Question 6What is the dose for prophylaxis and treatment?
The standard dose of enoxaparin for prophylaxis in pregnancy and the postpartum period is 40 mg administered subcutaneously every 24 hours (TABLE 3). Therapeutic anticoagulation (sometimes referred to as a “weightadjusted” dose) is usually achieved with 1 mg/kg every 12 hours.
Dalteparin can be given in a prophylactic dose of 5,000 U subcutaneously every 24 hours and a therapeutic dose of 200 U/kg every 24 hours.15 Dosing may need to be adjusted with advancing gestation as plasma volume, renal clearance, and tissue proteins increase.
The various LMWH preparations are not equivalent in their pharmacokinetics. Generally, clinicians familiarize themselves with a single agent. It also is important to note that dosing regimens in pregnancy are not evidence-based but largely “borrowed” from nonpregnant regimens. They also vary widely in the available literature.
TABLE 3
Common low molecular weight heparins
| BRAND NAME | GENERIC NAME | PROPHYLACTIC DOSE | THERAPEUTIC DOSE |
|---|---|---|---|
| Lovenox | Enoxaparin | 40 mg every 24 hours | 1 mg/kg every 12 hours |
| Fragmin | Dalteparin | 5,000 U every 24 hours | 200 U/kg every 24 hours |
| Note: All doses are subcutaneous | |||
Question 7Under what conditions can LMWH be given?
Generally, LMWH can replace UH in any condition that warrants prophylactic or therapeutic anticoagulation in pregnancy, except the acute management of pulmonary embolism and in women with mechanical heart valves.
Prophylactic dosing can be offered to women with a previous thromboembolic event such as deep vein thrombosis (DVT) or pulmonary embolism that was not associated with a reversible and temporary predisposing risk factor such as immobilization or trauma. (In general, pregnancy is not seen as a reversible or temporary risk factor.)
Prophylactic or therapeutic dosing is sometimes offered to women with a hereditary thrombophilia, antiphospholipid syndrome, or other vasculopathies and connective-tissue diseases. In addition, LMWH is an accepted first-line therapeutic anticoagulant for acute DVT in pregnancy.
Not for use in treating acute pulmonary embolism. Evidence is insufficient to support the use of LMWH as a first-line anticoagulant for acute pulmonary embolism. To date, IV loading with UH is the standard of care, with conversion to LMWH after 4 to 5 days of therapeutic UH anticoagulation. This may change as experience with LMWH increases.
Not for use with mechanical prosthetic heart valves. Because of case reports of recurrent thromboembolism resulting in maternal and fetal death in pregnant women with mechanical prosthetic heart valves on therapeutic LMWH, the manufacturer of enoxaparin warns against its use in pregnancy in these women.9 However, similar outcomes have been reported with UH and warfarin. This forces clinicians to consider potentially less effective and more problematic agents for anticoagulation in this fortunately rare circumstance.
Contemporary management involves converting from warfarin to subcutaneous heparin or the heparin pump once pregnancy is established and before organogenesis (at approximately 6 weeks’ gestation), followed by frequent monitoring of aPTT. Alternatively, warfarin can be resumed after organogenesis (at about 12 weeks) and continued into the third trimester, followed by conversion to heparin pump, subcutaneous injections, or an IV drip near term. Both options carry significant maternal and fetal risk and should be performed in a multidisciplinary fashion along with cardiology and vascular medicine.16
Question 8How do I start and stop LMWH?
Start LMWH as a subcutaneous injection without IV loading. A baseline complete blood count for platelet count is reasonable. Patient education is straightforward.
Prophylactic dosing can be initiated on an outpatient basis immediately after patient education and procurement of the medicine.
Therapeutic dosing for DVT usually is begun during hospitalization, with 1 mg per kilogram given subcutaneously every 12 hours. Barring other comorbidities, discharge can be achieved after patient education. The exception is treatment of acute pulmonary embolism.Conversion to LMWH is achieved once the patient is fully anticoagulated.
Discontinuation. Pregnancy is a period of shifting maternal and fetal status, when indications for delivery can develop suddenly and with little warning (eg, abruptio placenta, nonreassuring antenatal testing).
LMWH dosing regimens in pregnancy are not evidence-based but largely “borrowed” from nonpregnant regimens.
A major consideration is the long half-life of LMWH. If a patient has had a recent subcutaneous injection of LMWH followed by an urgent indication for delivery, she may be anticoagulated during her delivery and be at increased risk for hemorrhage. Similarly, she may not be a candidate for epidural or spinal anesthesia because of the risk of epidural hematoma. If cesarean section is indicated, she may need general anesthesia, which is associated with increased maternal morbidity. If hemorrhage occurs, she may require transfusion of blood products, which carries the risks of infection and transfusion reactions.
Three strategies for peripartum management with LMWH are: