The first thrombotic event in purely obstetric antiphospholipid syndrome patients and in antiphospholipid antibody carriers: comparison of incidence and characteristics.

PURPOSE: The long-term risk of thrombosis after pregnancy in women with purely obstetric antiphospholipid syndrome (OAPS) is not well defined. The current study's primary outcome was to evaluate the incidence and characteristics of the first thrombotic event in OAPS, identifying the risk factors for thrombosis in OAPS was its secondary one. METHODS: Patients with purely OAPS were consecutively enrolled between September 1999 and September 2019. Subjects without a history of pregnancy morbidity or thrombosis but with persistent positivity for one or more antiphospholipid antibodies (aPL carriers) made up the control group. The study groups included 94 OAPS patients and 124 aPL carriers who were matched for clinical and laboratory parameters. RESULTS: An event rate of 0.49/100 patient years was registered in OAPS patients during a mean follow-up of 8.7 years ± 5.5 SD. Kaplan-Meier survival analysis revealed that the cumulative incidence of thromboembolic events was not significantly different in OAPS patients vs aPL carriers. Arterial thrombosis and cerebrovascular events were the more frequent types of vascular involvement in the two groups. As far as risk factors for thrombosis were concerned, the presence of lupus anticoagulant significantly prevailed in both thrombotic OAPS patients and thrombotic aPL carriers with respect to purely OAPS patients and aPL carriers who did not develop thrombosis (p = 0.01 and p = 0.00, respectively). CONCLUSION: Just as for aPL carriers, closer monitoring and possibly, a pharmacological prophylaxis should be reserved for OAPS patients at highest risk of developing the first thrombotic event.

IgG phosphatidylserine/prothrombin antibodies as a risk factor of thrombosis in antiphospholipid antibody carriers.

The clinical significance of IgG/IgM antiphosphatidylserine/prothrombin (aPS/PT) antibodies was prospectively evaluated in a cohort of 191 antiphospholipid antibody (aPL) carriers using commercial ELISA assays. IgG aPS/PT antibodies were detected in 40 (20.9%) and IgM aPS/PT in 102 (53.4%) of the carriers. Both IgG and IgM aPS/PT antibodies were significantly associated with triple aPL positivity (Lupus anticoagulants [LAC] plus anti-ß2Glycoprotein I plus anticardiolipin antibodies) (p = 0.0000 for both). There was a significant prevalence of IgM aPS/PT in the individuals with isolated LAC positivity (p = 0.005). Fourteen of the aPL carriers (7.3%) developed a first thrombotic event. There was a significant prevalence of IgG aPS/PT antibodies but not of IgM aPS/PT in the thrombotic patients (p = 0.015). The cumulative incidence rate of thrombotic events was significantly higher in the IgG aPS/PT positive (p = 0.035) but not in the IgM aPS/PT positive carriers. Logistic regression analysis assessing the independent effect of IgG /IgM aPS/PT antibodies, triple aPL positivity, genetic/acquired thrombosis risk factors and autoimmune disorders on thrombosis development uncovered a significant association only for the risk factors (Odds Ratio = OR: 12.451, 95% Confidence Interval = CI: 2.519-61.537, p = 0.002) and for triple aPL positivity (OR: 4.725, 95% CI: 1.135-19.674, p = 0.033). Logistic regression evaluating the independent effect of IgG and IgM aPS/PT on thrombosis development uncovered a significant association only for the former (OR: 3.962, 95% CI: 1.174-13.37, p = 0.026). The risk score for thrombosis in aPL carriers could be more effective if IgG aPS/PT antibodies are added to triple aPL positivity and thrombosis risk factors.

Relationship between antiphosphatidylserine/prothrombin and conventional antiphospholipid antibodies in primary antiphospholipid syndrome.

BACKGROUND: Antiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are emerging as an important marker for antiphospholipid syndrome (APS). We aimed to compare their performance with that of conventional antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA), anticardiolipin (aCL), and anti-ß2-glycoprotein I (anti-ß2GPI) in APS and to assess their frequency in APS-negative (APS-ne) patients. METHODS: We considered 160 APS patients and 128 APS-ne patients with clinical criteria for APS but tested negative for conventional aPL. Immunoglobulin (Ig)G/IgM aPS/PT, IgG/IgM aCL, and IgG/IgM anti-ß2GPI were detected using ELISA assay and LA with a series of coagulation tests. RESULTS: IgG aPS/PT were significantly associated with IgG aCL, IgG anti-ß2GPI, and LA (p<0.0001 for all). IgM aPS/PT were significantly associated only with LA (p<0.0001) instead. There was a significant correlation between IgG aPS/PT and both IgG aCL and IgG anti-ß2GPI levels (ρ=0.42 and ρ=0.40, respectively). Both IgG aPS/PT and IgM aPS/PT positivity significantly correlated with LA (ρ=0.44 and ρ=0.5, respectively). IgG and IgM aPS/PT were significantly more frequent in triple than in double and in single positivity (p<0.0001). According to multivariate analysis, IgG and/or IgM aPS/PT were independent risk factors for LA. APS/PT antibodies were found in 9.4% of the APS-ne patients vs. 2% of healthy control (p=0.043); those antibodies were significantly more frequent in the thrombosis with respect to the pregnancy morbidity subset (p=0.01). CONCLUSIONS: Our data attribute a clinical relevance to both IgG and IgM aPS/PT antibodies. In particular, the significant prevalence of aPS/PT in APS-ne patients suggests including them as additional laboratory criterion for APS.

