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Background/Aim: A reduction in portal vein inflow velocity seems to predispose to the emergence of portal vein thrombosis (PVT). Nonselective β-blockers (NSBBs), used to prevent variceal bleeding, may increase the development of PVT by reducing portal vein inflow velocity. In this retrospective case-control study, we evaluated the risk factors and clinical features of a first event of PVT in 130 cirrhotics, 19 (15%) with (PVT group) and 111 (85%) without PVT (non-PVT group). Patients and Methods: Patient evaluation and NNBB treatment were carried out according to the AASLD guidelines. Results: PVT was prevalently partial (84%) and asymptomatic (84%). Patients with PVT were treated with different regimens, and resolution of thrombosis was observed in about 50% of the cases. In both groups, HCV was the most frequent cause of cirrhosis and Child-Pugh score A was prevalent. Ascites and esophageal varices were more frequent in the PVT group (P = 0.05 and

We describe a case of spontaneous internal jugular vein thrombosis occurring as the first sign of occult lung cancer. The peculiarity of the case was the unusual site of thrombosis and the lack of risk factors for DVT (only a moderated reduction of protein S without inherited thrombophilia) as well as the absence of clinical signs of cancer. This report shows once again the strong association between idiopathic venous thromboembolism and cancer. Hypercoagulation tests confirmed the association between cancer and thrombophilia. Reduction of protein S has been discovered recently in patients with lung cancer but further data are required to confirm this finding. Combined treatment (chemotherapy and radiotherapy) associated with oral anticoagulation therapy was started in our patient at the moment of diagnosis.

Background: Coronary heart disease was commonly associated to specific risk factors as smoking, diabetes, dyslipidemia, and hypertension since Framingham study confirmed their role. However, a lot of reports in the Literature are focused to find further risk factor for coronary heart disease in particular for subjects with early onset of disease. Aim: The aim of the study was to look for an association between inherited thrombophilia and early onset of acute coro- nary syndrome. Patients and Methods: We selected 25 patients with acute coronary syndrome with early onset (i.e. 50 yy) and tested them for several thrombophilic gene variants. Other common risk factors for coronary heart disease were also considered in se- lected patients. Blood samples were taken from antecubital vein of selected patients and in order to extract DNA for gene analysis. Evaluated thrombophilic gene variants were the following: factor V Leiden gene variant, prothrombin A20210G gene variant, MTHFR C677T gene variant, ACE I\D gene variant, APO-B Arg-3500-Trp and Arg-3500-Gln mutations and APO-E Arg-112-Cys and Arg-158-Cys mutations. Results: Smoking was the only common risk factor for ACS significantly increased in the group with ACS compared to controls. No significant differences were found concerning diabetes, dyslipidemia, and hypertension in both groups. Ho- mozygosis for MTHFR C677T and ACE del\del gene variant were found to be more frequent in the group of subjects with ACS compared to control group. Discussion: Early onset of ACS seems to be associated to the presence of combined risk factors. In this panel, we may in- clude acquired common risk factors for ACS in particular smoking and such gene variant associated to thrombotic disor- ders as MTHFR C677T gene variant and ACE del\del genotype. Further studies are needed to confirm this association.

Cancer and its related therapies are acquired thrombophilic risk factors. Patients with a malignancy can suffer a thrombotic complication such as deep venous thrombosis (DVT) in the lower extremities with a possible following pul- monary embolism. Recently, an increased association between upper extremity DVT and malignancy has been observed and several risk factors were identified. However, few data are available for the association between upper extremity DVT and inherited thrombophilia in oncological patients. Here we report a case of upper extremity DVT complicated by fatal pulmonary embolism in an oncological patient receiving chemotherapy and carrying 2 heterozygous genetic thrombo- philic risk factors.

Background: In patients with venous thromboembolism (VTE), assessment of the risk of recurrent VTE and major bleeding may help to guide intensity and duration of anticoagulant therapy. Methods: We used the Registro Informatizado de Enfermedad Tromboemb?lica (RIETE) to identify predictors of poor adherence to guidelines in patients with- and without cancer, and to assess the rate and severity of VTE recurrences and major bleeding during the course of anticoagulation in Italian patients with deep vein thrombosis (DVT). Results: A total of 3541 patients with objectively diagnosed VTE were enrolled in Italy, of whom 1832 (52%) initially presented DVT. Of these, 409 (22%) patients had already known cancer at baseline. In all, 32% of patients with cancer and 74% of those without cancer received long-term therapy with vitamin K antagonists, 55% and 19% respectively received long-term therapy with low-molecular-weight heparin, and 11% and 5.3% respectively received long-term therapy with Fondaparinux. During the 3-month study period, DVT patients with cancer experienced an increased rate of DVT recurrences (odds ratio: 3.1; 95% CI: 1.2-8.2), major bleeding episodes (odds ratio: 4.3; 95% CI: 2.2-8.4), all-cause death (odds ratio: 11; 95% CI: 6.7-19), and fatal bleeding (odds ratio: 11; 95% CI: 1.1-101), compared with those without cancer. Interestingly, the rate of major bleeding events outweighed the rate of VTE recurrences, both in patients with cancer (19 major bleeds vs. 4 PE recurrences and 8 DVT recurrences) and in those without cancer (16 major bleeds vs. 5 PE recurrences and 9 DVT recurrences). Conclusions: In real life, adherence of VTE therapy to guidelines is poor. During the course of anticoagulation, the rate of major bleeding events exceeded the rate of VTE recurrences.

