[Polymorphism of the plasminogen activator inhibitor type 1 gene, plasminogen level and thrombosis in patients with antiphospholipid syndrome].

The frequency of venous and arterial thromboses and plasminogen level were investigated in 78 patients with antiphospholipid syndrome (APS), 35 of whom with systemic lupus erythematosus (SLE+APS) and 43 - with primary APS (PAPS). The levels and genotype of plasminogen activator inhibitor type 1 (PAI-1) were determined in 45 patients with APS, of whom 21 patients with SLE + APS and 24 patients with PAPS. A control group included 10 healthy individuals without autoimmune disease signs and thromboses on period of investigation and in past history. It was shown for the first time that for one third of 67 patients with APS and thromboses high positive levels of antiphospholipid antibodies (aPL) are associated with low plasminogen levels. The levels of PAI-1 antigen measured by ELIZA method, which detects active, latent and bound with plasminogen activator PAI-1, were opposed with frequency of thromboses in APS patients. Correlation between the high and increased levels of PAI-1 and high positive aPL levels was found for one third of 43 patients with APS and thrombosis. One of the possible mechanisms of this interconnection was considered. It was shown that arterial and, to a more extent, venous thromboses are associated with the 4G/5G polymorphism of PAI-1 gene and high plasma level of the inhibitor in 79% of APS patients. At the presence of the 4G allele patients with SLE+APS had higher PAI-1 levels than patients with PAPS. The obtained results show that measuring the levels of plasminogen and PAI-1 as well as the 4G/5G polymorphism of PAI-1 gene which is associated with thromboses may have the practical significance for identification of high risk of thrombosis in APS patients.

[Plasminogen activator inhibitor type 1 gene polymorphism and thromboses in patients with antiphospholipid syndrome].

AIM: To estimate the prevalence of plasminogen activator inhibitor type 1 (PAI-1) gene polymorphism in patients with antiphospholipid syndrome (APS) and its implication in vascular disorders. SUBJECTS AND METHODS: The investigation enrolled 138 patients: 103 with APS, including 47 with systemic lupus erythematosus (SLE) + APS and 56 with primary APS (PAPS), 15 with SLE without APS, 20 with idiopathic thrombosis (IT), a control group (30 apparently healthy individuals). Thrombosis at various sites was recorded in 91 (88%) of the 103 patients with APS. The authors analyzed both the presence of thrombotic events in all the groups and the number of cases of thrombosis in each patient. Antiphospholipid antibodies, such as lupus anticoagulant, anticardiolipin antibodies, and anti-beta2-glycoprotein type 1 antibodies, were studied in all the patients. To diagnose a genotype in patients by the code encoding for PAI-1, DNA isolated from peripheral blood by standard methods was used and further investigated by real-time polymerase chain reaction. RESULTS: Out of 91 patients with APS and thrombosis, 27 (30%) had the 4G/4G genotype, which corresponded to homozygous mutation in the PAI-1 gene, 50 (55%) had the 4G/5G genotype (heterozygous mutation), and 14 (15%) had the 5G/5G (a normal genotype). The PAI-1 4G/5G genotype was present in 22 (70%) of 31 patients with SLE + APS and lower limb deep vein thrombosis versus 17 (470%) of 36 patients with PAPS (odds ratio (OR) 2.73; 95% confidence interval (CI), 0.89 to 8.59; p = 0.08) and in 9 (90%) of 10 patients with SLE + APS and pulmonary artery thromboembolism versus 8 (40%) of 20 patients with PAPS (OR 13,5; 95% CI, 1.23 to 344.98; p = 0.02). The incidence of thrombosis per 100 person-years was higher in the PAI-1 4G/4G and 4G/5G groups: 35.4 and 28.1 cases per 100 person-years, respectively. Thromboses were least often in the group of patients with the PAI-1 5G/5G genotype (18.6). CONCLUSION: The prevalence of the PAI-1 5G/5G genotype in patients with APS and thrombosis was significantly lower than in those with SLE without APS or thrombosis. The 4G/5G polymorphism in APS in the presence of SLE was associated with venous thromboembolisms whereas in PAPS there was no relationship between the PAI-1 genotype, a history of thrombosis, and its localization.

[Recurrent thromboses and hemorrhagic complications in patients with antiphospholipid syndrome during therapy with warfarin plus aspirin].

