No abstract

Summary. Background: Prophylaxis of venous thromboembolism (VTE) in hospitalized medical patients is largely underused. We sought to assess the value of a simple risk assessment model (RAM) for the identification of patients at risk of VTE. Methods: In a prospective cohort study, 1180 consecutive patients admitted to a department of internal medicine in a 2-year period were classified as having a high or low risk of VTE according to a predefined RAM. They were followed-up for up to 90 days to assess the occurrence of symptomatic VTE complications. The primary study outcome was to assess the adjusted hazard ratio (HR) of VTE in high-risk patients who had adequate in-hospital thromboprophylaxis in comparison with those who did not, and that of VTE in the latter group in comparison with low-risk patients. Results: Four hundred and sixty-nine patients (39.7%) were labelled as having a high risk of thrombosis. VTE developed in four of the 186 (2.2%) who received thromboprophylaxis, and in 31 of the 283 (11.0%) who did not (HR of VTE, 0.13; 95% CI, 0.04-0.40). VTE developed also in two of the 711 (0.3%) low-risk patients (HR of VTE in high-risk patients without prophylaxis as compared with lowrisk patients, 32.0; 95% CI, 4.1-251.0). Bleeding occurred in three of the 186 (1.6%) high-risk patients who had thromboprophylaxis. Conclusions: Our RAM can help discriminate between medical patients at high and low risk of VTE. The adoption of adequate thromboprophylaxis in high-risk patients during hospitalization leads to longstanding protection against thromboembolic events with a low risk of bleeding.

No abstract

While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence. Design and MethodsWe followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion. ResultsAfter a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5-12.5) after 1 year, 19.6% (17.5-21.7) after 3 years, 29.1% (26.3-31.9) after 5 years, and 39.9% (35.4-44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82-2.90) in patients whose first VTE was unprovoked, 2.02 (1.52-2.69) in those with thrombophilia, 1.44 (1.03-2.03) in those presenting with primary DVT, 1.39 (1.08-1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06-1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change. Interpretation and ConclusionsBesides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age. 1-6 While it is generally accepted that patients with thromboembolic events of unknown origin have a more than two-fold higher rate of recurrent VTE in comparison to patients whose thrombosis is associated with acquired, transient risk factors, 1-6 whether other of the patients' baseline features can help to identify those subjects who might benefit from prolonged anticoagulation is unclear. For example, it is virtually unknown whether aging, an important risk factor for VTE, 4 is also associated with an increased risk of recurrence. The role of thrombophilic abnormalities, especially those that are highly prevalent in western countries (i.e., factor V Leiden and prothrombin G20210A mutation), is controversial.5-14 Although recent data suggest that clinical presentation with primary PE 15 and male sex 16-18 increase the risk of recurrent VTE, these findings still await confirmation. Finally, whether the duration of anticoagulation following the initial thrombotic episode has any influence on the subsequent rate of recurrent VTE is uncertain. 2,19-22Here we report on the prospective long-term followup of a large series of patients with proximal DVT and...

There is a statistically significant and clinically important association between idiopathic venous thrombosis and the subsequent development of clinically overt cancer, especially among patients in whom venous thromboembolism recurs during follow-up.

