TIPPS: Thrombophilia in Pregnancy Prophylaxis Study

Inclusion Criteria:

One or more of the following:

• Previous preeclampsia
• Previous unexplained intra-uterine growth restriction

• Previous recurrent miscarriage:

  • three(3) or more unexplained miscarriage at less than 10 weeks gestation;
  • two (2) or more unexplained fetal loss between 10 and 16 weeks gestation;
  • one (1) or more unexplained fetal loss at or greater than 16 weeks gestation
• Previous abruptio placenta

• Previous personal history of VTE:

  • Previous documented secondary proximal VTE,
  • Previous documented calf-vein thrombosis (idiopathic or secondary),
  • Previous superficial phlebitis
• First degree relative with symptomatic thrombophilia
• Pregnancy - > 4weeks gestation and < 20 weeks gestation
• Thrombophilia:

• Two abnormal tests, and no normal tests

  • 3.1 Protein S
  • 3.2 Protein C
  • 3.3 Antithrombin

• Two positive tests

  • 3.4 Anticardiolipin IgM (>30 U/ml)
  • 3.5 Anticardiolipin IgG (>30 U/ml)
  • 3.6 Anti-b2 glycoprotein IgG (>20 U/ml)
  • 3.7 Anti-b2 glycoprotein IgM (>20 U/ml)
  • 3.8 Lupus anticoagulant

• One positive test

  • 3.9 Factor V Leiden (heterozygous or homozygous)
  • 3.10Prothrombin gene defect (heterozygous or homozygous)

Exclusion Criteria:

• Less than 4 weeks gestation or greater than 20 weeks gestation
• No confirmed thrombophilia

• Contraindication to heparin therapy

  • History of heparin induced thrombocytopenia
  • Platelet count less than 100,000 109/L
  • History of osteoporosis or steroid use
  • Actively bleeding
  • Documented peptic ulcer within 6 weeks
  • Heparin, bisulfite or fish allergy
  • Severe hypertension (SBP >200mmhg and/or DBP >120mmHg)
  • Serum creatinine greater than 80 umol/L (1.3mg/dl) and an abnormal 24 hour urine creatine clearance (<30ml/min)
  • Severe hepatic failure (INR >1.8)
• Geographic inaccessibility

• Need for anticoagulants, discretion of the investigator such as but not limited to:

  • Recurrent fetal loss and phospholipid antibody syndrome
  • Prior idiopathic proximal VTE:
  • History of idiopathic DVT or PE treated with anticoagulants (> 1 month of heparin or warfarin) or IVC interruption;
  • Idiopathic is a VTE occurring outside all of the following periods: antepartum, postpartum, oral contraceptive use, surgery, immobilization, cast, and malignancy
  • Mechanical heart valve
• Legal lower age limitations (country specific)
• Prior participation in TIPPS
• Unable/unwilling to provide informed consent