AIM: To estimate the frequency of relapses of thrombotic and hemorrhagic complications during moderately intensive therapy for antiphospholipid syndrome (APS) with warfarin with and without aspirin. SUBJECTS AND METHODS: Eighty-two patients diagnosed as having the antiphospholipid syndrome were examined. Group 1 patients (n = 49) received warfarin alone as an antithrombotic drug; Group 2 patients (n = 33) had a combination therapy with warfarin plus aspirin. The efficiency of therapy was evaluated from the number and rate of recurrences of thromboses and transient ischemic attacks (TIA) and its safety was assessed from the frequency and number of hemorrhages during the study. The genetic variants of cytochrome P450 CYP2C9 were determined in 52 of the 82 patients; mutations in the gene for vitamin K epoxide reductase complex 1 (VCORC1) were revealed in 22 patients. RESULTS: During the follow-up, antithrombotic therapy was ineffective in 18.4 and 36.6% of the Groups 1 and 2 patients, respectively (p = 0.07). The rate of poor outcomes (thromboses and TIA) was 7 and 14.8 cases per 100 person-years, respectively. The first six months of warfarin therapy proved to be most risky for thrombotic events to occur--this period was responsible for 37% of bleedings. Hemorrhagic complications of antithrombotic therapy developed in 46.9 and 60.6% of Groups 1 and 2 patients, respectively (p = 0.26). Major hemorrhages were observed more frequently in the combination (warfarin plus low-dose aspirin) therapy group than in the warfarin monotherapy group. Mutant cytochrome P450 gene variants (CYP2C9*2 and CYP2C9*3) were present in 38.5% of the patients; VCORC1 gene mutations were observed in 27.3%. The number of nasal and gingival hemorrhages was increased in patients with CYP2C9*3 and homozygous VCORC1 gene mutations. CONCLUSION: Moderately intensive warfarin therapy (international normalized ratio 2.0-3.0) could generally reduce the frequency of recurrent thrombotic events by at least 2-fold as compared with that before warfarin administration. The efficiency of using warfarin alone or in combination with aspirin in APS was found to be similar; and its safety was higher during monotherapy therefore it is undesirable to combine warfarin with antiaggregants in real clinical practice. The determination of CYP2C9 and VCORC1 genotypes in patients with APS before warfarin use allows excessive hypocoagulation and related hemorrhages to be avoided.

[Clinical and laboratory criteria for diagnosis in antiphospholipid syndrome: what is it important for a practitioner to know (a lecture)].

The antiphospholipid syndrome (APS) is antibody-induced thrombosis, whose diagnostic basis is the obligatory presence of serological markers along with clinical manifestations. Its laboratory markers are antiphospholipid antibodies (aPAs), the highest informative value has been proven for lupus anticoagulant (LA), cardiolipin antibodies, fl-glycoprotein 1. LA should be determined at a laboratory in accordance with the recommendations of the International Society on Thrombosis and Hemostasis. Obstetric abnormality in APS should be regarded as a thrombotic complication and its management in this case does not differ from that and prevention of thrombosis, aPAs may be detectable in various illnesses, but their blood presence is not an indication for immunosuppressive therapy. The paper describes a case of primary APS in a female patient.

[Cardiovascular aspects of antiphospholipid syndrome].

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia diagnosed based on the presence of a single clinical sign (thrombosis or and obstetric problem) and one serological criterion (anticardiolipin antibodies and/or lupoid anticoagulant and/or antibodies against b2-glycoprotein-1. Clinical feature of the syndrome are diverse and depend on localization and diameter of the affected Bessel. This review focuses on cardiovascular aspects of APS. Cradiovascular system disorders are arbitrarily divided into valvular pathology, coronary and myocardial lesions. The relationship between antiphospholoipid antibodies and atherosclerosis is discussed.

[Subclinical and clinical manifestations of atherosclerosis in antiphospholipid syndrome].

