Thrombophilia Pregnancy and Childbirth Obstetric embolism
Conditions
Interventions
Intervention group: 5000 IU dalteparin once daily (od) from randomisation until 20 weeks gestational age, then 5000 IU twice daily (bid) until the onset of labour. 5000 IU dalteparin od for 6 weeks p
Sponsors
Ottawa Hospital Research Institute (OHRI) (Canada) - formerly Ottawa Health Research Institute
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. High-risk pregnant women with a confirmed thrombophilia 2. Who have had any of the following pregnancy complications: 2.1. Recurrent miscarriages 2.2. Stillbirth 2.3. Pre-eclampsia (high blood pressure in pregnancy where protein leaks into the urine) 2.4. Very small birth weigh baby (called intrauterine growth restriction) 2.5. Bleeding in the placenta before delivery (called abruptio placenta) 2.6. Family history of blood clots in the legs or lungs 2.7. Personal history of phlebitis or blood clots in the legs or lungs 3. Confirmed thrombophilia 4. 18 years of age or older
Exclusion criteria
Exclusion criteria: 1. Greater than 19 weeks + 7 days gestational age at the time of randomisation 2. Contraindication to heparin therapy including: 2.1. History of heparin induced thrombocytopenia 2.2. Platelet count of less than 100,000 x 106/L 2.3. History of osteoporosis or steroid use (increased risk of osteoporosis and osteoporotic fracture with heparin therapy) 2.4. Actively bleeding 2.5. Documented peptic ulcer within 6 weeks (contraindication to anticoagulation) 2.6. Heparin, bisulfite or fish allergy 2.7. Severe hypertension (systolic blood pressure [SBP] greater than 200 and/or diastolic blood pressure [DBP] greater than 120 - contraindication to anticoagulation) 2.8. Severe hepatic failure (international normalised ratio [INR] greater than 1.8) (increased likelihood of bleeding) 3. Women with serum creatinines greater than 80 and an abnormal 24 hour creatinine clearance. Women with serum creatinines less than 80 do not require a normal 24 hour creatinine clearance to be eligible. 4. Geographic inaccessibility (less likely to comply with required follow-up visits and care) 5. Need for anticoagulants as judged by the local investigator such as but not limited to: 5.1. Women with recurrent foetal loss with antiphospholipid antibody syndrome 5.2. Women with prior idiopathic proximal VTE: 5.2.1. History of pulmonary embolism (PE) or DVT treated with anticoagulants (over one month of heparin or warfarin) or inferior vena cava (IVC) interruption 5.2.2. Idiopathic refers to a VTE that occurs outside all of the following periods: antepartum, postpartum, oral contraceptive use, surgery, immobilisation, cast, and/or malignancy 5.2.3. Proximal refers to a VTE that occurs above the bifurcation of the popliteal vein 5.3 Women with mechanical heart valves 6. Women less than 18 years of age 7. Women unable/unwilling to providing informed consent 8. Prior participation in TIPPS
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is a composite outcome that includes any of the following events (1 - 4): 1. Objectively documented VTEs including: 1.1. Deep vein thrombosis (DVT) 1.2. Pulmonary embolism (PE) 1.3. Sudden death 2. Severe or early onset pre-eclampsia: 2.1. Early onset defined as 32 weeks + 0 day using the time of diagnosis of pre-eclampsia as the index time 2.2. Severe being pre-eclampsia with any of the following: 2.2.1. Blood pressure (BP) greater than 180/110 2.2.2. Increased liver function tests (LFTs) 2.2.3. Thrombocytopenia 2.2.4. Oliguria (less than 30 cc/hr urine output) 2.2.5. Pulmonary oedema 2.2.6. Seizures 2.2.7. Coagulopathy 2.2.8. Proteinuria greater than 5 g/24 hours 3. Intrauterine growth restriction (IUGR), for which both of following criteria must be fulfilled: 3.1. Infant birth weight less than the 10th percentile in relation to normals for sex and gestational age and 3.2. One ultrasound (U/S) indicating two or more of the following criteria: 3.2.1. Oligohydroamnios 3.2.2. Cerebral redistribution (abnormal middle cerebral artery Doppler waveform with a pulsitility index less than the 5th percentile) 3.2.3. Increase in head circumference to abdominal circumference ratio over 1.1 3.2.4. Abnormal umbilical artery Doppler waveform 4. Foetal loss, either: 4.1. Miscarriage: foetal loss prior to 20 weeks gestation 4.2. Stillbirth: foetal loss at or greater than 20 weeks gestation | — |
Secondary
| Measure | Time frame |
|---|---|
| To achieve the secondary objectives the following outcomes will be determined: 1. Pregnancy induced hypertension (PIH), with or without proteinuria 2. Pre-term delivery (less than 37 weeks estimated gestational age) 3. Abruptio placentae 4. Major and minor haemorrhage 5. Thrombocytopenia (50% decrease from baseline) 6. Fractures 7. Bone mineral density (BMD) at six weeks postpartum 8. Non-compliance with study medication and/or follow up | — |
Countries
Australia, Canada, United Kingdom, United States of America
Outcome results
None listed