title: Post-thrombolysis haemostasis changes after rt-PA treatment in acute cerebral infarct. Correlations with cardioembolic aetiology and outcome.
abstract: BACKGROUND
  Little is known, in man, in the post-thrombolytic molecular dynamics of haemostasis, particularly the effect of rt-PA on antifibrinolytic components such as alpha2 anti-plasmin and Factor XIII.
  
  
  OBJECTIVE
  The purpose of this study was to systematically determine changes in coagulation and fibrinolytic parameters after thrombolysis with rt-PA during 24h. We also aimed to correlate these parameters with different acute ischemic stroke subtypes and global outcome.
  
  
  METHODS
  Eighty consecutive patients with cerebral infarcts treated with rt-PA had their plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, Factor XIII, fibrin(ogen) degradation products (FDP) and D-Dimers measured at baseline (h0), 2 (h2) and 24h (h24) after initiation of thrombolysis. Correlations between the variations of these components were statistically studied, using the Spearman rank test or the Pearson test. These haemostatic parameters were also compared with cardioembolic and non cardioembolic patients, as well as between poor and favourable outcome patients.
  
  
  RESULTS
  Between h0 and h2, a decrease in fibrinogen, plasminogen, alpha2-antiplasmin, and factor XIII was observed, while an increase in FDP and D-Dimers took place. These values returned to the initial levels at h24. At 2h, the decrease in fibrinogen was significantly correlated with that of plasminogen (0.48, p=0.01), alpha2-antiplasmin (0.48, p=0.004), and factor XIII (0.44, p=0.01); the decrease in plasminogen was significantly correlated with those of antifibrinolytic components, factor XIII (0.47, p=0.02) and alpha2-antiplasmin (r=0.77, p<0.001). These variations were independent of NIHSS. Cardioembolic infarcts showed a statistically significant greater h0-h2 decrease in plasminogen (p=0.04) and an h0-h2 increase in FDP (p=0.02). Poor outcome was linked to low plasminogen values at 2 and 24h.
  
  
  CONCLUSIONS
  Supposed to be fibrin-specific, rt-PA induces a decrease in circulating fibrinogen, significantly linked to a decrease in plasminogen. A collateral increase in antifibrinolytic agents such as factor XIII and alpha2-antiplasmin is also observed. At 2h, a significant decrease in plasminogen and a significant increase in fibrin(ogen) degradation products (FDP) are observed in cardioembolic infarcts, and appear as early independent predictors of this aetiology. A low plasminogen value at 2h is potentially predictive of poor prognosis at 3months.
authors.affiliation: Department of Neurology, Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shangaï, China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Pôle Information Médicale Evaluation Recherche Hospices Civils de Lyon, Lyon, France and Université Lyon 1 et Equipe d'Accueil 4129 Lyon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Berthiller
authors.affiliation: Cerebrovascular Unit, Department of Neurology, Université Claude Bernard, Lyon, France. Electronic address: laurent.derex@chu-lyon.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Derex
authors.affiliation: Cerebrovascular Unit, Department of Neurology, Université Claude Bernard, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Trouillas
authors.affiliation: Cerebrovascular Unit, Department of Neurology, Université Claude Bernard, Lyon, France.
authors.forename: Laho
authors.initials: L
authors.lastname: Diallo
authors.affiliation: Laboratoire d'hématologie, CBPE, Hospices Civils de Lyon, Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Hanss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000097:blood* / Q000188:drug therapy*; D005176:Factor XIII / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005573:Formycins / Q000097:blood; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010958:Plasminogen / Q000378:metabolism; D012265:Ribonucleotides / Q000097:blood; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D005573:Formycins; D012265:Ribonucleotides; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; C020332:formycin diphosphate; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D005176:Factor XIII; D010959:Tissue Plasminogen Activator
keywords: Alpha2-antiplasmin; Factor XIII; Fibrin; Fibrinogen; Plasminogen; Thrombolysis