Cystic fibrosis (CF) is caused by a mutation of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). We examined platelet function in CF patients because lung inflammation is part of this disease and platelets contribute to inflammation. CF patients had increased circulating leukocyte-platelet aggregates and increased platelet responsiveness to agonists compared with healthy controls. CF plasma caused activation of normal and CF platelets; however, activation was greater in CF platelets. Furthermore, washed CF platelets also showed increased reactivity to agonists. CF platelet hyperreactivity was incompletely inhibited by prostaglandin E 1 (PGE 1 ). As demonstrated by Western blotting and reverse-transcriptase-polymerase chain reaction (RT-PCR), there was neither CFTR nor CFTR-specific mRNA in normal platelets. There were abnormalities in the fatty acid composition of membrane fractions of CF platelets. In summary, CF patients have an increase in circulating activated platelets and platelet reactivity, as determined by monocyte-platelet aggregation, neutrophilplatelet aggregation, and platelet surface P-selectin. This increased platelet activation in CF is the result of both a plasma factor(s) and an intrinsic platelet mechanism via cyclic adenosine monophosphate ( IntroductionCystic fibrosis (CF) is the most common lethal genetic disease in whites, affecting approximately 1 in 2500 live births. 1 In 1989, Kerem et al 2 ; Riordan et al 3 ; and Rommens et al 4 identified the genetic mutation responsible for CF and cloned its protein product, which is called the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a member of the adenosine triphosphate (ATP)-binding cassette family of transporters and acts chiefly as a chloride channel, although it has various other functions including regulation of alternate chloride channels and epithelial sodium channels, and transport of ATP. [5][6][7] Defects in CFTR cause reduced chloride secretion into airways and enhanced sodium reabsorption, thereby resulting in dehydrated airway secretions, poor mucociliary clearance, and airway obstruction. 1 Obstruction of the airways, along with poorly understood altered host defense mechanisms and an enhanced inflammatory response, leads to chronic airway infection and inflammation. This, in turn, causes an influx of polymorphonuclear cells that, when they become senescent and release their DNA into the airway mucous, contribute to thickening of airway secretions. 8 The self-perpetuating cycle of obstruction, infection, and inflammation eventually causes pulmonary parenchymal destruction and respiratory failure. The life expectancy for CF patients in the United States is currently approximately 33 years. 9 Previous studies have shown that CF patients have increased ex vivo platelet aggregability, increased release of thromboxane A 2 (TXA 2 ), 10-12 and a blunted response to prostaglandin E 1 (PGE 1 )-induced inhibition of platelet aggregation. 13,14 Platelets contain or generate many inf...

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