Acquired Factor X Deficiency in Light Chain (AL) Amyloidosis Is Rare and Associated with Advanced Disease

Background: Acquired factor X (aFX) deficiency has a known association with AL amyloidosis and can be associated with an increased risk of bleeding. However, it is unclear who develops amyloid aFX deficiency and whether this is associated with adverse prognosis. We therefore evaluated the prevalence of aFX deficiency in AL amyloidosis patients evaluated at our center and studied its impact on prognosis.

Material and Methods: From 1/1/2010 to 12/31/2016, 137 patients with systemic AL amyloidosis had a FX level done at our center at their first evaluation. Patients who were on warfarin at the time of FX testing (N=33) were excluded from further analysis leaving a sample size of 104 patients. Patients were divided into 2 groups: FX <50%, FX ≥50%. Descriptive analysis of baseline characteristics between the two groups was compared using the Fisher's exact test for continuous variable and Wilcoxon Rank Sum Test for categorical variables. Survival analysis was conducted using the Kaplan-Meier estimator. Univariate and multivariate analysis was performed for overall survival using the Cox proportional hazards regression. We adjusted for FX, age, stage, cardiac involvement, number of non-cardiac organ involvement in the multivariate analysis.

Results: Of 104 patients, 10 had FX <50% and 94 ≥50%. Only 2 patients had FX <10%. Table 1 shows the baseline characteristics of the groups. The median follow up of survivors was 21.53 months (0-139.5). Compared to patients with normal FX levels, patients with low FX levels were more likely to have advanced disease (p=0.05), higher NT-proBNP (median 8732.5 vs 1497.0, p=0.002), and higher cTnT (median 0.1 vs <0.011, p=0.03). In the 10 patients with aFX deficiency, no bleeding events were seen in the first 12 months after FX level was checked. On Kaplan-Meier analysis, the median survival of patients with aFX deficiency was 9.3 months compared to 118.4 months in those without (p= 0.008) (Figure 1). On univariate analysis, decreasing FX was associated with higher hazards of death (p=0.001), as was stage III/IV and presence of cardiac involvement. On multivariate analysis, only stage III/IV (i.e. presence of severe cardiac disease) was significantly associated with mortality (Table 2).

Conclusions: The prevalence of aFX deficiency in an academic center setting was 10%. FX deficiency was significantly associated with advanced stage and adverse cardiac biomarkers. While no bleeding events were seen in this small cohort, the presence of aFX deficiency was associated with increased hazards of death, although this was predominantly driven by stage (and thus severity of cardiac involvement). We conclude that while aFX deficiency is rare in systemic AL amyloidosis, it is a marker of advanced disease. A larger cohort study is warranted to confirm our findings.

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