Box 2.

Causes of ADAMTS13 deficiency

Autoimmune antibodies
•	Inhibitory IgG antibody of ADAMTS13 causes profound ADAMTS13 deficiency in acquired TTP
•	The level of the inhibitory antibody is low (< 10 units/mL) in most cases.
•	The prevalence and significance of non-inhibitory antibodies of ADAMTS13 remain unclear.
Mutations of the ADAMTS13 gene
•	Patients with hereditary TTP are doubly heterozygous or homozygous of mutant alleles. No abnormal phenotypes have been identified in carriers of single mutant alleles.
•	More than 65 different mutations have been identified, including nonsense, missense, deletion, and splicing. The mutations span the entire spectrum of ADAMTS13 domain structure.
•	At least 27 polymorphisms have been detected. Certain cis-combinations of polymorphisms may compromise protease secretion/activity.
•	Genotype-phenotype correlation is unclear because only a few of the mutations have been detected recurrently in more than one pedigree.

Ig: immunoglobulin; TTP: thrombotic thrombocytopenic purpura.