title: Vitamin K antagonists favourably modulate fibrin clot properties in patients with atrial fibrillation as early as after 3days of treatment: Relation to coagulation factors and thrombin generation.
abstract: BACKGROUND
  Atrial fibrillation (AF) increases the risk of thromboembolism that is reduced by vitamin K antagonists (VKAs). We sought to investigate changes in plasma fibrin clot phenotype at the onset of oral anticoagulation.
  
  
  METHODS
  Forty consecutive AF patients (aged 45-83 years, CHA2DS2-VASc score 3.0±1.5) who started therapy with warfarin or acenocoumarol were studied. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), along with clotting factors (F), thrombin generation (TG) profiles and protein C (PC) levels were determined on days 3, 5, 7, 28 and 56±1 since the first dose.
  
  
  RESULTS
  AF patients had 16% higher median of Ks and 15% lower median of CLT as early as on day 3 of VKA therapy compared with the baseline (both p<0.001), reaching the plateau values on day 7 and 5, respectively. Higher Ks values on days 1 and 3 were found in AF patients with further stable anticoagulation (both p<0.05). Moreover, FIX explained 32% of the total variability in Ks. Multivariate analysis adjusted for potential confounders including time as a predictor showed that vitamin K-dependent (VKD) factors, PC and TG parameters were the predictors of Ks (all p<0.0001), while only the lag phase of TG and thrombin peak predicted CLT (both p<0.05) in AF patients. Regression analysis of time-series showed however, that CLT was also predicted by VKD factors and PC (all p<0.05).
  
  
  CONCLUSIONS
  Plasma fibrin clot properties in AF patients are favourably modified as early as after 3days of VKA administration, which might contribute to antithrombotic effectiveness.
authors: Department of Cardiac Surgery, Anaesthesiology and Experimental Cardiology, Institute of Cardiology, Jagiellonian University, Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland. Electronic address: michal.zabczyk@uj.edu.pl.
authors: Michał
authors: M
authors: Ząbczyk
authors: John Paul II Hospital, Krakow, Poland; Department of Electrocardiology, Institute of Cardiology, Jagiellonian University, Medical College, Krakow, Poland.
authors: Jacek
authors: J
authors: Majewski
authors: John Paul II Hospital, Krakow, Poland; Department of Electrocardiology, Institute of Cardiology, Jagiellonian University, Medical College, Krakow, Poland.
authors: Grzegorz
authors: G
authors: Karkowski
authors: Faculty of Health Science, Jagiellonian University, Medical College, Krakow, Poland.
authors: Krzysztof Piotr
authors: KP
authors: Malinowski
authors: Department of Cardiac Surgery, Anaesthesiology and Experimental Cardiology, Institute of Cardiology, Jagiellonian University, Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland.
authors: Anetta
authors: A
authors: Undas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D063285:Fibrin Clot Lysis Time / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000378:metabolism*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D001779:Blood Coagulation Factors; D014812:Vitamin K; D005337:Fibrin; D013917:Thrombin
keywords: Atrial fibrillation; Clot lysis time; Clotting factors; Fibrin clot permeability; Vitamin K antagonists