Outcomes during anticoagulation in patients with symptomatic vs. incidental splanchnic vein thrombosis.

INTRODUCTION: Current guidelines recommend the use of anticoagulant therapy in patients with symptomatic splanchnic vein thrombosis (SVT) and suggest no routine anticoagulation in those with incidental SVT. METHODS: We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry to assess the rate and severity of symptomatic venous thromboembolism (VTE) recurrences and major bleeding events appearing during the course of anticoagulation in patients with symptomatic or incidental SVT. RESULTS: In March 2017, 521 patients with SVT were recruited. Of them, 212 (41%) presented with symptomatic SVT and 309 had incidental SVT. Most (93%) patients received anticoagulant therapy (median, 147 days). During the course of anticoagulation, 20 patients developed symptomatic VTE recurrences (none died) and 26 had major bleeding (fatal bleeding, 5). On multivariable analysis, patients with incidental SVT had a non-significantly higher risk for symptomatic VTE recurrences (adjusted hazard ratio [HR]: 2.04; 95%CI: 0.71-5.88) and a similar risk for major bleeding (HR: 1.12; 95%CI: 0.47-2.63) than those with symptomatic SVT. Active cancer was associated with at increased risk for VTE recurrences (HR: 3.06; 95%CI: 1.14-8.17) and anaemia (HR: 4.11; 95%CI: 1.45-11.6) or abnormal prothrombin time (HR: 4.10; 95%CI: 1.68-10.1) were associated with at increased risk for major bleeding. CONCLUSIONS: The rates of recurrent SVT and major bleeding were similar between patients with incidental or symptomatic SVT. Because the severity of bleeding complications during anticoagulation may outweigh the severity of VTE recurrences in both groups, further studies should identify those SVT patients who benefit from anticoagulant therapy.

The use of nonselective beta blockers is a risk factor for portal vein thrombosis in cirrhotic patients.

Background/Aim: A reduction in portal vein inflow velocity seems to predispose to the emergence of portal vein thrombosis (PVT). Nonselective ß-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 <0.000, respectively). Treatment with NSBBs was significantly more frequent in the PVT group than in the non-PVT group (P < 0.000). PVT was associated with higher prevalence of chronic renal disease (P = 0.002), higher PT impairment (P = 0.003) and lower AST and ALT (P = 0.000). At multivariate logistic regression analysis, history of esophageal varices (P = 0.007) and NSBB treatment (P = 0.0003) were independent risk factors significantly associated with PVT. Conclusions: Esophageal varices and NSBB treatment were independent risk factors of PVT. Larger studies should evaluate the risk between variceal bleeding and portal vein thrombosis of using NSBBs, particularly in the prevention of first bleeding in nonadvanced liver cirrhosis.

Different outcome of six homozygotes for prothrombin A20210A gene variant.

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.

High prevalence of metabolic syndrome in patients with ankylosing spondylitis.

The objective of this work is to investigate the occurrence of atherosclerosis and metabolic syndrome (MetS) in ankylosing spondylitis (AS) patients (pts). Twenty-four consecutive AS pts (men, 87.5%; median age, 50.5 years; median disease duration, 16.5 years), fulfilling the modified 1984 New York criteria for AS criteria, and 19 age- and sex-matched controls were investigated. Clinical atherosclerosis was evaluated by physical examination for cardiovascular (CV) diseases and history or drug use for CV events. Subclinical atherosclerosis was detected by mean intima media thickness (a-IMT) and maximum IMT (max-IMT) of carotid arteries using ultrasonography. Laboratory investigations including fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides were assessed by standard methods, while homocysteine was assessed by chemiluminescence. MetS was assessed using the updated NCEP-ATP III criteria. Disease activity was defined according to the International Ankylosing Spondylitis Assessment Study criteria. The 10-year CV risk (%) profile was evaluated in agreement to the Progetto Cuore criteria. No major CV event was detected in the study population. No significant differences were found when AS pts and controls were compared according to the mean a-IMT (0.52+/-0.26 vs 0.51+/-0.13 mm), max-IMT (0.92+/-0.20 vs 0.85+/-0.39 mm), prevalence of abnormal max-IMT >1 mm (27.2 vs 5.3%), and 10-year CV risk (9.9+/-9.6 vs 3.6+/-1.8%). Systolic blood pressure (p=0.04), triglyceride to HDL cholesterol ratio (p=0.002), and LDL cholesterol (p=0.03) were found significantly higher in AS pts than in controls; on the contrary, HDL cholesterol was pointed out as significantly lower (p<0.001). MetS was found in 11/24 (45.8%) AS pts and in 2/19 (10.5%) controls (p=0.019). No significant relationship emerged in MetS prevalence among AS pts regarding the mean value of age, disease duration, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index, and the Italian version of Health Assessment Questionnaire. This preliminary report points out a higher prevalence of MetS in AS pts than in controls. Further studies are needed to confirm this finding.

Benign intracranial hypertension associated to blood coagulation derangements.

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 (beta2-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.

Phenotypic APC resistance as a marker of hypercoagulability in primitive cerebral lymphoma.

