Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparing Anti-XA Levels in Post-Cesarean Patients With BMI >35 Undergoing Enoxaparin Thromboprophylaxis With Weight Based Dosing Twice Daily Versus Fixed Dose 40 Milligrams Daily
Brief Summary: Pregnant and recently postpartum women are at significantly higher risk of developing a blood clot in their arms or legs known as a deep venous thrombosis (DVT) and/or a blood clot in their lungs known as a pulmonary embolism (PE) compared to their non pregnant counterparts. It is estimated that this risk increases anywhere from 4 to 50 times higher in pregnant versus non-pregnant women and further increases almost 11 fold in the post partum period. This risk is almost doubled when the patient undergoes cesarean delivery. In 2011, the American College of Obstetricians and Gynecologists (ACOG) issued updated guidelines stating that for patients undergoing cesarean delivery with additional risk factors for clot or thromboembolism, protective (prophylactic) treatment with low molecular weight heparin (LMWH) a type of blood thinner should be considered. However, no specific guidelines about which risk factors should be considered, or what medication doses should be used were provided. The American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines published in 2012 delineated who should be given prophylaxis based on various risk factors, however acknowledged that the recommendations were based on weak quality evidence.

ACOG endorses either once or twice a day dosing for high risk patients after delivery and states that adjustments for obese women should be made on a case by case basis. However, there are limited studies on the dosing of LMWH in specific subpopulations including post operative patients, pregnant patients and obese patients. All of these studies have urged further investigation of the correct dosing for these high risk subjects due to changes associated with pregnancy and the level of medication in the blood that may put these patients at higher risk of venous thromboembolism. Many previous studies have shown that women in these high risk categories do not achieve protective levels of the medication measured with a laboratory test; anti Xa level. The investigators hypothesize that due to their dual risk, obese post-operative recently pregnant women may not be adequately protected with the daily fixed dose and might need more frequent dosing to protect them.

The objective of this study is to assess what proportion of women achieve the desired anti Xa level with the fixed daily dose versus twice daily weight based dosing (0.5 mg/kg).


Options:
A: Inclusion Criteria:

* Women with a body mass index \>35 who have undergone cesarean delivery in the last 12 hours who will receive thromboprophylaxis with enoxaparin
* Subjects who consent to the study.

Exclusion Criteria:

* Women with a previous history of deep venous thrombosis or pulmonary embolism
* Women who are currently receiving another form of low molecular weight heparin or unfractionated heparin.
* Women who are receiving other concomitant anticoagulant medications, such as warfarin, lepirudin, or argatroban.
* Subjects who are unable or unwilling to give informed consent.
* Women who, in the judgment of the investigators, would not be in the best interest of the patient to participate in the study.
* Allergy to enoxaparin.
* Women with renal impairment
* Women with contraindications to Lovenox treatment such as women with active bleeding or thrombocytopenia
B: 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
C: Inclusion Criteria:

Women must be at high risk for thromboembolism for one of the following reasons:

1. Known low risk thrombophilia (Known = diagnosed prior to enrollment and low risk thrombophilia includes heterozygous factor V Leiden or prothrombin gene variant or protein C deficiency or protein S deficiency. If not previously tested then assumed not to have thrombophilia).
2. Immobilization (defined as \>90% of waking hours in bed, of a week or more at any point in the antepartum period).

OR any two of the following reasons:

1. Postpartum infection (fever (temperature\>38.5oC) and clinical signs/symptoms of infection and elevated neutrophil count (higher than local lab normal))
2. Postpartum hemorrhage (Estimated blood loss \>1000 ml during delivery and postpartum)
3. Pre-pregnancy BMI \>25 kg/m2
4. Emergency cesarean birth (emergency = not planned prior to onset of labour)
5. Smoking \>5 cigarettes per day prior to pregnancy
6. Preeclampsia (blood pressure ≥ 140mmHG systolic and/or ≥90 mmHg diastolic on at least one occasion and proteinuria (1+ on urine dipstick or 300mg/dl or total excretion of 300mg/24 hours) or typical end-organ dysfunction.
7. Infant birth weight (adjusted for sex and gestational age) \<3rd percentile (i.e., small for gestational age).

Exclusion Criteria:

1. Less than 6 hours or more than 36 hours since delivery at the time of randomization
2. Need for anticoagulation as judged by the local investigator, may include but not limited to:

   1. Personal history of previous provoked or unprovoked VTE (DVT or PE)
   2. Continuation of LMWH that was started in the antenatal period for VTE prophylaxis
   3. Mechanical heart valve
   4. Known high-risk thrombophilia (Known = diagnosed prior to enrolment and high-risk thrombophilia includes deficiency of antithrombin (at least 1 abnormal lab result), persistently positive anticardiolipin antibodies (\> 30U/ml on two measurements a minimum of six weeks apart), persistently positive Anti B2 glycoprotein antibodies (\> 20U/ml on two measurements a minimum of six weeks apart), persistently positive lupus anticoagulant (positive on two measurements a minimum of six weeks apart), homozygous factor V Leiden (FVL), homozygous prothrombin gene mutation (PGM), compound heterozygosity factor V Leiden (FVL) and prothrombin gene mutations (PGM), more than 1 thrombophilia (any combination of 2 or more: FVL, PGM, protein C deficiency, protein S deficiency). If not previously tested then assumed not to have thrombophilia).
3. Contraindication to heparin therapy, including:

   1. History of heparin induced thrombocytopenia (HIT)
   2. Platelet count of less than 80,000 x 106/L on postpartum Complete Blood Count(CBC)
   3. Hemoglobin ≤ 75 g/L on postpartum CBC
   4. Active bleeding at any site (not resolved prior to randomization)
   5. Excessive postpartum vaginal bleeding (\>1 pad per hour prior to randomization).
   6. Documented gastrointestinal ulcer within 6 weeks prior to randomization
   7. History of heparin or LMWH allergy
   8. Severe postpartum hypertension (systolic blood pressure (SBP) \> 200mm/hg and/or diastolic blood pressure (DBP) \> 120mm/hg)
   9. Severe hepatic failure (INR \>1.8 if liver disease suspected)
4. Have received more than one dose of heparin or LMWH since delivery
5. \< age of legal majority in local jurisdiction (age \<18 in Canada)
6. Prior participation in PROSPER
7. Unable or refused to consent
D: Inclusion Criteria:

* patients with unexplained recurrent pregnancy loss (RPL)

Exclusion Criteria:

* previous history of Diabetes Mellitus or thyroid dysfunction or cardiac disease
* Thrombocytopenia (\<100000/ml)
* bleeding tendencies
* ectopic pregnancy
* past history of vascular thrombosis
* uterine anomalies
* multiple gestation

Answer: A