Abstract

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder that presents with microangiopathic hemolytic anemia and thrombocytopenia, fevers, renal insufficiency and neurologic features. We reviewed clinical, laboratory, and outcome data for TTP cases with severely deficient versus non-severely deficient ADAMTS13 activity levels.

Methods: Mean and median data were from the Surveillance, Epidemiology and Risk Factors for TTP (SERF-TTP) study group for idiopathic TTP cases, the Canadian Apheresis Group (CAG), and five published series (Zheng 2004, Raife 2004, Vesely 2003 (Oklahoma TTP-HUS Registry), Matsumoto 2004 (Japan Referral Center), Bennett 2007).

Results: Compared to TTP cases with near-normal ADAMTS13 activity levels (n= 282), TTP cases with severe ADAMTS13-deficiency (n=185) were more likely to have severe thrombocytopenia, normal renal function and neutralizing ADAMTS13 antibodies. Severe ADAMTS13 deficient TTP cases have better overall survival after therapeutic plasma exchange (TPE) but are more likely to relapse. TTP patients with severe ADAMTS13 deficiency were primarily categorized as idiopathic or ticlopidine-associated, while TTP patients with non-severely deficient ADAMTS13 activity levels were frequently categorized as idiopathic, secondary to drugs (clopidogrel, quinine), stem cell transplantation, or cancer.

Conclusions: Severe ADAMTS13 deficiency is most commonly idiopathic, has better survival following TPE, and a 35–40% spontaneous relapse rate. By contrast, non-ADAMTS13 deficient TTP cases are usually associated with an underlying disorder or external insults. Amongst this cohort, four series have 47–62% survival rates and three series, which contain mostly idiopathic cases, have 83–90% survival rates following TPE. From this, we propose that TTP may occur by three possible mechanism; ADAMTS13-deficient (antibody-mediated), an immunologic mediated pathway independent of ADAMTS13 (i.e. quinine) that is responsive to TPE, and endothelial injury related TTP that is unresponsive to TPE.

Platelet count mean (x10^9/L)Creatinine mean (mg/dl)ADAMTS13 neutralizing antibodies (%)Survival %Relapse %
* <15% ADAMTS13 activity cutoff 
Severe ADAMTS13 Deficiency (<10–15%) 
SERF-TTP (n=30) 19 1.3 83 97 41 
Zheng (n=16) 19 1.6 44 81 38 
Bennett (n=26) 15  85  
Oklahoma (n=18) 12 1.8 94 81 38 
Raife (n=50) * 13 1.2  92 35 
Japan (n=34)  35 91  
Canada (n=11) 16 2.4  82  
Not Severely Deficient ADAMTS13 Activity (> 15%) 
SERF-TTP (n=22) 57 3.9 35 90 
Raife (n=57) * 44 2.7  83 
Canada (n=17)  57 4.1 88  
Zheng (n=13) 40 3.0 54  
Bennett (n=13)    62  
Japan (n=66)   62  
Oklahoma (n=94 ) 23   47 
Platelet count mean (x10^9/L)Creatinine mean (mg/dl)ADAMTS13 neutralizing antibodies (%)Survival %Relapse %
* <15% ADAMTS13 activity cutoff 
Severe ADAMTS13 Deficiency (<10–15%) 
SERF-TTP (n=30) 19 1.3 83 97 41 
Zheng (n=16) 19 1.6 44 81 38 
Bennett (n=26) 15  85  
Oklahoma (n=18) 12 1.8 94 81 38 
Raife (n=50) * 13 1.2  92 35 
Japan (n=34)  35 91  
Canada (n=11) 16 2.4  82  
Not Severely Deficient ADAMTS13 Activity (> 15%) 
SERF-TTP (n=22) 57 3.9 35 90 
Raife (n=57) * 44 2.7  83 
Canada (n=17)  57 4.1 88  
Zheng (n=13) 40 3.0 54  
Bennett (n=13)    62  
Japan (n=66)   62  
Oklahoma (n=94 ) 23   47 

Author notes

Disclosure: No relevant conflicts of interest to declare.