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:

 

Patents:

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.

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