Michal Zabczyk1, Krzysztof Plens1, Wioletta Wojtowicz1, Anetta Undas2. 1. From the Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Poland (M.Z., A.U.); Data Analysis Center, Krakow Cardiovascular Research Institute, Poland (K.P.); Department of Mechanical Engineering, Cracow University of Technology, Krakow, Poland (W.W.); and Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland (A.U.). 2. From the Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Poland (M.Z., A.U.); Data Analysis Center, Krakow Cardiovascular Research Institute, Poland (K.P.); Department of Mechanical Engineering, Cracow University of Technology, Krakow, Poland (W.W.); and Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland (A.U.). mmundas@cyf-kr.edu.pl.
Abstract
OBJECTIVE: Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism with a high recurrence rate after anticoagulation cessation. Recently, we have reported that prothrombotic clot phenotype in venous thromboembolism patients is associated with an increased risk of recurrent deep-vein thrombosis. APPROACH AND RESULTS: We tested whether abnormal clot properties are predictive of recurrent PE. We investigated 156 consecutive white patients aged 18 to 65 years after the first-ever provoked or unprovoked PE (n=89), with or without deep-vein thrombosis. Plasma fibrin clot permeability (Ks), turbidity measurements, calibrated automated thrombography, and efficiency of fibrinolysis using clot lysis time, maximum D-dimer levels, and rate of increase in D-dimer levels were evaluated at ≥3 months of anticoagulant therapy, at least 4 weeks since the anticoagulation withdrawal. The primary end point was recurrent PE during a median follow-up of 50 months. Recurrent PE was diagnosed in 23 (14.7%; 5%/yr) patients. Recurrent PE was associated with formation of denser fibrin networks reflected by lower Ks (P=0.007) and impaired fibrinolysis, as evidenced by prolonged clot lysis time (P=0.012) and reduced maximum rate of increase in D-dimer levels in the lysis assay (P=0.004). Patients with recurrent PE had higher plasma D-dimer (P<0.001) and thrombin peak (P=0.007) compared with the remainder, whereas turbidity measurements and maximum D-dimer levels did not differ in the recurrence. Multivariate model showed that independent predictors of recurrent PE were female sex, unprovoked venous thromboembolism, higher plasma D-dimer, reduced Ks, and reduced maximum rate of increase in D-dimer levels in the lysis assay (all P<0.05). CONCLUSIONS: Altered fibrin clot properties including formation of more compact clots displaying impaired susceptibility to lysis may predispose to recurrent PE.
OBJECTIVE: Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism with a high recurrence rate after anticoagulation cessation. Recently, we have reported that prothrombotic clot phenotype in venous thromboembolism patients is associated with an increased risk of recurrent deep-vein thrombosis. APPROACH AND RESULTS: We tested whether abnormal clot properties are predictive of recurrent PE. We investigated 156 consecutive white patients aged 18 to 65 years after the first-ever provoked or unprovoked PE (n=89), with or without deep-vein thrombosis. Plasma fibrin clot permeability (Ks), turbidity measurements, calibrated automated thrombography, and efficiency of fibrinolysis using clot lysis time, maximum D-dimer levels, and rate of increase in D-dimer levels were evaluated at ≥3 months of anticoagulant therapy, at least 4 weeks since the anticoagulation withdrawal. The primary end point was recurrent PE during a median follow-up of 50 months. Recurrent PE was diagnosed in 23 (14.7%; 5%/yr) patients. Recurrent PE was associated with formation of denser fibrin networks reflected by lower Ks (P=0.007) and impaired fibrinolysis, as evidenced by prolonged clot lysis time (P=0.012) and reduced maximum rate of increase in D-dimer levels in the lysis assay (P=0.004). Patients with recurrent PE had higher plasma D-dimer (P<0.001) and thrombin peak (P=0.007) compared with the remainder, whereas turbidity measurements and maximum D-dimer levels did not differ in the recurrence. Multivariate model showed that independent predictors of recurrent PE were female sex, unprovoked venous thromboembolism, higher plasma D-dimer, reduced Ks, and reduced maximum rate of increase in D-dimer levels in the lysis assay (all P<0.05). CONCLUSIONS: Altered fibrin clot properties including formation of more compact clots displaying impaired susceptibility to lysis may predispose to recurrent PE.
Authors: Sravya Kattula; Yaqiu Sang; Gustaaf de Ridder; Anna C Silver; Emma G Bouck; Brian C Cooley; Alisa S Wolberg Journal: J Thromb Haemost Date: 2021-09-06 Impact factor: 5.824
Authors: Stephen R Baker; Michal Zabczyk; Fraser L Macrae; Cédric Duval; Anetta Undas; Robert A S Ariëns Journal: J Thromb Haemost Date: 2019-03-08 Impact factor: 5.824