Background: Recent studies have focused on the role of inflammation in the development of atherosclerosis (AT), there are some similarities in the inflammatory/immunologic response observed in AT and rheumatoid arthritis (RA), the prototype of autoimmune disease. Molecular and cellular mediators of inflammation in RA may be the key to development of atherosclerotic lesions in these patients (1,2). Objectives: To investigate whether the intima-media thickness (IMT) of the common carotid arteries is greater in RA patients than healthy subjects, and to investigate the presence of inflammation and atherogenic lipoprotein markers and their possible correlation with IMT. Methods: We studied 21 patients (15 F, 6 M; age 48-62 median 55) with RA according to the criteria established by the American College of Rheumatology, and 10 controls (6 F, 4 M; age 44-66, median 52). The healthy subjects were compared with RA patients with regard to risk factors for AT, including age, sex, smoking, blood pressure, body mass index and postmenopausal status. Clinical variables reflecting RA were measured: patient's global assessment, physician's global assessment, patient's assessment of pain, physical disability score (HAQ), acute-phase reactant level, numbers of tender and swollen joints, duration of morning stiffness, disease activity score (DAS 28). Laboratory variables relevant to RA: activity erythrocyte sedimentation rate, C-reactive protein level and rheumatoid factor positivity were measured. Laboratory variables relevant dyslipidemic status: serum total cholesterol, trygliceridies, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprtein AI (Apo AI), apolipoprotein B (Apo B) were determined. IMT and plaques were measured in the left and right common carotid arteries (CCA). Three measurements of ITM were made in common carotid arteries and were averaged to determine the mean IMT (3). Mann-Wythney test was used to compare mean value between two groups. Results: The mean ± SD IMT of the left and right CCA was significantly greater in 21 RA patients than in 10 control subjects (1.09±0.3 vs. 0.68±0.3; p=0.0029). Total plasma levels of cholesterol (173±26.2 vs. 182.6±44.6), HDL-cholesterol (58.5±20.3 vs. 60.2±26), LDL-cholesterol (95.3±28.6 vs. 100.1±32.8), were in the normal range in RA patients and were similar to those in the controls; the concentration of triglycerides (122.1±55.6 vs. 154.5±51.8; p=0.8), ApoAI (167.4±52.2 vs. 213.3±68.3; p=0.9) and ApoB (117.8±46.8 vs. 146±33.1; p=0.9) levels were lower in the RA patients than in controls, but this was not statistical significant. In the RA group, IMT did not correlate with inflammatory variables, atherogenic markers, and parameters of activity of RA. Conclusion: In the present study, we demonstrated that the IMT of the common carotid was significantly higher in RA patients than in controls. Our study may contribute to explain the increase in cardiovascular death reported in RA and will allow physicians early stratification of patients with vascular disease.1. Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation 1999; 100:2124-6.; 2. Manzi S, Wasko MC. Inflammation-mediated rheumatic diseases and atherosclerosis. Ann Rheum Dis 2000; 59:321-5.; 3. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Inimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation 1986; 74, 1399-406.

Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old) and stroke (48 years old), respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous) thromobotic events; chronic liver disease might modulate this risk.

