Presenting ADAMTS13 Antigen Level Correlates with Clinical Outcome in Acute Thrombotic Thrombocytopenic Purpura
Authors: Alwan Ferras , Vendramin Chiara , Langley Katy , Ellis Debra , Thomas Mari , Westwood John Paul , Scully Marie 
Published: November 2019

Abstract
Background:
Acute immune-mediated Thrombotic Thrombocytopenic Purpura (TTP) is a life-threatening disorder caused by acquired antibodies to the Von Willebrand factor cleaving protease ADAMTS13. Its prevalence has been estimated at four to thirteen cases per million per year and is characterized by hemolytic anemia, thrombocytopenia and multiorgan microthrombi. Untreated, mortality has been documented at 90% but even with treatment, it remains around 10-20%. Plasma Exchange (PEX) is the mainstay of treatment but immunosuppressive/immunomodulatory therapy is often also required. Whilst understanding of the disease process has increased greatly in recent times and a number of factors been implicated as possible markers of disease severity, there has been little evaluation of the effect of ADAMTS13 antigen levels on clinical outcome.
Since January 2009, the United Kingdom TTP registry has been collecting information on all acute presentations of TTP across the country.
Aims:
A prospective study to evaluate the effect of the ADAMTS13 antigen titer on clinical outcomes in acute, immune-mediated TTP.
Methods:
Acute, immune-mediated TTP was defined as microangiopathic hemolytic anemia and thrombocytopenia with ADAMTS13 activity <10% (FRETS vWF-73 assay, NR: 64-134%) or 10-20% with detectable anti-ADAMTS13 IgG. Congenital TTP cases were excluded. ADAMTS13 antigen was quantified using an in-house ELISA technique (normal range 74-134%).
Results:
There were 312 acute episodes of acquired TTP involving 292 patients over 87 months. Median ADAMTS13 activity was <5% (range <5% - 19%). Median ADAMTS13 antigen at presentation was 4% (range 0.5 - 146%). 72% of patients had antigen levels<10% at presentation. The mortality rate was 10.3% (died = 32). Median ADAMTS13 antigen levels were significantly lower in patients who died compared to survivors (survivors 4.2% (range 0.5-146%) vs died 1.6% (0.5-21.5%), p=0.0007). Mortality increased with lower ADAMTS13 antigen levels: those with an antigen level in the lowest quartile (antigen <1.5%) had a mortality of 18% compared with 3.8% for those in the highest quartile (antigen >11.65%) (p=0.0046). Patients with relapsed TTP had significantly higher presenting ADAMTS13 antigen levels compared to new presentations (new presentation 3.25% vs relapse 10%, p<0.0001).
Patients with ADAMTS13 antigen <4% required more plasma exchanges to remission defined as platelet count of 150x109/l (median 8 exchanges vs 10, p=0.036). This cohort also had a significantly higher median anti-ADAMTS13 IgG titer (ADAMTS13 antigen <4%, median IgG 58% (range 1-174%) vs antigen >4% median IgG 28% (5-189%), p<0.0001) and was more likely to have a markedly elevated cardiac troponin (five times the upper limit of normal) at presentation (p=0.009).
Conclusion:
ADAMTS13 antigen levels appear to correlate with the clinical outcome in acute, immune-mediated TTP. A presenting antigen level below 4% was associated with an increased risk of mortality, more refractory disease and a greater prevalence of severe cardiac events.

Disclosures
Alwan: Octapharma: Research Funding; Ablynx: Research Funding. Scully:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding.