Antithrombotic therapy with rivaroxaban in five patients with paroxysmal nocturnal haemoglobinuria and thrombotic events.

Five patients with paroxysmal nocturnal haemoglobinuria and thrombotic complications under oral antithrombotic treatment with vitamin K antagonist were switched to receive the direct oral anticoagulant rivaroxaban an factor Xa inhibitor. In all five patients haematological and biochemical parameters and adverse events were evaluated for a period of twelve months. Therapy with rivaroxaban was well tolerated in all cases and one patient showed a significant reduction of bleeding and transfusion requirement. All patients obtained a significant reduction in days of hospitalization with a consequent improvement in their quality of life after rivaroxaban treatment.

Anticoagulant therapy with rivaroxaban in a young patient with paroxysmal nocturnal hemoglobinuria.

The new direct oral anticoagulants such us rivaroxaban, could play an important role in the anticoagulant treatment of patients with paroxysmal nocturnal hemoglobinuria where anticoagulant treatment is complex to run, since they have shown a reduction in serious bleeding complications compared to antithrombotic therapy with classical vitamin k antagonist.

Effectiveness and safety of therapy with vitamin K antagonists in Italian patients aged 80 years or older: a multicentre retrospective study comparing the Zeus algorithm with the PARMA algorithm or manual therapy.

BACKGROUND: The use of oral anticoagulant therapy (OAT) has constantly increased in the prevention of thromboembolism, particularly in patients 80 years of age or older. OBJECTIVE: The aim of this multicentre study was to evaluate the efficacy and safety of vitamin K antagonists (VKAs) in elderly patients managed with a computer dosing algorithm compared with a dosage decided by expert physicians. MATERIALS AND METHODS: Nine Italian thrombosis centres utilising the Zeus dosing algorithm were involved. The before-after study enrolled patients managed firstly by medical staff (manual system) or with the PARMA algorithm for 12 months from July 2008 to June 2009 and then with the Zeus algorithm during the analogous period from 2010 to 2011. Of 7605 patients in the OAT maintenance phase, 2281 were older than 80 years (mean age 84.2 years). Data for these 2281 patients managed with both modalities were analysed. RESULTS: Of the 2281 patients 80 years of age or older, 1776 underwent OAT for atrial fibrillation (AF). Use of a dosing algorithm increased the OAT quality: time in therapeutic range (TTR) was significantly (p < 0.001) higher during the Zeus period than during the manual period (71.6 vs. 68.8 %). The TTR achieved with Zeus was similar to that obtained with the PARMA algorithm. In addition, patients managed with Zeus took a weekly drug dosage significantly (p < 0.01) lower than that both suggested by PARMA and prescribed by expert physicians, with a reduced number of adverse events. CONCLUSIONS: This study confirms that the effectiveness and safety of VKA therapy in patients 80 years of age or older increases with computer dosing algorithms.

Oral anticoagulant therapy in Italian patients 80 yr of age or older with atrial fibrillation: a pilot study of low vs. standard PT/INR targets.

BACKGROUND: Oral anticoagulation therapy (OAT), which aims to prevent thromboembolism in patients with atrial fibrillation (AF), is underused in subjects who are over the age of 80 yr because of the associated bleeding risk. The aim of this study was to evaluate the efficacy and safety of OAT with low (2.0) vs. standard (2.5) PT/international normalised ratio (INR) targets in patients over the age of 80. MATERIALS AND METHODS: Of 233 patients aged 80 yr or older with AF on OAT, 58 had unstable PT/INR values and achieved reduced targets. These patients were enrolled as a group (A) in a case-control study and were treated with a low (2.0) PT/INR target. They were compared with a second group (B) of 58 additional patients who were matched for age and CHADS scores and treated with a standard (2.5) PT/INR target. Group A OAT parameters were also compared before and after the PT/INR reduction. The time in the therapeutic range (TTR%), PT/INR values >5, haemorrhages and strokes were prospectively evaluated in the two groups after 2 yr of follow-up. RESULTS: Of the 116 enrolled patients, 55 group A and 57 group B patients were evaluated. The TTR was 72.59% in group A and 64.43% in group B (P < 0.01). The percent of PT/INR values >5 was 0.68% for group A and 1.42% for group B (P < 0.05). Haemorrhages and thromboses occurred only in group B patients. The before and after analysis in group A showed that a low INR target produced an increase in the TTR (53.05% vs. 72.59%; P < 0.0001) and a reduction in the PT/INR values > 5 (1.72% vs. 0.68%; P < 0.001). CONCLUSIONS: A low PT/INR target seems effective and safe in Italian patients with AF over the age of 80. Further trials are needed to confirm the hypothesis generated by this study.