Background Benign Intracranial Hypertension (BIH) may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors' control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH. Patients and methods The incidence of prothrombotic abnormalities among a randomly investigated cohort of 17 patients with BIH, was compared with 51 healthy subjects matched for sex, age, body mass index, height and social background. Results The number of subjects with protein C deficiency was significantly higher in patients than in controls (3 vs 1, p < .001; Fisher Exact Test). Moderate to high titers of anticardiolipin antibodies (β2-Glycoprotein type I) were found in 8 out of 17 patients. Increased plasma levels of prothrombin fragment 1+2, fibrinopeptide A (FPA), and PAI-1 were demonstrated in patients group (5.7 ± 1.15 nM vs 0.45 ± 0.35 nM; 8.7 ± 2.5 ng/mL vs 2.2 ± 1.25 ng/mL; 45.7 ± 12.5 ng/mL vs 8.5 ± 6.7 ng/mL, respectively; p < .001; Fisher Exact Test). Gene polymorphisms for factor V Leiden mutation, prothrombin mutation 20210 A/G, MTHFR 677 C/T, PAI-1 4G/5G, ACE I/D were detected in 13 patients. Discussion In agreement with other authors our data suggest a state of hypercoagulability in BIH associated with gene polymorphisms. Our findings also showed that mutations in cardiovascular genes significantly discriminate subjects with a BIH history. The association between coagulation and gene derangements, usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism in BIH. So, a prothrombotic tendency may exist that would, at least in part, explain some cases of BIH. Although based on a small population, these findings raise the exciting possibility of using these haemostatic factors as markers for selecting high-risk subjects in BIH disease.

Solitary plasmacytoma accounts for a small percentage of plasma cell neoplasms. The disease often affects older people and is potentially curable. Only a few cases of solitary jaw plasmacytoma have been described in the literature. Here we report the case of a 76-year-old woman affected by chronic hepatitis C infection and isolated plasmacytoma of the left jaw. Plasmacytoma was diagnosed in January 2001, but the swelling of the mandible had been present since 1993. Two different pathologists made the diagnosis on the basis of biopsy material from the mandibular swelling.

Background. Cancer is one of the most common acquired causes of venous thromboembolism. Aim. To evaluate haemostasis disorders in patients with non-metastatic gastric cancer. Patients and methods. We studied 11 patients with non-metastatic gastric cancer (9 males and 2 females, median age 54 years) and 20 healthy subjects (15 males and 5 females, median age 48 years) control. We measured prothrombin time, activated partial thromboplastin time, coagulation time, clot lysis time, fibrinogen, clotting factors (II, VII, VIII, IX, X), C protein, S protein, AT Ill, activated protein C resistance, prothrombin 1+2 fragment, tissue plasminogen activator, and D-Dimer in all subjects. Results. Fibrinogen plasma levels were significantly higher in patients with non-metastatic gastric cancer than in control group (505±24 mg/dl vs 336±30 mg/dl, p

Venous thromboembolism (VTE) is still one of the main causes of morbility and mortality in surgical or medical hospitalized patients. Typical onset is surely deep vein thrombosis (DVT) of the leg (distal or proximal), less frequently of the upper limbs. The most dangerous manifestation of VTE still remains pulmonary embolism (PE). DVT annual incidence overall is influenced by the age, increasing from 1/10.000 for individuals younger than 40 years to 1-2/100 for those older than 60 years, while PE annual incidence in general population is about 0.7/1000, accountable for 10% of deaths [1] in hospitalized patients (60% for medical illness) [2, 3]. Virchow famous triad (blood stasis, vascular damage, hypercoagulability) remains from 1856 to this day the physiopathological mainstay, although enriched with recent acquisitions. Diagnosis often delayed by poor signs and symptoms in nearly 70% of VTE. Sequelae of VTE, not secondary for relevance, include embolization (mainly pulmonary embolism), post-thrombotic syndrome and recurrence, all weighty in terms of morbidity and mortality and patient’s quality of life.

