Role and clinical importance of Helicobacter pylori infection in hemodialysis patients.

Dyspepsia is an extrarenal symptom frequently found in hemodialysed patients; it is due to chronic renal failure, and uremic gastritis is a specific associated condition in chronic renal failure (CRF). On the other hand, in the general population, Helicobacter pylori infection is an important dyspepsia-related risk factor; its close connections with gastro-duodenal pathology are already known, above all the peptic disease in a really exclusive way. By observation of a dyalitic group of patients, opportunely matched with a no CRF group, we evaluated CRF-associated uremia and Helicobacter pylori infection which could eventually interact causing symptoms and lesions. A statistical analysis of obtained data allowed us to conclude that, although there is not, from an epidemiological view-point, a larger diffusion of Helicobacter pylori among dyalitic patients compared to general population, moreover the infection is uremia-synergic in causing gastro-duodenal symptoms and lesions. These findings, therefore, suggest systematically investigation a possible Helicobacter pylori infection in CRF patients and its relation to gastritis grading, and searching for probable active peptic lesions.

Increased levels of C-reactive protein and fibrinogen influence the risk of vascular events in patients with NIDDM.

AIM: To evaluate the predictive role of hs-CRP and fibrinogen for cardio- and cerebrovascular events in a population of patients with type 2 diabetes. METHODS: We studied 156 patients with type 2 diabetes, mean age 66+10 years, and 156 sex and age matched control subjects. Patients underwent physical examination, EKG, measurement of body mass index and blood pressure. A blood sample was drawn to evaluate glycaemia, total and HDL/LDL cholesterol, triglycerides, high sensitive C-reactive protein (hs-CRP), fibrinogen. Finally, patients underwent an ecocolordoppler examination of the common carotid arteries until the bifurcation. In a follow-up of 5+/-1.2 years we evaluated the following events: transient ischemic attack, ischemic stroke, stable or unstable angina, acute myocardial infarction, critical limb ischemia and cardiovascular death. RESULTS: During the follow-up the prevalence of fatal (p<0.05) and non fatal events (p<0.0001) was higher in patients with diabetes in comparison with controls. The variables independently associated with non fatal events were: fibrinogen (p<0.0001), presence of asymptomatic carotid lesion (p<0.005), obesity (p<0.05) and plasma levels of hs-CRP (p<0.05), while fibrinogen (p<0.001) and age were (p<0.05) independently associated with fatal events. CONCLUSION: Our data show that in patients with diabetes mellitus, that in the follow-up the presence of high plasma levels of hs-CRP and fibrinogen are predictive for fatal or non fatal events.

Successful treatment of gastrointestinal bleeding with recombinant factor VIIa after kidney transplantation in patients with pancytopenia.

Hemostatic disorders can often complicate transplantation procedures. Moreover, antihemmorhagic drugs may not efficiently control bleeding that occurs in such cases. We report on a patient who underwent kidney transplantation complicated by bone marrow aplasia and gastric bleeding who was successfully treated with recombinant activated FVII (Novoseven). In May 2005, a 53-year-old man affected by chronic renal insufficiency underwent kidney transplantation. At the beginning of June, laboratory tests showed progressive reduction in the blood cell count with anemia, granulocytopenia, and thrombocytopenia related to the development of marrow insufficiency. We commenced transfusion therapy and administered hematologic growth factors. On June 3, 2005, the patient underwent surgical procedure to repair the abdominal wall. Two days thereafter, the postsurgical period was complicated by an episode of melena. The patient received additional treatment with packed red cells, platelets, and fresh-frozen plasma. The gastrointestinal bleeding continued until June 9, 2005, when therapy with recombinant activated FVII (Novoseven) was commenced at an initial dose of 90 microgr/kg. The first bolus did not significantly reduce the blood loss; it was therefore administered as a successive bolus at the same dosage that was able to stop bleeding. Endoscopic examination performed the day after showed the absence of the hemorrhagic lesion in the gastric mucosa. In the subsequent days, the need for transfusion was dramatically reduced with no episode of bleeding. At the same time, the laboratory and clinical findings of marrow insufficiency disappeared. Our case report showed that the use of a global antihemorrhagic factor, such as Novoseven, can successfully control gastrointestinal bleeding even in complicated patients despite failure of traditional antihemostatic therapy.

Home therapy for deep vein thrombosis and pulmonary embolism in cancer patients.

