By Robin Liang, PhD in TREC
There is a continuous search for finding laboratory markers that are associated with an increased risk of venous thromboembolism (VTE). While the focus has been mainly on procoagulant pathways that form the clot, there have been relatively few studies that
examine fibrinolytic (clot-breaking) activity in relation to the risk of VTE.
In the Thrombophilia Hypercoagulability Environmental risk for Venous Thromboembolism (THE-VTE) study, a two-center population-based case-control study, researchers set out to investigate fibrinolysis and VTE risk. Patient data was collected to assess acquired risk factors such as plaster cast use, immobilization, oral contraceptive use, malignancy and surgery. Blood samples from VTE patients and their partners, who served as controls, were collected 3 months after the patients stopped anticoagulation therapy. Participants in the study were followed for recurrent VTE for a mean of 4.8 years.
Blood samples were analyzed using clot lysis time (CLT) assays to measure fibrinolytic ability. Additionally, the researchers examined the endogenous thrombin potential (ETP) as a measure of coagulability to examine the relationship between CLT and ETP as well as their combined effects on the development of VTE.
The researchers found that VTE patients had a longer CLT and those with hypofibrinolytic values above the 90th percentile (as measured in control subjects) had a 1.8-fold increased risk of getting a first VTE. There was a clear dose-response relationship between CLT and risk for first VTE. The risk for VTE was 1.7-fold higher in both patients with a prolonged CLT but a normal ETP and those with only an elevated ETP but a normal CLT. The greatest risk (2.9-fold) was found to be in those patients who had both a prolonged CLT and a higher ETP compared to controls. Overall, these results in this study support the hypothesis that increased thrombin generation decreases clot lysis.
While the study found an association between hypofibrinolysis and first VTE, it found only a weak association between CLT and recurrent VTE. This implies that CLT is not a useful marker in the clinics to predict and prevent recurrent VTE. More research is needed to identify effective laboratory markers that can predict risk of VTE.
Reference: Karasu A, Baglin TP, Luddington R, Baglin CA, van Hylckama Vlieg A. (2016), Prolonged clot lysis time increases the risk of a first but not recurrent venous thrombosis. British Journal of Haematology. doi:10.1111/bjh.13911