Prevalence of antiphospholipid antibodies in Chilean patients with rheumatoid arthritis

Antiphospholipid (aPL) antibodies found in patients with autoimmune diseases are also detected in those with inflammatory diseases. The purpose of this study was to examine the prevalence of these antibodies in patients with rheumatoid arthritis (RA), and to evaluate the association of these antibodies with thrombosis and/or other clinical characteristics of this inflammatory disorder. Eighty-four patients with RA and 82 normal controls were studied. Anticardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies and the lupus anticoagulant (LA) activity were determined. Seven out of 84 (8.3%) patients were positive for aCL, six out of 84 (7.2%) for anti-beta(2)GPI, and six out of 84 (7.2%) for aPT, while in controls the overall prevalence of aPL antibodies was 3.6% (3 out of 82). All patients and controls were LA negative. There was no correlation between the presence of aPL with thrombosis and/or other clinical features of the antiphospholipid syndrome. We found aPL antibodies in 19.1% (16 out of 84) of the patients with rheumatoid arthritis and this prevalence was statistically higher than in normal controls (P<0.003). In this study, the presence of aPL antibodies was not associated with the development of thrombosis and/or thrombocytopenia. Whether the presence of aPL antibodies implies an increased risk for thrombosis and atherosclerosis in these patients should be studied further.     

A prospective study of antibodies to β2-glycoprotein I and prothrombin, and risk of thrombosis

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by thrombosis/pregnancy morbidity associated with the persistence of lupus anticoagulant (LA) and/or anticardiolipin (aCL) antibodies. We assessed the contribution of antibodies to beta2-glycoprotein I (anti-beta2GPI) and prothrombin (anti-PT) to the thrombotic risk in a cohort of 194 consecutive patients with persistent LA and/or aCL. Median follow-up was 45 months. A total of 39 patients (20.1%) had one documented episode of thrombosis during follow-up. Eleven of these patients had no previous thrombosis before enrollment in the study and 28 had recurrences of thrombosis. There were 21 venous and 18 arterial thrombotic events and the overall incidence of thrombosis was 5.6% per patient-year. After multivariate analysis, the male sex (P = 0.025), a previous thrombosis (P < 0.01), the presence of anti-beta2GPI (P = 0.001), and the presence of anti-PT (P = 0.03) remained as independent risk factors for recurrent thrombosis. Only IgG anti-beta2GPI and anti-PT were associated with an increased risk of thrombosis (P < 0.01 and P = 0.005). Patients testing positive for anti-beta2GPI had a higher rate of thrombosis than did antiphospholipid patients without anti-beta2GPI (8.0% vs. 3.1% per patient-year). Similarly, a higher rate of thrombosis was found in patients with positive anti-PT compared with patients without anti-PT (8.6% vs. 3.5% per patient-year). Considering only the group of 142 LA positive patients, the highest incidence of thrombosis was found in LA patients positive for both anti-beta2GPI and anti-PT (8.4% per patient-year). In conclusion, the presence of IgG anti-beta2GPI and anti-PT in patients with LA and/or aCL and mainly in those with LA predicts a higher risk of thromboembolic events.     

The anticardiolipin assay is required for sensitive screening for antiphospholipid antibodies.

The importance of testing for anticardiolipin antibodies (aCL) in the diagnosis of antiphospholipid syndrome (APS) in patients with thrombosis has recently been challenged (ISTH SSC meeting, Boston 2002). We have analyzed the antiphospholipid serology of 123 patients with persistent antiphospholipid antibodies (aPL) attending our hematology department. The cohort was tested for anti-beta(2)-glycoprotein I (beta(2)-GPI) antibodies and aCL of IgG and IgM class and for lupus anticoagulant (LA). Ninety-six of these patients fulfilled Sapporo clinical criteria for APS and 70 of these patients had venous and/or arterial thrombosis. Patients with LA plus anti-beta(2)-GPI antibodies had significantly higher levels of IgG aCL and anti-beta(2)-GPI antibodies than those exhibiting positivity for only LA or anti-beta(2)-GPI antibodies (P < 0.05). Patients with aCL IgG levels over 60 GPLU were found in all cases to be positive for LA and anti-beta(2)-GPI antibodies; 25.2% (31/123) of all patients and 26.04% (25/96) of patients fulfilling Sapporo clinical criteria for APS were positive for aCL only. The mean IgG aCL level in the Sapporo clinical criteria positive patients who had aCL only was 11.5 GPLU (normal < 5 GPLU). These data indicate that omission of aCL testing from the clinical investigation of APS could lead to a failure to diagnose the syndrome in a proportion of patients.     

Estimation of antiphospholipid antibodies in a prospective longitudinal study of children with migraine

The aim of this study was to determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in children with migraine. The values of anticardiolipin (aCL) and antibeta2 glycoprotein I (antibeta2GPI) antibodies were assayed by an ELISA method in 52 children with migraine and 22 children with tension-type headache. The control group consisted of 61 apparently healthy children at regular preventive visits. Two monoclonal beta2GPI dependent aCL (HCAL and EY2C9) were used as calibrators. Lupus anticoagulant (LA) was determined by a modified dilute Russell viper venom time test. Persistently positive aPL were observed during the follow-up in 16.3% of children with migraine (9.3% for aCL, 7.0% for antibeta2GPI and 0% for LA) and in 16.7% of children with tension-type headache (11.1% for aCL, 5.6% for antibeta2GPI and 0% for LA). The prevalence of aPL did not differ significantly between patient groups and healthy children. The prevalence of aPL does not appear to be increased in an unselected group of children with migraine, however, the possible role of aPL in individual cases of paediatric migraine can not be excluded.     

The presence of IgG antibodies against β2-glycoprotein I predicts the risk of thrombosis in patients with the lupus anticoagulant

BACKGROUND: Lupus anticoagulant (LA) is a strong risk factor of thrombosis. However, a subgroup of patients positive for LA is unaffected by thrombosis and currently no predictive markers are available to identify patients positive for LA at increased risk for thrombosis. OBJECTIVE: The aim of the study was to investigate whether anti-beta-2-glycoprotein I (anti-beta2GPI) or anticardiolipin antibodies (ACA) are associated with an increased risk of thrombosis in patients persistently positive for LA. PATIENTS AND METHODS: A cohort of 87 consecutive patients persistently positive for LA was investigated, 55 with and 32 without a history of thrombosis. Immunoglobulin G (IgG) and M (IgM) antibodies against beta2GPI and cardiolipin were determined by enzyme-linked immunoassay. RESULTS: Patients positive for LA with thrombosis had significantly higher levels of anti-beta2GPI IgG (median 16.7 standard units, interquartile range 3.0-75.2, P = 0.002) and of ACA IgG (41.1 IgG phospholipid units per mL, 8.9-109.0, P = 0.002) than those without thrombosis (2.6, 1.4-7.9 and 9.7, 4.6-22.1, respectively). Levels of anti-beta2GPI IgM and ACA IgM did not differ significantly between LA patients with and without thrombosis (P = 0.25 and 0.12, respectively). Elevated anti-beta2GPI IgG was associated with an increased risk for thrombosis (OR = 4.0, 95% CI 1.2-13.1), especially for venous thromboembolism (OR = 5.2, 95% CI 1.5-18.0). CONCLUSIONS: Increased levels of anti-beta2GPI IgG were associated with thrombosis. We conclude that anti-beta2GPI IgG levels above normal predict an increased risk of thrombosis in patients persistently positive for LA.     

Revised classification criteria for antiphospholipid syndrome and the thrombotic risk in patients with autoimmune diseases

BACKGROUND: The classification criteria for antiphospholipid syndrome (APS) were updated in 2006. Objective: The aim of the study was to analyze associations between clinical complications and laboratory test abnormalities typical for APS in a group of patients with autoimmune diseases, based on the recently updated criteria. PATIENTS/METHODS: Three hundred and thirty-six patients were enrolled into the study, with the majority (n = 235) suffering from systemic lupus erythematosus. Laboratory determinations included: lupus anticoagulant (LA), anticardiolipin (aCL) and anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies (ABs) [of both immunoglobulin G (IgG) and IgM class]. RESULTS: A significant association was found between laboratory and clinical features of APS; odds ratios (ORs) for thrombosis associated with the presence of LA, aCL, and anti-beta(2)GPI Abs were 4.04 [95% CI: 2.44-6.68], 3.71 (95% CI 2.32-5.92) and 2.57 (95% CI 1.60-4.1), respectively. Detailed analysis showed marked differences between the risk of clinical complications associated with the presence of an antibody in the IgG class (OR 4.15, 95% CI 2.42-7.12, and OR 4.77, 95% CI 2.37-9.61 for aCL and anti-beta(2)GPI, respectively) and in the IgM class (OR 2.2, 95% CI 1.31-3.70, and OR 1.9, 95% CI 1.15-3.14 for aCL and anti-beta(2)GPI, respectively). The postulated inclusion of anti-beta(2)GPI antibody positivity into the previous laboratory criteria changed only slightly the number of patients diagnosed with APS (from 112 to 117). CONCLUSIONS: The updated APS classification criteria clearly represent a step forward. However, our results argue against the use of overall positivity for aCL or anti-beta(2)GPI, and favor a clear distinction between the IgG and IgM classes of antiphospholipid ABs. Patients with both LA and anti-beta(2)GPI IgG or LA and aCL IgG positivity may represent the subgroups at the highest risk of thrombotic complications.     

