Role of ADAMTS13 in the management of thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP)
BRITISH JOURNAL OF HAEMATOLOGY
2013; 163 (4): 514-519
Warfarin reversal: schism between clinical practice and published guidelines
2013; 53 (3): 476-479
Thrombotic thrombocytopenic purpurawhat is new?
JOURNAL OF CLINICAL APHERESIS
2013; 28 (1): 30-35
The clinical presentation of thrombotic thrombocytopenia purpura (TTP) and other thrombotic microangiopathies (TMAs) can often be similar. The role of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in diagnosing TTP is accepted by most researchers but continues to be debated in a few studies. We report the experience of our single-centre academic institution, where ADAMTS13 is used to diagnose TTP and guide plasma exchange (PLEX). Patients presenting to our institution with thrombotic microangiopathy (60 patients) between January 2006 and December 2012 were divided into two groups based on ADAMTS13 activity and clinical history. Patients with ADAMTS13 activity <10% were included in the TTP (n = 30) cohort while patients with activity >11% were classified as 'other microangiopathies' (TMA, n = 30). PLEX was only initiated in patients with a high likelihood of TTP and discontinued when the baseline ADAMTS13 activity was >11%. Patients with severe ADAMTS13 deficiency (TTP group) showed significant presenting differences: lower platelet counts, less renal dysfunction, higher presence of neurological abnormalities, and greater haemolysis markers as compared to non-deficient patients (TMA group). Most importantly, patients without severe ADAMTS13 deficiency were safely managed without increased mortality despite receiving no PLEX or discontinuing PLEX after a short course (upon availability of ADAMTS13 results). In conclusion, ADAMTS13 can be used to diagnose TTP and guide appropriate PLEX therapy.
View details for DOI 10.1111/bjh.12569
View details for Web of Science ID 000326034200013
View details for PubMedID 24111495
A functional deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif), a von-Willebrand factor (VWF) cleaving protease, is central to the pathogenesis of congenital and acquired thrombotic thrombocytopenic purpura (TTP). ADAMTS13 testing has evolved from assays that required long denaturation and incubation times to ones that employ a modified recombinant VWF with improved standardization and turn around times. While plasma exchange is a mainstay in the treatment of TTP, increased use of rituximab, an antibody against CD20, has proved helpful in the treatment of patients with exacerbations and relapses. The next generation of drugs focuses on using recombinant ADAMTS13 and molecules that block the interaction of VWF and platelets to prevent thrombotic microangiopathy. The increased awareness and availability of ADAMTS13 testing has also made it possible to detect atypical presentations of TTP such as patients with macrovascular neurological symptoms without accompanying hematological findings as well as help diagnose other causes of thrombotic microangiopathies e.g. atypical hemolytic uremic syndrome. The use of ADAMTS13 testing in the management of TTP should continue to grow especially with newer assays with greater sensitivity, reproducibility, and timelier availability.
View details for DOI 10.1002/jca.21264
View details for Web of Science ID 000315218300006
View details for PubMedID 23420593