title: Prothrombotic Fibrin Clot Phenotype Is Associated With Recurrent Pulmonary Embolism After Discontinuation of Anticoagulant Therapy.
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.
  
  
  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.affiliation: 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.).
authors.forename: Michal
authors.initials: M
authors.lastname: Zabczyk
authors.affiliation: 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.).
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Plens
authors.affiliation: 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.).
authors.forename: Wioletta
authors.initials: W
authors.lastname: Wojtowicz
authors.affiliation: 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.
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001780:Blood Coagulation Tests; D016009:Chi-Square Distribution; D004334:Drug Administration Schedule; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012372:ROC Curve; D012008:Recurrence; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D020246:Venous Thrombosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005337:Fibrin; D013917:Thrombin
keywords: fibrin; fibrinolysis; pulmonary embolism; recurrence; thrombosis