Anti-platelet factor 4 (PF4)/heparin antibodies (Abs) and activation of platelet FcyRlla are involved in the pathogenesis of heparin-induced thrombocytopenia (HIT). However, the actual basis of the observed thrombocytopenia and thrombosis are not well understood, and markers of risk or diagnosis and targeted therapies remain limited. This Project focuses on furthering our understanding of the cellular events underiying the thrombocytopenia and thrombosis in HIT. We believe that platelets, leukocytes and endothelium, and derived microparticles (MP) contribute to both the thrombocytopenia and thrombosis. In this Project, we propose three novel interrelated cellular mechanisms that underiie the thrombocytopenia and prothrombotic nature of HIT:

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL110860-02
Application #
8534255
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$196,769
Indirect Cost
$81,861
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Cines, Douglas B; Lebedeva, Tatiana; Nagaswami, Chandrasekaran et al. (2014) Clot contraction: compression of erythrocytes into tightly packed polyhedra and redistribution of platelets and fibrin. Blood 123:1596-603
Yeung, Jennifer; Tourdot, Benjamin E; Fernandez-Perez, Pilar et al. (2014) Platelet 12-LOX is essential for Fc?RIIa-mediated platelet activation. Blood 124:2271-9
Cines, Douglas B; Cuker, Adam; Semple, John W (2014) Pathogenesis of immune thrombocytopenia. Presse Med 43:e49-59
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Zhi, Huiying; Rauova, Lubica; Hayes, Vincent et al. (2013) Cooperative integrin/ITAM signaling in platelets enhances thrombus formation in vitro and in vivo. Blood 121:1858-67
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Cuker, Adam; Rux, Ann H; Hinds, Jillian L et al. (2013) Novel diagnostic assays for heparin-induced thrombocytopenia. Blood 121:3727-32

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