Do Current Antiphospholipid Antibody Syndrome Guidelines Effectively Target at-Risk Obstetric Patients?
Authors: Thapar Kanika , Patel Nimesh , Gbadamosi Bolanle , Ezekwudo Daniel E , Jaiyesimi Ishmael , Smith Marc 
Published: October 2019

Abstract
Introduction: The incidence of spontaneous miscarriages is 1%, and up to 50% of recurrent fetal losses (RFL) have unclear etiology. Antiphospholipid syndrome (APS) has been reported in 5-15% of women with RFL. Current clinical criteria for APS include venous thromboembolism (VTE) and /or fetal loss. In addition to the clinical criteria, laboratory confirmation must be obtained using tests for lupus anticoagulant (LA), anticardiolipin (ACL) and beta-2 glycoprotein I antibodies (β2GPI). These tests are often provided by many laboratories as panels; moreover, given the relatively large number of tests, judicious ordering of these panels is warranted to contain costs and to avoid mislabeling patients who have clinically insignificant positive results. Some existing literature suggests that patients with recurrent fetal loss and ACL antibodies are over-tested and/or over-diagnosed. We aim to determine the frequency and likelihood of positive antiphospholipid antibody (APA) among patients with fetal loss.
Materials and Methods: A retrospective search was conducted for APA panels using data from our laboratory information system from Jan 2014 to Jan 2015. Recorded variables included age, ordering physician subspecialty and indication for testing. For patients with fetal loss, the number of losses and gestational age at the time of loss were recorded. Specimens were classified as positive, indeterminate or negative. For positive and indeterminate tests, the results of LA, ACL, and β2GPI antibody tests and titers were noted.
Results: Our search identified 430 panels ordered for APA. The median age was 42 (range: 1-92). The three highest ordering physician subspecialties were Ob/Gyn (20.2%), Internal Medicine (17.7%) and Heme/Onc (17.2%). The three most common indications for ordering the APA panel were venous thromboembolism (26.5%), fetal loss (18.4%), and autoimmune disease (15.4%). The largest percentage of positive results came from panels ordered by Heme/Onc 45% (20/44) and for the indication of VTE 40.9% (18/44). Fetal loss (n=74) accounted for 4.5% (2/44) of positive results. Further investigation of the fetal loss cases showed that 82.4 % (61/74) met criteria for appropriate APA testing. There was no statistically significant difference for gestational age < 10 weeks (1 positive, 4 indeterminate, and 30 negative specimens) or > 10 weeks (1 positive, 1 indeterminate, and 37 negatives; p=0.334); ordering physician subspecialty and the APA testing result. Both fetal loss patients that tested positive for APS had increased titers of ACL IgM and β2GPI IgM.
Conclusions: Despite being the second most common indication for APA testing, fetal loss only accounted for 4.5% of positive results. Compared to historical data that report an incidence of 5-15% APS in patients with recurrent fetal loss, we found an incidence of only 2.7%. The reason for this discrepancy is not clear. Confounding factors such as inappropriate work-ups or incomplete testing are unlikely as 82.7% of patients meet standard testing criteria and our APA panels included multiple tests for LA, ACL and β2GPI. Larger studies are needed to confirm our findings, as this may call for redefinition of APA testing guidelines to better target at risk obstetric patients.

Disclosures
No relevant conflicts of interest to declare.