Antiphospholipid, anti-beta 2-glycoprotein-I and anti-oxidized-low-density-lipoprotein antibodies in antiphospholipid syndrome

Antiphospholipid antibodies (aPL), anti-beta 2-glycoprotein I (anti-beta 2-GPI) and anti-oxidized-low-density lipoprotein (LDL) antibodies are all implicated in the pathogenesis of antiphospholipid syndrome. To investigate whether different autoantibodies or combinations thereof produced distinct effects related to their antigenic specificities, we examined the frequencies of antiphospholipid syndrome (APS)-related features in the presence of different antibodies [aPL, beta 2-GPI, anti-oxidized low density lipoprotein (LDL)] in 125 patients with APS. Median follow-up was 72 months: 58 patients were diagnosed as primary APS and 67 as APS plus systemic lupus erythematosus (SLE). Anticardiolipin antibodies (aCL), anti-beta 2-GPI and anti-oxidized LDL antibodies were determined by ELISA; lupus anticoagulant (LA) by standard coagulometric methods. Univariate analysis showed that patients positive for anti-beta 2-GPI had a higher risk of recurrent thrombotic events (OR = 3.64, 95% CI, p = 0.01) and pregnancy loss (OR = 2.99, 95% CI, p = 0.004). Patients positive for anti-oxidized LDL antibodies had a 2.24-fold increase in the risk of arterial thrombosis (2.24, 95% CI, p = 0.03) and lower risk of thrombocytopenia (OR = 0.41 95% CI, p = 0.04). Patients positive for aCL antibodies had a higher risk of pregnancy loss (OR = 4.62 95% CI, p = 0.001). When these data were tested by multivariate logistic regression, the association between anti-beta 2-GPI and pregnancy loss and the negative association between anti-oxidized LDL antibodies and thrombocytopenia disappeared.     

Anti-beta 2 glycoprotein I antibodies and the risk of myocardial infarction in young premenopausal women

BACKGROUND: Contrasting data have been reported on the association between the presence of anti-phospholipid antibodies (aPL) and arterial thrombotic events, particularly those in coronary arteries. This discrepancy is perhaps related to the confounding effect of traditional risk factors. Among them, coronary atherosclerosis appears to be the most important in studies conducted in middle-aged and elderly patients. OBJECTIVE: To minimize such confounding effects, a multicenter case-control study on the association between aPL and myocardial infarction (MI) was carried out in a rare cohort of young premenopausal women. METHODS: We evaluated 172 cases hospitalized for a first MI before the age of 45 years and 172 controls individually matched with cases for age, sex and geographical origin. Clinical and laboratory data were collected and levels of anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) and anti-nuclear antibodies (ANA) were measured. RESULTS: A significant association between MI and IgG/IgM anti-beta2GPI antibodies was observed; the results were confirmed after adjusting for smoking and hypertension (anti-beta2GPI IgG OR = 2.47, 95% CI 1.81-3.38; anti-beta2GPI IgM 4th quartile OR 3.68, 95% CI 1.69-8.02). The association between anti-beta2GPI antibodies and MI was detected in both subgroups with and without coronary artery stenosis. Whereas the association of aCL IgG with MI was modest, ANA showed no significant association with MI. No aPL were found in unselected patients (mainly males) who recently developed acute MI. CONCLUSIONS: Anti-beta2GPI antibodies are a significant risk factor for MI in young premenopausal women independently of other risk factors, including the degree of coronary artery stenosis.     

