CHAPTER 14 – Platelet Polymorphisms

The first 30 years of investigations into platelet polymorphisms focused on the alloimmune thrombocytopenias. The nature of the alloantigen, the identification of the alloantibody, and the immune basis for antibody formation were discovered for those platelet membrane antigens most commonly responsible for alloimmune thrombocytopenia. Based on this knowledge, rational treatment strategies were developed for fetal and neonatal alloimmune thrombocytopenia (FNAIT) and posttransfusion purpura (PTP) (see Chapter 53). As molecular biologists uncovered the genetic bases for these polymorphisms, DNA testing became a useful addition to patient evaluation and management. The second phase of platelet polymorphism history began when investigators started to consider the genetic basis of common multifactorial diseases, such as vascular thrombosis. The impact of genetic variations as modifiers of disease processes led to the investigation of platelet polymorphisms as risk factors for arterial thrombosis and modifiers of hemorrhage. This new area of medicine presents unique challenges for the platelet researcher, such as the accurate detection of a small but real effect on the platelet and the clinical phenotype affected by the inherited sequence variation. Although in its infancy, this area of platelet biology promises to have a signifi cant impact on future strategies for managing disorders such as myocardial infarction, stroke, and peripheral vascular disease. We have now entered a third phase comprising the intersection of information derived from the sequencing of the human genome with the study of inherited variations of platelet genes. This phase has identifi ed large numbers of sequence variations in platelet genes via very different approaches than previously used by immunohematologists, using comprehensive genome searches for polymorphisms and resequencing specific genes. In the first half of this chapter we consider the genetic basis for platelet alloantigens and the evidence for alterations in protein antigenicity and function. The second half of the chapter covers the clinical consequences of these inherited variations.