Safety of fondaparinux in the prevention of venous thromboembolism in elderly medical patients: results of a single-center, retrospective study.

AIM: Venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality in acutely ill medical patients. Fondaparinux is recommended for the prevention of VTE in this setting, but little information is available on its safety and effectiveness in unselected, "real world" patients. The aim of this paper was to assess the safety and efficacy of fondaparinux in elderly acutely ill medical patients. METHODS: Single center, retrospective study. All patients >60 years, admitted for acute medical disease, bedridden for at least four days and treated with fondaparinux were evaluated. Occurrence of objectively documented, symptomatic VTE, and of bleeding events during the treatment period and follow-up were reported. RESULTS: Two hundred and ten patients (median age 81 years) were treated with fondaparinux. Seventy patients received fondaparinux 1.5 mg daily, 140 received the 2.5 mg daily dose. However, 29 patients in the first group (with a CrCl≥50 mL/min) and 84 patients in the last group (with a CrCl<50 mL/min) did not receive the correct dose of fondaparinux. During treatment, one episode (0.48%, 95% CI 0.1% to 2.6%) of major bleeding and 6 episodes (2.86%, 95% CI 1.3% to 6.1%) of clinically relevant non major bleeding were recorded. Only one thromboembolic event (0.48%, 95% CI 0.1% to 2.6%) was documented. Thirty-nine patients died; no death was related to VTE, unlike one death was due to major bleeding. Cancer was the only significant predictor of bleeding at statistical analysis. CONCLUSION: In elderly acutely ill hospitalized medical patients, thromboprophylaxis with fondaparinux 2.5 or 1.5mg daily is safe and effective in preventing VTE without increasing bleeding risk.

Cavernous transformation of the portal vein associated to multiorgan developmental abnormalities.

Initial diagnosis of cavernous transformation of the portal vein (portal cavernoma) is rarely made in adults. Its main clinical manifestation is upper gastrointestinal hemorrhage due to variceal bleeding. More rarely, diagnosis is made from obstructive jaundice. In children, this condition is frequently associated to prehepatic portal hypertension and congenital anomalies, the most frequent of which are atrial septal defects or malformations of the biliary tract or of the inferior vena cava. We describe here a case of a 23-year-old female presenting with massive hematemesis due to the presence of esophageal and small intestinal varices. She had a cavernous transformation of the portal vein with prehepatic portal hypertension associated with heretofore unreported malformations such as right pulmonary hypoplasia, cardiac dextroposition, and right renal ectopia. A unifying hypothesis (e.g. an intrauterine vascular insult) to explain the pathogenesis of these defects seems unlikely. Appropriate tests failed to identify specific functional abnormalities in these organs. Although she bled more than once, the combination of sclerotherapy and beta-blockers has been, thus far, able to control the major clinical consequences of this disease.

Gastric mucosa as an additional extrahepatic localization of hepatitis C virus: viral detection in gastric low-grade lymphoma associated with autoimmune disease and in chronic gastritis.

The hepatitis C virus (HCV) has been linked to B-cell lymphoproliferation and autoimmunity, and has been localized in several tissues. The clinical observation of an HCV-infected patient with Sjögren's syndrome (SS) and Helicobacter pylori (HP) positive gastric low-grade B-cell non-Hodgkin's lymphoma (NHL), which did not regress after HP eradication, led us to investigate the possible localization of HVC in the gastric microenvironment. HCV genome and antigens were searched in gastric biopsy specimens from the previously mentioned case, as well as from 9 additional HCV-infected patients (8 with chronic gastritis and 1 with gastric low-grade B-cell NHL). HCV-specific polymerase chain reaction (PCR) and immunohistochemistry procedures were used. The gastric B-cell NHL from the patient with SS was characterized by molecular analyses of B-cell clonality. HCV RNA was detected in both the gastric low-grade B-cell NHL and in 3 out of 6 gastric samples from the remaining cases. HCV antigens were detected in the residual glandular cells within the gastric B-cell NHL lesions, in glandular cells from 2 of the 3 additional gastric lesions that were HCV positive by PCR, and in 1 additional chronic gastritis sample in which HCV-RNA studies could not be performed. By molecular analyses, of immunoglobulin genes, the B-cell NHL from the patient with SS was confirmed to be a primary gastric lymphoma, subjected to ongoing antigenic stimulation and showing a significant similarity with rheumatoid factor (RF) and anti-HCV- antibody sequences. Our results show that HCV can localize in the gastric mucosa.