UNLABELLED: Thrombosis is the most frequent complication and the second cause of death in patients with malignant disease. Primary central nervous system non-Hodgkin's lymphoma represents a rare pathology. Resistance to APC is usually linked to a factor V (FV) gene mutation changing an Arg 506 to a Gln in the APC cleavage site. AIM: In our study, we aimed at investigating the presence of activated protein C resistance (APC-r) and other markers of hypercoagulability in 25 selected patients with a diagnosis of primitive cerebral lymphoma who had suffered from an ischemic episode of TIA and/or stroke. PATIENTS AND METHODS: 25 selected patients with a diagnosis of primitive cerebral lymphoma and 50 healthy subjects acted as control group, were tested. We measured APC-r, natural clotting inhibitors, F1 + 2, aPTT and PAI-1 according to international guidelines. Genomic DNA was extracted from peripheral white blood cells and in order to detect FV Leiden gene polymorphism. RESULTS: Our results showed that 11 out of 25 patients had a poor response to APC (< or = 0.70, which represents the cut-off point in our general population) without deficiencies in natural clotting inhibitors. All patients had high plasma levels of F1+2 and PAI-1 compared to those found in healthy subjects (2.65 +/- 0.75 nM/L vs 0.40 +/- 0.35 nM/L; 67.5 +/- 18.5 ng/mL vs 17 +/- 11.5 ng/mL, respectively). In 9 patients resistance to APC was not associated to a FV gene defect demonstrating that such phenomenon may occur also as an acquired condition. However, the patients with resistance to APC showed the highest plasma values in F1 + 2 and PAI-1. CONCLUSION: In cerebral lymphoma with hypercoagulability the resistance to APC is not caused by the FV Arg 506-->Gln mutation (82%). APC resistance not caused by this FV gene defect may be an additional risk factor for thrombophilia in this selected population.

Apolipoprotein A-I-dependent cholesterol esterification in patients with rheumatoid arthritis.

Growing evidence suggests that atherogenesis is associated with inflammation or defective removal of cholesterol excess from peripheral cells. Apolipoprotein A-I [ApoA-I] activates the enzyme Lecithin-Cholesterol Acyl-Transferase to esterify cell cholesterol for transport to liver. Haptoglobin [Hpt] was previously found able to bind ApoA-I, and suggested to reduce the enzyme activation. The aim of this study was to demonstrate that enhanced levels of Hpt, as present during inflammation, are associated with low enzyme activity and increased thickness of the arterial wall. Enzyme activity and Hpt concentration were analysed in patients with rheumatoid arthritis having the same plasma levels of antioxidants (ascorbate, urate, alpha-tocopherol, retinol) or oxidation markers (nitrotyrosine, lipoperoxide) of healthy subjects. Cholesterol esterification, determined as ratio of cholesteryl esters with cholesterol in high-density lipoproteins, was lower in patients than in controls, and negatively correlated with the intima-media wall thickness of the common carotid. The ratio of Hpt with ApoA-I was negatively correlated with the enzyme activity, while positively correlated with intima-media wall thickness. The results suggest that high Hpt levels might severely impair the enzyme activity, thus contributing to cholesterol accumulation in vascular cells, and lesion formation in the endothelium.

The role of d-dimer as first marker of thrombophilia in women affected by sterility: implications in pathophysiology and diagnosis of thrombophilia induced sterility.

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. PATIENTS AND METHODS: We selected 79 patients with unexplained primary or secondary infertility. We excluded 40 patients affected by hydrosalpinx, uterine fibroids, uterine malformations, endocrinological and immunological diseases, luteal insufficiency, cytogenetical alterations. All remaining 39 patients were tested for d-dimer and divided in two groups: the patients of group A (25 patients) showed increased plasma d-dimer, in group B were included 14 patients with normal plasma level of d-dimer. After this step all 39 patients were screened for MTHFRC677T, PTHRA20210G, Factor V Leiden polimorphisms, protein C, protein S, AT III, anticardiolipin IgM and IgG, lupus anticoagulant. In the control group were included 15 age matched women without sterility problems referred to our outpatient's section of vascular medicine for suspected deep venous thrombosis.Statistical analysis was based on chi2 test, differences were considered to be significant if p < 0.05. RESULTS: D-dimer was increased in 25/39 and 20/25 showed inherited/acquired thrombophilia while patients with normal d-dimer showed inherited/acquired thrombophilia in 7/14 (p: < 0.05, s). DISCUSSION: D-dimer is a well known marker of hypercoagulable state, in particular its high predictive negative value in case of suspected thrombosis has been recognised by several reports. Yet, increased d-dimer has been identified also for subclinical thrombophilia besides for vascular thrombosis. Our data, in fact, for the first time suggest an interesting role of d-dimer to identify women affected by unexplained primary or secondary infertility and thrombophilia. So, probably there is a role for d-dimer in these subjects for its predictive positive value. Of course, further data on large based population are needed to confirm our results, because these findings may speed up a diagnostic screening in these patients also for a good cost/effectiveness of this test.

Thromboembolic events and haematological diseases: a case of stroke as clinical onset of a paroxysmal nocturnal haemoglobinuria.

Some haematological diseases are associated to an increased risk of thromboembolic events. We report a case of paroxysmal nocturnal haemoglobinuria (PNH) in which a cerebrovascular event represented the first clinical manifestation of disease. PNH is associated to thromboembolic events, generally of venous districts often involving unusual locations such as mesenteric vessels, sagittal veins, inferior vena cava and renal veins.To our knowledge arterial thrombotic episodes are rare and the involvement of arterial cerebral vessels is exceptional. Then, our case points out the importance of investigating about haematological disorders in all patients presenting with a stroke, in which the common predisposing conditions are excluded.

Congenital and acquired thrombotic risk factors in lymphoma patients bearing upper extremities deep venous thrombosis: a preliminary report.

BACKGROUND: Congenital thrombotic risk factors, oncological diseases and its therapies have been related to an increased occurrence of upper extremities deep venous thrombosis (UEDVT). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Internal jugular vein thrombosis as first sign of metastatic lung cancer.

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.

Solitary plasmacytoma of the jaw occurring in an elderly woman affected by hepatitis C virus infection: a case report.

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.