title: Thromboelastometry versus free-oscillation rheometry and enoxaparin versus tinzaparin: an in-vitro study comparing two viscoelastic haemostatic tests' dose-responses to two low molecular weight heparins at the time of withdrawing epidural catheters from ten patients after major surgery.
abstract: BACKGROUND
  Monitoring low molecular weight heparins (LMWH's) in the perioperative period is prudent in patients at high risk of coagulative complications, especially when the patient has an epidural catheter requiring withdrawal, which is associated with the risk of spinal haematoma. The aim of this study was to evaluate the in vitro dose-responses of two different LMWH's on two different viscoelastic haemostatic tests, using blood sampled from patients with normal routine coagulation parameters, on the day after major surgery when their epidural catheters were due to be withdrawn.
  
  
  METHODS
  Enoxaparin or tinzaparin were added in vitro to blood from ten patients who had undergone oesophageal resection, to obtain plasma concentrations of approximately 0, 0.5, 1.0 and 1.5 IU/mL. Coagulation was monitored using thromboelastometry (ROTEM®) using the InTEM® activating reagent; and free oscillation rheometry (FOR: ReoRox®), activated using thromboplastin. Clot initiation was measured using ROTEM-CT, ReoRox-COT1 and ReoRox-COT2. Clot propagation was measured using ROTEM-CFT, ROTEM-Alpha Angle and ReoRox-Slope. Clot stability was measured using ROTEM-MCF and ReoRox-G'max, and clot lysis was measured using ROTEM-ML and ReoRox-ClotSR.
  
  
  RESULTS
  Clot initiation time assessed by thromboelastometry and FOR was prolonged by increasing concentrations of both LMWH's (P < 0.01). Equivalent doses of tinzaparin in international units (anti-FXa units) per millilitre prolonged clot initiation more than enoxaparin (P < 0.05). There was significant inter-individual variation - the ranges of CT and COT1 at LMWH-concentrations of 0 and 1.5 IU/mL overlapped. None of the tests reflecting clot formation rate or stability showed a dose-response to either LMWH but clot lysis showed a tentative negative dose-response to the LMWH's.
  
  
  CONCLUSIONS
  Clot initiation time's dose-dependent prolongation by LMWH's in this study agrees with previous research, as does tinzaparin's stronger anti-coagulative effect than enoxaparin at equivalent levels of anti-FXa activity. This casts doubt on the validity of using anti-FXa assays alone to guide dosage of LMWH's. The significant inter-individual variation in dose-response suggests that the relationship between dose and effect in the postoperative period is complicated. While both ROTEM and FOR may have some role in postoperative monitoring, more research is needed before any conclusion can be made about their clinical usefulness.
authors.affiliation: Medical Faculty, University of Lund, Lund, Sweden. odt@cantab.net.|Department of Paediatric Anaesthesia and Intensive Care, SUS Lund University Hospital, Lund, Sweden. odt@cantab.net.
authors.forename: Owain
authors.initials: O
authors.lastname: Thomas
authors.affiliation: Medical Faculty, University of Lund, Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Department of Clinical Chemistry, Department of Clinical Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Nahreen
authors.initials: N
authors.lastname: Tynngård
authors.affiliation: Medical Faculty, University of Lund, Lund, Sweden.|Department of Anaesthesia and Intensive Care, SUS Lund University Hospital, Lund, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Schött
mesh_terms: D000767:Anesthesia, Epidural / Q000295:instrumentation*; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000379:methods / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000494:pharmacology*; D004947:Esophagus / Q000601:surgery*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006490:Hemostatics; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D012212:Rheology; D013916:Thrombelastography / Q000706:statistics & numerical data*; D013997:Time Factors; D000078222:Tinzaparin
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006490:Hemostatics; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin