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Objective: IgG and IgM antibodies directed at β2-glycoprotein I are included in the classification criteria for the antiphospholipid syndrome (APS) while the IgA antibodies against β2-glycoprotein I (IgA aβ2GPI) are not. Conflicting data about the significance of IgA aβ2GPI and APS manifestation can be found and more studies are necessary in order to define the diagnostic value of IgA aβ2GPI. In the present article, we investigated the possible role of IgA aβ2GPI as marker of APS., Methods: A cohort of 314 patients with APS and systemic autoimmune disease was investigated for the presence of IgA aβ2GPI and its association with clinical manifestation of APS., Results: Eighty-nine patients presented IgA aβ2GPI, 68 cases associated with others antiphospholipid antibodies (aPL) and in 21 cases being the only aPL present. In primary APS IgA aβ2GPI are highly coincidental with other aPL (92,2%) while most of the isolated IgA aβ2GPI were present in the SLE group (16/21). No association between IgA aβ2GPI and APS manifestations: thrombosis and pregnancy morbidity was found, while a positive association between IgA aβ2GPI and the presence of anti-nDNA, anti-RNP, anti-Sm, anti-SSA, anti-SSB antibodies was encountered., Conclusion: Our study does not show association between IgA aβ2GPI and APS manifestations and does not support the inclusion of IgA aβ2GPI as a classification criteria for APS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The antiphospholipid antibodies present in antiphospholipid syndrome (APS) are directed at a number of phospholipid-binding proteins: β2 glycoprotein I (β2GPI), prothrombin, and so on. Antibodies directed at β2GPI are accepted as a classification criterion for APS, while the presence of antiprothrombin antibodies is not. In the present article, we investigated the possible role of antiphosphatidylserine/prothrombin antibodies (aPS/PT) as marker of APS on a cohort of 295 individuals with APS (95 primary APS and 45 secondary APS) and APS-related diseases. We found aPS/PT to be highly associated with venous thrombosis (immunoglobulin G [IgG] aPS/PT odds ratio [OR], 7.44; 95% confidence interval [CI], 3.97-13.92 and IgM aPS/PT OR, 2.54; 95% CI, 1.35-4.77) and obstetric abnormalities (IgG aPS/PT OR, 2.37; 95% CI, 1.04-5.43), but not with arterial thrombosis. A very high degree of concordance between the concentration of aPS/PT and lupus anticoagulant activity was demonstrated. Therefore, we support the inclusion of aPS/PT determination as second-level assay to confirm APS classification.

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.

Clinical effects of recombinant human erythropoietin (rHuEPO) such as thrombosis, convulsions, hyperviscosity, hypertension, and angiogenic effect in culture cells have been described. We studied the rHuEPO effect on endothelial damage markers and endothelial function markers: tissue-type plasminogen activator (t-PA), nitrate (NO3), thrombomodulin (TM), and von Willebrand factor (vWF). Twenty-six peritoneal dialysis patients treated with rHuEPO and 19 controls were included. The study design for rHuEPO patients consisted of four periods: long-term treatment (rHuEPO-1); 2 months of withdrawal (rHuEPO-2); and 4 months on 5000 IU/week rHuEPO subcutaneously, with markers being measured after 2 months (rHuEPO-3) and after 4 months (rHuEPO-4). After 2 months of rHuEPO withdrawal, a decrease in hemoglobin level appeared (11+/-1.8 g/dL to 9.2+/-1.5 g/dL, p < 0.01). After rHuEPO reintroduction, this value reached 10.6+/-1.5 g/dL at two months, and 11.1+/-1.4 g/dL at four months. A significant increase in t-PA ratio was observed from two months without rHuEPO to two months on rHuEPO, returning to previous values after four months. Similarly, TM increased for patients with creatinine clearances (CrC) < 5 mL/min. No changes in the higher-than-normal plasma vWF levels were found during the various periods. A statistically significant lower value was found in controls compared with rHuEPO-4 patients. A statistically significant increase in NO3 levels was observed in the pre-venous occlusion (VO) test immediately after the re-introduction of rHuEPO. This increment returned to prior values four months after rHuEPO was reintroduced. Our results show that rHuEPO treatment causes an increase in some endothelial damage markers (TM, t-PA) and modifies endothelial function markers (t-PA ratio, NO3). These changes might favor thrombosis and atherosclerosis.

The aim of this study was to determine if the measurement of anti-beta2-glycoprotein I antibodies (abeta2-GPI) in serum levels contributes to the better characterization of the clinical situation of patients with antiphospholipid syndrome (APS). For this purpose abeta2-GPI of both isotypes was measured in 42 patients with APS and 32 SLE patients without APS. Clinical records of all patients were thoroughly reviewed. The presence of abeta2-GPI was correlated with the clinical manifestations of APS and compared with the presence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) activity. There was a positive correlation between levels of aCL and abeta2-GPI for both IgG and IgM isotypes (rho of Spearman=0.82 and 0. 64 respectively, P=0.0001). Both antibodies presented significantly higher titres in LA positive patients (P<0.05). The specificity for APS was 91% for IgG abeta2-GPI vs 75% for IgG aCL and 87% for IgM abeta2-GPI vs 81% for IgM aCL. 68% of patients with thrombosis of 100% of patients with thrombocytopenia showed positive tests for all three markers (aCL, LA, abeta2-GPI). Simultaneous presence of circulating LA and high titres of both aCL and abeta2-GPI identify a subset of patients with primary APS (PAPS) who have a more severe clinical course of the disease. Although the specificity of abeta2-GPI IgG is higher than that of aCL IgG, when all three tests are performed abeta2-GPI testing provides only additional information to that of aCL and LA. Therefore, we concluded that the abeta2-GPI test should not be considered as a substitute for conventional LA or aCL assays. However, performance of abeta2-GPI seems to be important in PAPS with high aCL titres, to alert the physician about the risk for the worst course of the illness.

