Dose Adjusting Enoxaparin Thromboprophylaxis Dosage According to Anti-factor Xa Plasma Levels Improve Pregnancy Outcome

HaEmek Medical Center, Israel

Status: Completed

Conditions: Thromboembolism; Preeclampsia; Fetal Demise; Fetal Growth Restriction; Abruptio Placentae

Treatments: Drug: enoxaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT01068795

0048-09-EMC ANTIXA-02

0048-09-EMC

Details and patient eligibility

About

The risk of venous thromboembolism increases in pregnancy. Thrombophilia whether genetic or acquired, is a hypercoagulable disorder that may increase the risk of venous thromboembolic events. Clinically, these events are presented as maternal deep vein thrombosis and pulmonary emboli. Thrombophilias are also associated with adverse fetal outcomes including intrauterine growth restriction, intrauterine fetal death, severe preeclampsia, placental abruption and recurrent abortions.

Pregnant women who experienced one or more of the above complications are advised to be examined for the presence of the genetic or the acquired form of thrombophilia.

Low molecular weight heparin prophylaxis, an anticoagulant, is advised for pregnant women with a history of thromboembolism, and many experts recommend prophylaxis for pregnant patients with a known thrombophilia and history of adverse pregnancy outcomes associated with these hypercoagulable states.

Physiologic changes in normal pregnancy, including weight gain, increased renal clearance and volume of distribution, may decrease the availability of low molecular weight heparin (Enoxaparin or Dalteparin), or produce a less predictable response in pregnant women compared with nonpregnant women. There are no clear recommendations for use of prophylactic low molecular weight heparin in pregnancy. Clinicians tend to use doses suggested for nonpregnant patients. Regarding pregnant patients taking enoxaparin or dalteparin, the American College of Obstetricians and Gynecologists states that "because of the lack of data regarding adequate dosing during pregnancy, anti-factor Xa levels may be monitored".

Two recently published studies demonstrated that plasma anti-factor Xa levels during pregnancy were lower than expected, indicating that many pregnant patients may receive a subprophylactic dosing.

Our objective is to check pregnancy outcome among thrombophilic women treated with an adjusted enoxaparin thromboprophylaxis dosage according to anti-factor Xa plasma levels compared to women with fixed dosage.

Enrollment: 144 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

WOMEN WITH

• Singleton gestation
• A history of fetal demise, fetal growth restriction, placental abruption, preeclampsia, recurrent abortions or maternal thromboembolic event.
• Acquired or congenital thrombophilia treated with low molecular weight heparin

Exclusion criteria

• Women treated empirically with low molecular weight heparin
• Women with a history of pregestational diabetes.
• Significant polyhydramnios or oligohydramnios, major fetal structural, generic or chromosomal malformations

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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144 participants in 2 patient groups

enoxaparin fixed

No Intervention group

Description:

enoxaparin dosage will be fixed during pregnancy

enoxaparin adjusted

Experimental group

Description:

enoxaparin dosage will be adjusted according to anti-factor Xa plasma levels

Treatment:

Drug: enoxaparin