Introduction: Whole blood transfusions are indicated for the resuscitation of patients with hemorrhagic trauma. In Sweden, whole blood is stored for 14 days at 4°C. If possible, refrigerated blood is rewarmed to 37°C before transfusion to avoid hypothermia. Platelets contribute to hemostasis and can be activated with several pathways. During storage, shedding of platelet surface receptors takes place. Further research on how platelet storage in whole blood and rewarming before transfusion affect platelets is needed. Aim: The aim was to study how storage in whole blood and rewarming to 37°C affect platelet function, platelet activatability, and changes in platelet surface receptors. Method: Whole blood from two healthy donors was stored for 14 days. During these 14 days, two blood samples were taken on day 0, before and after leukocyte reducing filtration, 1, 3, 7, and 14. One of the two blood samples from each whole blood product was tested at room temperature and the other was rewarmed to 37°C. The blood samples were mixed with antibodies and platelet agonists and analyzed on a flow cytometer. The blood samples were also analyzed on a cell counter. Results: This study shows distinct changes in platelet spontaneous activation, platelet count, and platelet receptor shedding by increased storage time in cold-stored whole blood and even more with rewarming to 37°C. Conclusion: This study shows that during storage, spontaneous platelet activation and shedding of GPIb and GPIIb increases while platelet count decreases. All these factors are likely affecting the platelet function and hemostatic function negatively.

Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and a cellular infiltrate dominated by eosinophils. Numerous epidemiological studies have related the exacerbation of allergic asthma with an increase in ambient inhalable particulate matter from air pollutants. This is because inhalable particles efficiently deliver airborne allergens deep into the airways, where they can aggravate allergic asthma symptoms. However, the cellular mechanisms by which inhalable particulate allergens (pAgs) potentiate asthmatic symptoms remain unknown, in part because most in vivo and in vitro studies exploring the pathogenesis of allergic asthma use soluble allergens (sAgs). Using a mouse model of allergic asthma, we found that, compared with their sAg counterparts, pAgs triggered markedly heightened airway hyperresponsiveness and pulmonary eosinophilia in allergen-sensitized mice. Mast cells (MCs) were implicated in this divergent response, as the differences in airway inflammatory responses provoked by the physical nature of the allergens were attenuated in MC-deficient mice. The pAgs were found to mediate MC-dependent responses by enhancing retention of pAg/IgE/FcεRI complexes within lipid raft–enriched, CD63(+) endocytic compartments, which prolonged IgE/FcεRI-initiated signaling and resulted in heightened cytokine responses. These results reveal how the physical attributes of allergens can co-opt MC endocytic circuitry and signaling responses to aggravate pathological responses of allergic asthma in mice. / Dissertation