Abstract Number: PB0469
Meeting: ISTH 2020 Congress
Background: Recently, we have shown that low APC response to in vivo thrombin formation increases the thrombotic risk of factor V Leiden (FVL) carriers. In vivo thrombin formation in this approach, termed SHAPE, was induced by low-dose administration of recombinant activated factor VII (rFVIIa) followed by hemostasis biomarker monitoring.
Aims: To extend this approach to patients with TUO, with a positive self-history of unprovoked VTE (VTE+) as well as a positive family history, in whom no established thrombophilic risk factor was detectable.
Methods: Blood samples were collected before and during a period of 8 hours following injection of 15 µg/kg rFVIIa from patients with TUO (n=21), VTE+ patients with FVL or prothrombin 20210G>A mutation (n=27), and healthy controls (n=29). APC levels were measured using an oligonucleotide-based enzyme capture assay (OECA). Prothrombin activation fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and D-dimer were measured additionally.
Results: D-dimer levels remained within the reference range. F1+2 levels increased after rFVIIa injection without showing significant differences between cohorts. A comparable increase of TAT was observed in both TUO patients and VTE+ mutation carriers, from a median of 21.3 to 51.1 pmol/L (P=0.002), and from 21.3 to 43.9 pmol/L, respectively (P< 10-4) (Fig. 1A). In the controls TAT increased from 21.3 to 30.89 pmol/L (P=0.024). APC increased from 0.80 to 3.84 pmol/L (P=0.001) in the TUO cohort, from 1.14 to 5.82 pmol/L (P< 10-4) in VTE+ mutation carriers, and from 0.79 to 3.18 pmol/L (P=0.001) in the control group. The increase of APC levels was significantly smaller in the TUO cohort than in the VTE+ mutation carriers (P=0.019) (Fig. 1B).
Conclusions: A low APC response to an increased in vivo thrombin formation is a frequent finding among patients with thrombophilia of unknown origin, suggesting that a low APC response might be an independent risk factor of VTE.
To cite this abstract in AMA style:Rühl H, Reda S, Winterhagen FI, Berens C, Müller J, Oldenburg J, Pötzsch B. Familial Thrombophilia of Unknown Origin (TUO) Is Associated with Low Activated Protein C (APC) Response to in vivo Thrombin Formation in Stimulated Hemostasis Activity Pattern Evaluation (SHAPE) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/familial-thrombophilia-of-unknown-origin-tuo-is-associated-with-low-activated-protein-c-apc-response-to-in-vivo-thrombin-formation-in-stimulated-hemostasis-activity-pattern-evaluation-shape/. Accessed December 2, 2022.
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