Abstract

Background: The Surveillance, Epidemiology & Risk Factors for TTP (SERF-TTP) study is the largest prospective cohort of idiopathic TTP cases to date.

Methods: Patients with first episode of idiopathic TTP were enrolled at 11 sites in the US. Exclusion criteria include solid organ or allogeneic stem cell transplant, anti-neoplastic therapy or malignancy. All patients underwent therapeutic plasma exchange (TPE). Remission is defined as platelet count >150,000/mm3. ADAMTS13 activity was measured by fluorescence resonance energy transfer assay (FRETS-vWF73, Peptides Int.). ADAMTS13 inhibitor was assessed by ELISA (Technozym ADAMTS13 INH ELISA, Technoclone) and functional inhibition of normal ADAMTS13 activity (modified FRETS). Differences between the groups was evaluated by Chi-square test, t-test or Fisher’s exact test.

Results: Complete data is available for 57 cases. 84% were female & median age was 42. ADAMTS13 was severely deficient (<10%) in 53%, moderate (10–50%) in 8%, & normal (>50%) in 39%. Adverse events were frequent & most commonly include citrate toxicity and allergic reactions. Long-term followup was available for 56 patients, and overall relapse rate was 25% with median time to relapse of 11 months. The relapse rate was 41% in patients with severe ADAMST13 deficiency & 0% in patients with normal ADAMTS13 activity (p=0.0077).

Conclusions: Severe ADAMTS13 deficiency does not define all cases of idiopathic TTP, yet is associated with a unique syndrome characterized by severe thrombocytopenia, normal renal function, presence of ADAMTS13 neutralizing autoantibodies & high risk of relapse. Non-ADAMTS13 deficient idiopathic TTP has clinical features similar to thrombotic microangiopathies associated with stem cell transplant or drugs such as quinine, yet has a better than expected overall survival after TPE. There is likely an alternate disease mechanism for this cohort, possibly immunologic, which may be responsive to TPE and warrants further study.

ADAMTS13 < 10% n=30ADAMTS13 > 50% n=22p-value
* t-test, ** Fisher’s Exact Test, # Chi-Square Test 
Presenting Labs 
Hemoglobin (mean) 8.5 9.2 0.22* 
Platelet count (mean x10^9/L) 19 57 <0.0005* 
Serum creatinine (mean) 1.33 3.9 0.0012* 
ADAMTS13 antibody (neutralizing & non-neutralizing) % 100 63.6 0.0004** 
ADAMTS13 neutralizing antibody % 83 35 .0003# 
Presenting Symptoms 
Neurologic symptoms present 45 52.4 0.23# 
Diarrhea 23 30.4 0.79# 
Infection 40 43.5 0.79# 
Past Medical History 
Connective Tissue Disease % 10 8.5 0.28# 
Family history of TTP % 4.6 0.11# 
Remission Labs 
Hemoglobin (mean) 12.2 8.5 0.16* 
Platelet count (mean x10^9/L)) 169 152 0.15* 
Serum creatinine (mean) 1.02 3.7 0.0009* 
Outcomes 
Therapy-related Adverse events % 71 55 0.24# 
Time (days) to remission (plt > 150,000) 9.7 9.2 0.89* 
Early remission (< 8 days) % 73 57 0.20# 
30 day Exacerbation rate % 35 28 0.63# 
30 day Survival % 96.6 90.0 0.56** 
Long-term Relapse % 41 0.0077** 
ADAMTS13 < 10% n=30ADAMTS13 > 50% n=22p-value
* t-test, ** Fisher’s Exact Test, # Chi-Square Test 
Presenting Labs 
Hemoglobin (mean) 8.5 9.2 0.22* 
Platelet count (mean x10^9/L) 19 57 <0.0005* 
Serum creatinine (mean) 1.33 3.9 0.0012* 
ADAMTS13 antibody (neutralizing & non-neutralizing) % 100 63.6 0.0004** 
ADAMTS13 neutralizing antibody % 83 35 .0003# 
Presenting Symptoms 
Neurologic symptoms present 45 52.4 0.23# 
Diarrhea 23 30.4 0.79# 
Infection 40 43.5 0.79# 
Past Medical History 
Connective Tissue Disease % 10 8.5 0.28# 
Family history of TTP % 4.6 0.11# 
Remission Labs 
Hemoglobin (mean) 12.2 8.5 0.16* 
Platelet count (mean x10^9/L)) 169 152 0.15* 
Serum creatinine (mean) 1.02 3.7 0.0009* 
Outcomes 
Therapy-related Adverse events % 71 55 0.24# 
Time (days) to remission (plt > 150,000) 9.7 9.2 0.89* 
Early remission (< 8 days) % 73 57 0.20# 
30 day Exacerbation rate % 35 28 0.63# 
30 day Survival % 96.6 90.0 0.56** 
Long-term Relapse % 41 0.0077** 

Author notes

Disclosure: No relevant conflicts of interest to declare.