Thrombophilic screening in young patients (< 40 years) with idiopathic ischemic stroke: a controlled study.

INTRODUCTION: Despite extensive clinical and laboratory investigations, the etiology of ischemic stroke remains unknown in approximately one third of patients. MATERIALS AND METHODS: Thirty-four consecutive patients less than 40 years old (Males 13, Females 21, mean age 26.6 years, range 2-39) with documented ischemic stroke underwent, one year after the acute event, laboratory evaluation of antithrombin, protein C, free and total protein S, activated protein C resistance, fibrinogen, factor VII:C, homocysteine levels and antiphospholipid antibodies (APA). Moreover, prevalence of F5 R506Q, F2 G2021A and homozygosis for thermolabile variant C677T of the methylenetetrahydrofolate reductase (MTHFR) were also evaluated and compared to the results obtained in 120 normal controls. RESULTS: Antithrombin and protein C levels resulted normal in all cases. One patient (2.9%) showed free protein S deficiency and 3 patients (8.8%) had activated protein C resistance. Homocysteine levels above 15 µmol/L were found in one patient (2.9%). APA were found in 21 patients (61.7%) and in only 2 out of 120 (1.66%) controls (OR=95.31; 95% C.I.: 18.22-667.81). The multivariate analysis selected that the presence of APA was significantly associated with an increased risk of stroke (OR=156.60; 95% C.I.: 25.99-943.47) in this cohort of patients. The combination between APA and cardiovascular risk factors determined a risk of 29-fold (OR=29.31; 95% CI: 3.28-261.69). DISCUSSION: Our data suggest that the presence of APA is associated with an increased risk of idiopathic ischemic stroke in young patients. Furthermore, also the combination of APA and cardiovascular risk factors is significantly associated with development of idiopathic ischemic stroke.

Early hospital discharge with oral antimicrobial therapy in patients with hematologic malignancies and low-risk febrile neutropenia.

Although consensus exists relating criteria for the identification of low-risk patients with febrile neutropenia, no clear indication on how to manage these patients has been so far provided particularly in outpatients affected by hematologic malignancies. The feasibility and safety of early discharge was prospectively evaluated in 100 outpatients with hematologic malignancies and febrile neutropenia. A strategy considering the risk-index of the Multinational Association of Supportive Care in Cancer (MASCC) was applied. High-risk patients were entirely managed at hospital. Low-risk patients were early discharged if they were afebrile since 48 h and not on supportive therapy requiring hospitalization. Out of 90 low-risk episodes, in 69 instances (76.7%), patients were discharged after a median of 4 days and continued home therapy with oral cefixime (78%) or other antibiotics. Only five outpatients (7.2%) had fever recurrence. Twenty-one low-risk patients were not early discharged due to worsening conditions (three deaths), need of multiple daily dose therapy, or discharge refuse. No clinical characteristic was able to predict the eligibility for early discharge. The MASCC risk-index is a useful aid in the identification of high-risk febrile neutropenia needing whole in-hospital treatment. As for low-risk patients, hospitalization at least in the first days of fever is required. Cefixime could be included among the oral antibacterial drugs to be used in the outpatient treatment of adult patients with febrile neutropenia.

