The causes of thrombosis and pregnancy loss in antiphospholipid syndrome (APS) are still unknown, although several hypotheses have been proposed and hypofibrinolysis has been implicated. Anti-tissue-type plasminogen activator (tPA) antibodies may induce fibrinolytic defects and preliminary data indicate an association with thrombosis in APS. We measured plasma anti-tPA antibody levels in 91 consecutive patients with APS, 91 healthy controls, 40 patients with antiphospholipid antibodies without APS symptoms, and 23 patients with systemic lupus erythematosus (SLE) without antiphospholipid antibodies and APS symptoms. Patients with APS had anti-tPA antibody levels higher than controls (P ‫؍‬ .0001), patients with SLE (P ‫؍‬ .0001), and asymptomatic antiphospholipid patients (P ‫؍‬ .05). A subgroup of 53 patients had plasma levels of tPA antigen higher (P ‫؍‬ .0001) and tPA activity lower (P ‫؍‬ .05) than controls, with an inverse correlation (r ‫؍‬ ؊0.454; P ‫؍‬ .003) between anti-tPA antibody levels and tPA activity and no correlation with tPA antigen. The 2 patients with the highest antibody levels had tPA activity below the normal range. Their antibodies were, respectively, IgG1 and IgG3; both recognized human tPA, recombinant tPA, and the catalytic domain of tPA, but not ␤ 2 -glycoprotein I, prothrombin, or plasminogen. Our data indicate that anti-tPA antibodies specifically interacting with the catalytic domain of tPA can be found in patients with APS, representing a possible cause of hypofibrinolysis. (Blood.

Abstract. Calabresi L, Simonelli S, Conca P, Busnach P, Cabibbe M, Gesualdo L, Gigante M, Penco S,

A reduction in fibrinolysis has been described in association with thrombosis in the primary antiphospholipid syndrome (PAPS). In this study, we measured anti‐tissue‐type plasminogen activator (t‐PA) antibodies and anti‐fibrin‐bound t‐PA antibodies as possible causes of hypofibrinolysis in 39 patients with PAPS. We also evaluated the differences in anti t‐PA antibodies between patients without previous thrombosis (20 patients) and patients with previous episodes of thrombosis (19 patients: deep vein thrombosis in nine, ischaemic stroke in six, arterial leg thrombosis in one, hepatic vein thrombosis in one, thrombophlebitis in one and cerebral venous thrombosis in one). Anti‐t‐PA antibodies were measured by an enzyme‐linked immunosorbent assay (ELISA), and anti‐t‐PA fibrin‐bound antibodies were measured by a solid‐phase fibrin immunoassay (SOFIA) in 39 patients with PAPS and in 39 controls matched for gender and age. High levels of IgG anti‐t‐PA were found in three out of 39 patients with PAPS, and all three patients had a history of thrombosis; four other patients, one of whom had a history of thrombotic events, had high titres of antibodies directed against fibrin‐bound t‐PA. In addition, patients with ischaemic stroke had significantly higher levels of IgG anti‐t‐PA than patients without thrombosis (P = 0·029). In conclusion, our data showed that, in patients with PAPS, the highest levels of anti‐t‐PA antibodies were present in subjects with previous thrombotic events. The discrepancy in the results obtained with two methods of detection of anti‐t‐PA antibodies, ELISA and SOFIA, indicates a different interaction of the antibodies with the t‐PA molecules, which are directly bound to polystyrene plates in ELISA and bound to fibrin as a bridging molecule in SOFIA.

Background: NxStage System One cycler (NSO) is a widespread system for home daily dialysis. Few data are available on the impact of this “low dialysate volumes system” on the removal rate of poorly diffusible, time-dependent solutes like β₂-microglobulin (β₂M). Methods: Single-session and weekly balances of β₂M were performed and compared in 12 patients on daily NSO, 13 patients on standard high-flux bicarbonate dialysis (BHD), 5 patients on standard post-dilution on line hemodiafiltration (HDF), and 13 patients on automated peritoneal dialysis (APD). Results: Intradialytic fall of plasma water β₂M levels (corrected for rebound) was 65.2 ± 2.6% in HDF, 49.8 ± 9.1% in BHD, and 32.3 ± 6.4% in NSO (p < 0.001 between all groups). Single treatment dialysate removal was much less in APD (19.4 ± 20.4 mg, p < 0.001) than in any extracorporeal technologies, and was less in NSO (126.2 ± 35.6 mg, p < 0.001) than in BHD (204.9 ± 53.4 mg) and HDF (181.9 ± 37.6 mg), with no differences between the latter 2; however weekly removal was higher in NSO (757.3 ± 213.7 mg, p < 0.04) than in BHD (614.8 ± 160.3 mg) and HDF (545.8 ± 112.8 mg). Extrapolated β2M adsorption to the membrane was negligible in BHD, 14.7 ± 9.5% of total removal in HDF and 18.3 ± 18.5% in NSO. Integration of single session data into a weekly efficiency indicator (K × t) showed total volume of plasma cleared in NSO (33.4 ± 7.7 L/week) to be higher than in BHD (26.9 ± 7.2 L/week, p < 0.01) and not different than in HDF (36.2 ± 4.7 L/week); it was negligible (3.2 ± 1.0) in APD. Conclusions: Weekly β₂M removal efficiency proved equal and highest in HDF and NSO (at a 6/week prescription), slightly lesser in BHD and lowest in APD.