Science
Recent groundbreaking research at the BloodCenter of Wisconsin suggests a new paradigm by which the pathogenic HIT antibodies cause platelet activation, the basis of thrombocytopenia and thrombosis in HIT. These studies show that pathogenic platelet-activating HIT antibodies bind and activate PF4-treated platelets in a heparin-independent manner. To achieve proof-of-concept that this new knowledge can be leveraged to develop novel HIT diagnostic testing, Drs. Padmanabhan and Aster developed a flow cytometer-based test, the PEA (PF4-dependent P-selectin Expression Assay). The PEA has been shown to detect pathogenic antibodies earlier in the course of HIT than the SRA in one study (Chest, Oct 2017), and with greater accuracy in another (Chest, Sep 2016). In more recent studies, it has also shown promise in monitoring response to therapy (Chest, Sep 2017; Blood, Feb 2018).
In the News:
-
Lead inventor Dr. Padmanabhan received the National Blood Foundation Award for Innovative Research for this body of work
-
This research was featured in the “Latest and Greatest” section of the American Society of Hematology’s Newsletter
-
Healio, a medical news, education and information website for physicians and health care practitioners included this research in: "ASH 2015: Several pearls fished from sea of abstracts"
-
A manuscript on the PEA was selected as the Chest Editor’s Pick and the paper of the month on Chest’s Podcast (Sep 2016)
-
Retham President & CMO, Dr. Padmanabhan received the Lecturer Award from the American Society for Apheresis (April 2018)
-
Curtis Jones, co-inventor of the HITDx technology, received the Best Abstract Award from the American Society for Apheresis.
-
Hear Dr. Padmanabhan speak about HIT epidemiology, diagnosis and treatment on the Clinical and Translational Sciences Institute (CTSI) of Southeastern Wisconsin's Discovery Radio
Patents:
-
Method of Detecting Platelet-Activating Antibodies That Cause Heparin-Induced Thrombocytopenia/Thrombosis. US 9,851,367
-
Method of Detecting Platelet-Activating Antibodies That Cause Heparin-Induced Thrombocytopenia/Thrombosis. US 10,215,767
Peer-reviewed Publications:
1. Heparin-independent binding of HIT antibodies to platelets: Implications for HIT pathogenesis. Padmanabhan A et al. Blood 2015 Jan 1;125(1):155-61
2. A PF4-dependent CD62p expression assay selectively detects serotonin-releasing antibodies in patients suspected of HIT. Padmanabhan A et al. Thrombosis & Haemostasis, 2015 Nov 25;114(6):1322-3
3. A novel PF4-dependent platelet activation assay identifies patients likely to have heparin-induced thrombocytopenia/thrombosis (HIT). Padmanabhan A et al. Chest. 2016 Sep; 150(3):506-15.
4. A PF4-dependent platelet activation assay (PEA) facilitates early detection of pathogenic HIT antibodies. Jones CG, Pechauer SM, Curtis BR, Bougie DW, Irani MS, Dhakal B, Pierce B, Aster RH and Padmanabhan A. Chest. Oct 2017; 152(4):e77-e80.
5. Intravenous immunoglobulin for treatment of severe refractory heparin-induced thrombocytopenia. Padmanabhan A et al. Chest. Sep 2017 Volume 152, Issue 3, Pages 478–485. Chest Podcast, Sep 2017. Transfusion News (2017). ASH Newsletter, the Hematologist (2017)
6. Normal plasma IgG inhibits HIT antibody-mediated platelet activation: implications for therapeutic plasma exchange. Jones CG, Pechauer SM, Curtis BR, Bougie DW, Aster RH and Padmanabhan A. Blood. 2018 Feb 8; 131(6):703-706.
7. Disease burden, complication rates, and health-care costs of heparin-induced thrombocytopenia in the USA: a population-based study. Dhakal, B., Kreuziger, L. B., Rein, L., Kleman, A., Fraser, R., Aster, R. H., ... & Padmanabhan, A. (2018). The Lancet Haematology, 5(5), e220-e231.
8. Serotonin release assay (SRA)-negative HIT, a newly recognized entity: Implications for diagnosis and management. Pandya, K. A., Johnson, E. G., Davis, G. A., & Padmanabhan, A. (2018). Thrombosis research, 172, 169-171.
9. Use of intravenous immunoglobulin G to treat spontaneous heparin‐induced thrombocytopenia. Irani, M., Siegal, E., Jella, A., Aster, R., & Padmanabhan, A. (2019). Transfusion, 59(3), 931-934.
10. Intravenous immunoglobulin as an adjunct therapy in persisting heparin-induced thrombocytopenia. Park, B. D., Kumar, M., Nagalla, S., De Simone, N., Aster, R. H., Padmanabhan, A., ... & Rambally, S. (2018). Transfusion and Apheresis Science, 57(4), 561-565.