The role of real-time ultrasonography in predicting esophageal varices in hemophiliacs co-infected with hepatitis C and human immunodeficiency virus.

BACKGROUND AND OBJECTIVES: Endoscopic procedures are the gold standard for the diagnosis of esophageal varices but these invasive methods are complex to perform in hemophilic patients co-infected with hepatitis C virus/human immunodeficiency virus (HCV/HIV). Real-time ultrasonography has been reported to be an effective, non-invasive procedure able to monitor patients with chronic liver disease and to give useful information for the diagnosis of liver cirrhosis, portal hypertension and the presence of esophageal varices. DESIGN AND METHODS: Seventy patients with severe hemophilia were evaluated by esophago-gastro-duodenoscopy (EGDS) and ultrasonography; 40 had HCV/HIV co-infection and 30, comparable for age and HCV exposure time, were HCV+/HIV-. Hepatic longitudinal diameter, splenic longitudinal diameter, portal vein diameter and the average speed of portal flow were measured. The congestion index was calculated. RESULTS: Thirteen out of 40 (32.5%) HCV/HIV coinfected patients had esophageal varices. None out of 30 HCV+/HIV- patients had esophageal varices (p< 0.001). Univariate analysis showed that the 13 HCV/HIV coinfected patients with esophageal varices had significantly higher hepatic longitudinal diameter (p=0.006), splenic longitudinal diameter (p=0.0002), portal vein diameter (p=0.0005) and congestion index (p=0.0001) than did the remaining 27 HCV/HIV coinfected patients. The stepwise logistic regression analysis indicated that, of the various ultrasonographic parameters evaluated, splenic longitudinal diameter and portal vein diameter had the greatest diagnostic efficiency in diagnosing a high proportion of patients with esophageal varices. The diagnostic efficiency of the combined criterion expressed by the area under the ROC curve was 0.8803. Interpretation and Conclusions. Real-time ultrasonography, by evaluation of splenic longitudinal diameter and portal vein diameter, is an effective non-invasive technique able to classify correctly a large proportion of HCV/HIV co-infected hemophilic patients with esophageal varices.

A long-term study of young patients with essential thrombocythemia treated with anagrelide.

BACKGROUND AND OBJECTIVES: Essential thrombocythemia (ET) can be complicated by life-threatening thrombosis and has a risk of converting into acute leukemia. Cytoreductive therapy may reduce the risk of thromboembolic complications. Herein, we report the results of a long-term study of patients with ET treated with anagrelide to control thrombocytosis. DESIGN AND METHODS: Thirty-nine (34 evaluable) patients (median age, 33 years; 24 previously untreated) were enrolled between 1989-1996; the mean platelet count prior to therapy was 1197x10(9)/L. Only 9 out of 34 evaluable patients were at high risk of thrombosis (platelet count more than 1500x10(9)/L). The initial dose of anagrelide (0.5 mg/bid for 7 days) was increased by 0.5 mg/day (maximum dose: 3 mg/day) until a response was seen. RESULTS: A complete response (platelets < 450x10(9)/L for >1 month) was seen in 15 /34 (44%) patients and a partial response (platelets 450-600x10(9)/L for >1 month) was seen in 17/34 ( 50%), so that the some kind of response was seen in 32/34 (94%) of the patients at a median time of 4.2 months after starting treatment. Seventeen patients (50%) are still being treated and have achieved platelet control for a maximum follow-up of 12.5 years. Late onset anemia occurred in 4/39 patients. Three out of 39 patients (8%) had cardiac disorders. INTERPRETATION AND CONCLUSIONS: Anagrelide appears suitable for controlling thrombocytosis in ET patients over the long-term. This drug may be used in patients younger than 60 years, with the exclusion of women of child-bearing potential and subjects aged 40-60 years with a history of major thrombotic events. Anagrelide should not be administered to patients with cardiac disorders, and a careful approach to patients should include monitoring of heart function before and during treatment.

