Plasma procoagulant phospholipid clotting time and venous thromboembolism risk

Res Pract Thromb Haemost. 2021 Dec 20;5(8):e12640. doi: 10.1002/rth2.12640. eCollection 2021 Dec.


Background: Negatively charged procoagulant phospholipids, phosphatidylserine (PS) in particular, are vital to coagulation and expressed on the surface membrane of extracellular vesicles. No previous study has investigated the association between plasma procoagulant phospholipid clotting time (PPLCT) and future risk of venous thromboembolism (VTE).

Objectives: To investigate the association between plasma PPLCT and the risk of incident VTE in a nested case-control study.

Methods: We conducted a nested case-control study in 296 VTE patients and 674 age- and sex-matched controls derived from a general population cohort (The Tromsø Study 1994-2007). PPLCT was measured in platelet-free plasma using a modified factor Xa-dependent clotting assay. Logistic regression was used to estimate odds ratio (OR) with 95% confidence intervals (CI) for VTE with PPLCT modelled as a continuous variable across quartiles and in dichotomized analyses.

Results: There was a weak inverse association between plasma PPLCT and risk of VTE per 1 standard deviation increase of PPLCT (OR 0.93, 95% CI 0.80-1.07) and when comparing those with PPLCT in the highest quartile (OR 0.89, 95% CI 0.60-1.30) with those in the lowest quartile. Subjects with PPLCT >95th percentile had substantially lowered OR for VTE (OR 0.35, 95% CI 0.13-0.81). The inverse association was stronger when the analyses were restricted to samples taken shortly before the event. The risk estimates by categories of plasma PPLCT were similar for deep vein thrombosis and pulmonary embolism.

Conclusion: Our findings suggest that high plasma PPLCT is associated with reduced risk of VTE.

Keywords: clotting; extracellular vesicles; phosphatidylserines; phospholipids; venous thromboembolism.