Outpatient treatment of deep vein thrombosis (DVT) has become a common practice in uncomplicated patients. Few data are still present in patients with comorbidity (such as cancer) or concomitant symptomatic pulmonary embolism. Cancer patients with DVT are often excluded from home treatment because they have a higher risk of both bleeding and recurrent DVT. We tested the feasibility and safety of the Home Treatment (HT) program for acute DVT a PE in cancer patients. Patients were treated as outpatients unless they required admission for other medical problems, were actively bleeding or had pain that requires parenteral narcotics. Outpatient treatment was with low molecular weight heparin (LMWH) followed by warfarin or with LMWH alone. An educational program for patients was implemented. Two-hundred and seven patients with cancer were evaluated, 36 (17.4%) of whom had metastatic disease. Treatment with LMWH and warfarin was prescribed to 106 (51.2%) and LMWH alone to 102 (48.8%). One hundred and twenty-seven patients (61.3%) were entirely treated at home. There were no differences between patients treated at home and hospitalized patients with regard to gender, mean age, site of cancer, presence of metastases, and treatment. After 6 months, recurrent thrombo-embolism occurred in 8.7% of patients treated at home and in 5.6% of hospitalized patients (P=0.58); major bleeding in 2.0% and 1.5%, respectively (P=0.06). Twenty-seven patients (33%) in the hospitalized, and 33 (26%) in the home-treatment group, died after a follow-up of 6 months. These results indicate that, regarding cancer patients with acute DVT and/or PE, there is no difference between hospitalised and home-treated patients in terms of major outcomes.

Prolonged prothrombin time, Factor VII and activated FVII levels in chronic liver disease are partly dependent on Factor VII gene polymorphisms.

BACKGROUND: Prothrombin time is a benchmark for functional assessment in cirrhosis and Factor VII levels (FVII), crucial in determining the prothrombin time, are genetically determined. METHODS: We have evaluated the prothrombin time, a number of haemostatic variables synthesised by the liver (FII, FV, FVII and activated FVII, AT and fibrinogen) and two polymorphisms of the FVII gene (5'F7 and 353R/Q) in: (a) patients with liver cirrhosis (n=118), (b) patients with chronic hepatitis (n=102) and (c) controls (n=100). RESULTS: By one-way analyses of variance, the prothrombin time and the mean levels of the FII, FV, FVIIc, FVIIa, and AT were statistically different between cirrhotics, chronic hepatitis patients and controls. The allele frequency of the FVII polymorphisms did not differ between the three groups. Those rare patients (4.6%) who were homozygous for the type 2 alleles had markedly reduced FVIIc and FVIIa levels. The analysis carried out taking into account Child class versus FVII genotype showed that the mean FVIIc levels were comparable for different genotypes within each Child's class, with the exception of the patients homozygous for the type 1 allele. CONCLUSION: Our findings help to explain the not infrequent finding of a severely prolonged prothrombin time in patients who are otherwise in a good functional class.

Leukocyte count, diabetes mellitus and age are strong predictors of stroke in a rural population in southern Italy: an 8-year follow-up.

Stroke incidence rates in the Mediterranean area are higher compared to northern European countries. In this study, we present the 8-year prospective data from a small rural Sicilian town. This population, consisting of 1351 subjects (622 males and 729 females), is homogeneous for ethnic background with traditional healthy dietary habits and shows low cholesterol mean levels. We found that the risk of stroke was significantly associated with the record of at least one previous neurological symptom (PNS), such as lack of strength, loss of vision or speech or possible drop attacks, and high hematocrit in males, and to high body mass index (BMI) and waist-hip ratio (WHR), diabetes, hypertension, high leukocyte count in females. We also documented age-related differences: stroke was associated in younger subjects (age<65 years) with diabetes, high BMI, high uric acid levels and in older patients (age>/=65 years) with high WHR, hypertension, diabetes, PNS, leukocyte count and hematocrit above the 95th percentile. Multivariate analysis demonstrated an independent association between stroke and age, diabetes, leukocyte count, hypertension and PNS. In conclusion, in this rural Sicilian population, the incidence rate of stroke is 1.72 cases per 1000/year in the subjects between 40 and 75 years of age. The risk factors associated with stroke are different in younger and older subjects. Leukocyte count, as an expression of an undergoing inflammatory process, may have a relevant role at least in the elderly.

Molecular and clinical aspects of factor VII deficiency.

