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Aim: The study aims to evaluate the incidence of recurrent thromboses in patients with primary antiphospholipid syndrome (PAPS) and its association with the presence of different antiphospholipid antibodies (aPLs) and known thrombogenic risk factors. Methods: This retrospective study included 52 patients. The median age of the patients was 38.5 years [31.5; 43.5], and the duration of the disease was 9.0 years [3.1; 13.0]. aPLs, including IgG/IgM/IgA antibodies to cardiolipin (aCLs), IgG/IgM/IgA anti-beta2-glycoprotein I (anti-β2-GPI), IgG anti-domain I-β2-GPI (anti-β2-GPI DI) antibodies, IgG/IgM antibodies to the phosphatidylserine/prothrombin complex (aPS/PT), and other thrombosis risk factors were included for analysis. Results: Recurrent thrombosis was reported in 34 (65%) out of 52 patients and 18 (35%) did not have it. The main reason for the recurrence of thrombosis was the lack of anticoagulant therapy: in 18 (52.9%) out of 34 patients with recurrent thrombosis. Three patients were taking warfarin at the time of thrombosis recurrence, but target international normalized ratio (INR) levels were not achieved. Other patients with recurrent thrombosis were taking direct oral anticoagulants (DOACs). The risk of recurrent thrombotic events with positive IgG aCL was 10.33 (P = 0.002) and 21 (P = 0.007) times higher were examined in enzyme-linked immunoassay (ELISA) and chemiluminescent assay (CLA), respectively. The risk of thrombosis was 4.58 times higher in patients who were IgA aCL-positive (P = 0.01). Compared with other antibodies, with positive IgG values of anti-β2-GPI and IgG aPS/PT by ELISA, a lower probability of thrombosis recurrence was observed: 7.56 and 7.25, respectively. A high risk of recurrent thrombosis [odds ratio (OR) = 32.0] was observed in IgG anti-β2-GPI (CLA). The combination of IgG aCL with IgG anti-β2-GPI and with IgG anti-β2-GPIDI is more informative with respect to the risks of thrombosis recurrence compared to double positivity for aCL with anti-β2-GPI (OR = 20.71 vs. OR = 10.18). Triple positivity for IgG aCL with IgG anti-β2-GPI and with IgG aPS/PT also shows better results compared to positivity for aCL with anti-β2-GPI (OR = 6.06 vs. OR = 5.79). Among other risk factors, arterial hypertension (AH) and obesity were significant in relation to the recurrence of thrombosis. AH occurred in 22 (42%) of 52 patients with PAPS. AH was associated with recurrent thrombosis in PAPS patients: 18 (53%) out of 34 with recurrent thrombosis had AH versus 4 out of 18 without recurrent thrombosis (P = 0.003). Conclusions: Recurrent thrombosis in antiphospholipid syndrome (APS) is largely associated with IgG aCL, IgG anti-β2-GPI, IgG anti-β2-GPIDI, IgG aPS/PT, and IgA aCL positivity. AH was a significant risk factor for recurrent thrombosis.

Aim. To determine the significance of antibodies to the phosphatidylserine/prothrombin complex (aPS/PT) in patients with systemic lupus erythematosus (SLE) antiphospholipid syndrome (APS). Materials and methods. A total of 190 patients were included in the study: 123 (64.7%) with reliable SLE and 55 (29%) with PAPS. The control group included 100 relatively healthy subjects of comparable age. All patients were tested for classical aPL as well as IgG/IgM-anti-PS/PT by enzyme immunoassay. Results. Based on the average values of IgG/IgM aPS/PT of the control group, the levels of positivity were allocated mean (M) + 3 or 5 standard deviations (SD): M+3SD and M+5SD. IgG aPS/PT levels above 73.6 U/ml (M+5SD) were more accurate diagnostic, for IgM aPS/PT above 18.0 U/ml. IgG-aPS/PT were detected in 84 (44%) of 190 patients. Levels above diagnostic levels were detected in 68 (65%) of 104 patients with APS (55 with PAPS and 59 with SLE+APS). Thrombosis was significantly more common in patients with IgG aPS/PT compared with patients negative for IgG aPS/PT. Arterial but not venous thrombosis was associated with IgG aPS/PT positivity. Conclusion. The frequency of detection of IgG aPS/PT in the examined patients was 44%, IgM aPS/PT 29% and their combination 19% of 190 patients. Half of the patients with probable APS had positive IgG aPS/PT and third IgM aPS/PT. Median IgG aPS/PT were significantly higher in patients with APS compared to patients without APS and the control group. Thrombosis was associated with IgG aPS/PT. Arterial thrombosis was significantly more frequently reported in patients with IgG aPS/PT. The sensitivity of IgG aPS/PT for reliable APS at levels greater than 73.6 units/ml was 59%, specificity 92%, for IgM aPS/PT 35% and 91%, respectively.

