Improving platelet storage and blood transfusion: unveiling the role of apolipoprotein A-IV
Platelets are small anucleate cells in the blood. At the sites of injury, platelet adhesion and
aggregation are the primary wave to stop bleeding. Platelet transfusion is therefore a lifesaving
procedure to prevent blood loss and the platelets are an important product of Canadian Blood
Services. Differing from other blood products, platelets are sensitive to low temperature, and are
usually stored at room temperature with gentle agitation in gas-permeable containers. It is
currently impossible to stop platelet metabolism/exhausting under these conditions, but
decreasing their activation/energy expenditure may be a useful strategy to improve their quality
and extend their shelf time in blood banks. Notably, platelets are also inflammatory cells, with
the P-selectin and other proteins synthesized during storage also possibly contributing to
inflammation and alloimmune response following transfusion.
The PI’s lab recently found that apolipoprotein A-IV (apoA-IV), an abundant blood plasma
protein, can bind to platelets via platelet IIb3 integrin (GPIIbIIIa). ApoA-IV can inhibit
platelet activation and decrease P-selectin expression, therefore may be able to decrease platelet
energy expenditure and P-selectin-mediated inflammation/alloimmune response.
We will test this hypothesis and examine platelet activation/metabolism during storage with and
without apoA-IV including apoA-IV mutant proteins. The quality of platelets will be examined
using our platelet adhesion/aggregation assays in vitro and the state-of-the-art intravital
microscopy that can visualize the platelet behavior in alive animals. Whether apoA-IV may
affect inflammation/immune response will be also examined in apoA-IV deficient and control
mice following blood transfusions.
We expect that apoA-IV may significantly improve the platelet quality during storage and
decrease the transfusion-related inflammation/alloimmune response. The proposed studies are
therefore related to CBS research priorities: 1) promote appropriate blood product (i.e. plasma
apoA-IV) utilization, 2) minimize the adverse effects of blood product (foreign antigens)-
induced alloimmune response after blood transfusion, 3) optimize blood product (e.g. platelets)
quality during storage.
aggregation are the primary wave to stop bleeding. Platelet transfusion is therefore a lifesaving
procedure to prevent blood loss and the platelets are an important product of Canadian Blood
Services. Differing from other blood products, platelets are sensitive to low temperature, and are
usually stored at room temperature with gentle agitation in gas-permeable containers. It is
currently impossible to stop platelet metabolism/exhausting under these conditions, but
decreasing their activation/energy expenditure may be a useful strategy to improve their quality
and extend their shelf time in blood banks. Notably, platelets are also inflammatory cells, with
the P-selectin and other proteins synthesized during storage also possibly contributing to
inflammation and alloimmune response following transfusion.
The PI’s lab recently found that apolipoprotein A-IV (apoA-IV), an abundant blood plasma
protein, can bind to platelets via platelet IIb3 integrin (GPIIbIIIa). ApoA-IV can inhibit
platelet activation and decrease P-selectin expression, therefore may be able to decrease platelet
energy expenditure and P-selectin-mediated inflammation/alloimmune response.
We will test this hypothesis and examine platelet activation/metabolism during storage with and
without apoA-IV including apoA-IV mutant proteins. The quality of platelets will be examined
using our platelet adhesion/aggregation assays in vitro and the state-of-the-art intravital
microscopy that can visualize the platelet behavior in alive animals. Whether apoA-IV may
affect inflammation/immune response will be also examined in apoA-IV deficient and control
mice following blood transfusions.
We expect that apoA-IV may significantly improve the platelet quality during storage and
decrease the transfusion-related inflammation/alloimmune response. The proposed studies are
therefore related to CBS research priorities: 1) promote appropriate blood product (i.e. plasma
apoA-IV) utilization, 2) minimize the adverse effects of blood product (foreign antigens)-
induced alloimmune response after blood transfusion, 3) optimize blood product (e.g. platelets)
quality during storage.
Principal Investigator / Supervisor
NI, Heyu
Co-Investigator(s) / Trainee
LAZARUS, Alan
BRANCH, Donald
Institution
Unity Health Toronto
Program
Intramural Research Grant Program
Province
Ontario
Total Amount Awarded
$400,000
Project Start Date
Project End Date