title: Short-term venous stasis induces fibrinolytic activation but not thrombin formation.
abstract: OBJECTIVE
  Venous stasis is a well-known risk factor for the development of venous thromboembolism. It is likely that stasis increases the risk of thrombosis by inducing hypercoagulability via the hypoxic procoagulant activation of endothelial and mononuclear cells and the accumulation of activated clotting factors. However, increased rates of thrombin formation have not been demonstrated in response to venous stasis in vivo.
  
  
  METHODS
  In this study, we used the venous occlusion (VO) test to determine, if stasis triggers thrombin formation in healthy individuals (n=25) and patients with additional thrombotic risk factors, such as inherited thrombophilia (n=19) and symptomatic atherosclerosis (n=15). Thrombin formation was monitored by measuring plasma levels of free thrombin using a highly sensitive oligonucleotide enzyme capture assay (OECA) in addition to the plasma levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin-complexes (TAT). The plasma levels of activated protein C (APC) were additionally measured using an APC-OECA.
  
  
  RESULTS
  VO induced a significant (p<0.05) increase in the levels of tissue-type plasminogen activator and plasmin-α2-antiplasmin-complexes. In all three cohorts, the majority of samples obtained during VO showed no quantifiable thrombin or APC levels. Consistent with these findings F1+2 and TAT did not change.
  
  
  CONCLUSIONS
  We conclude that short-term venous stasis induces a profibrinolytic response due to the activation of endothelial cells, but not a prothrombotic response, even in the presence of additional thrombophilic risk factors. Furthermore, our results support the hypothesis that the stasis-induced profibrinolytic activation of endothelial cells occurs independently from thrombin formation.
authors: Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn.
authors: Heiko
authors: H
authors: Rühl
authors: Jens
authors: J
authors: Müller
authors: Jana
authors: J
authors: Wäschenbach
authors: Johannes
authors: J
authors: Oldenburg
authors: Oliver
authors: O
authors: Dewald
authors: Bernd
authors: B
authors: Pötzsch
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000378:metabolism; D002138:Calibration; D003029:Coagulants / Q000737:chemistry; D003324:Coronary Artery Disease / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006487:Hemostasis; D006720:Homozygote; D006801:Humans; D000860:Hypoxia; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000737:chemistry; D010641:Phenotype; D011486:Protein C / Q000096:biosynthesis; D011516:Prothrombin / Q000096:biosynthesis; D012307:Risk Factors; D013917:Thrombin / Q000096:biosynthesis*; D019851:Thrombophilia / Q000097:blood / Q000378:metabolism; D013927:Thrombosis / Q000473:pathology; D054556:Venous Thromboembolism / Q000378:metabolism*; D055815:Young Adult
chemical_list: D003029:Coagulants; D009841:Oligonucleotides; D011486:Protein C; D011516:Prothrombin; D013917:Thrombin