Abstract

Background:

Screening for deficiency of ADAMTS- 13, a von Willebrand factor-cleaving protease, is commonly performed when there exists a clinical suspicion for thrombotic thrombocytopenic purpura (TTP). The clinical utility of ADAMTS13 testing at presentation has been questioned, as initial treatment decisions are variably influenced by results. Furthermore, current literature remains inconclusive about the differences in response to plasma exchange therapy in patients with severe (<5%) and non-severe (>5%) ADAMTS13 deficiency.

Methods:

With IRB approval, we performed a single center, retrospective review of patients undergoing plasma exchange therapy at Duke University Medical Center for indication of thrombotic microangiopathy from 2007 through June 2013. We retrospectively identified patients with “severe” deficiency (ADAMTS13² 5%, n=22) and those without severe deficiency (ADAMTS13 >5% or “non-severe” n=22). Cases of TTP associated with bone marrow transplantation, and chemotherapeutic agents were excluded. We trended daily laboratory values for creatinine, platelets, and LDH through completion of TPE . Time to recovery of laboratory abnormalities to normal was noted. We compared the time to resolution of laboratory abnormalities between patients with ADAMTS13² 5% (“severe”) to those with level >5% (“non-severe”).

Results:

Demographic and clinical information for TTP patients with ADAMTS13<5% and >5% are shown in the Table below. All patients underwent plasma exchange therapy plus steroids after diagnosis with TTP. Patients in both groups were comparable with respect to age and gender, but there were more episodes of recurrent TTP (n=9) in the ADAMTS13 <5% group compared to >5% (n=4). Patients with severe ADAMTS13 deficiency required more TPE (n=19 ) than patients with non-severe ADAMTS13 deficiency (n=13). There were 5 deaths in the non-severe ADAMTS13 cohort as compared to no deaths in the severe ADAMTS13 deficiency.

Recovery of platelet count, LDH and Cr level to within normal range are shown for each group within 7, 14 and 21 days of presentation. Recovery of platelet counts for both groups were comparable. No recovery of platelet counts was seen in 3 patients for each group. The majority of patientÕs with and without severe ADAMTS13 deficiency appeared to recover platelet count by day 14 (81% for severe v. 75% for non-severe ADAMTS13 deficiency). Recovery of LDH differed in the two groups. Patients with non-severe ADAMTS13 deficiency were more likely to show no recovery in LDH (38% v. 4% in severe deficiency) or delayed LDH recovery (62% normalized LDH by D21 in non-severe v 95% in severe deficiency). As previously reported, patients with non-severe ADAMTS13 deficiency were more likely to have renal disease and less likely to recover renal function. Few patients in the severe deficiency group presented with abnormal renal function, but in those who had renal dysfunction, the majority (71%) recovered renal function by day 14.

Conclusions:

Our studies show the temporal resolution of laboratory parameters in patients with severe and non-severe ADAMTS13 deficiency. We show that both groups have similar platelet recovery patterns in response to TPE. However, patients with non-severe ADAMTS13 deficiency have delayed normalization of LDH, higher rates of ESRD and higher mortality. Although additional prospective analysis will need to be performed, this data provides preliminary data showing differing disease pathophysiology of the two groups and that patients with non-severe ADAMTS13 may benefit from alternative/adjunctive therapies to reduce mortality.

Table
Clinical FeaturesADAMTS13 <5%ADAMTS13>5%
Total number 22 22 
Males (M)/Females (F) 7(M)/15(F) 9(M)/13(F) 
Age (mean) 49 50 
Recurrent episodes 
Mean # TPE 19 13 
Deaths 
Platelet Count Recovery 
Total number with abnormal plts 22 21 
No recovery 3* 
Plts >150K by day ² 7 13 (59%) 9 (45%) 
Plts>150K by day ² 14 18 (82%) 15 (75%) 
Plts >150K by day ² 21 21 (86%) 15 (75%) 
LDH normalization 
Total number with elevated LDH 22 21 
No recovery 1 (5%) 8 (38 %) 
Normal LDH by day ²7 15(68 %) 6 (29%) 
Normal LDH by day ²14 20 (91%) 10 (48%) 
Normal LDH by day ²21 21 (95%) 13 (62%) 
Renal function recovery 
Total number with abnormal Cr values at presentation 12 
No recovery+ 9* 
Normal Cr by day 7 3 (42.85%) 
Normal Cr by day 14 5 (71.42%) 1 (8.33%) 
Normal Cr by day 21 5 (71.42%) 3 (16.66%) 
Clinical FeaturesADAMTS13 <5%ADAMTS13>5%
Total number 22 22 
Males (M)/Females (F) 7(M)/15(F) 9(M)/13(F) 
Age (mean) 49 50 
Recurrent episodes 
Mean # TPE 19 13 
Deaths 
Platelet Count Recovery 
Total number with abnormal plts 22 21 
No recovery 3* 
Plts >150K by day ² 7 13 (59%) 9 (45%) 
Plts>150K by day ² 14 18 (82%) 15 (75%) 
Plts >150K by day ² 21 21 (86%) 15 (75%) 
LDH normalization 
Total number with elevated LDH 22 21 
No recovery 1 (5%) 8 (38 %) 
Normal LDH by day ²7 15(68 %) 6 (29%) 
Normal LDH by day ²14 20 (91%) 10 (48%) 
Normal LDH by day ²21 21 (95%) 13 (62%) 
Renal function recovery 
Total number with abnormal Cr values at presentation 12 
No recovery+ 9* 
Normal Cr by day 7 3 (42.85%) 
Normal Cr by day 14 5 (71.42%) 1 (8.33%) 
Normal Cr by day 21 5 (71.42%) 3 (16.66%) 

Disclosures

Arepally:TEVA Pharma: Consultancy.

Author notes

*

Asterisk with author names denotes non-ASH members.