title: Women with unexplained recurrent pregnancy loss do not have evidence of an underlying prothrombotic state: experience with calibrated automated thrombography and rotational thromboelastometry.
abstract: BACKGROUND
  Where unexplained recurrent pregnancy loss (RPL) is attributed to an underlying maternal prothrombotic state, empirical prophylactic anticoagulation may be recommended.
  
  
  METHODS
  In the present study we used calibrated automated thrombography and rotational thromboelastometry to determine the procoagulant potential of these women as a rationale for anticoagulation. Fifty women with ≥three consecutive unexplained losses prior to 14 weeks' gestation or one loss after this time were compared with forty-one parous women with no miscarriages. Exclusion criteria included antiphospholipid syndrome, inherited thrombophilia and prior venous thromboembolism. Thrombin generation in platelet poor plasma and whole blood thromboelastometry was performed outside pregnancy to determine the presence or not of an underlying prothrombotic state.
  
  
  RESULTS
  Peak thrombin and endogenous thrombin potential were not significantly increased in subjects relative to controls. The use of low tissue factor (1 pM) to better reflect physiological conditions and assay modification to better assess the protein C pathway (5 pM in the presence of thrombomodulin) provided no additional discrimination. Consistent results were shown with thromboelastometry; mean parameters were equivalent between subjects and controls.
  
  
  CONCLUSIONS
  These data demonstrate that global coagulation assays provide no evidence of an underlying hypercoagulable state in women with unexplained RPL; this is in keeping with the results of recent randomised controlled trials and strengthens the evidence base against use of anticoagulants in this setting.
authors.affiliation: King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK. Electronic address: s.bennett1@nhs.net.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Bennett
authors.affiliation: Department of Haematological Medicine, Glasgow Royal Infirmary, UK.
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Bagot
authors.affiliation: Department of Maternal Medicine, King's College Hospital NHS Foundation Trust, London, UK.
authors.forename: Adjoa
authors.initials: A
authors.lastname: Appiah
authors.affiliation: Department of Maternal Medicine, King's College Hospital NHS Foundation Trust, London, UK.
authors.forename: Jemma
authors.initials: J
authors.lastname: Johns
authors.affiliation: Department of Maternal Medicine, King's College Hospital NHS Foundation Trust, London, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Ross
authors.affiliation: King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK.
authors.forename: Lara N
authors.initials: LN
authors.lastname: Roberts
authors.affiliation: King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Patel
authors.affiliation: King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK.
authors.forename: Roopen
authors.initials: R
authors.lastname: Arya
mesh_terms: D000026:Abortion, Habitual / Q000097:blood*; D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000502:physiology; D002138:Calibration; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood*; D011446:Prospective Studies; D013916:Thrombelastography / Q000379:methods*; D013917:Thrombin / Q000032:analysis / Q000378:metabolism*; D019851:Thrombophilia / Q000097:blood*; D055815:Young Adult
chemical_list: D013917:Thrombin
keywords: Fetal loss; Hypercoagulability; Miscarriage; Rotational thromboelastometry; Thrombin generation