Risk of Arterial and Venous Thrombosis in Patients with “Indeterminate” Lupus Anticoagulant Testing
Authors: Sundaram Suchitra , Edwin Natasha Catherine , Rogers Heesun J. , Silver Bernard J. , McCrae Keith R. 
Published: October 2019

Background: Laboratory criteria for antiphospholipid antibody syndrome (APS) include lupus anticoagulant (LAC), anti cardiolipin antibodies, and anti-β2 glycoprotein antibodies. International Society of Thrombosis and Hemostasis (ISTH) criteria for the diagnosis of LAC include a positive screening test, positive mixing study, phospholipid dependence and absence of a co-existing factor inhibitor or anti-coagulant drug effect. Patients with test results that fulfill some but not all of the above criteria are considered to have indeterminate LAC. While a positive LAC is an established risk factor for thrombosis, there are limited data about the significance of indeterminate LAC test results.

Objective: Our study aimed at determining the prevalence of venous and arterial thrombotic events in patients with indeterminate LAC.

Results: We reviewed the clinical course of 500 patients that underwent LAC testing at Cleveland Clinic from 1/11/2008 to 12/28/2010; 346 had indeterminate results. Patients with indeterminate results while on warfarin (n=52) and enoxaparin (n=4) were excluded. Patients treated with heparin at the time of testing (n=50) were included, as heparin in the plasma was neutralized prior to testing. Multivariate logistic regression modeling was performed using XLSTAT software to study the value of various thrombotic risk factors as predictive factors for venous and arterial thrombosis. Associations between categorical variables were tested using the χ2 test or Fisher's exact test. Differences were considered statistically significant at an alpha level of 0.05.

In our final cohort of 281 patients with indeterminate results, there were 110 males (39.1%) and 171 females (60.8%), with a median age of 52.5 yrs. Thrombotic manifestations of patients with indeterminate LAC are summarized in Table 1. There were a total of 170 venous thrombotic events in 119 patients (42.5%). Seventy-nine patients had one or more (≥1) instances of deep vein thrombosis (DVT); 45 patients had pulmonary embolism. There were 17 patients with porto-mesenteric thrombosis and 6 patients with other venous thrombotic events. Forty-five patients had concurrent malignancy (16 %) and 22 (8%) had other prothrombotic risk factors including factor V Leiden (n=14), prothrombin G20210A mutation (n=6), elevated homocysteine (n=1), and protein S deficiency (n=1). On multivariate analysis, a relationship was confirmed between the presence of associated prothrombotic disorders and venous thrombosis (OR = 3.36, 95% CI: 1.31- 8.61, P=0.012) (Table 2).

Arterial thrombosis was noted in 63 patients, with stroke, myocardial infarction and acute limb ischemia being most common (Table 1). On multivariate analysis, taking into account atherosclerotic risk factors, co-existing hypertension, hyperlipidemia and smoking history were associated with arterial thrombosis (Table 2).

Conclusion: Indeterminate results are common among patients referred for LAC testing. In this retrospective cohort, patients with indeterminate LAC had significant rates of venous and arterial thrombosis. Close observation, analysis of other prothrombotic risk factors, and repeat testing of these individuals at a later date should be considered.

Disclosures

No relevant conflicts of interest to declare.