Thrombotic antiphospholipid syndrome (APS) is a condition affecting young people in whom a thromboembolic event occurs in the presence of circulating antiphospholipid antibodies (aPL).The aim of this study was the evaluation of the incidence of recurrent thrombosis and its risk factors in antiphospholipid syndrome.Material and methods. The retrospective study included 98 patients with aPL who were followed up at the institute from 2014 to 2023, of whom 66 (67%) were women and 32 (33%) were men. Of the 98 patients with aPL, 48 (49%) had a diagnosis of systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL), including antibodies to cardiolipin (IgG/IgM aCL), antibodies to ß2-glycoprotein 1 (IgG/IgM aß2GP1), antibodies to ß2-glycoprotein IgG against domain 1 (IgG aß2GP1-D1), antibodies to phosphatidylserine/prothrombin complex (IgG/ IgM aPS/PT) and other thrombotic risk factors. aPL was assessed by enzyme-linked immunosorbent assay (ELISA) and chemoluminescence assay (CHLA).Results. Thrombosis recurrence was reported in 62 (63%) of 98 patients, and 36 (35%) did not. The main cause of recurrent thrombosis was treatment with direct oral anticoagulants (DOACs). 24 (38.7%) of 62 patients with recurrent thrombosis were treated with DOACs, the duration of which ranged from 6 to 24 months. The next most common cause of recurrent thrombosis was the lack of continuous anticoagulant therapy in 20 (32.5%) of the patients. In 17 (27.4%) of the patients, the recurrence occurred while they were still taking warfarin. In 10 (41.7%) of the 24 patients, the recurrent thrombosis was arterial in origin. This was associated with recurrent cerebral circulation problems. The level of positivity did not matter, but all had triple IgG aPL positivity. 5 had lupus anticoagulant (LA) at the onset of the disease before anticoagulant use. IgG aPS/PT was most important in association with recurring thrombosis in the ELISA: 45 (72.6%) of 62 patients with recurring thrombosis were positive for IgG aPS/PT, compared with 19 (52.8%) of 36 patients without recurring thrombosis. The detection of all aPL was more frequent in CHMA than in ELISA. However, the definition of aPL in ELISA is recommended according to the latest classification criteria. Triple IgG positivity for aCL of IgG aß2GP1, IgG aß2GP1-D1 and CHMA remained a risk factor for recurrent thrombosis and increased the risk of recurrence more than threefold. Obesity was a risk factor for recurrent thrombosis, with a 5-fold increased risk of recurrent thrombosis in obese compared to non-obese patients (p=0.01).Conclusions. Recurrent thrombosis in APS is largely associated with IgG aCL, IgG aß2GP1, IgG aß2GP1-D1, IgG aPS/PT. Triple IgG aPL positivity in any combination significantly increased recurrent thrombosis risk.The presence of any type of aPL IgG in both ELISA and CHLA influenced the recurrence rate of thrombosis in APS.Obesity was a significant risk factor for recurrent thrombosis.