Treatment strategies and pregnancy outcomes in antiphospholipid syndrome patients with thrombosis and triple antiphospholipid positivity. A European multicentre retrospective study.

Previous thrombosis, diagnosis of systemic lupus erythematosus (SLE) and triple antiphospholipid (aPL) antibody positivity have recently been found to be independent factors associated to pregnancy failure during conventional therapy in women with antiphospholipid syndrome (APS). This study aimed to assess the effect of various treatment strategies on pregnancy outcomes in women with APS and the risk factors for pregnancy failure. One hundred ninety-six pregnancies of 156 patients diagnosed with APS were analysed: 118 (60.2%) of these had previous thrombosis, 81 (41.3%) were diagnosed with SLE, and 107 (54.6%) had triple aPL positivity. One hundred seventy-five (89.3%) were treated with conventional therapies (low-dose aspirin [LDA] or prophylactic doses of heparin + LDA or therapeutic doses of heparin + LDA), while 21 (10.7%) were prescribed other treatments in addition to conventional therapy. The pregnancies were classified into seven risk profiles depending on the patients' risk factors - thrombosis, SLE, and triple aPL positivity - and their single, double or triple combinations. It was possible to find significant difference in outcomes correlated to treatments only in the thrombosis plus triple aPL positivity subset, and logistic regression analysis showed that additional treatments were the only independent factor associated to a favourable pregnancy outcome (odds ratio=9.7, 95% confidence interval=1.1-88.9, p-value<0.05). On the basis of this retrospective study, we found that APS pregnant patients with thrombosis and triple aPL positivity treated with additional therapy had a significant higher live-birth rate with respect to those receiving conventional therapy alone.

IgA anticardiolipin and IgA anti-ß2 glycoprotein I antibody positivity determined by fluorescence enzyme immunoassay in primary antiphospholipid syndrome.

BACKGROUND: Primary antiphospholipid syndrome (PAPS) is an autoimmune disease characterized by thrombosis and/or pregnancy morbidity as well as blood antiphospholipid (aPL) antibodies such as anticardiolipin (aCL), anti-ß2 glycoprotein I (anti-ß2GPI) antibodies of the IgG/IgM isotype and lupus anticoagulant (LA). The clinical significance of aCL and anti-ß2GPI antibodies of the IgA isotype in PAPS is still a controversial issue. METHODS: Sera and plasma were collected from 84 PAPS patients (54 with thrombosis and/or pregnancy morbidity and 30 with pregnancy morbidity alone), 66 seronegative patients (subjects with clinical manifestations of PAPS although with negative results on conventional antiphospholipid antibody testing), and 78 healthy blood donors. IgA aCL and IgA anti-ß2GPI were determined using fluorescence enzyme immunoassay (FEIA), (EliATM, Phadia AB, Uppsala, Sweden). For comparison purposes, the sera were also tested for IgG/IgM aCL/anti-ß2GPI antibodies using the same immunoassay method. LA was assayed following internationally accepted guidelines. RESULTS: Present respectively in 19% and 50% of the PAPS patients studied, IgA aCL and IgA anti-ß2GPI antibody frequencies were both statistically significant (p=0.001 and p<0.001, respectively). The mean titers of both IgA aCL and IgA anti-ß2GPI antibodies were higher in the thrombotic patients, but only the latter were significantly associated with thrombosis. Isolated IgA anti-ß2GPI antibody positivity was significantly prevalent (p=0.04) in seven (10.6%) of the seronegative patients. CONCLUSIONS: Positivity to IgA anti-ß2GPI antibody detected using FEIA was found to be clinically relevant in PAPS patients. Moreover the prevalence of isolated IgA anti-ß2GPI antibody positivity was significant in the seronegative patients.

Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study.

OBJECTIVES: To assess risk factors for a first thrombotic event in confirmed antiphospholipid (aPL) antibody carriers and to evaluate the efficacy of prophylactic treatments. METHODS: Inclusion criteria were age 18-65 years, no history of thrombosis and two consecutive positive aPL results. Demographic, laboratory and clinical parameters were collected at enrolment, once a year during the follow-up and at the time of the thrombotic event, whenever that occurred. RESULTS: 258 subjects were prospectively observed between October 2004 and October 2008. The mean ± SD follow-up was 35.0 ± 11.9 months (range 1-48). A first thrombotic event (9 venous, 4 arterial and 1 transient ischaemic attack) occurred in 14 subjects (5.4%, annual incidence rate 1.86%). Hypertension and lupus anticoagulant (LA) were significantly predictive of thrombosis (both at p<0.05) and thromboprophylaxis was significantly protective during high-risk periods (p<0.05) according to univariate analysis. Hypertension and LA were identified by multivariate logistic regression analysis as independent risk factors for thrombosis (HR 3.8, 95% CI 1.3 to 11.1, p<0.05, and HR 3.9, 95% CI 1.1 to 14, p<0.05, respectively). CONCLUSIONS: Hypertension and LA are independent risk factors for thrombosis in aPL carriers. Thromboprophylaxis in these subjects should probably be limited to high-risk situations.