No abstract

Sickle cell disease is an autosomal recessive genetic red cell disorder with a worldwide distribution. Growing evidence suggests a possible involvement of complement activation in the severity of clinical complications of sickle cell disease. In this study we found activation of the alternative complement pathway with microvascular deposition of C5b-9 on skin biopsies from patients with sickle cell disease. There was also deposition of C3b on sickle red cell membranes, which is promoted locally by the exposure of phosphatidylserine. In addition, we showed for the first time a peculiar “stop-and-go” motion of sickle cell red blood cells on tumor factor-α–activated vascular endothelial surfaces. Using the C3b/iC3b binding plasma protein factor Has an inhibitor of C3b cell-cell interactions, we found that factor H and its domains 19-20 prevent the adhesion of sickle red cells to the endothelium, normalizing speed transition times of red cells. We documented that factor H acts by preventing the adhesion of sickle red cells to P-selectin and/or the Mac-1 receptor (CD11b/CD18), supporting the activation of the alternative pathway of complement as an additional mechanism in the pathogenesis of acute sickle cell related vaso-occlusive crises. Our data provide a rationale for further investigation of the potential contribution of factor H and other modulators of the alternative complement pathway with potential implications for the treatment of sickle cell disease.

No abstract

The ageing population and the increase in life expectancy have put new social and health questions into the public health agenda of western countries. Hematological cancer incidence peaks in older population as a logical consequence of a longer lifespan promoting prolonged exposure to carcinogens and accumulation of genetic alterations. Hematological cancer represents a major cause of mortality in this age group despite recent progress observed in the management of cancer in the general population. Autologous stem cell transplantation (ASCT) represents a therapeutic option in the treatment of a large proportion of lymphomas and multiple myeloma, but their role in the onco-geriatric setting remains an open question, due to the presence of chronic disease. Ageing is characterized by progressive decrements in physiologic reserves and abilities to compensate for physical and/or functional limitations, which increase the risk of developing morbidity and disability. These events explains the extreme diversity of ageing individuals in terms of clinical and functional status. As a consequence, life expectancy in the elderly is influenced not only by the neoplastic diseases itself but also by the various co-morbidities common to this age group. The management of elderly people with hematological diseases potentially curative, should therefore combine both geriatric and tumor assessments. Among the elderly patients identified as being candidates for AHSCT, after the mobilization of progenitor cells from the bone marrow into the peripheral blood, the aphaeresis procedure is the most common method for collecting an adequate number of stem cells. The proper selection of patients may greatly improve the results and the toxicity related to cancer treatment in the elderly. We recommend the adoption of some form of geriatric assessment in the evaluation of any patient who is 70 years and older, this review intends to offer an overview of the state of art in ASCT in elderly patients.

A family with a new congenital abnormality of antithrombin III (AT III) is presented. 5 members, all females, were affected. The proposita has had several thrombotic manifestations. The other patients, so far, are asymptomatic. Antithrombin activities were all decreased regardless of the method used (chromogenic or clotting) and regardless of the presence or absence of heparin in the assay system. AT III antigen, on the contrary, was normal in all patients regardless of the method used (electroimmunoassay, radial immunodiffusion or Laser nephelometer). The crossed immunoelectrophoresis without heparin showed in plasma the presence of an abnormal peak which was more anodal than the normal counterpart. The same pattern was seen in serum. In the heparin-modified cross-immunoelectrophoresis a normal pattern was seen in plasma and an abnormal one in serum. In the latter the anodal peak was in fact larger than the normal counterpart. Chromatographic studies using Heparin-Sepharose column failed to show changes in heparin affinity, and indicated that both the normal and the abnormal peak were contained in the major AT III area. The toponym AT III Trento is proposed to describe this abnormality. These studies further emphasize the great heterogeneity of AT III defects. This is the first AT III abnormality to show an abnormal crossed-immunoelectrophoresis in the absence of heparin.