Introduction. The Global Antiphospholipid Syndrome Score (GAPSS) is a tool proposed to quantify the risk of clinical manifestations associated with antiphospholipid antibodies (aPL) and certain cardiovascular risk factors.Objective. To validate GAPSS in a cohort of patients with systemic lupus erythematosus in Russia.Material and methods. 115 patients with SLE were included in the study, including 51 (44%) patients with systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS), 14 (12%) – SLE with aPL, and 50 (44%) – SLE.Results. There was a history of thrombosis in 58 (50%) patients with 115, of them 14 (24%) had arterial thrombosis, 29 (50%) – venous, 15 (26%) – combined. Pregnancy against the background of the disease occurred in 43 women included in the study. Of them, 29 (67%) had obstetric pathology. Patients with thrombosis and obstetric pathology had a GAPSS score of 7.17±5.64, versus 4.48±4.55 without these manifestations (p=0.0003). There was a significant association between GAPSS levels and thrombosis – patients with thrombosis had a GAPSS of 7.31±5.70, those without thrombosis – 4.00±4.81 (p=0.001). GAPPS values were higher in arterial thrombosis compared to venous thrombosis (10.40±25.30 versus 5.82±5.28; p=0.01). GAPSS levels ≥6 and ≥10 were analyzed to select GAPSS values at which a high risk of recurrent thrombosis and/or obstetric pathology could be indicated. All GAPSS levels had a significant association with clinical manifestations of APS. The quality of GAPSS by ROC analysis showed an area under the curve (AUC) for GAPSS of 0.697.Conclusion. GAPSS can be used to assess the risk of recurrence or development of thrombosis and/or obstetric pathology in patients with SLE in the Russian Federation. The GAPSS ≥6 values should be used to stratify patients with SLE into high risk group for recurrence of vascular complications. Further prospective follow-up is needed to confirm the value of GAPSS.

The study of antiphospholipid antibodies (aPL), not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood.The aim of this study – to determine the clinical significance of IgG antibody testing for domain I β2 -glycoprotein 1 (β2 -GP1DI) – IgG anti-β2 -GP1DI in patients with APS with and without SLE.Materials and methods. The study included 187 patients with APS with or without SLE, 49 patients formed a comparison group, and 100 relatively healthy individuals formed a control group. IgG/IgM antibodies to cardiolipin and IgG/ IgM anti-β2 -GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG antiβ2 -GP1DI was determined by chemiluminescence assay in all patients and controls.Results. IgG anti-β2 -GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE+APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of comparison group and in none of control group. IgG anti-β2 -GP1DI was significantly associated with PAPS and SLE+APS compared with patients with SLE (p=0.0002 and p=0.0001, respectively). The association of IgG anti-β2 -GP1DI with clinical manifestations of APS (thrombosis (χ2 =9.69; p=0.001) and obstetric pathology (χ2 =4.19; p=0.04)) was detected. There was a significant association of IgG anti-β2 -GP1DI with arterial thrombosis (χ2 =8.84; p=0.002) and with late gestational obstetric pathology (χ2 =6.35; p=0.01). High specificity of IgG anti-β2 - GP1DI depending on the diagnosis and clinical manifestations of APS was noted despite low sensitivity: specificity for thrombosis was 84%, for obstetric pathology – 94%, for APS – 89%. Isolated IgG anti-β2 -GP1DI positivity was reported in 2% of 50 aPL negative patients and was not associated with APS manifestations.Conclusion. The frequency of IgG anti-β2 -GP1DI detection was higher in patients with APS compared to patients with SLE, comparison group and control (p˂ 0.05). Positive IgG anti-β2 -GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (χ2 =8.84; p=0.002 and χ2 =6.35; p=0.01). Specificity of IgG anti-β2 -GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity: 89%, 94%, and 84%, respectively.

Classical serological markers of antiphospholipid syndrome (APS) are antibodies to cardiolipin, antibodies to β2-glycoprotein 1, and lupus anticoagulant. The utility of testing other antiphospholipid antibodies, not included in the classification criteria for improving the diagnosis of autoimmune thrombophilia continues to be debated. The review presents literature data on the study of antibodies to prothrombin and the phosphatidylserine/prothrombin complex in patients with systemic lupus erythematosus and APS.

