Prophylactic Enoxaparin Dosing for Prevention of Venous Thromboembolism in Pregnancy.
Prophylactic Enoxaparin Dosing for Prevention of Venous Thromboembolism in Pregnancy.
Enoxaparin is a type of low molecular weight heparin (LMWH), or anticoagulant, used to
 prevent and treat blood clots. Formation of blood clots, or venous thromboemboli (VTE) in
 pregnancy can have dangerous and even life-threatening effects on the mother and fetus.
 Enoxaparin is the preferred medicine to prevent clotting in pregnant patients who are at risk
 for VTE, because it has been studied to be safe and effective in pregnancy without any harms
 to the fetus. Although this medication is routinely used and is recommended by several
 prominent medical groups, the optimal dosing for prevention of VTE is still unclear. The
 range of standardly prescribed dosing regimens of Enoxaparin includes 40mg daily and 1mg/kg
 daily, but these two dosing strategies have never been compared in a head to head fashion.
When pregnant patients are diagnosed by their physician as being at risk for VTE, or when
 they enter the perinatology practice on a previously-prescribed prophylactic enoxaparin
 regimen, they will be offered a chance to discuss participation in the study. The patient
 will be consented and those who are not already receiving enoxaparin will be prescribed one
 of the two dosing regimens, at their physician's discretion, at that same clinic visit.

 A baseline blood sample will be drawn to assess coagulation using thromboelastography [TEG].
 TEG is a point-of-care device which measures the viscoelastic properties of clot formation.
 This device can provide rapid and detailed information about coagulation changes. TEG will be
 used to assess coagulation changes after commencing treatment with enoxaparin (see later).

 As per routine care, the patient will be instructed by the clinic nurse on how to fill her
 prescription at the pharmacy, how to give herself the injection subcutaneously once daily in
 the morning, and how to troubleshoot the injection process. As per routine care, the patient
 will have the opportunity to ask all questions necessary about this process, and her
 understanding and ability to comply with the injection procedures will be assessed by the
 clinic RN. The patient will be given a new prescription as needed by her physician at her
 regularly scheduled MD appointment. At any time, as per routine care, the patient can have
 the opportunity to review or troubleshoot the injection process with the RN or MD in the
 clinic. At each clinic visit, as per routine care, approximately 1-2 times per month as per
 routine care, the patient will be weighed and her weight recorded in her prenatal chart. At
 each of these visits the patient will also be asked a series of questions as per the study
 flowsheet in the chart, about potential side effects or adverse events she may have
 experienced since her last visit. In addition, she will receive a phone call from one of the
 study investigators once to twice per month to enquire about side effects, medication
 tolerability, and medication compliance. At 3 predetermined intervals throughout the
 pregnancy, the patient will be instructed to give a blood sample at the outpatient
 laboratory. When at all possible, these blood draws will be coordinated to coincide with the
 patient's regularly scheduled prenatal care blood draws, to minimize venipuncture episodes.
 The study blood sample results will test for: anti-Xa level , which is a marker of the
 effective prophylactic range of Enoxaparin, serum creatinine, which is a marker of kidney
 function and renal clearance of medication, and also for coagulation analysis (using TEG) to
 assess the coagulation effects of enoxaparin. TEG is a point-of-care device which measures
 the viscoelastic properties of clot formation. This device can provide rapid and detailed
 information about coagulation changes. The anti-XA level sample results will be blinded to
 the medical care providers and to the patient, and used for research purposes only. At or
 shortly after the patient reaches 36 weeks gestation, she will be switched from enoxaparin to
 unfractionated heparin (UFH), as per standard of care to avoid any potentially unexpected
 bleeding events associated with the onset of labor at term. When the patient comes to the
 hospital for Labor and Delivery, routine labor and delivery care will ensue at the discretion
 of the medical care team. 24 hours after delivery, or at the discretion of the medical care
 team, the patient will be restarted on her Enoxaparin dosing arm, as per standard of care.
 She will be instructed to continue the enoxaparin for 6 weeks, and will receive a
 prescription from the in-hospital providers for this. The patient will return for a 6 week
 follow-up visit in the clinic as per standard of care, and a final study blood draw will be
 performed at that time.

 If the patient misses her 6 week appointment, she will receive a phone call to reschedule as
 per standard of care, and will be instructed over the phone to discontinue her Enoxaparin and
 to come in for a blood draw.
Inclusion Criteria:

 1. >18 years of age

 2. Warrants prophylaxis against venous thromboembolism in pregnancy according to American
 College of

 Obstetrics and Gynecology Practice Bulletin 2000, reaffirmed in 2008:

 -  history of idiopathic thrombosis

 -  history of thrombosis related to pregnancy or oral contraceptive use

 -  history of thrombosis accompanied by an underlying thrombophilia other than homozygous
 for the factor V Leiden mutation, heterozygous for both the factor V Leiden and the
 prothrombin G20210A mutation, or AT-III deficiency

 -  without a history of thrombosis but who have an underlying thrombophilia and a strong
 family history of thrombosis

 -  Known thrombophilia except for those listed above, with a history of adverse pregnancy
 outcome (APO) as defined by: ¡Ý3 pregnancy losses in the 1st trimester, ¡Ý2 pregnancy
 losses/stillbirth in 2nd trimester, ¡Ý1 pregnancy loss/intrauterine fetal demise
 (IUFD) in the 3rd trimester, intrauterine growth restriction (IUGR), abruptio
 placentae, or severe pre-Eclampsia prior to 34 weeks gestation.

 Exclusion Criteria:

 1. Need for therapeutic-level anticoagulation as determined by physician

 2. Renal disease as defined by serum creatinine >1.0

 3. Weight >90kg

 4. Allergy to enoxaparin