Antiphosphatidylserine antibodies in patients with autoimmune diseases and HIV-infected patients: effects of Tween 20 and relationship with antibodies to beta2-glycoprotein I

Antiphospholipid antibodies (aPL) react with negatively charged phospholipids, which may often be complexed with a protein cofactor such as beta2 glycoprotein (beta2GPI) and prothrombin. Cofactor requirements may be assessed by measuring antibodies to beta2GPI or by adding Tween 20 to some reagents in the assays for aPL (anticardiolipin and antiphosphatidyIserine). We have measured anticardiolipin antibodies (aCL), antiphosphatidylserine antibodies (aPS), and anti beta2 glycoprotein antibodies (abeta2GPI) in the serum of 10 normal subjects, 20 patients with systemic autoimmune diseases (SAD) diagnosed as having systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS), and 12 patients with HIV infection. Adding Tween 20 to aPS, the assay couldn't differentiate protein cofactor dependent from independent antibodies, but this can be done by measuring abeta2GPI (P= 0.0008). There was a significant correlation between aCL and a(beta)2GPI in the control group and in the patients with SAD, but not in the HIV-positive (HIV+) patients.After excluding the HIV+ patients, the best Spearman correlation was obtained between a(beta)2GPI and aCL (0.64, P< 0.0005). In 3 out of 7 patients with positive a(beta)2GPI and in 5 out of 6 patients with moderate or high positive aCL of the group of SAD, there was a history of venous thrombosis. The presence of moderate or high values of aCL either alone or together with a(beta)2GPI was significantly associated with a history of venous thrombosis (P < 0.05). Moderate or high aCL concentrations and their association with a(beta)2GPI seems to be useful for the assessment of the risk of venous thrombosis in unselected patients with SLE or APS.     

Antibodies to beta2-glycoprotein-I: relation of anticardiolipin antibodies with clinical and laboratory parameters in patients with systemic lupus erythematosus

OBJECTIVES: There are controversial reports on the frequency of antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). Thus, we aimed to determine the frequency and clinical importance of aPL isotypes in Turkish patients with SLE. DESIGN AND METHODS: Fifty-nine patients with SLE and 41 healthy controls were included. Serum aPL levels were measured both in patients and healthy subjects by ELISA. RESULTS: Fifteen of the patients with SLE had the antiphospholipid syndrome (APS) (25.4%). The percentage of anticardiolipin antibody (aCL)-positive SLE patients among all patients was 56%. At least one isotype of anti-beta(2)-glycoprotein I (beta(2)-GPI) antibody was positive in 83% of patients. The positivity rates of aCL and anti-beta(2)-GPI antibodies in patients with or without APS were higher than the healthy controls. There were positive correlations between isotypes of IgM aCL, IgG and IgM anti-beta(2)-GPI and manifestations of APS. CONCLUSION: It seems that the isotypes of IgM aCL, IgG and IgM anti-beta(2)-GPI are correlated with manifestations of APS. They may play a role in pathogenesis and may be helpful in establishing the diagnosis.     

The association of VP1 unique region protein in acute parvovirus B19 infection and anti-phospholipid antibody production

BACKGROUND: Previous studies have postulated a connection between human parvovirus B19 (B19) infection and anti-phospholipid antibodies (aPL). Recently, the phospholipase domain of B19 has been linked to B19-VP1 unique region (VP1u). To elucidate the roles of VP1u in B19 infection and aPL production, the major reactivity of anti-B19-VP1u, anti-cardiolipin antibody (aCL), and anti-beta2-glycoprotein I (beta2GPI) antibody was evaluated. METHODS: Sera from 102 clinically suspected cases of B19 infection were analyzed by nested PCR and ELISA. Humoral responses of anti-B19-VP1u and anti-B19-VP1uD175A IgM/IgG antibodies, aCL and the anti-beta2GPI antibody were assessed by Western blot and ELISA. Absorption experiments were also performed to determine the binding specificity of immunoglobulins to B19-VP1u, CL and beta2GPI. RESULTS: Sera from patients with the diagnostic pattern DNA+/IgM+/IgG+ had a high frequency (57%) for recognition of CL and beta2GPI. Furthermore, adsorption experiments were performed by adding purified B19-VP1u, which partially suppressed the reactivity of anti-B19VP1u to CL and beta2GPI. CONCLUSIONS: Serum from patients with acute B19 infection has a high frequency in recognition of CL and beta2GPI, and the phospholipase domain observed in the B19-VP1u may have contributed to the production of aPL. These findings may provide a clue for understanding the roles of B19-VP1u in B19 infection and aPL production.     