AIM: To evaluate intima-media complex (IMC) thickness in patients with antiphospholipid syndrome in terms of clinical-laboratory manifestations and thrombosis risk factors. MATERIAL AND METHODS: The trial included 206 patients (57 males and 149 females, age 16-59, mean age 35.9 years). Of them, 58 (28%) patients had primary antiphospholipid syndrome (PAPS) alone, 148 had documented concomitant systemic lupus erythematosus (SLE). Seventy two (48.6%) SLE patients had antiphospholipid syndrome (APS), 29 (19.6%)--anticardiolipin antibodies (aCL) level above 40 IU in two and more measurements without clinical symptoms of APS. In addition to standard tests, APL (lupus anticoagulant), aCL and antibodies to beta-2 glycoprotein, blood lipids were measured. Thrombosis and atherothrombosis risk factors were evaluated. Ultrasound dopplerography estimated thickness of IMC in the carotid and femoral arteries. The control group consisted of 89 donors free of autoimmune diseases. RESULTS: Mean values of IMC thickness did not differ between the groups. Atherosclerotic plaques (ASP) were detected in 25 (12%) of 206 patients: in 5 (9%) from PAPS group, 10 (14%) from SLE+APS, in 4 (14%) and 6 (13%) from SLE groups aPL+ and aPL-, respectively. Mean age of patients with ASP was 46 +/- 6.9 years (32-55 years). ASP occurrence was associated with older age: ASP were detected in 10 (38%) of 26 patients aged over 51 years (24 plaques), in 10 (20%) of 50 patients aged 41-50 years (18 plaques) and in 5 (10%) of 50 patients aged 41-50 years (18 plaques) and in 5 (10%) of 50 patients aged 31-40 years (9 plaques, p = 0.001). IMC thickness and plaques were associated with prior arterial and venous thromboses and occurred significantly more frequently in patients with myocardial infarction and transient ischemic attacks (p < 0.001). Thrombosis and atherothrombosis risk factors were associated with changed IMC thickness. The level of aPL and their type had no effect on IMC thickness and ASP incidence in the groups studied. CONCLUSION: Increased IMC thickness was associated with age irrespective of APS presence. In SLE, ASP appeared at younger age than in PAPS patients. Atherothrombosis risk factors affect IMC thickness irrespective of the level and type of aPL.

[Warfarin in the treatment of antiphospholipid syndrome].

AIM: To assess efficacy and safety of warfarin therapy and its combination with low-dose acetylsalicylic acid (ASA) in antiphospholipid syndrome (APS). MATERIAL AND METHODS: The trial enrolled 60 APS patients. They were divided into two groups: group 1 (n = 39) on antithrombotic therapy with warfarin; group 2 (n = 21) on combined therapy with warfarin and ASA. Efficacy of the treatments was assessed by the number and frequency of thrombosis recurrences and transient ischemic attacks (TIA) while safety was evaluated by frequency and number of hemorrhages during the study. Genetic variants of cytochrome P450 (CYP2C9*1, CYP2C9*2 and CYP2C9*3) were studied in 30 patients (25 females, 5 males) with APS. CYP2C9 gene genetic variants were determined by polymerase chain reaction and restrictase analysis. RESULTS: The thrombosis rate was 19.6 per 100 man-day, TIA rate was not less than 8 per 100 man-day, total rate of thrombotic complications (thromboses and TIA) before warfarin individual dose adjustment--27.6 per 100 man-day. Doses of anticoagulant were adjusted and the patients on treatment were followed up for 15.7 months, on the average. For this period thrombosis occurred in 6 cases (7.6 per 100 man-day), TIA also in 6 cases (7.6 per 100 man-day). This corresponded to thrombotic complications rate 15.1 per 100 man-year. Hemorrhages (major and minor) occurred in 19 (48.7%) patients of group 1 and in 13 (61.9%) patients of group 2 (p = 0.33). Total rate of CYP2C9*2 and CYP2C9*3 carriage was 36.7%. The CYP2C9*2 variant was detected in 7 (23.3%) patients, who were all heterozygous carriers. The CYP2C9*3 variant was seen in 4 (13.3%) patients: 3 heterozygous and 1 homozygous. Females of reproductive age with mutations had more frequent menorrhagies than carriers of a wild-type variant. Patients with CYP2C9*3 had also more frequent nasal hemorrhages and gingival bleeding (p = 0.005) compared to carriers of CYP2C9*1 and CYP2C9*2. Episodes of MHO rise > 5.0 in warfarin therapy were observed in 50% carriers of CYP2C9*3 and in none homozygous carriers of CYP2C9*1 (p = 0.024). CYP2C9*3 patients needed lower maintenance doses of warfarin, in CYP2C9*1 and CYP2C9*2 patients anticoagulant doses were comparable. CONCLUSION; Efficacy of warfarin for secondary prophylaxis of thrombosis was found similar to that of warfarin use in combination with low-dose ASA (MHO 2.0-3.0). Safety of monotherapy was higher. Determination of CYP2C9 genotype in APS patients before treatment with oral anticoagulants may help in planning individual policy and in reducing the risk of warfarin overdosage at the start of therapy.

[The role of hyperhomocysteinemia in systemic lupus erythematosus and antiphospholipid syndrome].

