Markers of platelet, endothelial cell and blood coagulation activation in leprosy patients with antiphospholipid antibodies.

OBJECTIVE: To evaluate plasma levels of markers of platelet, endothelial cell and blood coagulation activation in leprosy patients with or without antiphospholipid antibodies (aPL) and to compare them to those found in patients with antiphospholipid syndrome (APS). METHODS: 42 patients with leprosy (35 lepromatous and 7 borderline): 29 aPL(+) and 13 aPL(-), as well as 26 healthy subjects as normal controls (NC) and 79 control aPL patients without leprosy (59 with and 20 without APS) were included in the study. Plasma soluble P and E selectin (sPsel and sEsel), and VCAM-1 (sVCAM-1), prothrombin F1 + 2 fragment (F1 + 2), thrombin-antithrombin complexes (TAT) and D dimer (DD) were measured by ELISA. The protein C pathway was assessed by the ProC global test. RESULTS: Leprosy patients with aPL presented increased median levels of sPsel [ng/ml (82.0 vs 36.0, p < 0.001)] and sVCAM-1 [ng/ml (495 vs 335, p < 0.001)] compared to NC, as observed in control aPL patients without leprosy. Levels of sPsel in aPL(+) patients with leprosy were significantly higher than in aPL(-) ones (52.5 ng/ml), p = 0.005. However, plasma markers of thrombin generation were increased in control aPL patients without leprosy but not in those with leprosy. ProcC global test was abnormal in 24.1% of leprosy patients with aPL compared to 4.4% of NC (p < 0.024), and to 57.2% of control patients with aPL without leprosy (p = 0.005). CONCLUSIONS: We demonstrated that although patients with leprosy present a high prevalence of aPL, and platelet and endothelial cell activation in vivo to the same extent than patients with APS, they do not show a procoagulant state.

Markers of platelet, endothelial cell and blood coagulation activation in leprosy patients with antiphospholipid antibodies

OBJECTIVE: To evaluate plasma levels of markers of platelet, endothelial cell and blood coagulation activation in leprosy patients with or without antiphospholipid antibodies (aPL) and to compare them to those found in patients with antiphospholipid syndrome (APS). METHODS: 42 patients with leprosy (35 lepromatous and 7 borderline): 29 aPL(+) and 13 aPL(-), as well as 26 healthy subjects as normal controls (NC) and 79 control aPL patients without leprosy (59 with and 20 without APS) were included in the study. Plasma soluble P and E selectin (sPsel and sEsel), and VCAM-1 (sVCAM-1), prothrombin F1 + 2 fragment (F1 + 2), thrombin-antithrombin complexes (TAT) and D dimer (DD) were measured by ELISA. The protein C pathway was assessed by the ProC global test. RESULTS: Leprosy patients with aPL presented increased median levels of sPsel [ng/ml (82.0 vs 36.0, p smaller 0.001)] and sVCAM-1 [ng/ml (495 vs 335, p smaller 0.001)] compared to NC, as observed in control aPL patients without leprosy. Levels of sPsel in aPL(+) patients with leprosy were significantly higher than in aPL(-) ones (52.5 ng/ml), p = 0.005. However, plasma markers of thrombin generation were increased in control aPL patients without leprosy but not in those with leprosy. ProcC global test was abnormal in 24.1 per cent of leprosy patients with aPL compared to 4.4 per cent of NC (p smaller 0.024), and to 57.2 per cent of control patients with aPL without leprosy (p = 0.005). CONCLUSIONS: We demonstrated that although patients with leprosy present a high prevalence of aPL, and platelet and endothelial cell activation in vivo to the same extent than patients with APS, they do not show a procoagulant state.

Apheresis: the Italian experience / Aférese: a experiência italiana

The Italian experience is a long one, beginning with granulocyte collection in the late Bruni R. months of 1972 and progressively expanding to new application and new techniques, many of which Italian in origin and diffusion. This is true for sequestration, multiple Carlier P. component collection, ascitapheresis, dy-platelet collection, but is also true for the new application of known techniques such as cascade, filtration for disorders such as acute Guillain Barr Syndrome, KT, Cyclosporin induced or secondary hypertriglericeridemia, lepromotous vasculitis leptospirosis, hyperacute kidney rejection, autoimmune pure redcell aplasia and many other disorders treated by plasma exchange for the first time in Italy and in general terms in Italy this intermediate level of complexity techniques have found a wide if not enthusiastic acceptance. Twenty-four years later the general appreciation and interest have not modified their impact onto transfusion medicine and Italy continues to be among the leaders also because of the presence in the country of a couple of industries of international excellence involved in apheresis and/or related fields. The presence of Italy in apheresis was marked by the first international Society (ESFH, European Society for Hemapheresis) set up in 1982, with its first meeting organized in Florence the following year and the one of 2001 that will be held in Italy. The Italian presence in apheresis is also marked by the large Italian participation in the international meetings, frequently as invited speakers and chairmen. Furthermore, many well recognized investigators got their training in Italy and Italy is proud of their achievements.