Lupus anticoagulant is significantly associated with inflammatory reactions in patients with suspected deep vein thrombosis

OBJECTIVE: Lupus anticoagulant (LA) and antiphospholipid antibodies (aPL) are suggested as risk factors for development of deep vein thrombosis (DVT) among patients without systemic lupus erythematosus (SLE). Other conditions, e.g. inflammation, are reported to induce LA and it is uncertain whether the association between LA and DVT is causal. In this study the associations between aPL, LA and inflammation were investigated in 170 consecutive patients without SLE, but with a tentative diagnosis of DVT. MATERIAL AND METHODS: DVT was diagnosed in 64 patients. LA was determined according to the criteria of the International Society of Thrombosis and Haemostasis. The concentration of anticardiolipin (aCL) and beta(2)-glycoprotein I (anti-beta(2)-GPI) antibodies as well as C-reactive protein (CRP) was determined with sensitive and precise methods. RESULTS: LA was demonstrated in 8 patients with DVT and in 10 patients without DVT, relative risk 1.33 (CI: 0.55-3.18). No significant association was observed between aCL or anti-beta(2)-GPI and DVT. Patients suffering from DVT had significantly higher concentrations of CRP than patients without DVT. However, CRP was also significantly higher in patients positive for LA than in patients without LA irrespective of the presence of DVT (p<0.001). CONCLUSIONS: The present study supports a strong association between inflammatory reactions and development of LA in patients with suspected DVT, whereas no significant association was demonstrated between LA or aPL and DVT.     

Clinical laboratory testing for the antiphospholipid syndrome

The first aCL test was developed in 1983 and subsequently standardized. Although in the last 6 to 7 years, new and more specific tests have become available, the aCL ELISA and the LA tests are still the first choice to be used in diagnosis of APS. While there is now doubt that the anticardiolipin test is useful in the diagnosis of APS, limitations of the assay have caused uncertainty and misinterpretation of the value of the test. Utilization of validated ELISA kits with well-tested calibrators and an "in-house standard" may enable more reproducible measurements. Reporting results semiquantitatively preserves the clinical utilize of the test without the misinterpretation of a quantitative result that may lack precision. The development of newer tests such as the beta2GPI ELISA and the APhL ELISA Kit, utilizing the phospholipid mixture, give promise to a more specific and reliable diagnosis of APS, while retaining good sensitivity. Other tests such as ELISA for prothrombin antibodies and annexin V antibodies are still under development and will require standardization and extensive evaluation. The aCL test should continue to be done and included in the Sapporo criteria. The aCL test is not as specific as the anti-beta2GPI test, but it is very sensitive and together with the LA test should capture the majority of the APS patients. IgA aCL and anti-beta2GPI positivity alone is rare but occasionally found and shown to be associated with major clinical manifestations of APS. Therefore, it is now recommended to include both tests, IgA aCL and IgG, IgM and IgA anti-beta2GPI to confirm diagnosis of APS.     

Lupus anticoagulants and the risk of a first episode of deep venous thrombosis

We have determined lupus anticoagulants, anti-beta2 glycoprotein I (beta2GPI) and antiprothrombin antibodies in the Leiden Thrombophilia Study, a population-based case-control study designed to determine risk factors for deep venous thrombosis (DVT). Lupus anticoagulant (LAC) was measured in 473 patients and 472 control subjects. Four control subjects (0.9%) and 14 patients (3.1%) had a positive LAC, resulting in a 3.6-fold increased risk [odds ratio (OR) 3.6, 95% CI: 1.2-10.9]. Of the total population, 49 were positive for anti-beta2GPI antibodies: 15 controls (3.4%) and 34 patients (7.5%), implying a 2.4-fold increased risk (95% CI: 1.3-4.2). Antiprothrombin antibodies were present in 114 subjects: 48 controls (11.0%) and 66 cases (14.6%) with an OR of 1.4 (95% CI: 1.0-2.1). When LAC was considered in the co-presence of antiprothrombin or anti-beta2GPI antibodies the OR increased to 10.1 (95% CI: 1.3-79.8). A LAC without a positive anti-beta2GPI or antiprothrombin test was not associated with a risk for DVT (OR 1.3, 95% CI: 0.3-6.0). This study demonstrates that the presence of LAC, anti-beta2GPI antibodies and antiprothrombin antibodies are risk factors for DVT in a general population. The strongest association holds for the combination LAC and the presence of anti-beta2GPI or antiprothrombin antibodies.     

