Pediatric antiphospholipid syndrome: clinical features and therapeutic interventions in a single center retrospective case series

Abstract

Background/purpose Pediatric antiphospholipid syndrome (APS) is a thromboinflammatory disease characterized by the presence of circulating antiphospholipid antibodies and either thrombotic events or pregnancy morbidity. The objective of this study was to review a large institution’s experience to better understand the characteristics of children with APS. Methods We conducted a retrospective review of pediatric APS at a tertiary referral center. The electronic medical record system was queried from 2000 through 2019, and 21 cases were included based on meeting the revised Sapporo Classification criteria by age 18 or younger. Comparisons between primary and secondary APS patients were made with two-tailed t-tests. Results Twenty-one patients were included with a median age at diagnosis of 16 years and median follow-up of 5.8 years. Secondary APS was slightly more common than primary APS (11 vs. 10 cases) and was primarily diagnosed in the context of systemic lupus erythematosus. Two thirds of patients (67%) also had “non-criteria” manifestations of APS including thrombocytopenia, autoimmune hemolytic anemia, and livedo reticularis/racemosa. Almost half of patients (43%) had recurrent thrombosis, typically when patients were subtherapeutic or non-adherent with anticoagulation. Damage Index in Patients with Thrombotic APS (DIAPS) scores indicated a chronic burden of disease in both primary and secondary APS patients. Conclusion This case series of pediatric APS provides important context regarding disease phenotypes displayed by children with APS. High prevalence of non-criteria clinical manifestations highlights the need to consider these characteristics when developing pediatric-specific classification criteria and when considering this relatively rare diagnosis in pediatric practice.

Case Report: A case of recurrent thrombosis in pediatric antiphospholipid syndrome associated with pediatric onset systemic lupus

“…There was no similar case reported before. Clinically, in addition to the three major characteristics of recurrent thrombosis, abnormal pregnancy and positive aPL, there are also some atypical symptoms in APS children, such as cardiovascular disease, migraine, heart valve damage, pulmonary hypertension and livedo reticularis ( 19 ), and our patient also presented with livedo reticularis on both lower extremities during the second course of the disease. But the patient developed recurrent arteriovenous thrombosis at the onset, which was not in line with the diagnosis of SLE at that time, and the antiphospholipid antibody was negative, so it was considered to be related to the vascular embolism caused by NS.…”

Antiphospholipid syndrome: advances in diagnosis, pathogenesis, and management

“…One registry of 121 children reported a mean age at onset of antiphospholipid syndrome of 10.7 years 12. Non-thrombotic manifestations of antiphospholipid syndrome such as thrombocytopenia and autoimmune hemolytic anemia might be more common in the pediatric population 13…”

Pediatric Presentation of Antiphospholipid Syndrome: A Review of Recent Literature With Estimation of Local Prevalence

“…A total of nine studies were identified and included in the final analysis. [14][15][16][17][18][19][20][21][22] Cumulatively, a total of 2,715 patients were described in the analyzed studies, including a total of 386 patients with a diagnosis of pediatric APS. Of the pediatric population 65% were females, 160 (41%) had a diagnosis of primary APS and 226 (58%) had secondary APS (SAPS), in detail 192 (49%) had an associated diagnosis of SLE, 4 had a Lupus-like disease, 4 had an autoimmune thyroiditis, 2 had a rheumatic fever, 2 had an immune thrombocytopenic purpura, 1 had a hemolytic-uremic syndrome, 1 had a Pauci-immune glomerulonephritis, 1 had a Behçet disease, and in 19 cases the authors did not specify the associated immunological disease.…”

“…All pediatric patients included in the analysis had a confirmed aPL. The reported rate of positivity for anticardiolipin antibodies (aCL) was as follows: IgGþ and/or IgMþ 70.1% (based on available studies 16,18,19,22 ); IgGþ 52.8% (based on available studies 16,19,24 ); IgMþ 35.2% (based on available studies 14,17,22 ). The reported rate for anti-b2-glycoprotein I antibodies was: IgGþ and/or IgMþ 58% (based on available studies [16][17][18][19]22 ); IgGþ 32.7% (based on available studies 14,21,22 ); IgMþ 14.3% (based on available studies 14,22 ).…”

“…The reported rate of positivity for anticardiolipin antibodies (aCL) was as follows: IgGþ and/or IgMþ 70.1% (based on available studies 16,18,19,22 ); IgGþ 52.8% (based on available studies 16,19,24 ); IgMþ 35.2% (based on available studies 14,17,22 ). The reported rate for anti-b2-glycoprotein I antibodies was: IgGþ and/or IgMþ 58% (based on available studies [16][17][18][19]22 ); IgGþ 32.7% (based on available studies 14,21,22 ); IgMþ 14.3% (based on available studies 14,22 ). Lupus anticoagulant (LA) was the most frequently detected aPL with a rate of positivity of 75% [14][15][16][17][18][19][20][21][22] and the reported rate of triple positive was 29.2%.…”