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=30 . | ADAMTS13 > 50% n=22 . | p-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 % | 0 | 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 | 0.0077** |
| . | ADAMTS13 < 10% n=30 . | ADAMTS13 > 50% n=22 . | p-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 % | 0 | 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 | 0.0077** |
Author notes
Disclosure: No relevant conflicts of interest to declare.
