Abstract

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.

Table 1.

Thrombus Sites*, by APA Group.

APA groupLimb DVTExtensive PECSVTParenchymal thrombosisArterial thrombosisTotal
* 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%) 
APA groupLimb DVTExtensive PECSVTParenchymal thrombosisArterial thrombosisTotal
* 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 2.

Prothrombotic Risk Factors, by APA Group.

APA GroupInfectionSurgery/TraumaSLEOther*NoneTotal
* 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%) 
APA GroupInfectionSurgery/TraumaSLEOther*NoneTotal
* 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%) 

Author notes

Disclosure: No relevant conflicts of interest to declare.