Effect of high intakes of fruit and vegetables on redox status in type 2 onset diabetes: a pilot study.

Evidence has accumulated indicating that oxidative stress may play a key role in the etiology of diabetic complications and the protective effects of antioxidant nutrients are a topic of intense research. The purpose of this study was both to obtain preliminary data on the effect of a diet high in fruit and vegetables on metabolic control and the oxidative status of patients with type 2 onset diabetes, and to identify the most useful biochemical parameters for future research. At the beginning of the study all subjects were asked to follow their usual diet and keep a seven-day food diary. Diabetic patients then received a dietary treatment designed to ensure a daily intake of 700-1000 g of fruit and vegetables; no dietary advice was given to controls. Dietary antioxidants, redox status markers, and parameters of metabolic control were measured in plasma and erythrocytes before and after the diet. Before following the diet, diabetic patients had lower levels of ascorbic acid, beta-carotene, and alpha-tocopherol/cholesterol ratio than controls. After the diet these parameters increased and there was also a reduction in total antioxidant capacity, uric acid, and malondialdehyde and a rise in reduced glutathione accompanied by a reduction in body mass index and cholesterol. In conclusion, a high consumption of fruit and vegetables by diabetic patients not receiving pharmacological treatment, seems to produce an improvement in some redox status parameters.

Gender differences in cardiovascular risk factors.

Coronary heart disease is less common in premenopausal women compared to age-matched men. This difference disappears in the post-fertile years, and is presumably related to the reduced levels of female sex hormones, with subsequent metabolic and hemodynamic modifications. Ovarian exhaustion induces a more atherogenic lipid profile, which may partly explain the increased risk of cardiovascular disease observed in post-fertile women as compared to age-matched fertile women. After the menopause, the combination of aging and estrogen deficiency negatively affects glucose metabolism. Diabetes mellitus blunts the beneficial condition associated with the female gender; furthermore, it increases the incidence of myocardial infarction, claudication and stroke in women more than in men. Finally, the unfavorable effects of menopause on the coronary risk seem to be mediated partly by changes in clotting and fibrinolytic factors.

Folate status and homocysteine level in Italian patients aged under 60 on oral anticoagulant therapy.

BACKGROUND: Folate deficiency occurs frequently and the related hyper-homocysteinaemia is considered a risk factor for thrombosis. We investigated folate status and homocysteine (Hcy) concentration in patients under 60 years on oral anticoagulant therapy (OAT) for previous venous or arterial thrombosis and in healthy blood donors. PATIENTS AND METHOD: Thirty-nine patients (mean age 35.2 years) on OAT for longer than 6 months and forty 44 healthy blood donors (mean age 36.0 years) were evaluated. Diet, serum folate (SF), red blood cell folate (RCF), homocysteinaemia, vitamin B12 levels and the mutation C677T of methylenetetrahydrofolate-reductase (MTHFR) gene were determined. RESULTS: The mean SF and Hcy concentrations were significantly higher in patients compared with blood donors (SF = 17.7 versus 10.5 nmol/L, P < 0.0001; Hcy = 11.7 versus 8.9 micromol/L, P = 0.009). Twelve out of 39 patients and 7 out of 44 blood donors were homozygous for the mutation C677T of MTHFR gene. Among the remaining subjects, non-homozygous for the mutation, the patients (27) had mean SF and Hcy levels significantly higher than the (37) blood donors (SF = 18.1 versus 10.8 nmol/L, P < 0.0001; Hcy = 10.3 versus 7.9 micromol/L P < 0.0006). CONCLUSION: Italian patients aged under 60 years on OAT and non-homozygous for the mutation C677T of MTHFR gene, had SF and Hcy concentrations significantly higher than the control group.