AIM: To assess the role of hyperhomocysteinemia (HHC) in development of vascular complications in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A total of 125 participants (24 males and 101 females aged 38 +/- 13 years) were divided into three groups: group 1--SLE patients (n=51); group 2--SLE+APS patients (n=49); group 3--primary APS patients (n=25). The patients had the disease for 14 +/- 11 years. Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) marked APS serologically. Homocystein (HC) was assayed by high performance liquid chromatography. HHC (HC > 15 mcg/l) was diagnosed in 82 of 125 (66%) patients: in 59% patients of group 1, 67%--of group 2 and 76%--of group 3. There was a relationship between HHC and digital necrosis (DN): 80% of DN patients had HHC while HHC was diagnosed in 57% patients free of DN (chi-square = 4.76, p = 0.03). Development of occlusions in APS was associated with HHC. Elevated levels of HC in blood was registered in 43 of 55 (78%) APS patients with thromboses vs. 9 of 19 (47%) patients with APS free of thromboses (p = 0.03). HHC occurred significantly more frequently in patients with arterial thromboses (in all 14 patients) than in patients with venous thromboses (in 16 of 23--69.6%, p = 0.03) and in the absence of thromboses (in 9 of 19, 47.4%, p = 0.04). HHC was associated with thromboses of cerebral, peripheral arteries (90 vs. 47% in patients without thrombosis, p = 0.005; 84 vs. 47%, p = 0.04, respectively), coronary vessels (79 vs. 47%, p = 0.04). In APS patients having arterial thromboses with duration of postthrombocytic period (PTP), estimated as time from thrombosis to entering the trial, less than 2 months, HC concentration was significantly higher (22.9 +/- 7.0 mcg/l) compared to patients with PTP more than 2 years (16.6 +/- 3.7 mcg/l (p = 0.04). CONCLUSION: More than 50% patients with SLE and APS, irrespective of APS variants, had an elevated HC level in the blood. Correlation between HHC and development of thromboses, primarily arterial, in APS gives grounds for the role of HHC in development of vascular complications in SLE and APS.

[Soluble CD40 ligand in systemic lupus erythematosus and antiphospholipid syndrome].

AIM: To investigate a clinical role of soluble (s) CD40 ligand in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A serum concentration of sCD40 ligand was measured with enzyme immunoassay (Bender Medsystems, Austria) in 21 patients with primary antiphospholipid syndrome (PAPS), in 25 patients with secondary APS (SAPS) associated with SLE, in 92 SLE patients and in 16 healthy donors. RESULTS: A sCD40 ligand concentration in sera of SAPS and SLE patients was significantly higher than in donors. Significant differences by the ligand level between the above patients were not seen. In PAPS sCD40 ligand concentration was normal. Elevated serum concentration of the ligand was observed in 9.5% patients with PAPS, 54.0%--with SAPS, 73.9%--with SLE. This rise in SLE and SAPS was not related with the disease activity or renal damage. Hyperexpression of the ligand in APS was associated neither with thromboses nor with a high concentration of IgG/IgM antibodies to cardiolipin. A direct correlation occurred between sCD40 ligand level and platelet count. In SLE and SAPS elevation of the ligand level correlated with increased thickness of carotid artery intima-media complex, hypercholesterinemia and diastolic dysfunction of left ventricular myocardium. CONCLUSION: Hyperexpression of sCD40L in SLE and SAPS is associated with developing cardiovascular diseases and atherosclerosis.

[Retinal vascular lesions in systemic lupus erythematosus and secondary antiphospholipid syndrome].

The study was undertaken to determine a possible association of retinal vascular lesion in systemic lupus erythematosus (SLE) with the antiphospholipid syndrome (APS). A hundred and ninety-four patients (160 females and 34 males, whose mean age was 30.7+/-8.9 years) with verified SLE were examined. Group I comprised 67 patients with retinal vascular lesions (Subgroup la (n = 13) with retinal vascular occlusions and Subgroup 1b (n = 54) without occlusions). Group 2 included 127 patients without retinal vascular lesions. APS was detected in 86 patients. Retinal vascular occlusions more frequently occurred in patients with APS (13.9%) than in those without APS (0.9%) (p = 0.0009) and more frequently in patients with APS and thrombocytopenia (24.3%) than in those with APS without thrombocytopenia (6.1%) (p = 0.0359). Extraocular thromboses were more frequently encountered in Subgroup 1a (69.2%) than in Subgroup 1b (33.3%) (p = 0.0399) and in Group 2 (22.8%), (p = 0.0010). Cerebral circulatory disorder (CCD) was observed in 30.7% in Subgroup la, in 14.8% in Subgroup 1b, and in 7.9% in Group 2 (p = 0.0268). Transient ischemic attack (TIA) occurred in 46.2% in Subgroup la, in 24.1% in Subgroup 2a, and in 14.9% in Group 2 (p = 0.0129). Thrombocytopenia was identified in 69.2% in Subgroup 1a, in 22.2% in Subgroup 2a (p = 0.0021), and in 12.6% in Group 2 (p < 0.0000). The frequency of elevated IgG of anticadiolipin (aCL) in Subgroup 1a (80%) exceeded that in Subgroup 1b (37.9%) (p = 0.0309) and Group 2 (30.7%) (p = 0.0096). Another isotype of aCL (IgM 80%) was observed in patients with retinal vascular occlusions, but the differences in this index were insignificant in the groups and subgroups. The association of pathological changes in retinal vessels in the presence of lupus anticoagulant (LA) was particularly noticeable (91.7 and 52% in Subgroup la and Subgroup 1b, respectively (p = 0.0191) and 47.1% in Group 2 (p = 0.0088). There was an association of amaurosis fugax with eyeground occlusions (p < 0.004), CCD and TIA (p < 0.0002), APS (p < 0.0003), and essential hypertension (p < 0.05). Thus, occlusive lesions in the fundus of the eye are a common manifestation of thrombogenesis in SLE in the presence of APS. The frequency of concomitance of retinal vascular occlusions with cerebral circulatory disorders should be referred to as severe manifestations of SLE. Amaurosis fugas is a manifestation of retinal vascular lesion and associated with the presence of APS and elevated blood pressure in patients with SLE. There is an association of an occlusive process in the fundus of the eye with different symptoms of APS and primarily with IgG of aCL, LA, and thrombocytopenia.

