APLA Syndrome and RPL

Antiphospholipid antibodies (aPL) include IgG and IgM antibodies that bind to phospholipids. In human reproduction, significant aPL include antibodies to diphosphatidylglycerol (cardiolipin), phosphatidlyserine, beta-2 glycoprotein-1, and the lupus anticoagulant (LAC). Although in some organ systems aPL manifest as a thrombophilia, their detrimental effects on pregnancy primarily are immune-mediated effects on the trophoblast. Women with positive LAC and/or antibodies to beta-2 glycoprotein-1 have a greater risk of thromboembolic events in some studies. Research on the immune-mediated negative effects of aPL during pregnancy have shown that aPL inhibit hCG release from human placental explants, block in-vitro trophoblast migration and invasion, inhibit the formation of giant, multi-nucleated syncytiotrophoblasts, inhibit trophoblast cell adhesion molecules, and activate complement on the trophoblast surface inducing an inflammatory response. aPL can be identified in 5% of women without any history of obstetrical complication and up to 20% of women with RPL. Current diagnostic criteria include the presence of a clinical condition (fetal loss, RPL, venous or arterial thrombosis) and positive laboratory tests (IgG or IgM aPL > 99%, LAC). aPL should be suspected in anyone with autoimmune disease, false-positive tests for syphilis, prolonged coagulation studies, positive autoantibody tests, or in women with poor obstetrical histories

(fetal loss, RPL, and intrauterine growth restriction). Multiple prospective, randomized controlled clinical trials have demonstrated the efficacy of treatment with unfractionated heparin and low-dose aspirin throughout pregnancy and post-partum. Clinical guidelines from the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine indicate that live-birth rates of approximately 75% are expected in appropriately treated patients. As with any autoimmune disorder, it is not unusual that autoantibody levels will fluctuate over time. Women diagnosed with APS should be advised to make certain lifestyle changes including avoiding estrogen-containing oral contraceptives, avoiding the use of tobacco products, maintaining a normal body mass index, and taking daily low-dose aspirin unless contraindicated.

References:

American College of Obstetrics and Gynecology Bulletin 132. Antiphospholipid antibody syndrome. Obstet Gynecol. 120:1514-1521, 2012.

Jaslow CR. Carney JL, and Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses.Fertil Steril 93: 1234-1243, 2010.

American Society for Reproductive Medicine Practice Committee. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril 98:1103-1101, 2012.

Kutteh WH. Antiphospholipid antibody syndrome and reproduction. Curr Opin Obstet Gynecol. 26: 260-265, 2014.