Natural history of platelet antibody formation against αIIbβ3 in a French cohort of Glanzmann thrombasthenia patients

. Treatment of the bleeding syndrome in Glanzmann thrombasthenia (GT) is often complicated by naturally occurring isoantibodies directed against the aIIb beta 3 integrin that cause the removal of or render ineffective transfused donor platelets. Such antibodies are produced after transfusion or pregnancy when the patients immune system comes into contact with normal platelets. Despite many reports of anti-aIIb beta 3 antibodies in GT patients, there is no consensus pertaining to their frequency, their long-term evolution in the circulation, or their formation in relation to either (i) the extent of the aIIb beta 3 deficiency in the patients platelets or (ii) the nature of the genetic defect (ITGA2B or ITGB3 genes). Antibody screening was performed on a large series of 24 GT patients in South-West France dividing the patients into two cohorts: (i) 16 patients with the French gypsy mutation (c.1544 + 1G>A) within ITGA2B that gives platelets totally lacking aIIb beta 3 and (ii) 8 patients carrying other defects of ITGA2B or ITGB3 with different expression levels of aIIb beta 3. Our results confirm that patients with premature termination mutations resulting in platelets lacking aIIb beta 3 are the most susceptible to form isoantibodies, a finding that may be useful in deciding the choice of therapy between platelet transfusion and the use of recombinant factor VIIa (FVIIa).