TIPPS: Thrombophilia in Pregnancy Prophylaxis Study (TIPPS)
Pregnancy, Thrombophilia, Pregnancy Complications
About this trial
This is an interventional treatment trial for Pregnancy focused on measuring Pregnancy, Thrombophilia, High-risk pregnancy, LMWH prophylaxis, Placenta mediated pregnancy complications
Eligibility Criteria
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 immunoglobulin M (IgM) (>30 U/ml)
- 3.5 Anticardiolipin immunoglobulin G (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 (Systolic Blood Pressure >200mmhg and/or Diastolic Blood Pressure >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 deep venous thrombosis (DVT) or pulmonary embolism (PE) treated with anticoagulants (> 1 month of heparin or warfarin) or inferior vena cava (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
Sites / Locations
- Saint Louis University
- University of Utah Health Sciences Centre
- Royal Alexandra Hospital
- QEII Health Sciences Centre
- Hamilton Health Sciences Centre
- The Ottawa Hospital, Civic Campus
- Mount Sinai Hospital
- Women's College Health Sciences Centre
- SMBD Jewish General Hospital
- St Mary's Hospital Centre
- Royal University Hospital
- CHA, Hopital Enfant Jesus
Arms of the Study
Arm 1
Arm 2
No Intervention
Active Comparator
Control
dalteparin sodium
Subjects randomized to control will receive identical obstetrical care and follow-up, but not antenatal dalteparin. Within 24 hours of delivery, all subject's, regardless of randomization allocation will receive dalteparin sodium 5,000 IU s.c. daily for 6 weeks post-partum
Subjects randomized to the treatment group will receive daily injections of dalteparin during the antenatal period. They will be taught how to self-administer sub-cutaneous injections of dalteparin 5000 IU once daily (o.d.) until gestational age 20, then twice daily (bid) until 37 weeks gestation or onset of labour. Within 24 hours of delivery, all subject's, regardless of randomization allocation will receive dalteparin sodium 5,000 IU s.c. daily for 6 weeks post-partum