Back to Search
Start Over
Poor responder to plasma exchange therapy in acquired thrombotic thrombocytopenic purpura is associated with ADAMTS13 inhibitor boosting: visualization of an ADAMTS13 inhibitor complex and its proteolytic clearance from plasma.
- Source :
-
Transfusion [Transfusion] 2015 Oct; Vol. 55 (10), pp. 2321-30. Date of Electronic Publication: 2015 Jun 08. - Publication Year :
- 2015
-
Abstract
- Background: Plasma exchange (PE) is the first-line treatment for primary acquired thrombotic thrombocytopenic purpura (aTTP) with severe deficiency of ADAMTS13 activity (ADAMTS13:AC). Some patients are poor responders to PE, raising concern over multiple pathogenetic pathways.<br />Study Design and Methods: Based on 52 aTTP patients in our national cohort study, we monitored plasma levels of ADAMTS13, clinical and laboratory findings, and outcomes. In a representative poor responder to PE, we examined an ADAMTS13 inhibitor (ADAMTS13:INH) complex in plasma milieu, by means of a large-pore isoelectric focusing (IEF) analysis.<br />Results: Of 52 aTTP patients, 20 were good responders and 32 were poor responders. In the latter group, plasma ADAMTS13:AC levels never increased to more than 10% of normal during 14 days after PE initiation. Mean (±SD) plasma ADAMTS13:INH titers (Bethesda unit/mL) were 5.7 (±4.5) before PE, but decreased to 1.4 (±0.8) on the fourth PE day and then remarkably increased to 14.8 (±10.0) on the 10th PE day, termed "inhibitor boosting," and then slowly decreased to undetectable level over 1 month. On admission, none of the routinely available clinical and laboratory markers differentiated these two groups. However, elevated pre-PE levels of ADAMTS13:INH were correlated with a poor response. We visualized an ADAMTS13:INH (immunoglobulin G) complex in a patient plasma by an IEF analysis and found proteolytic fragment of ADAMTS13 antigen by a two-dimensional IEF and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.<br />Conclusion: Findings from this cohort of aTTP patients demonstrated that inhibitor boosting often occurs in aTTP patients in Japan. Poor responders could be predicted by elevated pre-PE ADAMTS13:INH levels on admission, but not by routinely collected clinical or laboratory data.<br /> (© 2015 AABB.)
- Subjects :
- ADAMTS13 Protein
Adolescent
Adult
Aged
Aged, 80 and over
Child
Child, Preschool
Female
Follow-Up Studies
Humans
Infant
Japan
Male
Middle Aged
Retrospective Studies
ADAM Proteins antagonists & inhibitors
ADAM Proteins blood
ADAM Proteins deficiency
Autoantibodies blood
Immunoglobulin G blood
Plasma Exchange
Protease Inhibitors blood
Purpura, Thrombotic Thrombocytopenic blood
Purpura, Thrombotic Thrombocytopenic therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1537-2995
- Volume :
- 55
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Transfusion
- Publication Type :
- Academic Journal
- Accession number :
- 26058519
- Full Text :
- https://doi.org/10.1111/trf.13182