The antiviral drug ribavirin (RBV) is widely used in combination with interferon (IFN) in the treatment of chronic hepatitis C virus (HCV) infection. A major side effect of RBV is a reversible hemolytic anemia. We have evaluated the in vitro effects of RBV on erythrocyte adenosine triphosphate (ATP) content and on hexosemonophosphate shunt (HMS). The ATP levels were significantly decreased in the presence of RBV and the HMS was increased, suggesting the presence of red cell susceptibility to oxidation. In vivo, we have studied the hematologic effects of treatment with RBV alone or in combination with IFN in 11 patients with chronic hepatitis C: 6 were treated with RBV (1,000-1,200 mg/d) and 5 were treated with a combination of RBV and IFN (5 million U thrice weekly). Patients were studied at semi-monthly intervals from 0 to day 60 of therapy. Both treatments were associated with a significant reduction in hemoglobin levels (steady state level at day 45) and a marked increase in absolute reticulocyte counts. Erythrocyte Na-K pump activity was significantly diminished, whereas K-Cl cotransport and its dithiotreitol-sensitive fraction, malondialdehyde and methemoglobin levels were significantly increased. RBV-treated patients showed an increase in aggregated band 3, which was associated with a significantly increased binding of autologous antibodies and complement C3 fragments indicating an erithrophagocytic removal by reticuloendothelial system. (HEPATOLOGY 2000;31:997-1004.)Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, leading to cirrhosis, end-stage liver disease, and hepatocellular carcinoma worldwide. 1,2 A major therapeutic goal in HCV-infected patients is to achieve early eradication of the virus, and to prevent severe long-term clinical complications. Interferon alfa (IFN-␣) is currently the only therapy that has been shown to have beneficial effects in chronic hepatitis type C. However, with a standard regimen of 3 million U administered 3 times per week for 6 to 12 months, only a small fraction of approximately 15% to 20% of the patients showed a sustained response with normalization of serum alanine transferase levels and serum HCV-RNA clearance. 3 Ribavirin (1-␤-D-ribofuranosyl-1H-1, 2,4-triazole-3-carboxamide) (RBV) is a water soluble synthetic guanosine analog that exerts antiviral activity against DNA and RNA viruses after intracellular phosphorylation. 4 Current studies indicate that combination therapy with RBV and IFN is associated with higher rates of sustained virological, biochemical, and histological response compared to IFN monotherapy. [5][6][7][8][9][10] The major side effect of RBV treatment is the occurrence of a reversible hemolytic anemia in a substantial proportion of treated patients. 11 The underlying mechanism is unknown. Studies on steady-state pharmacokinetics of RBV have shown that erythrocyte concentration of RBV greatly exceeds plasma concentrations 12 and that RBV is a transported permeant for the (es) nucleoside transporter in human erythrocytes...

One hundred and five hepatitis B surface antigen (HBsAg) positive patients presenting with chronic persistent hepatitis (n=46) or chronic active hepatitis without cirrhosis (n= 59) were followed longitudinally for one to 16 years (mean 5.5 years) and underwent follow up biopsy. During a mean histological follow up of 3*7 years, active cirrhosis developed in 21 (20%) patients one to 13 years after entry to the study with a calculated annual incidence of 5.9%/o. The probability of evolution to cirrhosis was significantly higher in patients with chronic active hepatitis and bridging hepatic necrosis than in those with moderate chronic active hepatitis or chronic persistent hepatitis (p<0*0001). Cox multiple regression analysis showed that the following three variables independently implied poor prognosis: older age, presence of bridging hepatic necrosis, and persistence of hepatitis B virus DNA in serum (p<0-0001). These findings indicate that patients with severe chronic active hepatitis and persistent hepatitis B virus replication are at very high risk of rapid progression to cirrhosis.

To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western European, white patients (86% men; mean age, 44 years) with biopsy-proven cirrhosis was followed up for a mean period of 73 months and was studied for occurrence of hepatocellular carcinoma (HCC) and decompensation. At entry into the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV; 20% of patients were anti-HDV-positive); 48% of 252 patients tested were hepatitis B virus (HBV)-DNA-positive. During follow-up HCC developed in 32 (9%) of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free patients. Five years after diagnosis, the probability of HCC appearance was 6% and the probability of decompensation was 23%. After the first episode of decompensation the probability of survival was 35% at 5 years. Cox's regression analysis identified three variables that independently correlated with HCC: age, serum levels of platelets, and liver firmness on physical examination. HBV (HBeAg or HBV-DNA) and HDV (anti-HDV) markers at presentation had no prognostic value for the development of HCC. In conclusion, a high proportion of patients with HBsAg-positive compensated cirrhosis do not experience worsening of their condition for several years, but once decompensation occurs life expectancy is poor. European, white patients with compensated cirrhosis type B are at consistent risk for HCC. Prognostic factors for HCC reflect an advanced stage of cirrhosis and support the hypothesis that development of a tumor could be the likely consequence of long-standing hepatic disease.