Background/Purpose: Antiphospholipid antibody syndrome (APS) is an autoimmune, hypercoagulable state which may elicit thrombosis and pregnancy loss.  Although several tests exist to guide diagnosis of APS and SLE, their utilization has been highly variable among laboratories. Therefore, we have introduced a panel of nine tests and examined their sensitivity and specificity for supporting the diagnosis of APS in SLE and non-SLE patients at our Institution between 2010 and 2015.

Methods: 356 SLE and 288 non-SLE patients were evaluated for the presence of APS, as earlier defined (J. Thromb. Haemost. 4:295-306). SLE patients satisfied the ACR criteria for a definitive diagnosis (Arthritis Rheum. 25:1271-1277; Arthritis Rheum. 40:1725). Lupus anticoagulants were assessed in house on fresh samples within 24 h of acquisition by hexagonal phase phospholipid neutralization assay (HPPNA; delta <10 seconds; Stago, Parsippany, NJ), diluted Russell viper venom test (DRVVT; <1.2 normalized ratio; Stago), and platelet neutralization procedure (PNP; delta < 1 second) using a STA-R Evolution instrument (Stago). IgG, IgM, and IgA antibodies against β2-glycoprotein 1 (aβ2-IgG, aβ2-IgM, aβ2-IgA) and cardiolipin (aCL-IgG, aCL-IgM, aCL-IgA) were measured by Quest Diagnostics (Madison, NJ). Sensitivity and specificity for detection of APS was calculated in both SLE and non-SLE patients and compared amongst these assays by χ² test using GraphPad software (San Diego, CA).

Results: 77/356 SLE patients had APS when using a combination of nine tests. Table 1 shows the frequency of positive and negative test results and p value for each assay in the SLE cohort. HPPNA has provided by far the greatest sensitivity at 73% for detecting APS in SLE patients relative to all other tests. In contrast, HPPNA has lower specificity at 85% as compared to all other test. While not shown, HPPNA also exhibited the greatest sensitivity at 78% for detecting APS in 61/78 non-SLE patients. Importantly, the 2^nd most sensitive test for detection of APS in non-SLE patients was DRVVT at 14.3%; which was lower than that of HPPNA (chi-square p<0.0001). However, DRVVT had greater specificity at 96% for detection on APS in non-SLE subjects (p<0.0001).

Conclusion: This study indicates that HPPNA is the most sensitive but least specific assay for detecting APS both in SLE and non-SLE subjects. While it has been underutilized in a survey of 53 North-American Coagulation Laboratories (Am. J. Clin. Pathol. 134:764-773), these data clearly indicate the relevance of HPPNA for the clinical diagnosis of APS in patients who need long-term anticoagulation to prevent life-threatening thrombotic events.