A experiência italiana em aféreses é antiga e teve início nos últimos meses de 1972 e progressivamente se expandiu com novas aplicações e novas técnicas, muitas delas de origem italiana. Isto é real para sequestração, coleção multipla de componentes, citaféreses e coleção de plaquetas, mas também é verdade que novas aplicações como na sindrome de Guillain-Barré, PTT, hipertrigliceridemia secundária a ciclosporina, vasculite lepromatosa, leptospirose, rejeição renal aguda.

Trombocitopenia associada ao uso de sulfona? / Thrombocytopenia associated with the use of sulfones?

A trombocitopenia tem sido raramente descrita em associaçäo à terapêutica com as sulfonas. Relata-se caso de paciente, portador de hanseníase tuberculóide em tratamento com dapsona que evoluiu com plaquetopenia significativa, obtendo recuperaçäo dos valores próximos aos normais após substituiçäo dessa droga pela clofazimina

Characterization of a novel myeloid antigen regulated during differentiation of monocytic cells.

The monoclonal antibody HC1/6 generated against phorbol 12-myristate 13-acetate-treated U-937 cells recognizes a new cell surface antigen with a broad relative molecular mass ranging from 100 to 150 kDa. This antigen is also present on monocytes, platelets and endothelial cells and is weakly expressed by granulocytes. In contrast, it is absent from T, B and erythroblastoid cells. The antigen HC1/6 is also expressed by normal tissue macrophages in tonsil, lung and kidney, as well as in skin biopsies from pathologies such as sarcoidosis and lepromatous leprosy. The expression of the HC1/6 antigen is increased up to 5-fold when U-937 (promonocytic) and HL-60 (myelomonocytic) cell lines are stimulated with phorbol 12-myristate 13-acetate. Conversely, the expression of the HC1/6 antigen is down-regulated in monocytes upon treatment with interferon-gamma. These findings are discussed in relation with other myeloid cell surface markers.

Rifampin-induced immune thrombocytopenia. A case report.

In this report, a case of rifampin-induced immune thrombocytopenia with the following characteristics is described: (a) thrombocytopenia follows intermittent drug administration; (b) onset occurs within hours of drug ingestion; (c) IgG antirifampin antibody binds in vitro to normal platelets only in the presence of rifampin; (d) thrombocytopenia resolves quickly in the absence of rifampin; (e) using immunofluorescence microscopy, IgG binding to normal platelets was seen with the patient's serum only in the presence of rifampin, and (f) using fluorescence spectrofluorometry, an absence of rifampin binding to normal platelets was demonstrated. Although the serological studies are not definitive, the mechanism of thrombocytopenia in the patient can best be explained by the formation of immune complexes composed of rifampin-antirifampin antibody binding to platelets causing their rapid clearance from the circulation.

Primary and secondary autoimmune thrombocytopenia. A serological and clinical analysis.

In 357 thrombocytopenic patients, the autoimmune nature of the thrombocytopenia was established with the immunofluorescence test on paraformaldehyde-fixed platelets in suspension (PSIFT). In 142 patients, autoimmune thrombocytopenia (AITP) was accompanied by (an)other disease(s) and thus classified as secondary AITP. No significant difference was found in the distribution of the immunochemical characteristics of the autoantibodies between primary and secondary AITP. The results of survival studies with 51Cr-labelled platelets and organ sequestration measurements in 7 patients with idiopathic thrombocytopenia purpura (ITP) indicated that platelets with IgM autoantibodies were sequestered mainly in the spleen. An increased incidence of AITP was seen at 5 to 10 years of age, in the 3rd decade and in the 6th and 7th decades of life. AITP was slightly more common life in females. The following groups of accompanying diseases in 142 AITP patients were distinguished: autoimmune diseases of the blood, malignant diseases of the blood, generalized and organ-specific autoimmune diseases, carcinoma and a miscellaneous group of diseases. No significant differences were found in the immunochemical properties of the autoantibodies between the various categories of disease. In 7 cases, AITP was preceded by an established viral disease, in 1 case by lepra and in another by a vaccination. The PSIFT was found to be a suitable test for diagnosing AITP not only in idiopathic thrombocytopenia, but also in thrombocytopenia associated with another disease.

