Comprehensive Antiphopholipid Antibody Testing in Children with Acute Thromboembolism: Preliminary Findings from a Prospective Inceptional Cohort Study.

BACKGROUND: The significance of the lupus anticoagulant (LA) and other antiphospholipid antibodies (APA) in children with thromboembolism (TE) has not been as clearly defined in children as among adults. OBJECTIVE: To characterize TE presentation and prothrombotic risk factors among children with TE who are positive for the LA using the dilute Russell Viper Venom Time (dRVVT) as a screening test. METHODS: Children with acute TE were consecutively enrolled in a prospective inceptional cohort study and a compehensive APA testing battery was serially employed. APA testing included StaClot-LA, as well as ELISA for IgG and IgM binding to prothrombin, protein C, protein S, cardiolipin and β2GP1. RESULTS: 34 children who were dRVVT positive within 3 months of acute thrombosis were evaluated with the entire APA battery on 1 to 5 occasions over 3 months to 4 years. Multiple APA were detected in 20 (59% of) study participants (5 tests, n=1; 4 tests, n=2; 3 tests, n=6; 2 tests, n=11; 1 test, n=14). Findings were: dRVVT (100%), anti-prothrombin (50%), StaClot (18%), anti-protein S and ACA (12% each), anti-β2GP1 (6%) and anti-protein C (3%). TE presentation and prothrombotic risk factors were compared between these 20 children with multiple APA and 14 children who were dRVVT positive only (Tables 1 and 2). Children with LA-associated TE who had multiple APA were more likely to present with parenchymal sites of thrombosis (p=0.03) and appeared less likely to have otherwise-idiopathic TE (i.e., no additional prothrombotic risk factors identified), although the latter trend was not statistically significant. CONCLUSIONS: The majority of children with acute TE and a positive dRVVT in whom a comprehensive battery of APA is performed demonstrate multiple APA, among which anti-prothrombin antibodies are the most common. When compared to children positive for dRVVT only, children with LA-associated thrombosis who have multiple APA are particularly predisposed to parenchymal thrombotic events and may be more likely to experience otherwise-idiopathic TE. Future investigations will evaluate the risk of recurrent TE in children with thrombosis relative to findings on serial comprehensive APA testing. | APA group | Limb DVT | Extensive PE | CSVT | Parenchymal thrombosis | Arterial thrombosis | Total | |:------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | -------- | ------------ | ------- | ---------------------- | ------------------- | --------- | | * Some patients had >1 site. Abbreviations: DVT=deep venous thrombosis; PE=pulmonary embolism; CSVT=cerebral sinovenous thrombosis. Arterial thrombosis includes ischemic arterial stroke. | | Multiple APA | 8 (40%) | 6 (30%) | 2 (10%) | 6 (30%) | 3 (15%) | 20 (100%) | | dRVVT only | 7 (50%) | 4 (29%) | 0 (0%) | 0 (0%) | 3 (21%) | 14 (100%) | Table 1. Thrombus Sites*, by APA Group. | APA Group | Infection | Surgery/Trauma | SLE | Other* | None | Total | |:------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | --------- | -------------- | ------- | ------- | ------- | --------- | | * Includes anatomic anomaly, obesity, sedentary condition, oral contraceptive use, genetic thrombophilia, central venous catheter, and cardiac disease. Abbreviation: SLE=systemic lupus erythematosus. | | Multiple APA | 4 (20%) | 3 (15%) | 2 (10%) | 4 (20%) | 7 (35%) | 20 (100%) | | dRVVT only | 2 (14%) | 1 (7%) | 0 (0%) | 9 (64%) | 2 (14%) | 14 (100%) | Table 2. Prothrombotic Risk Factors, by APA Group.