title: Weight-adjusted LMWH prophylaxis provides more effective thrombin inhibition in morbidly obese pregnant women.
abstract: BACKGROUND
  Low molecular weight heparin (LMWH) prophylaxis has been recommended for morbidly obese pregnant women (>40kg/m(2)). There is very little data on the anticoagulant effects of LMWH in this group. We investigated two different dosing regimens; fixed dose and weight-adjusted dose on the anticoagulant effects of the LMWH tinzaparin used for thromboprophylaxis in obese pregnant women.
  
  
  METHODS
  Twenty morbidly obese pregnant women were started on a fixed dose of tinzaparin (4,500 iu/day) at 32weeks gestation and then changed to a weight-adjusted dose (75iu/kg/day) for the remainder of their pregnancy. Four-hour post LMWH, venous bloods were taken after each initial dose and repeated every two weeks until delivery. Twenty normal weight women who did not receive LMWH at the same gestation were used as controls.
  
  
  RESULTS
  Prior to LMWH prophylaxis, tissue factor pathway inhibitor (TFPI) levels in the obese group at 32weeks were significantly lower (p<0.001) and endogenous thrombin potential (ETP) and peak thrombin levels in obese group were significantly higher, compared with controls (p<0.0001; p<0.001). There was no significant difference between ETP levels before and after fixed LMWH. However, ETP levels were significantly lower post weight-adjusted dose compared with post fixed dose. There was a significant effect of LMWH on TFPI levels, (p<0.0001). ETP correlated positively with total body weight prior to LMWH (r=0.631) (p<0.05) and at fixed dose (r=0.578) (p<0.05).
  
  
  CONCLUSIONS
  Morbidly obese pregnant women have increased thrombin generation and reduced natural anticoagulant in third trimester. This prothrombotic state was more effectively attenuated by weight-adjusted than fixed LMWH doses.
authors.affiliation: Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Ireland. Electronic address: k.ismail@ucc.ie.
authors.forename: Siti K
authors.initials: SK
authors.lastname: Ismail
authors.affiliation: Coagulation Research Laboratory, Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James' Hospital, Dublin, Ireland.
authors.forename: Lucy
authors.initials: L
authors.lastname: Norris
authors.affiliation: Comprehensive Coagulation Centre, Department of Haematology, Cork University, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Shea
authors.affiliation: Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Ireland.
authors.forename: John R
authors.initials: JR
authors.lastname: Higgins
mesh_terms: D000328:Adult; D001835:Body Weight; D015331:Cohort Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D009767:Obesity, Morbid / Q000097:blood / Q000150:complications* / Q000473:pathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013917:Thrombin / Q000037:antagonists & inhibitors*; D000078222:Tinzaparin; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin; D013917:Thrombin
keywords: LMWH; Obesity; Pregnancy; Thrombin Generation; Thromboprophylaxis