title: Should studies on Glanzmann thrombasthenia not be telling us more about cardiovascular disease and other major illnesses?
abstract: Glanzmann thrombasthenia (GT) is a rare inherited bleeding disorder caused by loss of αIIbβ3 integrin function in platelets. Most genetic variants of β3 also affect the widely expressed αvβ3 integrin. With brief mention of mouse models, I now look at the consequences of disease-causing ITGA2B and ITGB3 mutations on the non-hemostatic functions of platelets and other cells. Reports of arterial thrombosis in GT patients are rare, but other aspects of cardiovascular disease do occur including deep vein thrombosis and congenital heart defects. Thrombophilic and other risk factors for thrombosis and lessons from heterozygotes and variant forms of GT are discussed. Assessed for GT patients are reports of leukemia and cancer, loss of fertility, bone pathology, inflammation and wound repair, infections, kidney disease, autism and respiratory disease. This survey shows an urgent need for a concerted international effort to better determine how loss of αIIbβ3 and αvβ3 influences health and disease.
authors.affiliation: Institut de Rhythmologie et de Modélisation Cardiaque, Plateforme Technologique d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France. Electronic address: nurdenat@gmail.com.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D004198:Disease Susceptibility; D005342:Fibrinolysis; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D013915:Thrombasthenia / Q000097:blood / Q000150:complications* / Q000235:genetics*
chemical_list: D039302:Integrin alphaVbeta3; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
keywords: Extended phenotype; Glanzmann thrombasthenia; Inflammation and immunity; Inherited platelet disorder; Thrombosis and cancer; β3-Integrins