Clinical Pathology: Hematology & Coagulation

• Inherited platelet disorders characterized by disorders of the platelet granules include Idiopathic dense-granule disorder (δ-storage pool disease); Hermansky-Pudlak syndrome; Chediak-Higashi syndrome; gray platelet syndrome; Paris-Trousseau/Jacobsen syndrome; and idiopathic α- and dense-granule storage pool disease.

• α-Granule disorders include gray platelet syndrome; Paris-Trousseau or Jacobsen syndrome; Quebec platelet syndrome; and arthrogryposis–renal dysfunction–cholestasis.

• Gray platelet syndrome is characterized by a lack of α-granules when the platelets are analyzed by electron microscopy. The contents of α granules that are both synthesized by the megakaryocyte (platelet factor 4 [PF4], β-thromboglobulin, and platelet-derived growth factor [PDGF]) and taken up from the blood (factor V and fibrinogen) are lacking. P-selectin, an α-granule marker, is retained.

• There are fewer than 100 cases worldwide. Gray platelet syndrome has both autosomal recessive and autosomal dominant patterns of inheritance. The genetic defects may involve several genes.

• Platelets appear “gray” (due to lack of α-granules), misshapen, and slightly large (macrothrombocytopenia) on peripheral blood smear.

• Electron microscopy of platelets shows decreased numbers or absence of α-granules.

• Clinically, patients have a variable bleeding disorder (mild to severe) associated with both abnormal platelet function and thrombocytopenia.