Gastric B-cell clonal expansion and Helicobacter pylori infection in patients with autoimmune diseases and with dyspepsia. A follow-up study.

BACKGROUND: It is not clear whether gastric B-cell clonal expansion, a possible precursor of mucosa-associated lymphatic tissue (MALT) lymphoma, is exclusively linked to Helicobacter pylori infection and virulence. METHODS: In this study we followed up, for up to 33 months, 16 VDJ polymerase chain reaction-positive patients (4 with dyspepsia, 9 with Sjögren's syndrome, and 3 with other autoimmune diseases). Of these, 12 were H. pylori-positive. In addition, in H. pylori-positive patients we tested whether the serum anti-cag-A (a potential marker of virulence) was preferentially associated with B-cell clonality. RESULTS: In all but one patient clonality appeared temporally unrelated to H. pylori infection. The prevalence of anti-cagA was not higher in H. pylori/VDJ-positive patients than in controls. CONCLUSIONS: These data indicate that, in addition to H. pylori, gastric B-cell clonality may be sustained by other agents/mechanisms. Anti-cag-A does not appear to be involved in the pathogenesis of clonality.

B-cell clonality and infection with Helicobacter pylori: implications for development of gastric lymphoma.

BACKGROUND: Although Helicobacter pylori has been implicated in the pathogenesis of gastric mucosa associated lymphoid tissue (MALT) and MALT lymphoma, it is not known how it may trigger these lesions and whether there is an identifiable pre-neoplastic stage. AIMS: To investigate the relation between MALT, H pylori infection, and B-cell clonality (a potential marker of pre-neoplastic lesions). PATIENTS: 141 subjects with simple dyspepsia. METHODS: Gastric biopsy specimens from all patients were examined for MALT and H pylori. Of these, 25 consecutive MALT positive specimens were scored for features of MALT lymphoma and VDJ clonality studied by polymerase chain reaction. RESULTS: Overall, prevalence was 62% for H pylori and 46% for MALT. VDJ clonality was frequent in the sub-group studied (nine of 25), mostly associated with lymphoid follicles (eight of nine or 89%), and with a high scoring for MALT lymphoma. VDJ clonality was equally frequent in patients with and without H pylori (seven of 20 and two of five or 35% and 40% respectively). CONCLUSIONS: B-cell clonality is unexpectedly common in subjects with simple dyspepsia and MALT raising clinical management questions. These findings also suggest that the cascade MALT formation--B-cell clonality--MALT lymphoma may not be uniquely associated with H pylori infection.

B cell clonality in gastric lymphoid tissues of patients with Sjögren's syndrome.

OBJECTIVE: To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjögren's syndrome (SS). METHODS: Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Organised MALT was found in 33.3% of the patients, compared with 21.5% of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality. CONCLUSION: Lymphoid accumulation in the gastric mucosa is common in Sjögren's syndrome, but full evidence for an antigen driven B cell expansion could not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa.

Helicobacter pylori, gastric MALT and B-cell clonality.

MALT, or mucosa associated lymphoid tissue, is normally not present in gastric tissue. Its presence is often associated with persistent antigenic stimulation. MALT is a precursor of gastric MALT lymphoma, a low-grade lymphoma whose incidence recently appears to have increased. Although much epidemiologic and clinical evidence has linked both MALT and MALT lymphoma to Helicobacter pylori infection, it is not known whether other agents and or mechanisms may also play a role and whether there is a clearly defined pre-neoplastic lesion. In particular, the clinical significance of B-cell clonality remains unknown. In a recent study we attempted to define the role of H. pylori and MALT in the genesis of B-cell clonality in a northern Italian patient population referred to us for simple dyspepsia. The results show that B-cell clonality is unexpectedly frequent in these patients regardless of the presence of H. pylori infection. These observations raise the possibility that agents and mechanisms other than H. pylori may be involved in the genesis of MALT lymphoma. Indeed, other studies conducted by our group in patients with Sjögren's syndrome indicate that genetic/immunologic factors and possibly viruses may play a role. The high prevalence of B-cell clonality in an otherwise healthy population suggests either that most of these patients are at risk of developing MALT lymphoma (in which case this condition at the moment may be greatly underdiagnosed) or that B-cell clonality is a very early step in the development of neoplasia, which requires several other factors and which will occur only in a restricted fraction of these patients. Careful follow-up studies will provide an answer to this question.