Background: Abdominal thrombosis in children is rare and understudied.
Aims: To apply the calibrated automated thrombogram (CAT) assay of thrombin generation with and without thrombomodulin to investigate thrombophilia in children with a history of abdominal thrombosis.
Methods: This investigation was conducted on biobank samples and clinical data from a consented prospective cohort study. Samples were collected at least 3 months following thrombus detection, on no interfering anticoagulants. Thrombophilia evaluations included antithrombin (AT), protein C (PC), protein S (PS), factor V Leiden (FVL), prothrombin 20210 mutation (PTM), factor VIII activity (FVIII), lipoprotein (a) (Lp(a)) and the antiphospholipid antibodies (APA), lupus anticoagulant (LA), anticardiolipin antibody (ACA) and anti-β2GP1 antibodies. Fibrinogen evaluations were performed as indicated. The calibrated automated thrombogram (CAT) assay of thrombin generation was performed with and without thrombomodulin (TM) using manufacturers procedures (CAT, CAT-TM, Diagnostica Stago). CAT detects increased thrombin generation. CAT-TM detects a failure to down-regulate thrombin generation by activated protein C. Results were stratified by participant age under 2 years, or 2 and greater to separate out presumed perinatal events.
Results: Table 1 shows thrombophilia results in 44 children. Samples were available for CAT assays in 21 participants and the CAT-TM in 19. Table 2 shows CAT and CAT-TM relative to individual assayed traits. CAT thrombin generation was increased in 3 children with consistent thrombophilia traits and 2 with fibrinogen abnormalities. CAT was negative in 16 children, none with defects expected in CAT. CAT-TM showed decreased thrombin suppression in 12 children, 2 with no expected traits. CAT-TM failed to detect 4 expected abnormalities.
|Number of Traits||Number of Participants|
|Traits detected: AT (3), PC (3), PS (2), FVL heter (5), FVL homo (1), PTM (1), fibrinogen
Abnormalities (5), elevated Lp(a) (7), elevated FVIII (7), APA (14)
|Group||N||Thrombophilia Traits Identified that Can be Detected in CAT or CAT-TM|
|< 2 years, CAT +||2||AT (2)|
|< 2 years, CAT –||5||No traits associated with increased thrombin generation|
|≥ 2 years, CAT +||3||PTM (1), [dysfibrinogenemia (2)]|
|≥ 2 years, CAT –||11||No traits associated with increased thrombin generation|
|< 2 years, CAT TM +||2||PC (1), FVL hetero (1)|
|< 2 years, CAT TM-||4||FVL homo & ACA (1)|
|≥ 2 years, CAT TM +||10||FVL hetero (1), Lp(a) (2), APA (3), Lp(a) & APA (2), Unknown (2)|
|≥ 2 years, CAT TM –||3||FVL hetero (1), APA (1), Lp(a) (1)|
Conclusions: Children with abdominal thromboses showed a high rate of abnormal thrombin generation in their steady state. Most abnormal CATs were corroborated with known consistent thrombophilia traits, but some unexplained positives were determined. Future work will evaluate the usefulness of the CAT and CAT-TM as a screening tool for hypercoagulability.
To cite this abstract in AMA style:Kuldanek S, Thornhill D, Jacobson L, Baird C, Chan A, Smith J, Shearer R, Manco-Johnson M. Abnormal Thrombin Generation in Children with Thrombosis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/abnormal-thrombin-generation-in-children-with-thrombosis/. Accessed November 29, 2021.
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