Abstract Number: PB0114
Meeting: ISTH 2020 Congress
Background: Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis resulting in restrictive blood flow in peripheral arteries. Patients with PAD are at increased risk of atherothrombotic events despite current optimal medical treatment. Risk stratification is necessary in clinical decision making, but identifying high-risk PAD patients remains challenging. The COMPASS-study showed that combined anticoagulant and antiplatelet therapy reduced cardiovascular (CV) mortality, illustrating the important role of coagulation in PAD.
Aims: To compare differences in coagulation status in PAD patients with or without a major CV event during follow-up.
Methods: Between May 2018 and January 2019, 120 patients objectively diagnosed with PAD using the ankle-brachial index (< 0.90) were enrolled in this prospective cohort study. The study was approved by the recognized medical ethical committee of MUMC+ and all participants gave written informed consent. Blood samples and patient data were collected at baseline. During a one-year follow-up period, CV events (myocardial infarction, cerebrovascular accident, acute limb ischemia) and (CV) mortality were recorded. Citrated platelet-poor plasma was used to perform thrombin generation (with and without tissue factor) and to measure coagulation factor complexes Factor IXa:Antithrombin (FIXa:AT), FXa:AT, FXIa:a1-antitrypsin, FXIa:AT, FXIIa:C1inhibitor and thrombin:AT (TAT).
Results: The investigated population was 68±10 years old, predominantly male (60%) and was adequately treated by antiplatelet drugs (100%), antihypertensive drugs (75%) and lipid-lowering drugs (97%). In twelve patients (10%) a CV event was recorded during follow-up. FXIIa:C1inhibitor complexes were significantly elevated in patients with a CV event versus patients without event (181×103 ± 46×103 vs 151×103 ± 47×103, p 0.039). Other coagulation factor complexes (Table 1) and thrombin generation (Table 2) were not different between the two groups.
Conclusions: Our findings show increased contact activation in PAD patients with increased risk of CV events despite contemporary medical treatment. Further studies are needed to confirm FXIIa as a potential biomarker and druggable target.
|Coagulation complex||Event||No event||p-value|
|FIXa:AT (pM)||120 (102-139)||103 (93-118)||0.066|
|FXa:AT (pM)||127 (120-148)||124 (116-139)||0.456|
|FXIa:α1AT (pM)||188 (155-256)||187 (144-230)||0.774|
|FXIa:AT (pM)||22.1 (19.2-28.3)||21.5 (18.9-24.1)||0.381|
|FXIIa:C1inh (U)||181×103 ±46×103||151×103 ±47×103||0.039*|
|TAT (pM)||2.43 (1.65-5.95)||2.33 (1.88-3.27)||0.848|
[Levels of coagulation factor complexes for PAD patients with events during follow-up and PAD patients without events during follow-up.]
|0 pM TF||Lag time (min)||15.2 (12.4-21)||14.3 (12-19.1)||0.600|
|1 pM TF||Lag time (min)||6.8 (6-9.4)||6.3 (5.7-7.3)||0.119|
|ETP (nM/min)||1262 (1046-1415)||1217 (1095-1344)||0.873|
[Thrombin generation with and without tissue factor for PAD patients with events during follow-up and PAD patients without events during follow-up.]
To cite this abstract in AMA style:Kremers B, Mees B, Daemen J-, van Oerle R, ten Cate H, ten Cate-Hoek AJ, Spronk H. Elevated Levels of Activated Factor XII Are Associated with an Increased Risk of Atherothrombotic Events in Peripheral Artery Disease [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/elevated-levels-of-activated-factor-xii-are-associated-with-an-increased-risk-of-atherothrombotic-events-in-peripheral-artery-disease/. Accessed January 27, 2022.
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