Prognostic Indicators in Severely ADAMTS13 Deficient TMA Patients.

Previous studies have shown that severe ADAMTS13 deficiency in TMA is associated with lower platelet counts, a greater number of plasma exchange procedures, and a higher rate of relapse compared to non-severely-deficient ADAMTS13. To further explore prognostic factors in TMA, we retrospectively analyzed associations between several pre-TPE laboratory analytes and the number of TPE procedures in a large cohort of surviving TMA patients. We evaluated TMA patients with severely deficient (<15%) pre-TPE ADAMTS13 activity levels (ADAMTS13-D patients) separately from TMA patients with non-severely deficient ADAMTS13 activity (ADAMTS13-N patients). In 37 ADAMTS13-D patients and 40 ADAMTS13-N patients we compared pre-TPE platelet counts and hematocrits (Hcts) with number of TPE procedures. Because TMA is associated with inflammatory conditions, in subsets of 23 ADAMTS13-N and 30 ADAMTS13-N patients we measured C-reactive protein (CRP) and the sepsis marker procalcitonin (PCT), and compared them to number of TPE. The median number of TPE procedures among ADAMTS-D patients with platelet counts below the median (13,000/μL) was 4-fold greater (36 TPE) than in patients with platelet counts above the median (9 TPE) (p=0.006, rank sum). Similarly, the median number of TPE in ADAMTS13-D patients whose Hcts were below the median (24%) was half (12 TPE) that of the cohort with Hcts above the median (26 TPE) (p=0.044). In ADAMTS13-D patients, CRP ≤1.0 ng/dL was associated with >2-fold more TPE procedures (median 6.5 TPE) than CRP>1.0 ng/dL (median 15 TPE) (p=0.0026). By contrast, there was no relationship between platelet count, Hct or CRP level and the number of TPE in ADAMTS13-N patients. However, evidence of sepsis (elevation of both PCT and CRP) was present in 40% of ADAMTS13-N patients, but was not associated with number of TPE procedures. No ADAMTS13-D patient had elevated PCT. In conclusion, lower pre-TPE platelet counts, higher Hcts and higher CRP levels were associated with significantly greater numbers of TPE in ADAMTS13-D TMA. By contrast, no laboratory parameter was associated with number of TPE in ADAMTS13-N patients. ADAMTS13 levels combined with other laboratory parameters may therefore be helpful in the prognosis, resource management, and guidance of adjunctive therapy in TMA. In addition, rapid assays such as PCT may allow early identification of sepsis in TMA patients, which may not have prognostic significance, but could prompt antibiotic treatment that may enhance outcome. The distinct difference in prognostic factors between ADAMT13-D and ADAMTS13-N patient subsets further supports the pathogenic importance of ADAMTS13 in TMA.