Stratification of patients into groups of high and low risk of adverse outcome is necessary for timely and early prevention of the disease, as well as the selection of adequate therapy.Objective: to validate the global risk scale for the development of clinical manifestations of antiphospholipid syndrome (GAPSS) in a cohort of patients with primary antiphospholipid syndrome (PAPS).Material and methods. The study included 64 patients with PAPS. Data on clinical manifestations, traditional cardiovascular risk factors, and antiphospholipid antibody profile were collected. GAPSS values were calculated for each patient by summing the scores corresponding to risk factors as follows: 3 points – for hyperlipidemia; 1 point – for arterial hypertension; 5 points – for antibodies to cardiolipin (aCL) IgG/IgM; 4 points – for antibodies to â2-glycoprotein 1 (anti-â2GP1) IgG/IgM and 3 points – for antibodies to the phosphatidylserine-prothrombin complex (aPS/PT) IgG/IgM.Results and discussion. GAPSS indicators were comparable in women and men with PAPS – 12.0 [9.0; 13.0] points. GAPSS values did not differ in patients with thrombosis and obstetric pathology: in thrombosis they were 10.0±4.46 (range 0.0–14.0) points, in obstetric pathology – 9.26±5.08 (range 0.0–14.0) points.The localization of thrombosis did not affect the GAPSS values, which reached 9.23±5.21 points in arterial thrombosis, 10.44±4.01 points in venous thrombosis, and 10.33±4.18 points in combined ones. Patients with recurrent thrombosis had higher GAPSS scores compared to patients without relapse: 8.19±5.25 points versus 11.00±3.65 points (p=0.01). There were no significant differences in GAPSS scores in obstetric pathology at different gestational ages.GAPSS values ≥6 showed a higher risk of thrombosis recurrence: odds ratio 5.23 (95% CI 1.34–20.37). GAPSS scores ≥6 demonstrated the highest accuracy, with sensitivity and specificity of 72% and 66%, respectively. According to ROC analysis, the AUC value for GAPSS was 0.675 (95% CI 0.542–0.808; p=0.01).Conclusion. The use of GAPSS makes it possible to identify patients at increased risk of recurrent thrombosis. GAPSS scores ≥6 have high sensitivity (72%) and specificity (66%), which can be used to stratify patients with PAPS into high and low risk groups for recurrent thrombosis.

The role of antiphospholipid antibodies (aPL), which are not included in the classification criteria, in antiphospholipid syndrome (APS) andsystemic lupus erythematosus (SLE) is not well understood.Objective: to determine the frequency of detection of IgG antibodies to domain 1 of β2-glycoprotein 1 (IgG-aβ2GP1-D1), IgA antibodiesto cardiolipin (aCL) and IgA antibodies to β2-glycoprotein 1 (IgA-a β2GP1) in patients with primary APS and APS in combination withSLE.Patients and methods. The study included 63 patients in whom IgG/IgM-aCL and IgG/IgM-aβ2GP1 were detected by enzyme-linkedimmunosorbent assay (ELISA) and IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GP1 and IgG-aβ2GP1-D1 by chemiluminescence analysis (CLA).Results and discussion. The detection rate of IgG-aβ2GP1-D1 was 76%, IgA-aCL – 56%, IgA-aβ2GP1 – 48%. Isolated positivity for IgA-aCL,IgA-aβ2GP1, IgG-aβ2GP1-D1 was not observed. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with high positivity forIgG/IgM-aCL and IgG/IgM-aβ2GP1. There was a statistically significant relationship between IgA-aCL/IgA-aβ2GP1 and the standard aPLprofile, as well as IgG-aβ2GP1-D1, IgG-aCL and IgG-aβ2GP1.Conclusion. A high detection rate of IgG-aβ2GP1-D1, IgA-aCL, IgA-aβ2GP1 was found in patients with APS. A statistically significant relationshipwas found between IgA-aCL/IgA-aβ2GP1 and the standard aPL profile, as well as IgG-aβ2GP1-D1 with IgG-aCL and IgG-aβ2GP1.

Objective. To study clinical significance of proinflammatory cytokines (tumor necrosis factor α – TNFα, interleukine 6 – IL6, IL18), soluble receptors of TNFα (sTNF-R), anti- inflammatory cytokines (IL10) and integral marker of cytokine-dependent cell immune response activation neopterin in antiphospholipid syndrome (APS).Material and methods. Serum concentration of cytokines and neopterin was evaluated by immunoenzyme assay with commercial kits “BioSource International, Inc.” (USA), “Bender MedSystems” (Austria) and “IBL” (Germany) in 39 pts with primary APS (PAPS), 53 pts with secondary APS (SAPS) associated with systemic lupus erythematosus (SLE), 164 pts with SLE and 54 healthy donors.Results. Level of Th1 cytokines (TNFα, IL18), sTNF-R and neopterin in PAPS, SAPS and SLE as well as Th2 cytokines (IL6, IL10) in SAPS and SLE were significantly higher than in donors (p