Fertility Associates of Memphis

ARTICLE ARCHIVE

Anticoagulant Treatment Of Thrombophilia In Pregnancy

Leslie Norman, MSN, WHNP
Kutteh Ke Fertility Associates of Memphis, PLLC

Conditions which predispose patients to developing thrombosis, or a blood clot, are referred to as thrombophilias. They are often associated with recurrent pregnancy loss, premature birth, and intrauterine growth retardation. Thrombophilias act by obstructing the normal flow of blood through the placenta from the mother to the growing fetus. Placental damage is thought to be a major cause of these problems. Autoimmune antibodies such as lupus anticoagulant (not the same as the disease lupus) and antiphospholipid antibodies are two of the most common acquired thrombophilias.

Low dose aspirin and heparin are medications that have been shown to significantly reduce complications related to the presence of certain thrombophilic conditions, and is therefore the preferred treatment. By decreasing the clotting tendency of the mother, the antibodies are less likely to interfere with the circulation of oxygen and nutrients from mother to fetus. The delivery rates dramatically improve as is the likelihood of normal growth. These medications may be used individually or in combinations. Each one has certain risks and benefits of which the mother should be aware.

Low Dose Aspirin
Low dose aspirin at a dose of 81 mg (baby aspirin) a day has been used in pregnancy for prevention of fetal growth retardation (or intrauterine growth restriction) and stillbirth in high-risk pregnancies. Low dose aspirin has been studied extensively and has been demonstrated to be safe in the mother and in the baby. Specifically, there was no increase in maternal abruption (premature separation of the placenta) and no change in clotting studies of newborns. However an expectant mother should not ingest any aspirin if she has a bleeding ulcer, hemophilia, or a known allergy to the drug. The risks to a healthy mother taking aspirin 81mg daily while pregnant are small but may include bleeding before and/or after labor. Aspirin is known to cross the placenta, and at regular doses (325mg) around the time of delivery, may temporarily affect the newborn’s clotting ability. Pregnant women on low dose aspirin should not take additional aspirin (salicylic acid) or use other aspirin-containing medications.

Low Dose Heparin
Heparin has long been used in anticoagulant therapy for a variety of conditions. It is a safe anticoagulant to use during pregnancy as it does not cross the placenta. Therefore, it poses no risk to the developing fetus. An expectant mother should not use the drug if she has uncontrollable active bleeding, a known allergy to heparin, or thrombocytopenia (a low platelet count). Heparin does interact with aspirin and other anticoagulants to increase the overall anticoagulant effect. The drug will also interact with tetracyclines, digitalis, antihistamines, and nicotine to decrease the anticoagulant effect.

Heparin places a pregnant woman at risk for osteoporosis (bone loss). This bone demineralization disease is dose-related; that is, a greater dose of heparin (especially over 15,000 units of heparin daily) results in a greater risk of developing osteoporosis. Because of this risk, all pregnant women on heparin therapy should take supplemental calcium, at least 1200mg daily. Another risk with heparin involves hemorrhage. Caution should be used after invasive procedures such as a spinal tap, spinal anesthesia, and with conditions such as sub-acute bacterial endocarditis, severe hypertension, liver disease, or hemophilia. It has been shown that the risk of hemorrhage is less than 5% in low risk patients. The presence of the drug in the bloodstream before delivery may result in the cancellation of an epidural anesthetic. It may also increase the risk of bleeding from surgical wounds or trauma during a vaginal delivery. Clotting studies performed during pregnancy keep these risks to a minimum. Protamine sulfate, a drug which neutralizes heparin, may be administered prior to birth to prevent these risks. The most likely disadvantage of heparin treatment is the fact that it must be given subcutaneously one to two times daily as it is inactive orally. This can cause irritation, bruising, redness, and/or mild pain at the injection site (usually the lower abdomen). Studies show no serious side effects in mothers or in babies whose mothers took heparin. The rates of prematurity, stillbirth, neonatal death, and congenital abnormalities for those who used heparin therapy have been similar to those in the normal population.

Prednisone
Prednisone was used more frequently in the past to suppress the mother’s manufacturing of the lupus anticoagulant protein; however, the preferred treatment for most thrombophilias includes aspirin 81mg and/or heparin. Recent studies have not demonstrated significant improvements in livebirths and have indicated increased maternal and fetal complications. Nevertheless, prednisone may be recommended for various conditions, alone or in combination with aspirin 81mg and heparin. It has been used for its anti-inflammatory properties as well as its ability to suppress the human immune system. It should not be used in those with systemic fungal infections, tuberculosis, adrenocortical insufficiency, or in those with certain thyroid diseases. When used with oral anticoagulants (such as aspirin), the clotting time of a mother may increase or decrease abnormally. This drug may cause a variety of increased risks including a hypoglycemic effect, the masking of symptoms of infection, increased blood pressure, and electrolyte imbalances in the mother. It can cross the placenta and affect the fetus.

In conclusion, low dose aspirin and heparin have been shown to be more effective and safe in the treatment of pregnant women with antiphospholipid antibodies and other hypercoaguable conditions. Our center has treated hundreds of women with heparin and aspirin with very good success and few side effects or complications related to heparin therapy.

References

1. Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-does aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol 174: 1584-1589, 1996.
2. Laskin CA, Bombardier C, Hanna ME, Mandel FP, Ritchie JWK, Farewell V, Farine D, Spitzer K, Fielding L, Soloninka Ca, Young M. Prednisone and aspirin in women with autoantibodies and unexplained recurrent pregnancy loss. N Engl J med 337, 148-153, 1997.
3. Lockshin MD. Antiphospholipid antibody. J Am Med Assoc. 227: 1549-1551, 1997.
4. Rai R, Cohen H, Dave M, Regan L. Randomized controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent misscariage associated with phospholipid antibodies. Brit Med J 314: 253-257, 1997.