Revisiting antiphospholipid antibodies: from targeting phospholipids to phospholipid binding proteins

The antiphospholipid syndrome (APS) is a multi-system prothrombotic disorder associated with circulating auto-antibodies directed against various phospholipid-binding proteins. The major clinical manifestations are recurrent arterial or venous thrombosis, but due to its heterogeneity, atypical presentations can obscure the diagnosis. Decisions regarding when to attribute complications to aPL are difficult. The most established tests are lupus anticoagulant (LA) detected by clotting assays and anticardiolipin (aCL) detected by ELISA. Although LA and aCL assays are clinically useful, these tests do not clearly differentiate antibodies with different specificities. Antibodies to beta2GPI are associated with thrombosis in the APS. Although these antibodies are detected by aCL assay (e.g. beta2GPI-dependent aCL), some aCL are not associated with the syndrome (e.g. beta2GPI-independent aCL). Regarding LAs, more studies are needed to determine if it is clinically important to differentiate specificities against beta2GPI or prothrombin. The role of aPLs in the pathogenesis of thrombosis requires further and intensive investigation. If autoantibodies to particular phospholipid binding proteins are shown to be associated with different clinical presentations or to confer different risks, the availability of more accurate diagnostic techniques will be required for the recognition of pathogenic aPLs. By now, clinical judgement, careful exclusion of other etiologies and serial aPL levels are helpful in this regard.     

Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: evaluation of 23 possible combinations of antiphospholipid antibody specificities

Summary. Objectives: To evaluate the clinical accuracy of antiphospholipid antibody (aPL) specificities both individually and/or in combination, in a wide cohort of systemic lupus erythematosus (SLE) patients in an attempt to identify a panel of tests that may provide the best accuracy for diagnosing antiphospholipid syndrome (APS). Patients and Methods: This study included 230 patients (218 women, mean age 42.7 ± 11.9 years, mean disease duration 12.2 ± 8.7 years), all fulfilling the 1982 criteria for SLE. All patients were tested for lupus anticoagulant (LA), anti‐cardiolipin (aCL), anti‐β₂glycoprotein I (anti‐β2GPI), solid phase anti‐prothrombin (aPT), anti‐phosphatidylserine/prothrombin (aPS/PT), and anti‐phosphatidylethanolamine (aPE) antibodies. Sensitivity, specificity and predictive values were calculated. The diagnostic accuracy for each combination of tests was assessed by ROC and their area under the curve analysis as well as by the Youden’s index (YI). Results: Testing for six aPL derived 23 possible combinations of results. Among them, LA + anti‐β₂GPI + aPS/PT had the best diagnostic accuracy for APS as a whole and individually for both thrombosis and pregnancy loss (AUC 0.712, OR 3.73 [95% CI 1.82–5.38], P = 0.0001, YI = 0.32 and AUC 0.709, OR 3.75 [95% CI 2.13–6.62], P = 0.0001, YI = 0.37 and AUC 0.677, OR 4.82 [95% CI 2.17–10.72], P = 0.0007, YI = 0.38, respectively) and the best specificity when compared with all the other obtainable combination of tests. Triple positivity for LA + anti‐β₂GPI + aPS/PT was more strongly associated with clinical events (thrombosis and/or PL) when compared with double or single positivity (OR 23.2 [95% CI 2.57–46.2] vs. OR 7.3 [95% CI 2.21–25.97], OR 5.7 [95% CI 2.12–17.01] or OR 3.11 [95% CI 1.56–7.8] for single positivity for LA, aPS/PT and anti‐β₂GPI, respectively). Conclusions: Combining LA, anti‐β₂GPI and aPS/PT improves the diagnostic power and helps in stratifying the risk for each patient, according to their aPL profile.     