Treatment of chronic hepatitis C with interferon (IFN) alone or with ribavirin is recommended for patients with persistently high levels of serum aminotransferase and detectable viraemia [1]. Approximately 2–3% of patients develop isolated thyroid disease while on IFN, of whom about 20–30% have an isolated elevation of thyroid peroxidase (TPO) antibodies [2]. Additionally, a few cases of isolated Type 1 diabetes mellitus have been described during IFN treatment in genetically predisposed patients [3, 4]. Just two cases of IFN-related isolated hypopituitarism have been reported, one of which resolved after 11 months [5]. Autoimmune polyglandular syndrome (APS) associated with IFN-α treatment has not been described previously. A 51-year-old woman suffering from chronic active hepatitis with detectable circulating hepatitis C virus-RNA (HCV-RNA) was examined. She had regular menstrual cycles. Thyroid function was normal and thyroid antibodies were undetectable. Therapy with IFN-α, 6 million units three times per week, was commenced and was continued for 6 months. At 1 month, elevation of TPO antibodies occurred (250 IU ml−1), with no thyroid functional disorder. Serum transaminase became normal and circulating HCV-RNA disappeared 3 months after beginning treatment. At 4 months, she reported amenorrhoea and asthenia. At 12 months, the patient reported polydipsia, polyuria and weight loss for about 2 weeks. Severe hyperglycaemia was documented (approximately 44 mmol l−1), so she was admitted to our unit. Ketoacidosis was detected, and promptly corrected. The following abnormalities were revealed: serum C-peptide 0.5 µU ml−1 (basal) and 0.8 µU ml−1 (6 min after 1 mg i.v. of glucagon); HbA1c 10.6%; follicle stimulating hormone (FSH) 3.5 U l−1; luteinizing hormone (LH) 2.5 U l−1; basal serum cortisol and ACTH were 2.4 µg dl−1 (normal range 4.1–22.4) and 2.5 pg ml−1 (normal range 6.1–55.0), respectively; pituitary gland autoantibodies by immunofluorescent assay (positive at 1 : 16 dilution); islet cell antibodies (ICA); glutamic acid decarboxylase antibodies (GADA); tyrosine phosphatase IA-2 antibodies (IA-2A) (positive at 38 JDF-U ml−1, 33 IU ml−1 and 48 IU ml−1, respectively). Serum growth hormone, prolactin, aldosterone and parathyroid hormone were normal. Serum cortisol rose to 23.2 µg dl−1 after corticotropin stimulation, suggesting recent onset of corticotropin deficiency, whereas, LH and FSH did not rise after GnRH stimulation. Magnetic resonance imaging showed a partial empty sell. Retrospective evaluation of serum samples stored at − 80 °C, collected for future viral investigation, showed that autoantibodies to pancreas and pituitary gland were undetectable before treatment with IFN was started. Molecular typing of class II major histocompatibility complex alleles revealed homozygosity for the known Type 1 diabetes-associated DR3 (DQB1 *0201 and DQA1 *0501) haplotype, demonstrating a susceptible genetic background for autoimmune diseases. At 16 months, the patient has normal thyroid function, liver function tests and absent blood HCV-RNA, but remains insulin dependent with amenorrhoea and adrenal insufficiency. ICA, GADA, IA-2A and pituitary gland antibodies remain positive (53 JDF-U ml−1, 84 IU ml−1, 44 IU ml−1 and 1 : 16 dilution, respectively). These findings suggested a type III APS, according to Neufeld's classification. IFN-α enhances MHC expression and may cause both the onset of organo-specific autoantibodies, and the clinical manifestations of autoimmune diseases, as occurred in our patient. The absence of autoantibodies does not exclude humoral or clinical autoimmunity during or after treatment. Therefore, we recommend strict clinical monitoring during, as well as after IFN-α treatment, in order to detect promptly any symptoms and signs of autoimmune disease. The clinical suspicion has to be confirmed by appropriate autoimmune and hormonal assays.

Congenital thrombotic risk factors, oncological diseases and its therapies have been related to an increased occurrence of upper extremities deep venous thrombosis (UEDVT). We studied seven patients bearing lymphoma (one Hodgkin's and six non-Hodgkin's) who developed UEDVT, one at diagnosis and six during chemotherapy (two of these six cases had implantation of a central venous catheter and four received Growth Colony Stimulating Factors in addition to chemotherapy). Patients were screened for: factor V G1691A (Leiden), prothrombin G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T mutations and antithrombin III, proteins C and S plasma activity. All patients were wild-type homozygotes for G20210A. One was heterozygote for factor V G1691A, the other 6 were wild-type homozygotes. Three of the 7 patients were homozygotes and 2 heterozygotes for the MTHFR mutation; the remaining 2 were wild-type homozygotes. Clotting inhibitor levels were normal in all patients. UEDVT in patients bearing haematological malignancies can occur irrespective of congenital thrombophilic alterations. However, in a subgroup of patients UEDVT could also depend on congenital thrombophilic alterations. A screening for inherited thrombophilia can identify high risk patients that could be specifically treated to prevent thrombotic complications.

Background D-dimer is considered a marker of hypercoagulable state and of endogenous fibrinolysis, so increased d-dimer is detectable in patients affected by thrombosis. Yet, several studies showed that also infertility, in particular secondary infertility due to recurrent fetal losses, has been often related to thrombotic events, in particular in women carrying thrombotic risk factors such as inherited thrombophilia (MTHFRC677T, PTHRA20210G, Factor V Leiden polimorphisms and/or inhAfter this screening we selected 39erited protein C, protein S, AT III deficiency) or acquired thrombophilia (primary antiphospholipid syndrome, acquired protein C, protein S, AT III deficiency, drugs induced thrombophilia). However, because its high predictive negative value in case of suspected thrombosis, increased d-dimer has been often associated to subclinical thrombophilia. The aim of this study is to investigate the role of d-dimer as first marker of thrombophilia in women affected by unexplained infertility and subsequently to search the cause of increased d-dimer, such as inherited and/or acquired thrombophilia.