[Sneddon's syndrome and systemic lupus erythematosus with cerebrovascular disturbances and widespread livedo].

A comparative clinical and instrumental analysis of 97 patients with Sneddon's syndrome (SS), a combination of cerebrovascular ischemic disturbances with widespread livedo, and 12 patients with systemic lupus erythematosus (SLE) with the same combination, has been conducted. Despite the presence of similar features related to antiphospholipid syndrome (APS)--cerebrovascular disturbances, livedo, fetal loss, peripheral venous thrombosis, thrombocytopenia, antibodies to phospholipids, etc--there were distinct differences between SS and SLE. In SS, no skin lesions ("butterfly", discoid lupus, photosensibilization) typical for SLE as well as sores of mucous oral cavity, polyarthritis, serosity, diagnostically significant titers of antinuclear factor and antibodies to DNA were observed. SS emerged with livedo (44%), cerebrovascular disturbances (24%) and systemic APS appearances (32%). SLE in 75% cases began with its classical symptoms and in 25% with systemic APS signs and never with livedo or cerebrovascular disturbances. For 10.5 +/- 8.0 years, no cases of SS were featured by typical SLE symptoms. Pathomorphological study indicated that SS and SLE were independent diseases. Their similarity was due to development of secondary APS, including cerebrovascular disturbances and livedo, in some patients with SLE.

[Catastrophic antiphospholipid syndrome: diagnosis and treatment].

AIM: To analyse data on patients who developed catastrophic antiphospholipid syndrome (CAPS) in primary and secondary APS, to assess outcomes of CAPS. MATERIAL AND METHODS: We analysed retrospectively the data on 164 patients with systemic lupus erythematosus (SLE) and APS, on 76 patients with primary APS (PAPS) treated in the Institute of Rheumatology from 1989. Verification of vascular complications was made using ultrasonic dopplerography (UDG) of peripheral vessels, echocardiography of the heart, CT of the brain, abdominal organs. Anticardiolipin antibodies (ACLab) and lupus anticoagulant (LA) served as serological markers of APS. RESULTS: In the observation period of 9.4 +/- 4.2 years, 33 patients (23 females and 10 males) out of 164 patients with SLE+APS developed CAPS, 8 of them survived while 25 died. CAPS patients had no differences by age, duration of the disease, its activity and symptoms from patients who had no CAPS. Ten out of 76 patients with PAPS developed CAPS, 7 of them died. The analysis of the concomitant factors which may initiate PAPS showed that in SLE and APS these factors consisted of initial menopause (n = 2), infection (n = 12), including pneumonia (n = 7), acute respiratory disease (n = 3), food poisoning (n = 1), abscess (n = 1). Cancer was in one patient, trauma after road accident in one patient. Trigger factor was not determined in 13 patients. In PAPS provoking factors were pneumonia (n = 2) and abscess (n = 1), in 7 patients these factors were not detected. CONCLUSION: Any infection in SLE patients should be adequately treated with antibiotics; APS patients treated surgically should receive parenteral anticoagulants instead of oral ones; puerperas with APS must receive adequate parenteral anticoagulant therapy for at least 6 weeks; in exacerbation of SLE, APS patients should receive parenteral anticoagulants with following hypocoagulation with oral anticoagulants.