Lupus anticoagulant is significantly associated with inflammatory reactions in patients with suspected deep vein thrombosis

Objective. Lupus anticoagulant (LA) and antiphospholipid antibodies (aPL) are suggested as risk factors for development of deep vein thrombosis (DVT) among patients without systemic lupus erythematosus (SLE). Other conditions, e.g. inflammation, are reported to induce LA and it is uncertain whether the association between LA and DVT is causal. In this study the associations between aPL, LA and inflammation were investigated in 170 consecutive patients without SLE, but with a tentative diagnosis of DVT. Material and methods. DVT was diagnosed in 64 patients. LA was determined according to the criteria of the International Society of Thrombosis and Haemostasis. The concentration of anticardiolipin (aCL) and β₂‐glycoprotein I (anti‐β₂‐GPI) antibodies as well as C‐reactive protein (CRP) was determined with sensitive and precise methods. Results. LA was demonstrated in 8 patients with DVT and in 10 patients without DVT, relative risk 1.33 (CI: 0.55–3.18). No significant association was observed between aCL or anti‐β₂‐GPI and DVT. Patients suffering from DVT had significantly higher concentrations of CRP than patients without DVT. However, CRP was also significantly higher in patients positive for LA than in patients without LA irrespective of the presence of DVT (p<0.001). Conclusions. The present study supports a strong association between inflammatory reactions and development of LA in patients with suspected DVT, whereas no significant association was demonstrated between LA or aPL and DVT.     

Occurrence of anti-prothrombin and anti-beta2-glycoprotein I antibodies in patients with history of thrombosis

New evidence indicates that antibodies to beta2-glycoprotein I (anti-beta2GPI) or to human prothrombin (anti-II)(or to both of these) are specific markers of the antiphospholipid syndrome (APS). They have been mainly associated with thrombotic complications in patients with APS. However, some studies have reported that elevated levels of anti-II, but not of anfi-beta2GPI, imply a risk of venous thrombosis (VT) or arterial thrombosis (AT) in subjects with no previous thrombosis and no antiphospholipid antibodies (aPL) by ELISA. The present study Included 180 patients with a history of thrombosis, 83 of them without aPL (group I) and the remaining 97 diagnosed as having APS (group II). Anti-beta2GPI was found in only 1 of the 83 patients from group I but was found in approximately 50% of those from group II (P < .0001). In contrast, positive anti-II was detected with a high prevalence in patients from group I (VT, 22.6%; AT, 26.7%) and in those from group II (VT, 37.5%; AT, 14.6%). No statistical differences were found in the prevalence of anti-II between the two groups of patients. On the other hand, such a difference was significant when compared with results in a normal group (1/67, 1.4%, P < .0001). These data Indicate that anti-II occurs frequently in patients with previous thrombosis either with or without lupus anticoagulant activity. Accordingly, testing of anti-II might be clinically useful in the evaluation for thrombophilla.     

Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: a 15-year longitudinal study

Summary. Objective: To evaluate the role of anti‐prothrombin (anti‐PT) antibodies in predicting thrombosis in patients with systemic lupus erythematosus (SLE). Methods: An inception cohort of 101 SLE patients (12 males, 89 females; mean age 30 ± 8 years), was considered. Clinical and laboratory evaluations were regularly performed during a 15‐year follow‐up (median 108 months) with a special focus on thromboembolic events. Serum samples were collected at time of diagnosis and at least once a year thereafter. IgG and IgM anti‐PT, anti‐cardiolipin (aCL) and anti‐β₂glycoprotein I (β₂GPI) antibodies were measured by enzyme‐linked immunosorbent assay (ELISA); lupus anticoagulant (LAC) was assayed by the dilute Russell’s viper venom time and activated partial thromboplastin time tests. The analytical specificity of anti‐PT ELISA was investigated. The timing of thrombosis occurrence was calculated using the Kaplan–Meier method. Results: In the 15‐year follow‐up, thrombosis occurred in 14 out of the 101 patients: venous thrombosis in nine cases and arterial thrombosis in five. IgG and/or IgM anti‐PT, anti‐β₂GPI and aCL antibodies, and LAC activity were detected in ten, nine, seven, and nine cases, with sensitivity for thrombosis of 71.4%, 64.3%, 50% and 64.3%, respectively. Thrombosis‐free survival was 90% at 5 years and 85.8% at 10 and 15 years, respectively. Thrombosis was predicted by anti‐PT (P = 0.001), anti‐β₂GPI antibodies (P = 0.002) and LAC activity (P = 0.001). Moreover, the risk of thrombosis progressively increased with the number of positive antiphospholipid antibody tests. The presence of four positive antibody tests was associated with a risk of thrombosis thirtyfold higher than in their absence. Conclusions: This longitudinal study shows that IgG anti‐PT antibodies are predictors of thrombosis in SLE patients.