Clinical Significance of Indeterminate Lupus Anticoagulant (LAC) Results.

The International Society of Thrombosis and Hemostasis (ISTH) criteria for the diagnosis of the lupus anticoagulant (LAC) include: Screening test that demonstrates the prolongation of a phospholipid-dependent (PL-D) clotting time; mixing test that confirms the presence of an inhibitor; the confirmation that the inhibitor is PL-D and exclusion of other coagulopathies. Test results that do not fulfill all the criteria are considered indeterminate. These indeterminate results are common (Kottke-Marchant et al. J Thromb Haemost. 2007; 5 Supplement 2: P-M-455), still there is no published data regarding clinical significance.

This study investigated the prevalence of thrombotic events in an initial cohort of unselected patients (n=256) from one tertiary hospital in the United States, who were tested for LAC and other antiphospholipid (aPL) antibodies from a 2 month period in 2006. The laboratory results (PT/INR, aPTT, dilute Russell's viper venom time (DRVVT), STACLOT and platelet neutralization (PNP)) were evaluated. The profile included 3 separate PL -D assays (DRVVT confirm, STACLOT, PNP). Samples containing heparin (>0.1U/ml) were pre-treated with Hepadsorb. The LAC profile was considered indeterminate if PL test results were positive, but without a positive aPTT or DRVVT mixing study. The initial cohort included 83 patients with indeterminate results. From this group, 18 patients were excluded: Four due to incomplete data, 2 due to high heparin level (anti Xa>1.0 U/ml), 5 due to other prothrombotic etiologies and 7 with other positive aPL antibodies. For an assessment of thrombotic history, we performed retrospective chart reviews and tabulated all Sapporo clinical features, malignancy and auto-immune disorders within 5 years before and 2 years after the index laboratory testing. Events that did not fulfill diagnostic criteria for thrombosis, ischemic events or obstetrical complications were excluded. The final analysis sample included 65 patients with indeterminate LAC, 106 with negative and 27 with positive LAC.

The final indeterminate LAC cohort included 65 patients, with mean follow-up of 18 months. Malignancy was present in 29% and autoimmune disease in 25% of patients. The most common thrombotic events were deep vein thrombosis (DVT) (28%), cerebral ischemic stroke (14%) and pulmonary embolism (14%). When compared to those with negative tests, indeterminate group patients were more likely males, relatively older, and more likely to have DVT, superficial thrombosis (ST) or myocardial infarction (MI) (P= 0.049, 0.021, 0.044, 0.005 and 0.045 respectively). Concurrent coumadin (warfarin) therapy was more prevalent in the indeterminate group, but it did not reach statistical significance (p=0.15). There was no statistical significant difference in the prevalence of cancer or autoimmune disease (P=0.19 and 0.48 respectively). In the multivariate analysis model none of the previous variables reached any statistical significance between the two groups. When compared the above clinical variables between indeterminate results and positive LAC results groups from the same cohort, we failed to show any major statistically significant differences. We noticed very poor retesting rate in the indeterminate group during the follow up period of 2 years (15% only).

Indeterminate results are common among patients referred for LAC testing. When compared to those with negative results, patients with indeterminate results are more likely to have a history of DVT, superficial thrombosis or MI, but none of the clinical variables reached statistical significance in a multivariate model. On the other hand, patients in the indeterminate group shared demographic and clinical profiles with those in the positive results group. This further highlights the need to study the clinical significance of indeterminate LAC results in a prospective study.

No relevant conflicts of interest to declare.