Box 3.

Diagnostic approaches in TTP

Clinical
•	Prompt diagnosis and treatment are critical to prevent serious complications or death.
•	The blood smears should be reviewed for every new case of thrombocytopenia.
•	TIA, stroke, or mental changes should alert to the possibility of TTP, especially if it is associated with thrombocytopenia.
•	In patients with a history of TTP, neurological symptoms should raise the suspicion of TTP relapse even in the absence of thrombocytopenia or microangiopathic hemolysis.
Laboratory
•	ADAMTS13 deficiency is severe (<10% or 5% of normal, depending on the assays used) in patients presenting with acute TTP. However, the sensitivity and specificity should be determined for each individual assay used.
•	Plasma mixing studies detect the presence of inhibitors of ADAMTS13 in 50% – 90% of the acquired TTP cases. Inhibitory activity is detectable in > 95% of the cases if IgG molecules are tested at high concentrations.
•	ELISA detects ADAMTS13-binding IgG in essentially all cases of acquired TTP. However, a confirmatory step with ADAMTS13 protein to identify false positive cases in 5% – 15% of the individuals without TTP.
•	Change in VWF multimers reflects the combined effects of ADAMTS13 deficiency and VWF-platelet binding. Ultra large multimers are detected when ADAMTS13 activity is < 15% – 20%. As the protease level decreases to < 10%, VWF-platelet binding causes progressive depletion of the ultra large and large multimers.
•	ADAMTS13 activity is near or less than 10% in hereditary TTP. The parents are obligate carriers with partial deficiency.

Ig: immunoglobulin; TIA: transient ischemic attacks; TTP: thrombotic thrombocytopenic purpura; vWF: von Willebrand factor.