Our June, 2019 Quick Question generated a near-unanimous response from 68 voters:
What laboratory assay confirms thrombotic thrombocytopenic purpura (TTP)?
- Shiga toxin test: 3% (2)
- Complement C3 level: 7% (5)
- ADAMTS13 activity: 83% (56)
- VWF multimers: 7% (5)
The Shiga toxin test correlates to Shiga toxin-induced hemolytic-uremic syndrome (ST-HUS), the “classic” HUS detected mainly in children and treatable with Soliris® (eculizumab), an anti-C5 formulation. The complement C3 level associates with atypical HUS (aHUS), found in all ages, where a complement abnormality activates platelets. Ultomiris® (ravulizumab), another Alexion anti-C5 inhibitor, is currently under FDA review for aHUS management. The diagnosis of TTP once hinged on the demonstration of “ultra-large VWF multimers” in VWF multimeric analysis, but since “a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13” (ADAMTS13) deficiency has been identified as the mechanism, the ADAMTS13 activity assay has become the preferred assay. In acquired TTP, the most prevalent form, the assay may be enhanced by autoantibody detection. Plasma exchange has been the mainstay TTP therapy for many years, however new treatments are under consideration, in particular, a recombinanct ADAMTS13 concentrate, as indicated in this excellent review article:
Teersteg C, Schiviz A, De Meyer SF, et al. Potential for recombinant ADAMTS13 as an effective therapy for acquired thrombotic thrombocytopenic purpura. Arteriocler Thromb Vasc Biol 2015;35:2336–42.