The Association of Factor V Leiden and Prothrombin Gene Mutation and Placenta-Mediated Pregnancy Complications: A Systematic Review and Meta-analysis of Prospective Cohort Studies

Marc Rodger and colleagues report the results of their systematic review and meta-analysis of prospective cohort studies that estimated the association of maternal factor V Leiden and prothrombin gene mutation carrier status and placenta-mediated pregnancy complications

Abnormal cytoplasmic extensions associated with active \u3b1IIb\u3b23 are probably the cause for macrothrombocytopenia in Glanzmann thrombasthenia-like syndrome

Mutations in the ITGA2B or ITGB3 genes that encode for the \u3b1IIb\u3b23 platelet integrin usually cause Glanzmann thrombasthenia, a severe autosomal recessive bleeding disorder characterized by absence of platelet aggregation, but normal platelet number and size. Several rare mutations cause a Glanzmann-like syndrome which manifests macrothrombocytopenia and usually displays autosomal dominant inheritance. The exact mechanism causing Glanzmann-like syndrome is unknown. One typical example of Glanzmann-like mutations causes deletion of 40 amino acids (p.647-686) in the \u3b23 \u3b2-tail domain (\u3b2TD_del) that was found in the heterozygous state in Italian and Japanese families. A second example is a missense mutation, C560R, located in the epidermal growth factor-like domain, found in the homozygous state in a French patient. Both mutations cause constitutive activation of \u3b1IIb\u3b23, but differ in their surface expression. In the current study, we generated cultured cells expressing \u3b23-\u3b2TD_del or \u3b23-C560R mutations along with wild-type \u3b1IIb, and examined the cells' ability to create tubulin-dependent protrusions compared to cells expressing wild-type \u3b1IIb\u3b23. Unlike cells expressing wild-type \u3b1IIb\u3b23, cells harboring each of the mutations exhibited abnormal cytoplasmic extensions on immobilized fibrinogen or Von Willebrand factor, which resembled extensions formed in megakaryocyte leading to proplatelets. Moreover, we showed that formation of abnormal extensions occurred also in wild-type \u3b1IIb\u3b23 cells when activated by activating antibody. These results suggest that the active conformation of \u3b1IIb\u3b23 can induce cytoskeletal rearrangements that lead to impaired proplatelet formation