title: Acute cigarette smoke exposure reduces clot lysis--association between altered fibrin architecture and the response to t-PA.
abstract: BACKGROUND
  Enhanced thrombolysis is a proposed mechanism for reduced mortality in cigarette smokers with STEMI ("smoker's paradox"). The mechanisms remain unclear but studies suggest fibrin architecture (FA) may affect thrombolysis. Our group has previously shown that acute cigarette smoke exposure (CSE) alters FA. This study was done to evaluate the association between FA, thrombolysis and CSE.
  
  
  RESULTS
  Otherwise healthy smokers (n=22) were studied before and after smoking two cigarettes. Non-smokers (n=22) served as controls. Two ex-vivo models were used to evaluate clot lysis of venous blood and these data were compared to FA as determined by SEM. In the first model, clot lysis in a glass tube at 60minutes after addition of t-PA was measured. The second model quantified lysis utilizing thromboelastography. With the latter, after a clot reached maximum strength, t-PA was added and clot lysis at 60min was noted. SEM studies were performed on platelet poor plasma mixed with thrombin and FA was examined at 20K. Clot lysis was similar in both groups except that post-smoking, TEG showed a significantly lower lysis compared to pre- and non-smoking clots. SEM analysis showed significantly thinner fibers and denser clots post-smoking.
  
  
  CONCLUSIONS
  Venous clots from smokers failed to show an enhanced lysis when exposed to t-PA. In fact, acute CSE was associated with changes in FA and increased resistance to thrombolysis. These findings in part may explain enhanced thrombogenicity but suggest that mechanisms other than enhanced fibrinolysis are likely to be responsible for "smoker's paradox."
authors.affiliation: Division of Cardiovascular Medicine, University of California San Francisco, Fresno, CA 93721, USA.
authors.forename: Rajat S
authors.initials: RS
authors.lastname: Barua
authors.forename: Fridolin
authors.initials: F
authors.lastname: Sy
authors.forename: Sundararajan
authors.initials: S
authors.lastname: Srikanth
authors.forename: Grace
authors.initials: G
authors.lastname: Huang
authors.forename: Usman
authors.initials: U
authors.lastname: Javed
authors.forename: Cyrus
authors.initials: C
authors.lastname: Buhari
authors.forename: Dennis
authors.initials: D
authors.lastname: Margosan
authors.forename: Waqas
authors.initials: W
authors.lastname: Aftab
authors.forename: John A
authors.initials: JA
authors.lastname: Ambrose
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008297:Male; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000097:blood*; D013927:Thrombosis / Q000097:blood* / Q000209:etiology*; D010959:Tissue Plasminogen Activator / Q000097:blood*
chemical_list: D005337:Fibrin; D010959:Tissue Plasminogen Activator