Treatment of antiphospholipid syndrome

Objective Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). Recent reports of thrombosis associated with adenovirus-based vaccines raised concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger clotting complications. Our objectives were to assess immunogenicity, safety, and aPL production in PAPS patients, after vaccinating with Sinovac-CoronaVac, an inactivated virus vaccine against COVID-19. Methods This prospective controlled phase-4 study of PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69 in naïve participants. Safety and aPL production were also assessed. Results We included 44 PAPS patients (31 naïve) and 132 CG (108 naïve) with comparable age ( p=0.982) and sex ( p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092), as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity (64.3% vs. 60.9%, p=0.689). Thrombotic events up to 6 months or other moderate/severe side effects were not observed. PAPS patients remained with stable aPL levels throughout the study at D0 vs. D28 vs. D69: anticardiolipin (aCL) IgG ( p=0.058) and IgM ( p=0.091); anti-beta-2 glycoprotein I (aβ2GPI) IgG ( p=0.513) and IgM ( p=0.468). Conclusion We provided novel evidence that Sinovac-CoronaVac has high immunogenicity and safety profile in PAPS. Furthermore, Sinovac-CoronaVac did not trigger thrombosis nor induced changes in aPL production.

Section: Antiphospholipid Antibodies and Vaccinationmentioning

confidence: 99%

Immunogenicity, safety, and antiphospholipid antibodies after SARS-CoV-2 vaccine in patients with primary antiphospholipid syndrome

Signorelli

Balbi

Aikawa

et al. 2022

“…The aPL-S includes criteria aPL, but also aPS/PT, that have emerged as new predicative tools of clinical manifestations of APS. 29,30 In more detail, when calculating the aPL-S, LA should be tested with three clotting tests (activated partial thromboplastin time [aPTT], dilute Russell viper venom time [dRVVT], and kaolin clotting time [KCT]) with mixing and phospholipid neutralizing assays, according to the guidelines suggested by the LA/aPL Scientific and Standardization Subcommittee of the International Society on Thrombosis and Haemostasis. 31 The solid assays aPL (aCL, ab2GPI and aPS/PT) are tested in both isotypes IgG and IgM, and are considered positive as high titers or medium/low titres.…”

Section: • Consistent With the 15th International Congressmentioning

confidence: 99%

16th International congress on antiphospholipid antibodies task force report on clinical manifestations of antiphospholipid syndrome

Sciascia

Radin

Cecchi

et al. 2021

Self Cite

The objectives of the 16th International Congress on Antiphospholipid Antibodies (aPL) Task Force on Clinical Manifestations of Antiphospholipid Syndrome (APS) were to critically analyze: a) the definition of “APS”; b) the current knowledge on non-traditional manifestations associated with aPL; and c) the risk stratification strategies in aPL-positive patients. The quality of evidence was assessed by the GRADE system. The task force concluded that: a) APS does not have a uniform definition given the heterogeneity of the clinical presentations and different aPL profiles; b) current literature supports the role for aPL testing in cases of thrombocytopenia and recurrent cardiac events but are limited by vast heterogeneity, providing an overall low-to-very low level of evidence; and c) risk stratification strategies in aPL-positive patients, such as aPL-Score and Global APS Score, can be useful in clinical practice. International multicenter studies are still highly needed to improve the quality of available evidence and consequently the strength of future recommendations.

“…We also confirm that LA is more strongly associated with aPS/ PT than with anti-b 2 GPI. Previous studies have demonstrated associations of both IgG and IgM aPS/PT to APS-related events, 6,7 but only few researchers reported multivariate adjustments for the criteria aPL 31,32 and/or conventional thrombotic risk factors. 20,33 In the current study, occurrence of IgM aPS/PT was the strongest risk factor for VTE in univariable analysis of Swedish SLE patients.…”

Section: Discussionmentioning

confidence: 99%

“…Autoantibodies directed against the phosphatidylserine/prothrombin complex (aPS/PT) have raised mounting clinical interest in recent years. 6,7 In the presence of calcium ions, prothrombin (factor II in the coagulation cascade) binds to negatively charged phospholipids e.g. phosphatidylserine through its vitamin K-dependent carboxylation domains.…”

Section: Introductionmentioning

confidence: 99%

“…6,9,10 A recent systematic review concluded that there is a strong evidence for positive associations between aPS/ PT antibodies and APS manifestations, suggesting that these tests merit clinical use. 7 Consequently, aPS/PT antibodies were also included in risk stratification scoring systems the antiphospholipid score (aPL-S) 11 and the global APS score (GAPSS) 12 to evaluate asymptomatic aPL positive patients. To what extent aPL contribute to accelerated atherosclerosis is debated, and no studies have investigated whether aPS/PT antibodies relate to measures of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Associations with thrombosis are stronger for antiphosphatidylserine/prothrombin antibodies than for the Sydney criteria antiphospholipid antibody tests in SLE

Elbagir

Grosso

Mohammed

et al. 2021

Objectives Antiphosphatidylserine/prothrombin complex antibodies (aPS/PT) are risk factors for thrombosis, yet further validation of their clinical relevance in different ethnic groups is required. We investigated the performance of aPS/PT of IgA/G/M isotypes among Sudanese and Swedish systemic lupus erythematosus (SLE) patients. Methods Consecutive SLE patients/matched controls from Sudan (n = 91/102) and Sweden (n = 332/163) were included. All patients fulfilled the 1982 ACR SLE classification criteria. IgA/G/M of aPS/PT, anti-cardiolipin and anti-β2glycoprotein I (anti-β2GPI) were tested in both cohorts, and lupus anticoagulant (LA) also in the Swedish cohort. Clinical antiphospholipid syndrome-related events and atherosclerosis, measured as carotid plaques were assessed for associations. Univariate and multivariate analyses adjusting for cardiovascular risk factors were performed. Results Sudanese SLE patients had higher levels of IgM aPS/PT, but using national cut-offs, the frequency of positivity was similar to Swedish patients for all isotypes. Among Swedish patients, all isotypes of aPS/PT associated with venous thromboembolism (VTE), while only IgA aPS/PT associated with arterial thrombosis (AT). aPS/PT antibodies associated strongly with LA and they were, independently, the best predictor for VTE. Double positivity for aPS/PT and anti-β2GPI associated with higher VTE risk than the conventional triple positivity. Carotid plaques did not associate with any antiphospholipid antibody. Conclusions IgA aPS/PT associated with AT, and the association of IgG/M aPS/PT with VTE outperforms LA and criteria antiphospholipid antibodies in Swedish SLE patients. Furthermore, double positivity for aPS/PT and anti-β2GPI performed better than conventional triple positivity. Future studies need to address if aPS/PT can replace LA, as this would simplify clinical procedures.