[Osteonecroses in systemic lupus erythematosus and antiphospholipid syndrome]. / Osteonekrozy pri sistemnoi krasnoi volchanke i antifosfolipidnom sindrome.

The purpose of the study was to analyze the incidence of osteonecroses (ON) in systemic lupus erythematosus (SLE) patients with and without antiphospholipid syndrome (APS), primary APS (PAPS) and to define a relationship of the development of ON to some risk factors for vascular diseases. The study included 369 patients, including 293 with SLE, 160 with secondary APS, 76 with PAPS. The patients aged 14 to 63 years (mean 31.9+/-10.9 years). The history of disease was 0.6 to 30 years (mean 9.1+/-7.5 years). Among them 32 (8.7%) patients with aseptic necroses of different bones were selected in accordance with the data of X-ray studies. ON was detected in 8.7 patients with SLE and APS. The X-ray signs corresponded to third-to-sixth-degree ON. The most common site of ON was the head of the femur, although another site of ON was observed and multiple ON was typical. Leukopenia, creatininemia, fibrinogen levels were associated with ON (p < 0.05 by the Mann-Whitney test). The activity of SLE was significantly associated with SLEDAI scale scores (p < 0.05 by the Wald-Wolfovitz test). Six patients with SLE and ON had high scores by this scale--more than 40 scores of the maximum 150 possible scores. APS was diagnosed in 87.5 of the patients with ON (28 of the 32 patients) and only in 61.7% of the patients without ON (in 208 of the 337 patients) (chi2 = 8.4; p = 0.004). The development of ON in the examinees was significantly associated with the presence of APS. The activity of SLE, particularly nephritis, arthritis, positive tests for phospholipid antibodies, the presence of arterial thromboses, thrombocytopenia at the height of disease, therapy with large doses of glucocorticoids.

[Serum nitrates in patients with systemic lupus erythematosus and antiphospholipid syndrome]. / Uroven' nitratov v syvorotke krovi patsientov s sistemnoi krasnoi volchankoi i antifosfolipidnym sindromom.

AIM: To elucidate clinical implications of nitrates (NO3) concentration as an indicator of nitric oxide (NO) level in blood serum of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS). MATERIAL AND METHODS: Blood serum concentration of NO3 was measured by high-performance liquid chromatography in a total of 41 patients with SLE (n = 17), PAPS (n = 14) and secondary APS (n = 9). Sera from 10 healthy subjects (donors) served as control. NO3 concentration > 40 mcmol/l was stated high. SLE activity was assessed by V. A. Nasonova's scale and SLEDAI index (SLEDAI > 9 indicated SLE exacerbation). Patients with PAPS were divided into two groups depending on clinical symptoms: 7 patients with significant thrombosis or history of more than two thrombotic complications (group 1); 7 patients with the history of two or less thromboses (group 2). RESULTS: The mean serum nitrate concentration in the SLE group was 43.59 mcmol/l (range 17.06-113.22). The nitrate level of the sAPS + SLE group was 49.81 +/- 27.54 and did not significantly differ from APS (33.67 +/- 14.70). By univariate standard analyses, serum nitrate concentration was significantly higher in patients with high disease activity (57.31 +/- 25.12 vs. 25.62 +/- 6.96, Mann-Whitney test, p < 0.01). The Spearman correlation coefficient of nitrate level with SLEDAI was 0.8 (p < 0.001). CONCLUSION: A nitrate level is increased in patients with active SLE and in APS patients with severe thrombotic complication.

[Morphologic features of the gastric mucosa in systemic lupus erythematosus and antiphospholipid syndrome]. / Morfologicheskie osobennosti slizistoi obolochki zheludka pri sistemnoi krasnoi volchanke i antifosfolipidnom sindrome.

Morphology of gastric mucosa is characterized in the presence of Helicobacter pylori (HP) and Herpes viruses (HSV-1 and CMV). A total of 85 patients were examined (20 patients with primary APS and 65 with SLE). Chronic active gastritis was revealed in 85% patients with APS and 96% with SLE. 60% patients with APS and 45% with SLE had mucosal erosions. HP was detected in 70-87% of cases. Mixed infection of the gastric mucosa was observed in all the groups which was significantly associated with increased fibroblast and plasma cell number in the tunica propria. Tissue eosinophilia of the antral part of the stomach was observed in 39% of SLE patients. Glucocorticoid therapy was not associated with erosions and was combined with vascular thrombosis of gastric mucosa.

[Antiphospholipid syndrome and exogenic risk factors in thromboses]. / Antifosfolipidnyi sindrom i ékzogennye faktory riska trombozov.

