needed to confirm this finding.
American Journal of Hematology 07/2009; 84(9):594-6. · 4.67 Impact Factor
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ABSTRACT: The ROtation ThromboElastoMetry analyser (ROTEM, Pentapharm, Munich, Germany) is useful for studying whole blood (WB) clot formation and lysis. Reduction of haematocrit (HCT) has been reported to influence traditional thromboelastography parameters without compromising "in vitro" blood coagulation. We performed this case-control study to evaluate ROTEM profiles in sideropenic anaemia patients with different degrees of reduction of HCT levels. Forty consecutively referred patients with sideropenic anaemia were enrolled. A group of 40 healthy age and gender matched subjects acted as a control. The influence of HCT on ROTEM was assessed in the study population and in a model of artificially reconstituted blood with modified HCT values. Cases presented significantly increased levels of maximum clot firmness (MCF) as compared to controls (p < 0.001) mimicking a sort of "hypercoagulable profile". However, thrombin generation tests failed to detect an increase in thrombin generation in cases as compared to controls. A statistically significant inverse linear correlation between HCT and MCF (p < 0.0001) was found. In addition, ROTEM profiles following "in vitro" manipulation of HCT confirmed the inverse linear correlation between HCT and MCF found in the study population. In conclusion, the increased clot firmness found by ROTEM in anaemic patients is likely to be related to the method in itself rather than representing a marker of hypercoagulability "in vivo". Since ROTEM is widely used by anaesthesiologists when deciding the optimisation of products supplementation during surgery, attention should be paid in the case of anaemic patients taking depending on the peculiar thrombo-elastography profile found.
Thrombosis and Haemostasis 12/2008; 100(6):1106-10. · 5.04 Impact Factor
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ABSTRACT: Common tests for the assessment of blood coagulation in the acute phase of deep vein thrombosis are of limited value for the evaluation of the associated hypercoagulability. The new rotation thromboelastometry by rotation thrombelastogram has the potential to provide information on whole blood clot formation and prothrombotic state in patients with acute deep vein thrombosis. Rotation thrombelastogram parameters were evaluated in whole blood of 30 patients with a first episode of acute deep vein thrombosis and 40 healthy controls. The effect of factor VIII and fibrinogen levels on rotation thrombelastogram assays was also assessed in the study population and in a model of blood supplemented by increasing amounts of fibrinogen. All assays performed were consistent with a remarkable hypercoagulable profile in deep vein thrombosis patients as compared with controls. In particular, maximum clot firmness and the area under curve values, which are expected to better correlate with the hypercoagulable state in the acute phase of deep vein thrombosis, were significantly higher in patients than in controls. As expected, fibrinogen was shown to be one of the main determinants of the hypercoagulability in rotation thrombelastogram assays. In a small subset of acute deep vein thrombosis patients, inherited thrombophilia had no influence on rotation thrombelastogram parameters. The new rotation thrombelastogram thromboelastometry is a useful tool to detect acute deep vein thrombosis-related hypercoagulability. Prospective studies are needed to define the potential applications of rotation thrombelastogram in the management of deep vein thrombosis patients.
Blood Coagulation and Fibrinolysis 08/2008; 19(5):355-60. · 1.24 Impact Factor
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ABSTRACT: Thrombotic events are uncommon disorders in childhood but increasingly recognized due to the progress made in the understanding of the hemostasis system and the importance of thromboembolic disorders in children. Multiple clinical underlying conditions and prothrombotic disorders contribute to the development of thrombosis in neonates and children. In recent years programs have emerged that specialize in the diagnosis, prevention, and treatment of thrombosis in children. This review summarizes the current knowledge of the risk factors for thromboembolic events in the venous and arterial systems in children, the use of antithrombotic prophylaxis, and the role of thrombophilia. First, the clinical manifestations and the problems of diagnosing venous thromboembolic diseases and cerebrovascular diseases in children are reviewed. The prophylactic use of anticoagulants in children is also discussed. Unfortunately there are no large prospective randomized trials in children, thus guidelines are based on small studies or on extrapolation of data from adults. Second, the impact of prothrombotic defects in pediatric patients and the issue of routine testing for these disturbances are reviewed.
Seminars in Thrombosis and Hemostasis 11/2006; 32(7):724-8. · 4.52 Impact Factor
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ABSTRACT: The term thrombophilia includes any inherited and acquired disorders associated with an increased tendency to venous thromboembolism (VTE). Inherited thrombophilia is one of the main determinants of VTE, and the presence of inherited thrombophilic defects exposed carriers to increased risks for VTE compared with noncarriers. There is no clear relationship between clinical manifestations and the type of underlying thrombophilic defect. Thus, the diagnosis of inherited thrombophilia has to be established on a laboratory basis. Carriers of thrombophilic defects may experience thrombosis at a younger age than noncarriers. However, a first thrombotic manifestation that occurs late in life may also be an expression of thrombophilia and this remains in many cases the only etiopathogenetic explanation for the event. Screening of family members of symptomatic probands has the potential to identify still asymptomatic carriers who may benefit from more appropriate thromboprophylaxis during high-risk situations for VTE. Women of fertile age who belong to these thrombophilic families might receive the greatest advantage from screening. Many inherited thrombophilic disorders can be considered risk factors for recurrent VTE, especially if more than one defect is present in the same patient. More intensive or prolonged duration of VTE treatment might be requested for the prevention of recurrent VTE in the most severe thrombophilic conditions. The availability of new methods for the assessment of thrombin generation in terms of endogenous thrombin potential are very promising tools for the identification of those carriers of inherited thrombophilia who will develop thrombosis or who will encounter recurrence of VTE.
Seminars in Thrombosis and Hemostasis 11/2006; 32(7):700-8. · 4.52 Impact Factor
