ACOG Guidelines at a Glance: The mystery of the antibodies still awaits a solution

Committee on Practice Bulletins-Obstetrics

ACOG Practice Bulletin No. 132: Antiphospholipid Syndrome, December 2012 (Replaces Practice Bulletin No. 118, January 2011). Obstet Gynecol. 2012;120(6):1514-1521. Full text of ACOG Practice Bulletin available to ACOG members at http://www.acog.org/Resources_And_Publications/Practice_Bulletins/Committee_on_Practice_Bulletins_--_Obstetrics/Antiphospholipid_Syndrome.

Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an autoimmune disorder defined by the presence of characteristic clinical features and specified levels of circulating antiphospholipid antibodies. Diagnosis requires that at least one clinical and one laboratory criterion are met. Because approximately 70% of individuals with APS are female (1), it is reasonably prevalent among women of reproductive age. Antiphospholipid antibodies are a diverse group of antibodies with specificity for binding to negatively charged phospholipids on cell surfaces. Despite the prevalence and clinical significance of APS, there is controversy about the indications for and types of antiphospholipid tests that should be performed in order to diagnose the condition. Much of the debate results from a lack of well-designed and controlled studies on the diagnosis and management of APS. The purpose of this document is to evaluate the data for diagnosis and treatment of APS.

Used with permission. Copyright the American College of Obstetricians and Gynecologists.

The mystery of the antibodies still awaits a solution 

By Charles J. Lockwood, MD, MHCM 

Dr. Lockwood is Dean of the College of Medicine and Vice President for Health sciences, the Ohio State University, Columbus, and Editor in Chief of Contemporary OB/GYN. 

The American College of Obstetricians and Gynecologists’ Practice Bulletin Antiphospholipid Syndrome (No. 132, December 2012) replaces the original bulletin from November 2005.¹ That there is little difference between these 2 documents should not be surprising, since there has been little progress in research into this still-quite-mysterious disorder during that interval. 

The new Practice Bulletin reviews the association of antiphospholipid syndrome (APS) with thrombosis, noting that most thrombotic events are venous and that among untreated APS patients, risk of recurrent venous thromboembolism (VTE) may be as high as 25% per year.¹ Pregnancy poses a particular risk of clotting (5% to 12%). Other hemostatic sequelae of the disorder include the presence of antiphospholipid antibodies (APA) in around 5% of stroke victims younger than 50 and the 40% to 50% prevalence of thrombocytopenia among APS patients. 

To test or not to test? 

Obstetrical sequelae include fetal loss after 10 weeks, recurrent (>2) embryonic losses, and an association with preeclampsia and uteroplacental insufficiency.¹ The Bulletin recommends testing women for APS only if they have had an unexplained fetal loss (>10 weeks) or 3 or more unexplained embryonic losses. Testing is also indicated in previously untested patients with current or prior venous or arterial thrombosis. 

The tests to be employed have not changed-they are a lupus anticoagulant assay and a screen for anticardiolipin and anti-beta-2-glycoprotein I antibodies. These tests must be positive on 2 occasions 12 weeks apart. 

Complexities of treatment 

According to ACOG, therapy with prophylactic anticoagulation is indicated in women with APS and prior thrombosis during pregnancy and for 6 weeks postpartum.¹ Similar therapy is warranted for women with APS associated with fetal loss or recurrent embryonic loss. Low-dose aspirin may be added in both cases. 

ACOG also opines that, “For women with APS who have not had a thrombotic event, expert consensus suggests that clinical surveillance or prophylactic heparin use antepartum in addition to 6 weeks of postpartum anticoagulation may be warranted.” This recommendation would apply if the diagnosis of APS was made based on the occurrence of 1 or more preterm births associated with eclampsia, severe preeclampsia, or features consistent with placental insufficiency, since ACOG does not recommend treatment for these indications. 

Looking back-and forward 

This unusual condition fascinated me as a young maternal-fetal medicine fellow and led to my career-long interest in the study of uterine hemostasis. 

However, it is frustrating to realize what little progress has been made in understanding APS in the ensuing 25 years. We still do not know how these antibodies arise, how they trigger losses, or how heparin prevents such losses. Pregnancy loss was long assumed to be due to uteroplacental thrombosis. However, thrombosis is rarely observed with embryonic losses, and whether it is a cause or consequence of later losses is unclear.² There is even recent evidence that inflammation and complement activation, not clotting, may be at the heart of the disease process.^3,4 Thus, there is much left to be discovered about these mysterious antibodies. 

Commentary References 

1. Committee on Practice Bulletins-Obstetrics, American College of Obstetricians and Gynecologists. Practice bulletin no. 132: antiphospholipid syndrome. Obstet Gynecol. 2012;120(6):1514-1521. 

2. Di Simone N, Luigi MP, Marco d, et al. Pregnancies complicated with antiphospholipid syndrome: the pathogenic mechanism of antiphospholipid antibodies: a review of the literature. Ann N Y Acad Sci. 2007;1108:505-514. 

3. Salmon JE, Girardi G, Holers VM. Activation of complement mediates antiphospholipid antibody-induced pregnancy loss. Lupus. 2003;12(7):535-538. 

4. Shamonki JM, Salmon JE, Hyjek E, Baergen RN. Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am J Obstet Gynecol. 2007;196(2):167.e1-167.e5. 

ACOG Abstract Reference

1. Lockshin MD. Antiphospholipid antibody. Babies, blood clots, biology. JAMA. 1997;277(19):1549-1551.