Factor VII (FVII) plays an important role in the initiation of blood coagulation, forming a complex with tissue factor (TF) which activates FIX and FX and FVII zymogen. FVII deficiency displays considerable phenotypic and molecular heterogeneity and there are inconsistencies between the clinical picture observed and the underlying clotting and molecular defects. We have reviewed the data available in the literature on FVII-deficient patients. Clinically, cases range from asymptomatic to patients with severe haemorrhagic tendencies. Asymptomatic patients typically have FVII activity levels of >20% and are heterozygotes, double heterozygotes or homozygotes. Mild FVII-deficient patients, with FVII activity levels >2%, may be double heterozygotes or homozygotes for FVII gene missense mutations. Undetectable FVII levels in severely affected patients are often due to severe gene defects such as frameshifts or mutations affecting the splice sites. The analysis of structure-function relationships in FVII deficiency is difficult due to the complexity of the interactions involving FVII. Also, assays using different reagents may give different results with a given plasma sample, and are not very accurate at low levels of FVII which, although relatively low, may be clinically significant, adding complexity to the analysis of FVII deficiency. The sensitivity of our methods for phenotypic evaluation of FVII deficiency remains inadequate.

[Influence of high environmental temperature on various parameters of blood coagulation in healthy subjects and in thrombosis risk patients]. / Influenza dell'elevata temperatura ambientale su alcuni parametri della coagulazione in soggetti sani ed in pazienti a rischio trombotico.

The effects of environmental hyperthermia (exposure to a hot, dry microclimate) on the human body were investigated with particular reference to certain clotting parameters in healthy subjects and patients at risk of thrombosis. The study covered 70 volunteers, 10 of them clinically healthy (6 males and 4 females) aged 37.7 +/- 9.7 and 60 patients at risk of thrombosis aged 18-60 and divided according to pathology as follows: 26 with ischaemic cardiopathy, 22 with metabolic disorders (12 diabetics, 8 with dyslipidaemia, 2 with hyperuricaemia) and 12 with obliterating arteriopathies of the lower extremities (Fontaine stage 2 and 3). The following standardised protocol was adopted: 2 hours exposure in a controlled climate chamber (40 degrees C, 40-50% humidity, standard air speed 4 m/min, barometric pressure 760 mmHg) for a total of 8 exposures (2 per week for 1 month). This approach was adopted in order to assess not only the effect of each single exposure but also the role of any adaptation to heat. Three blood samples were taken from each subject for each session: the first in basal conditions in a comfortable environment, the second at the end of the 2 hour exposure; the third 30 minutes after the end of the session. Simultaneously samples of arterial blood were taken for pH assays and a spleen echography was performed in basal conditions and at the end of the session for each subject. Each blood sample was tested for several parameters essentially attributable to blood concentration for a broader view of the biological effects of exposure to heart (Ht, blood protein, Nat, K+). The clotting factors under specific study were also assessed (platelet count and volume, beta-thromboglobulin, PF4, von Willebrand Factor VIII, thromboxane B2, fibronectin). Body weight, blood pressure and oral temperature were also measured in all subjects before and after each session. In all subjects both healthy and at risk of thrombosis oral temperature increased (1 +/- 0.4 degrees); on average blood pressure was already higher in basal conditions in the patient group; body weight fell by 900 +/- 120 G in both groups. Ht and blood protein increased significantly in both groups while electrolyte changes were insignificant and blood pH showed a tendency towards acidosis. Clotting parameters revealed a tendency towards thrombophilia in all subjects: platelet count and volume were already higher in the patient group in basal conditions and increased after exposure to hyperthermia. Beta-thromboglobulin, FP4, Factor VIII, thromboxane B2 and fibronectin all increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Patients requiring interruption of long-term oral anticoagulant therapy: the use of fixed sub-therapeutic doses of low-molecular-weight heparin.

