What To Do When You Suspect an Inherited Platelet Disorder

Inherited platelet disorders (IPDs) comprise a heterogenous group of diseases that include defects in platelet function and disordered megakaryopoiesis. Some IPDs overlap as both defects in function and thrombopoiesis, resulting in both altered aggregation and/or secretion and thrombocytopenia. This review examines the key features of the presentation of IPDs in children and adults and presents a diagnostic algorithm for the evaluation of these patients. In addition, recent advances in our understanding of the pathophysiology of platelet disorders are addressed, with attention given to some of the novel genetic associations. Finally, treatment options and future therapies are briefly discussed. Introduction: presentation of IPDs Many of the severe congenital thrombocytopenias or platelet dysfunction disorders manifest early in life with bleeding symp- toms, including mucosal bleeding such as epistaxis and gum bleeding and increased bruising with or without petechiae. Patients with inherited platelet disorders (IPDs) may also have life- threatening hemorrhaging in the gastrointestinal or genitourinary tracts or even intracranial hemorrhaging. Bleeding questionnaires have been developed for pediatric populations and for taking issues of diagnosing mild bleeding disorders in relatively hemostatically unchallenged individuals into consideration. 1 However, some cases of congenital thrombocytopenia may not be detected until a screening complete blood count is done in late childhood or even as an adult, particularly in patients with disorders for which platelet function is relatively normal. In these patients, it may be difficult to differentiate between mild chronic, acquired thrombocytopenia, also called mild immune thrombocytopenia (ITP), and congenital thrombocytopenia. If a family history of thrombocytopenia is present, a comprehensive workup is warranted to avoid costly and potentially inappropriate therapies and to ensure appropriate follow-up of clinical complications, such as a predisposition to oncologic disorders, increased risk of renal disease, or sensorineural hearing loss. Similar situations may exist for patients with inherited, mild platelet function defects, which may not manifest until a surgical or traumatic stress taxes the hemostatic system and results in significant bleeding. Many women with these mild disorders will present with menorrhagia, which may not be detected until she sees a gynecologist. Bleeding manifestations resemble those of type 1 or type 2 VWD—and the prevalence of IPDs may be as high as that seen in VWD—so diagnostic evaluation must rule out both diagnoses. Patients with thrombocytopenia and associated features suggestive of some of the rarer but well-characterized disorders may also have features suggestive of those diseases; these include: reduced or delayed pigmentation (Hermansky Pudlak syndrome); personal or family history of hearing loss, renal impairment, or cataracts (MYH9-related disorders); eczema, infection, and small platelets (Wiskott Aldrich syndrome (WAS) and X-linked thrombocytope- nia); limb abnormalities (thrombocytopenia absent radii (TAR)); and familial predisposition to leukemia/lymphoma (RUNX1 mutations).