AIM: To examine relationships between incidence rate of thromboses in antiphospholipid syndrome and exogenic risk factors (RF) of thrombosis. MATERIAL AND METHODS: The trial enrolled 131 patients (105 females and 26 males). They were divided into three groups: 23 patients with systemic lupus erythematosus (SLE, group 1), 63 patients with SLE and antiphospholipid syndrome (APS, group 2), 45 patients with primary APS (PAPS, group 3). Thrombosis RF questionnaire survey was made. Effects of corticosteroids and cyclophosphamide on occurrence of thrombosis were assessed. RESULTS: Such exogenic RF as intake of coffee, fat food, alcohol were not related to thromboses. Hypodynamia was more typical for APS patients (21.3%) than for SLE patients free of APS (8.7%). Overweight for was characteristic for APS patients (49 and 34.7%, respectively). The proportion of smokers was higher in APS patients, though smoking did not provoke thrombotic complications. A direct correlation was found between occlusion and corticosteroids administration, while occlusion and cyclophosphamide treatment correlated inversely. CONCLUSION: Venous thrombosis RF in patients with APS and PAPS are obesity and treatment with glucocorticosteroids.

[Antibodies to beta2-glycoprotein I and antibodies to cardiolipin in antiphospholipid syndrome: analysis of sensitivity and specificity]. / Antitela k beta2-glikoproteinu I i antitela k kardiolipinu pri antifosfolipidnom sindrome: analiz chuvstvitel'nosti i spetsifichnosti.

To study sensitivity and specificity of antibodies to beta 2-glycoprotein I (B2GP-I) and antibodies to cardiolipin (CL) in diagnosis of antiphospholipid syndrome (APS), we examined 19 patients with primary antiphospholid syndrome (PAPS), 23 patients with secondary APS (SAPS) and systemic lupus erythematosus (SLE) and 73 patients with SLE. Antibodies to B2GP-I and CL of IgG isotype were measured at enzyme immunoassay. The levels of IgG aCL and IgG aB2GP-I in the serum of PAPS patients were 69.9 +/- 116.0 GPL, 74.1 +/- 117.4 SGU, respectively; of SAPS and SLE patients 60.5 +/- 68.9 GPL and 66.2 +/- 88.3 SGU, respectively. These values were significantly higher than in SLE patients (19.5 +/- 27.6 GPL, p = 0.0025 and p = 0.0012; 14.5 +/- 41.9 SGU, p = 0.0001, respectively) and donors (3.9 +/- 3.8 GPL, p = 0.0001; 5.7 +/- 1.2 SGU, p = 0.001). By IgG aCL and IgG-aB2GP-I, PAPS and SAPS patients differed insignificantly (p > 0.05), but these values correlated positively (r = 0.85; p < 0.0005 for PAPS and r = 0.9, p < 0.005 for SAPS). Simultaneous detection of IgG aCL and IgG aB2GP-I occurred in 36.8% in PAPS, 52.4% in SAPS and 12.3% in SLE. 10.5% PAPS patients were positive by IgG aCL as well as 9.5% with SAPS and 13.4% with SLE. Isolated rise of IgG aB2GP-I concentration was observed in 21.1% patients with PAPS, in 9.5% patients with SAPS and 9.6% patients with SLE. Of 43 patients with a history of thrombosis, 46.5% were positive by IgG aCL and IgG aB2GP-I, 7.0% positive only by IgG aCL and 11.6% only by IgG aB2GP-I. Levels of IgG aCL and IgG aB2GP-I in patients with thrombosis (64.7 +/- 87.5 GPL and 66.0 +/- 94.8 SGU, respectively) were significantly higher than in patients without them (19.6 +/- 3.8 GPL, p = 0.009 and 16.4 +/- 52.2 SGU, p = 0.0001). In venous thrombosis IgG aCL and IgG aB2GP-I were higher than in arterial thrombosis (p < 0.004). For diagnosis of APS sensitivity and specificity of IgG aB2GP-I and IgG aCL were 60.0 and 83.8%; 57.1 and 73.5% (p > 0.05), respectively. As to thrombosis, the sensitivity and specificity were 58.1 and 84.6%; 54.5 and 72.7% (p > 0.005), respectively. Thus, IgG aB2GP-I is an essential additional marker of APS. In the presence of APS symptoms, but in negative results of APS test it is justified to confirm APS diagnosis by aB2GP-I test results. To make APS diagnosis more accurate, it is valid to make simultaneous measurements of aCL using standard B2GP-I dependent enzyme immunoassay and aB2GP-I.