Low serotonin uptake by platelets in leprosy and a new approach to prevent it.

The plasma of leprosy patients contains high levels of mucoproteins which are deficient in sialic acid. However, due to the increased mucoprotein level, the total sialic acid content of leprous plasma, calculated on protein, is increased when compared with normal human plasma. The low serotonin uptake observed with isolated platelets is probably due to their low sialic acid content. The inability of normal human plasma to correct the diminished serotonin uptake by isolated leprous platelets is in favor of a definite structural change in leprous platelets, related to their low sialic acid content. In patients with active disease and in those with lepra reactions, leprous plasma itself can correct the diminished uptake of serotonin by the isolated platelets. In patients with subsided lepra reactions, the leprous plasma is much less effective. In severe cases, where serotonin uptake is decreased even in platelet rich plasma, desoxyfructo-serotonin increased the uptake of serotonin.

[Immunologic factors and platelet vessel wall interactions (author's transl)]. / Facteurs immunologiques et interactions entre plaquettes et paroi vasculaire.

Platelet subendothelium interaction is an essential step in thrombosis and hemostasis which can be modulated by immunoglobulins, immune complexes, complement, and leukocytes. Antiplatelet antibodies can induce thrombocytopenia which is accompanied by a reduced vascular wall thickness and an increased fenestration. Antigen-antibody complexes can activate platelets inducing platelet release and aggregation. This reaction is amplified by the first component of complement C1q. Cytotoxic antibodies directed against endothelial cells have been observed in transplantation. These antibodies can be directed against HL-A antigens or specific endothelial antigens. Anticollagen antibodies have been detected in patients with leprosy. The C1q component can inhibit adhesion of platelets to collagen and platelet aggregation induced by collagen. The association of acquired or congenital C1q deficiency and vasculitis has been reported. C3a is taken up by endothelial cells and metabolized. C3a and C5a can modify vessel wall permeability and activate granulocytes which can become toxic for endothelial cells. Leukocyte cationic protein can reduce platelet aggregation. An anti-von Willebrand antibody could be the origin of hemostatic abnormalities and endothelial lesions. The involvement of immunologic factors in platelet vessel wall interactions is complex. Immune complexes and some antibodies seem capable of promoting thrombosis, while a component of complement (C1q) may also have an antithrombotic role.

Immunologic aspects of leprosy as related to leucocytic isoantibodies and platelet aggregating factors.

The incidences of various iso- and autoantibodies in a random population of 112 unselected leprosy patients is presented. Low titers of leucocytic isoantibodies and platelet aggregating factor were detected in the sera of a variable number of such patients. The leucoisoagglutinins were found in 8% of the sera of tuberculoid as well as lepromatous leprosy patients, whereas the leucoisocytotoxins were detected in a larger percentage of the lepromatous (40%) as well as tuberculoid (28%) cases. The platelet aggregating factors (PAF) were positive in 51.2% and 45% of lepromatous and tuberculoid cases respectively. Of the 21 positive sera for PAF, the antiplatelet factor by antihuman globulin consumption test could be demonstrated only in 66.6% and 50% of lepromatous and tuberculoid sera respectively. To study the frequencies of these newly detected antibodies or antibody-like factor and to compare their occurrences with other well-documented autoantibodies present in the sera of leprosy patients: cryoglobulins, antinucleoprotein antibody and thyroglobulin autoprecipitin were also studied in the sera of the same population of leprosy patients. It has been observed that the simultaneous occurrence of all these auto- and isoantibodies in the serum of one patient is a rare phenomenon. Leucocytic and platelet counts of these patients having antibodies against leucocytes and platelets were found to be within normal limits. Accordingly, it is suggested that the low levels of antileucocyte antibody and antiplatelet factor are probably harmless to the hosts. On the other hand, it is postulated that these antibodies may act as enhancing factors by being specifically adsorbed on the lymphoid cells, thus rendering them unresponsive to mitogenic stimulus in vitro. From these studies it seems that leprosy, especially the lepromatous type, is associated with some of the serological features suggestive of an autoimmune aberration.