title: Thromboelastography on plasma reveals delayed clot formation and accelerated clot lyses in HIV-1 infected persons compared with healthy controls.
abstract: BACKGROUND
  Thromboembolic events among HIV infected persons are a recognized clinical problem but the underlying mechanisms are poorly understood. To assess whether coagulation and fibrinolysis differ between long-term treated HIV infected individuals (HIV+) and healthy controls (CON), we investigated functional plasma coagulation by thrombelastography (TEG) and plasma markers of endothelial and platelet activation.
  
  
  METHODS
  In 67 successfully long-term treated HIV+ and 15 CON we analyzed stored plasma samples by TEG, with or without addition of tissue-type plasminogen activator (tPA), and measured levels of C-reactive protein, thrombomodulin, syndecan-1, sVE-cadherin, soluble CD40 ligand (sCD40L), adrenaline and noradrenaline.
  
  
  RESULTS
  Compared to CON, HIV+ had delayed clot formation (reaction (R)-time 14.2 min. vs. 11.2 min., p = 0.0004) and reduced clot formation rapidity (angle 22.6° vs. 48.6°, p = <0.0001). Clot lyses induced by tPA was accelerated in HIV+ displaying enhanced clot degradation after 30 and 60 min (53.9% vs. 24.2%, p < 0.0001 and 77.4% vs. 59.9%, p < 0.0001, respectively). sCD40L and TEG R-time correlated negatively in both HIV+ and CON (Rho =-0.502, p < 0.001 and rho =-0.651, p = 0.012).
  
  
  CONCLUSIONS
  No previous studies have examined plasma coagulation by TEG in HIV, however, we have previously demonstrated that HIV+ display hypocoagulability in whole blood by TEG in accordance with the results of this study. Others have reported of HIV associated changes in the hemostatic system in a pro-coagulant direction based on measurements of isolated components of the coagulation pahways. In disease conditions, the flowing blood may change from "normal" to hyper- or hypocoagulant or to hyper- or hypofibrinolytic. A balance may exist in the flowing blood, i.e. between blood cells and the plasma phase, so that pro-coagulant blood cells are balanced by a hypocoagulable plasma phase; thus alterations that may promote thromboembolic events in the patient may at the same time appear as a hypocoagulable profile when evaluated in vitro.
  
  
  CONCLUSIONS
  Plasma from long-term treated HIV infected persons displays a hypocoagulable profile with reduced fibrinolytic resistance as compared to healthy controls.
authors.affiliation: Department of Infectious Diseases 8632, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. frederikkefr@gmail.com.
authors.forename: Frederikke Falkencrone
authors.initials: FF
authors.lastname: Rönsholt
authors.affiliation: Department of Infectious Diseases 8632, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. jan.gerstoft@regionh.dk.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.affiliation: Department of Clinical Immunology 2031, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. henrik.ullum@regionh.dk.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.affiliation: Section for Transfusion Medicine 2032, Capital Region Blood Bank, Copenhagen University Hospital Rigshospitalet , Copenhagen, Denmark. per.johansson@regionh.dk.
authors.forename: Pär Ingemar
authors.initials: PI
authors.lastname: Johansson
authors.affiliation: Department of Infectious Diseases 8632, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. terese.katzenstein@regionh.dk.
authors.forename: Terese Lea
authors.initials: TL
authors.lastname: Katzenstein
authors.affiliation: Section for Transfusion Medicine 2032, Capital Region Blood Bank, Copenhagen University Hospital Rigshospitalet , Copenhagen, Denmark. sisse.ostrowski@gmail.com.
authors.forename: Sisse Rye
authors.initials: SR
authors.lastname: Ostrowski
mesh_terms: D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001798:Blood Proteins / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D063285:Fibrin Clot Lysis Time; D005342:Fibrinolysis; D015658:HIV Infections / Q000097:blood*; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D013916:Thrombelastography / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator