The present invention provides a method of enhancing an enzymatic activity of ADAMTS-13 and/or a method of reducing reactivity to an anti-ADAMTS-13 neutralizing antibody as well as a mutant of ADAMTS-13 prepared by the methods. The method of the present invention is characterized by substituting at least one charged amino acid in a disintegrin-like domain, a cysteine-rich domain or a spacer domain of ADAMTS-13 other than the following amino acids with a different amino acid: arginine at position 326, aspartic acid at position 330, aspartic acid at position 343 and arginine at position 349 in the disintegrin-like domain, aspartic acid at position 480, arginine at position 488, arginine at position 498, arginine at position 507, aspartic acid at position 533 and aspartic acid at position 543 in the cysteine-rich domain, and glutamic acid at position 641 and arginine at position 660 in the spacer domain. The present invention also provides a therapeutic agent for thrombotic disease comprising as an active ingredient the mutant of ADAMTS-13 prepared by the method.
