246 Chapter 16 4\-O 5 5 a Epinephrine § Collagen | time ——> | time ——> 5 5 2 noe 8 Ristocetn time ——> time ———> jure 16.2 Schematic representation of normal platelet aggregometry: Epinephrine and ADP are added (bold arrow) to induce primary (1) and secondary waves (2) of aggregation. Other agonists produce a monophasic curve. Nucleotide assays Storage pool and release defects can be diagnosed by measuring platelet ATP/ADP content and release. One-fourth of patients with storage pool defects may have normal platelet aggregometry, so ideally nucleotide content and release assays should both be performed in patients suspected to have platelet dysfunction [19]. These assays are only performed by select specialized centers Flow cytometry Platelet flow cytometry has emerged as a useful tool, particularly for the assessment of inherited surface glycoprotein disorders such as Bernard— Soulier syndrome (Gp-Ib/IX/V) and Glanzmann’s thrombasthenia (Gp-IIb/ Mla) [17]. It requires only a small amount of blood and is not limited by thrombocytopenia Electron microscopy Although not widely available, transmission electron microscopy (TEM) is helpful in the evaluation of dense granule defects (¢.g., in Hermansky—Inherited and Acquired Platelet Disorders 217 Pudlak syndrome; HPS) and ultrastructure abnormalities (e.g, MYH-9 disorders) As is obvious from the above discussion, no single diagnostic test can identify all platelet disorders. Some tests are indicated in all patients sus- pected of having a platelet disorder, whereas other tests should be per- formed selectively based on the suspicion for a particular defect. Disorders of platelets Often qualitative and quantitative platelet disorders coexist; however, we will review them separately to improve understanding of their pathophysi- ologic basis and to differentiate the therapeutic strategies employed. Plate- let transfusions are the only effective treatment in severe thrombocytopenia but other options, discussed in their respective sections, are available for disorders of platelet function. Qualitative platelet disorders Acquired platelet function disorders are more prevalent than inherited platelet disorders, yet the pathophysiology of congenital platelet disorders is better understood. A detailed discussion of all acquired and inherited qualitative disorders is beyond the scope of this chapter. The more common conditions are discussed below. Inherited platelet disorders Congenital platelet disorders are rare. They have been variably classified based on their mode of inheritance, the presence or absence of thrombo- cytopenia, and the various phases of hemostasis affected. Any step of platelet plug formation can be compromised including adhesion, aggrega- tion, secretion, interaction with the coagulation system, the cytoskeleton or even the second messenger systems involved. Some inherited disorders lead to thrombocytopenia and characteristic morphologic changes on the peripheral smear. Others are associated with phenotypic skeletal and neu- rologic abnormalities. A discussion of inherited platelet disorders is fol- lowed by an overview of their treatment. Platelet adhesion defects Bernard-Soulier syndrome First reported in 1948, Bernard-Soulier syndrome (BSS) is a rare inherited platelet disorder resulting from quantitative or qualitative defects in the