The formation of fibrin on peritoneal surface has been related to the appearance of adhesions both, in surgical and CAPD patients. It is known that mesothelial cells have fibrinolytic activity related with t-PA production. We studied plasma and overnight peritoneal effluent (OPE) from 20 CAPD stable patients. Antigenic PAI and t-PA were determined. These values and its correspondent peritoneal saturation indexes were compared to urea and creatinine MTCs, peritonitis incidence, UF capacity, protein losses, Pi, Ca, Na, CO2t, urea and creatinine OPE levels. Plasma t-PA 6.64 +/- 4.68 (2.4-20); Plasma PAI-I 24.8 +/- 17.1 (p < 0.001 in respect to controls) (4-62); OPEt-PA 1.46 +/- 0.95 (0.4-4.6); OPE PAI-I 7.3 +/- 5.6 (0-20.4). Peritoneal saturation ratios were for t-PA 29.6 +/- 21% (6-65) and for PAI-I 34 +/- 32% (7-132). In conclusion our data do not support strong relationship between peritoneal t-PA/PAI system and the functional characteristics of the peritoneal membrane although plasma PAI-I, after an increase in patients at early stages on CAPD, shows a tendency to decrease over time and frequent peritonitis. The values of peritoneal saturation ratios for t-PA/PAI are higher than expected for their molecular weight, which suggests local production. An elevated plasma t-PA levels has been found in older patients.

Platelet activity is closely related to endothelium and could release factors able to influence capillary wall and surrounding tissues. BTG is a protein included in platelet vesicles and a measure of its activation. Some alterations of peritoneum could be partially related to platelet activity. BTG peritoneal transport from blood is weight limited (36000) and consequently, high levels in effluent should represent local production. The aim of this study has been to characterize peritoneal effluent BTG.12 patients, on CAPD 27 +/- 15 mon., 5 diabetics were studied. Previous peritonitis was 0.3 +/- 0.4 e/year. Determinations performed: Plasma (P) (BTG, T. protein, albumin, platelet count, Hcto and Fibrinogen) and Effluent (EF) (BTG, T. protein, Fibrinopeptide A, FDP, Fibrinolytic act., Fibrinogen, Plasminogen and Mitogenic induced capacity on Swiss 3T3 mice fibroblasts). To evaluate peritoneal function we used mass transfer coefficients (MTC) and net UF.R.:BTG levels: P 118 +/- 14 EF 34 +/- 14 ng/ml P/EF (%) 31 +/- 13 (6-54%). Regression analysis: P BTG did not show significant relationship with any of the studied parameters. EF BTG showed direct significant correlation (p less than 0.05) with Creatinine-MTC (r: 0.81) and EF Fibrinogen (0.68) and in the limit of significance with EF T. prot (0.57) and EF Mitogenicity (0.62). P/EF BTF showed significant correlation with creatinine-MTC (0.77). The analysis of these values grouping patients showed: diabetes has no influence on BTG values, hypertensive patients show higher P/EF BTG values than normotensive (39 +/- 9 vs 23 +/- 11%, p less than 0.05) and no influences of peritonitis or CAPD period were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Human albumin and dextran 70 were used as volume expanders in extracorporeal circulation in two homogeneous series of patients. Comparative results were statistically processed. No significant differences were observed either to early postoperative bleeding or needed volume of transfused blood. Postoperative complications neither developed in the two groups of patients. The total number of platelets showed a 50 percent decrease in relation to basal extraction figures and those after immediate heparin neutralization. Results of platelet function tests were similar in both series, except for a statistical significant decrease in ADP-induced platelet aggregation in the group with dextran 70. Such decrease, however, was not followed by an increase of postoperative bleeding. Thus, dextran 70 has showed to be a valuable substitute for human albumin in extracorporeal circulation.

To investigate the likely influence of aluminium hydroxide intake (Al(OH)3) on haemoglobin concentrations and blood transfusion requirements we studied 27 long-term haemodialysis patients for 24 months divided in two equal periods: (P I and P II). All patients received oral iron as a fasting single dose, intravenous iron being used only occasionally. During P I Al(OH)3 was given thrice daily, during P II Al(OH)3 was reduced significantly by stopping the breakfast dose, thereby separating the oral iron from the influence of the binder. After Al(OH)3 reduction haemoglobin increased, the requirement for blood transfusion decreased, and the need for intravenous iron also decreased. Serum phosphorous did not change. This suggests that Al(OH)3 might interfere with erythropoiesis and we consider it advisable to avoid the morning dose of Al(OH)3 which in many cases is not necessary.