[Clinico-immunological aspects of antiphospholipid syndrome]. / Kliniko-immunologicheskie aspekty antifosfolipidnogo sindroma.

The article contains a description of the clinical-and-immunological specific features of the secondary (concomitant with systemic lupus erythematosus-SLE) and primary anti-phospholipid syndrome (APS). We followed up a total of 280 patients with SLE and 74 patients with primary APS; 96 of 280 SLE patients were males and 184 of them were females, mean age--31.2 +/- 11.1, mean disease duration--8.6 +/- 7.2 years. The APS group consisted of 15 males and 59 females, mean age--35.6 +/- 7.2, mean disease duration--11.9 +/- 8.5 years. Antibodies to cardiolipin (aCL) and lupous anticoagulant (LA) were determined for all patients. Antibodies to IgM beta 2-GP I (IgM anti-beta-GP I) were determined for 102 patients and antibodies to IgG anti beta 2-GP I were determined for 153 patients. The level of antibodies to beta 2 GP I in blood serum was found by immune-enzyme assay (QUNTA Life). The secondary APS was diagnosed in 115 (41%) patients from among 280 SLE patients. The group of patients with SLE and without APS and the group with primary APS were age-matched, however, patients with APS were older and had a longer disease duration. The diagnosis was made in one half of patients with primary APS in 6 and more years after the disease onset. Thrombotic complications were found in 117 (42%) from among 280 SLE patients. They were encountered reliably more often in APS versus SLE (chi 2 = 131, p < 0.0001). Venous thrombosis in veins of lower extremities prevailed in APS, while thrombophlebitis of the surface shin veins was predominant in patients without APS. An important features of APS is occlusion of veins located in the liver with a subsequent development of Budd-Chiari syndrome (9 patients); in retinal veins (13 patients); thrombophlebitis in axillary veins (7 patients) and in abdominal-cavity veins (2 patients). Loss of pregnancy at various gestational stages was registered in medical histories of 83 (76%) from among 109 pregnant women. The frequency rate of fetus loss was higher in primary APS (32 of 40 cases) versus its secondary variation (49 of 75 cases) with chi 2 = 8.3, p = 0.004. Thrombocytopenia was detected reliably more often in patients with secondary APS (chi 2 = 36, p < 0.0001). The clinical signs of both primary and secondary APS were found to be similar. However, arterial and venous thromboses combined with the relapsing syndrome of fetus loss were more often registered in primary APS. The detection of highly positive aCL titers is of a significant diagnostic value versus the detection of its low- and mean-positive values. The study of anti-beta 2-GP I is also of certain importance for a more reliable diagnosis of APS.

[Survival and prognostic factors of death risk in antiphospholipid syndrome: results of 8-year follow-up]. / Vyzhivaemost' i prognosticheskie faktory riska smerti pri antifosfolipidnom sindrome: rezul'taty 8-letnego nabliudeniia,

AIM: To evaluate survival and mortality in antiphospholipid syndrome (APS) as well as prognostic factors of APS deterioration. MATERIAL AND METHODS: We retrospectively studied 248 case histories of patients admitted to the Institute of Rheumatology for 8 years. Primary APS was diagnosed in 35 patients, SLE + APS (according to criteria of ACR, 1982)--in 122 patients and SLE without APS--in 91 patients. Mean age was 31.2 +/- 15.0 years (range from 14 to 63), median length of follow-up from the time of diagnosis was 11.9 +/- 5.4 years. During 8 year period all the patients annually and the latest 5 years at least twice a year were examined for the presence of IgG and IgM-anticardiolipin antibodies (aCL) and lupus anticoagulant (LA). Thrombotic events were verified with special techniques. RESULTS: Thirty-eight patients (15%) died during the follow-up period. Mean age of the decreased was 35.4 +/- 12.2 years (range 21-52 years) and the disease duration 8.6 +/- 8.2 years (range 0.6-20), the median length of the survival from the time of the diagnosis was 6.2 +/- 4.3 years. The 8-year survival for SLE patients without APS was 98%, for those with SLE + APS-75% and for patients with primary APS-83%. The presence of APS in SLE patients was significantly associated with high mortality (chi 2 = 12.3, freedom = 4, p = 0.006). Cox regression analysis revealed that the activity of the disease at onset, arterial thrombosis, especially recurrent, thrombocytopenia, valvular disease of the heart, capillaritis, digital necrosis and nephritis were independent risk factors for mortality (p < 0.05). CONCLUSION: Thus, long-term follow-up is necessary for patients with antiphospholipid antibodies especially with APS which lowers survival of SLE patients. Such patients need early corrective therapy to prevent thrombotic events.