Prevention of Fetal Death in the Antiphospholipid Antibody Syndrome

Abstract

The first treatment of pregnant women with antiphospholipid antibody syndrome (APLS) employed high doses of corticosteroids, plus low dose aspirin, with the goal of suppressing production of the autoantibody. Corticosteroids (usually prednisone), even when much lower doses are used, and even when tapered after midpregnancy, have been associated with significant maternal and obstetric risks and side effects: the most important are osteomalacia and preterm delivery (often precipitated by premature rupture of the membranes). Since the publication of a randomized trial demonstrating equivalent live birth rates of about 75% whether heparin or prednisone was used for treatment (plus low dose aspirin), the use of adjusted doses of heparin, together with low dose aspirin, has replaced prednisone for treatment of pregnant women; although prednisone may still be needed to treat manifestations of associated autoimmune disorders. A recent randomized trial has shown that the addition of heparin to aspirin is probably superior to treatment with aspirin alone. To achieve prophylactic levels of plasma heparin equivalent to those measured in patients who are not pregnant and are treated with the usual dose of standard heparin of 5000 IU every 12 h, the heparin dose required for treatment of pregnant women is usually higher. For that reason, heparin doses should be adjusted using the nadir APTT, or better plasma heparin measured by a factor Xa inhibition assay at the 2 h post-injection peak. Although low molecular weight heparin has been shown to be useful in prevention of fetal resorption in a mouse model, and appears to be equally safe for treatment of pregnant women, we still have no published data to show therapeutic equivalency, with respect to treatment of APLS-complicated pregnancy, to standard heparin preparations, and none that demonstrate any lower risk for the complication of most concern when heparin is given to pregnant women-osteopenia. Similarly, intravenous infusion of gamma globulins (IVG) appears on the basis of case reports to be effective additional treatment in cases where standard therapy has failed. Gamma globulin preparations contain anti-idiotypic antibodies that have been shown to bind to patient antiphospholipid antibodies. The place for the addition of IVG to standard therapy has not been defined, but clinically significant and corticosteroid-resistant thrombocytopenia complicating antiphospholipid antibody syndrome might be one indication for primary treatment with IVG +/- low dose aspirin. Overall, live birth rates in most treatment studies are in the range of 70-80%. The reported birth rate information, however, cannot be compared between studies. None of the studies reported have used tools such as logistic regression analysis to allow for such significant predictors of live birth as the number of prior miscarriages, maternal age, medical history, or a history of fetal death (loss of a viable and chromosomally normal fetus after the 10th gestational week).

The management of pregnant patients with antiphospholipid syndrome

“…4 Data in the literature supporting the beneficial vasodilating effects of aspirin in conditions as diverse as intrauterine growth retardation with umbilical placental insufficiency to pre-eclampsia and thrombosis secondary to platelet aggregation, all support the idea that treatment with aspirin will help to prevent the vascular and thrombotic complications associated with aPL. 5,6 Good results with low-dose aspirin alone, with success rates over 70%, have been achieved by our group 7 -9 and others 10 -14 in APS patients with two or more pregnancy losses. Aspirin daily doses used in these studies ranged between 75 and 100 mg.…”

Can anti-ovarian antibody testing be useful in an IVF-ET clinic?

“…The immunosuppressive action of these drugs could inhibit potential adverse effects of AOA on oocyte quality or gamete interaction [17]. Furthermore, corticosteroids could also help with implantation and embryonic development and have therefore been proposed for the treatment of recurrent pregnancy loss [18]. Corticosteroids are shown to stimulate estradiol and progesterone productions, which are immunoregulating biomolecules, during pregnancy, as it's well known that progesterone is needed to maintain pregnancy [19].…”

Pregnancy in patients with Wegener's granulomatosis: report of five cases in three women

“…They have never been evaluated in WG pregnancy,16 but in other conditions, such as antiphospholipid syndrome,26 they appeared to be safe.…”