INTRODUCTION: We tested the efficacy and safety of fixed doses of low-molecular-weight heparin (LMWH) in patients requiring interruption of vitamin-K antagonist (VKA) because of invasive procedures. METHODOLOGY: Preoperatively, patients discontinued VKA for 5 +/- 1 days; in those at low risk for thrombosis, LMWH was given at a prophylactic dosage of 3800 UI (nadroparin) or 4000 UI (enoxaparin) anti-factor (F) Xa once daily the night before the procedure. In patients at high risk for thrombosis, LMWH was started early after VKA cessation and given at fixed sub-therapeutic doses (3800 or 4000 UI anti-FXa twice daily) until surgery. Postoperatively, LMWH was reinitiated 12 h after procedure while VKA was reinitiated the day after. Heparin was continued until a therapeutic INR value was reached. The primary efficacy endpoints were the incidence of thromboembolism and major bleeding from VKA suspension (because of surgery) up to 30 +/- 2 days postprocedure. RESULTS: A total of 328 patients (55.4% at low risk and 44.6% at high risk for thrombosis) were enrolled; 103 (31.4%) underwent major surgery and 225 (68.6%) non-major invasive procedures. Overall, thromboembolic events occurred in six patients (1.8%, 95% confidence interval 0.4-3.2), five belonging to the high-risk group and one belonging to the low-risk group. Overall, major bleeding occurred in seven patients (2.1%, 95 confidence interval 0.6-3.6), six patients belonged to the high-risk group and one belonged to the low-risk group; most of the events occurred in the high-risk group during major surgery. CONCLUSION: LMWH given at fixed sub-therapeutic doses appears to be a feasible and safe approach for bridging therapy in chronic anticoagulated patients.

Modification of the lipidic and coagulative pattern in postmenopause women: effect of hormone replacement therapy.

AIM: We evaluated the changes of lipidic and coagulative pattern during menopause and the influence of hormone replacement therapy (HRT) on these parameters. METHODS: We considered 158 patients divided into 2 groups: Group I consisted of 127 women in physiological/surgical menopause and Group II of 31 women with childbearing potential. Subsequently, we considered a group III formed of 34 patients from menopausal women (group I) who underwent three months of HRT. We evaluated total-cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lpa), fibrinogen, antithrombin III (ATIII), factor VII (FVII) and tissue factor pathway inhibitor (TFPI). RESULTS: We found a worse lipid profile in the post-menopausal group compared to controls (TC 243.8+/-29.7 vs 217.9+/-32.7 mg%, P=0.002; TG 121.5+/-68.4 vs 88.6+/-53.0 mg%, P=0.039; LDL-C 163.0+/-27.9 vs 136.2+/-29.6 mg%, P=0.004; HDL-C 60.9+/-14.9 vs 64.1+/-14.6 mg%, P=ns). With regard to the coagulative pattern, fibrinogen was significantly higher in the post-menopausal group (fibrinogen: 273.3+/-67.4 vs 243.8+/-39.5 mg%, P=0.013; ATIII 112.2+/-11.7 vs 117.5+/-12.7% %, P=0.059; FVII 121.6+/-11.3 vs 117.6+/-10.8 mg%, P=ns; TFPI activity 2.5+/-2.3 vs 2.1+/-1.1 U/mL, P=ns; TFPI antigen 120+/-38 vs 127+/-39 U/mL, P=ns). Comparing the same parameters, before and after three months of HRT, in patients of Group III we observed a significant improvement of TC and TG levels (TC from 232.3+/-42.7 to 215.2+/-37.6 mg%, P=0.0001; TG from 103.7+/-56.8 to 95.0+/-44.3 mg%, P=0.059; HDL-C from 62.3+/-12.9 to 63.6+/-12.6 mg%, P=ns; LDL-C from 149.3+/-38.7 to 132.6+/-34.5 mg%, P=0.0001). The following changes were observed with regard to coagulative parameters: fibrinogen from 270.9+/-69.4 to 253.2+/-56.2 mg%, P=0.07; ATIII from 113.5+/-11.4 to 110.8+/-13.2 mg%, P=0.198; FVII from 108.6+/-18.0 to 104.4+/-17.5 mg%, 0.014. TFPI activity from 2.6+/-2.3 to 2.3+/-1.4 U/ml, P=ns; TFPI antigen from 68+/-13 to 87+/-22 U/mL, P=0.001. CONCLUSION: Our data confirm the presence of an alteration in lipidic and coagulative pattern in post menopausal women and positive changes after HRT.

[Long-term effects of indobufen on several parameters of blood platelet function in subjects at thrombotic risk]. / Studio degli effetti a lungo termine dell'indobufene su alcuni parametri di funzione piastrinica in soggetti a rischio trombotico.

Indobufen (200 mg b.i.d., by os, for 21 days) was gave to 16 patients with atherothrombotic risk in which platelet function was valued. In this subjects, indobufen significatively reduced platelet aggregation, beta-thromboglobulin, platelet factor the 4th and alpha-platelet granules' intake. No side effects were found.