Abstract Number: OC 10.2
Meeting: ISTH 2021 Congress
Background: Acute systemic painful vaso-occlusive episode (VOE) is the predominant clinical event requiring sickle cell disease (SCD) patients to seek emergency medical care. VOE often serves as an antecedent to acute chest syndrome (ACS), which is a type of acute lung injury and one of the leading causes of mortality in SCD. Based on clinical epidemiology, ACS is often preceded by thrombocytopenia and involves massive thrombosis across pulmonary artery branches in 10-20% of ACS patients. Although released during hemolysis adenosine diphosphate (ADP) is known to activate platelets by stimulating their purinergic receptors P2Y1 and P2Y12, antagonists of P2Y12 have not shown any benefit and the role of purinergic signaling in SCD remains poorly understood.
Aims: To elucidate the contribution of platelet purinergic signaling to the pathophysiology of pulmonary thrombosis in SCD humanized mice in vivo.
Methods: Here we used a novel multi-photon-excitation based quantitative fluorescence intravital lung microscopy (qFILM) to study platelet-dependent pulmonary thrombosis triggered by an intravascular administration of ADP or collagen into transgenic SCD mice. Intravital microscopy study was accompanied by an in vitro platelet aggregation turbidimetric assay using SCD and control mice platelet rich plasma samples.
Results: Using qFILM we discovered that pulmonary thrombosis involved entrapment of platelet aggregates in the bottlenecks located between the pulmonary arterioles and capillaries. Although ADP triggered pulmonary thrombosis in control mice, it failed to induce pulmonary thrombosis in SCD mice. In contrast, collagen evoked platelet-mediated pulmonary thrombosis identically in both control and SCD mice. Remarkably, in vitro platelet aggregation studies further confirmed that aggregation of SCD mouse platelets was largely impaired in response to ADP but not collagen.
Conclusions: Our preliminary findings suggest an impaired platelet purinergic signaling in SCD and warrant the need for further studies to understand the role of purinergic signaling in pathogenesis of ACS.
To cite this abstract in AMA style:Brzoska T, Menchikova EV, Kaminski TW, Vats R, Tutuncuoglu E, Tofovic SP, Jackson EK, Gladwin MT, Sundd P. Impairment of Platelet Purinergic Signaling in Sickle Cell Disease [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/impairment-of-platelet-purinergic-signaling-in-sickle-cell-disease/. Accessed September 24, 2021.
« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/impairment-of-platelet-purinergic-signaling-in-sickle-cell-disease/