Heparin

Women with APS and a previous history of thromboembolism are treated with high dose of heparin (e.g., Enoxaparin 40 mg, SC, b.d.) as thromboprophylaxis in pregnancy (Table 10.3).

For those with recurrent pregnancy loss or previous adverse pregnancy outcome, but without a history of thromboembolism,

Table 10.2. Recommendations in APS pregnancy.

Recommendations

  • Preconceptional assessment. Should include: detailed medical and obstetric history, documentation or confirmation of significant levels of aPL, review of medication, information of maternal and obstetric problems' risk and information of possible further treatments, blood tests (renal, blood cell count, liver, urine, ...). In those who have systemic lupus erythematosus (SLE), issues related to exacerbation of SLE also should be discussed. All patients should be assessed for evidence of anemia and thrombocytopenia, which occur in association with APS.
  • Detection of obstetric complications. After week 20, close control of hypertension and proteinuria, and ultrasound examination every 4-6 weeks should be done. In the third trimester, "high risk" women with APS (e.g., abnormal Doppler assessment of the uterine arteries or previous late pregnancy complications) should be offered 2-4 weekly scans, whereas those at the milder end of the APS spectrum (e.g., recurrent first trimester losses only) may be offered scans at 28 and 34 weeks gestation. In cases with suspected fetal growth restriction, biophysical profiles should be performed to further assess fetal well-being.
  • Uterine artery Doppler: Several studies have recommended uterine artery Doppler waveform analysis at 20 and 24 weeks gestation, since bilateral uterine artery notches at 22-24 weeks is associated with high likelihood for prediction of pre-eclampsia and fetal growth restricition (sensibility of 75%, specificity of 94%, negative predictive value of 94%).
  • Contraindications to pregnancy: pulmonary hypertension, uncontrolled arterial hypertension, recent (<6 months) throm-botic event.

there is as yet no consensus of opinion. Some studies have demonstrated that heparin therapy in addition to aspirin may contribute to improve fetal outcome, especially in women with recurrent first trimester loss. In this case, low dose of LMWH (e.g., Enoxaparin 40 mg, SC, daily) is usually used as soon as pregnancy is confirmed. Although optimal treatment for women with one or more late pregnancy losses (second-third trimesters), but no history of thromboembolism is controversial, most obstetricians support the use of heparin therapy in addition to low-dose aspirin.

Table 10.3 Subcutaneous heparin regime used in the treatment of APS during pregnancy.

Recurrent pre-embryonic and embryonic loss; no history of thrombotic events Unfractionated heparin(UFH):

  1. 5,000-7,500 U b.d. in the first trimester
  2. 5,000-10,000 U b.d. in the second and third trimesters LMWH: Enoxaparin 40 mg or dalteparin 5,000 U o.d.

Prior fetal death or early delivery because of severe preeclampsia/

placental insufficiency; no history of thrombotic events

UFH:

  1. 7,500-10,000 U b.d. in the first trimester
  2. 10,000 U b.d. in the second and third trimesters LMWH: Enoxaparin 40 mg or dalteparin 5,000 U o.d.

History of thrombotic events UFH:

1. 7,500 U every 8-12 h adjusted to maintain the mid-interval heparin levels in the therapeutic range

LMWH: weight-adjusted (e.g., enoxaparin 1 mg/kg or dalteparin 200 U/kg b.d.)

The potential complications of heparin treatment during pregnancy includes hemorrhage, osteoporosis, fracture, and hep-arin-induced thrombocytopenia. The reported rate of osteoporosis and associated fracture is low, though cases have occurred. Whether LMWH during pregnancy is associated with decrease of bone density remains controversial. Calcium and vitamin D supplements may be added during this treatment. Heparin-induced thrombocytopenia is infrequent in pregnant women.

Although Factor Xa levels may be used to monitor LMWH, experience has shown that doses are virtually never altered as a result, and therefore it is not necessary to measure Factor Xa levels routinely.

Stopping LMWH administration at least 12 h prior to elective delivery or any interventional procedure, and reintroduc-ing it 12 h after that is generally considered safe, but in case urgent delivery is necessary, reversal with protamine sulfate is possible.

The molecular weight of unfractionated heparin (UFH) ranges from 12-15 kD, and that of LMWH from 4-5 kD

therefore neither preparation is able to cross the placenta. Heparin is not excreted into breast milk, and it is safe during breast feeding.

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