ANA-positive primary immune thrombocytopaenia: a different clinical entity with increased risk of connective tissue diseases

Abstract

ObjectivePrimary immune thrombocytopaenia (ITP) is highly heterogeneous. ANA-positive primary ITP may resemble the preclinical stage of connective tissue diseases (CTDs), but is still considered primary ITP due to a controversial CTD risk assessment in this group. The objective of this study was to clarify the risk of CTD in ANA-positive patients with primary ITP.MethodsWe performed a retrospective cohort study and a meta-analysis. 586 patients with newly diagnosed primary ITP were followed up and Cox regression analyses were used to analyse the associations of ANA positivity and other immune parameters with CTD development.ResultsThe mean follow-up time was 37 (19–56) months. ANA was positive in 21.33% (125 of 586) of patients with primary ITP in our retrospective cohort, and the overall rate of ANA positivity in the meta-analysis was 17.06% (369 of 2163). The adjusted HR for CTD in ANA-positive primary ITP was 6.15 (95% CI 2.66 to 14.23, p<0.001). Five patients in the ANA-positive group developed SLE (5 of 125, 4.0%), significantly higher than in the ANA-negative group (0 of 461, 0%). A clinical model combining ANA, anti-Sjogren’s syndrome A antibody and C3 was successfully developed to predict the risk of CTD in patients with primary ITP. Increased risk of CTD (risk ratio=12.43, 95% CI 7.91 to 19.55, p<0.00001), especially SLE (risk ratio=30.41, 95% CI 13.23 to 69.86, p<0.00001), among ANA-positive patients with primary ITP was confirmed by a meta-analysis of previous studies and the present study.ConclusionsThe findings suggest that ANA-positive primary ITP is a clinical entity distinct from other primary ITPs and is associated with increased risk of developing CTDs, especially SLE.

The effect of antinuclear antibody titre and its variation on outcomes in children with primary immune thrombocytopenia

“…To date, no other study on primary ITP has reported an association between ANA titres and platelet counts in the paediatric population. An adult primary ITP cohort was studied using an ANA titre of 1:100 as a threshold for positive ANA, and found lower platelet counts at diagnosis in ANA‐positive patients compared to ANA‐negative patients (median value, 34 × 10 9 /l vs 46 × 10 9 /l, p value 0.015), which is consistent with our findings 12 . Furthermore, the results of our study showed that although children with higher ANA titres had lower platelet counts at the beginning, a subsequent more rapid rise in platelet counts was found, suggesting that high‐titre ANA did not result in a worse outcome of subsequent platelet counts in children with primary ITP.…”

The Rise and Rise of Lupus

“…81 Consistent with these findings, Liu et al, in a historical cohort study and in a meta-analysis, confirmed that ANA-positive primary ITP is a distinct subgroup of primary ITP associated with an increased risk of developing a CTD, especially SLE as compared with the ANA-negative ITP group. 82 In this study, ANA-positive primary ITP patients had a 48-fold higher risk of newonset SLE than ANA-negative ITP patients, suggesting that ANA positivity confers a high risk of developing lupus. 82 Of note, the highest risk of developing CTD was during the first 4 years after ITP diagnosis, and low C3 levels and positive anti-Ro antibodies were more frequently found in those who developed a CTD.…”

“…82 In this study, ANA-positive primary ITP patients had a 48-fold higher risk of newonset SLE than ANA-negative ITP patients, suggesting that ANA positivity confers a high risk of developing lupus. 82 Of note, the highest risk of developing CTD was during the first 4 years after ITP diagnosis, and low C3 levels and positive anti-Ro antibodies were more frequently found in those who developed a CTD. 81 In view of these findings, some authors recommend that patients with ITP, particularly those who are ANA positive, should be closely monitored for SLE, especially within the first 5 years of diagnosis, and preferably be evaluated by a rheumatologist to identify nonhematological manifestations suggestive of SLE.…”

“…Patients with immune thrombocytopenic purpura (ITP), previously known as idiopathic TP, and especially those who are ANA positive, are at an increased risk of developing SLE. 81,82 Zhu et al, in a nationwide study in the Taiwanese population, demonstrated that patients with ITP, followed for a mean time of 80 months, had a 26-fold higher risk of new-onset SLE than the control population (non-IPT). Compared with women, men had a lower risk of SLE while patients with Sjogren's syndrome had a significantly higher risk of evolving into SLE.…”

Clinical significance of antinuclear antibodies in primary immune thrombocytopenia

“…For the same reason, it is difficult to get evidence whether the presence of ANA results in a higher risk of developing systemic lupus in patients with primary ITP. 30 In a recently published retrospective Chinese study, 10 of 130 adult patients with primary ITP (7.7%) with a mean follow-up of 6 years developed systemic lupus. The median time from ITP diagnosis to systemic lupus onset was 2.5 years.…”