BACKGROUND: Glanzmann thrombasthenia (GT) is an inherited autosomal recessive platelet disorder characterized by a complete or partial lack, or mutation, of the GPIIb/IIIa complex (integrin α(IIb)β(3)) on the thrombocytes' surface, leading to a severe bleeding syndrome. MATERIAL AND METHODS: Molecular genetic analysis was performed in patients with suspected GT. The aim of the present study was...

Next-generation sequencing is transforming our understanding of human genetic variation but assessing the functional impact of novel variants presents challenges. We analyzed missense variants in the integrin αIIbβ3 receptor subunit genes ITGA2B and ITGB3 identified by whole-exome or -genome sequencing in the ThromboGenomics project, comprising ∼32,000 alleles from 16,108 individuals. We analyz...

In many scientific and engineering applications, we are tasked with the optimisation of an expensive to evaluate black box function f . Traditional methods for this problem assume just the availability of this single function. However, in many cases, cheap approximations to f may be obtainable. For example, the expensive real world behaviour of a robot can be approximated by a cheap computer si...

BACKGROUND Increasing attention is being given to the training of doctors to become teachers. This does not apply only to the schooling of teachers in undergraduate medical education: at the postgraduate level, general practitioner trainers (GP-trainers) receive special schooling to prepare them for their role. Yet the skills, knowledge and traits that should be expected in the competent GP-tra...

BACKGROUND Depression treatment by General Practitioners (GPs) and patient outcomes improved significantly after a comprehensive 20-h training program of GPs. This study examines whether the effects on patient outcomes are caused by the improvements in the process of care. METHODS Seventeen GPs participated in the training program. A pre-test-post-test design was used. A total of 174 patients...

Platelets play a critical role in the pathophysiology of atherothrombotic disease. A pivotal event contributing to the understanding of platelet-dependent clot formation was the development of the platelet aggregometer in 1962.1 An aggregometer specifically measures the ability of platelets to adhere via glycoprotein IIb/IIIa (integrin IIb 3), and thousands of articles using this technique have...

Glanzmann thrombasthenia (GT) is the most common inherited disorder of platelets. Most of the molecular defects previously identified in GT have been caused by point (or other small) mutations in the genes for glycoprotein (GP) IIb or GPIIIa. We have used single-strand conformation polymorphism (SSCP) analysis to rapidly identify single-base changes in the GPIIIa gene. Using genomic DNA from no...

Platelet function testing (PFT), usually performed by techniques such as light transmission aggregometry (LTA), has traditionally been used to diagnose inherited qualitative and quantitative defects in platelet function, such as von Willebrand disease or Glanzmann thrombasthenia. With the increased use of antiplatelet agents to prevent arterial thrombosis and the interest in identifying patient...