apyrase has been researched along with Leukopenia* in 1 studies
1 other study(ies) available for apyrase and Leukopenia
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Evidence of platelet activation at medically used hypothermia and mechanistic data indicating ADP as a key mediator and therapeutic target.
Hypothermia is used in various clinical settings to inhibit ischemia-related organ damage. However, prothrombotic effects have been described as potential side effects. This study aimed to elucidate the mechanism of hypothermia-induced platelet activation and subsequent prothrombotic events and to develop preventative pharmacological strategies applicable during clinically used hypothermia.. Platelet function was investigated ex vivo and in vivo at clinically used hypothermia (28°C/18°C). Hypothermic mice demonstrated increased expression of platelet activation marker P-selectin, platelet-leukocyte aggregate formation, and thrombocytopenia. Intravital microscopy of FeCl(3)-injured murine mesenteric arteries revealed increased platelet thrombus formation with hypothermia. Ex vivo flow chamber experiments indicated increased platelet-fibrinogen adhesion under hypothermia. We show that hypothermia results in reduced ADP hydrolysis via reduction of CD39 (E-NTPDase1) activity, resulting in increased levels of ADP and subsequent augmented primary and secondary platelet activation. In vivo administration of ADP receptor P(2)Y(12) antagonists and recombinant soluble CD39 prevented hypothermia-induced thrombus formation and thrombocytopenia, respectively.. The platelet agonist ADP plays a key role in hypothermia-induced platelet activation. Inhibition of receptor binding or hydrolysis of ADP has the potential to protect platelets against hypothermia-induced activation. Our findings provide a rational basis for further evaluation of novel antithrombotic strategies in clinically applied hypothermia. Topics: Adenosine Diphosphate; Analysis of Variance; Animals; Antigens, CD; Apyrase; Blood Platelets; Fibrinogen; Fibrinolytic Agents; Humans; Hydrolysis; Hypothermia, Induced; Leukopenia; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; P-Selectin; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIb-IX Complex; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y1; Receptors, Purinergic P2Y12; Recombinant Proteins; Thrombocytopenia; Thrombosis; von Willebrand Factor | 2011 |