Platelet pathology in carriers of the X-linked GATA-1 macrothrombocytopenia

Abstract

Previous investigations from our laboratory have characterized the ultrastructural and cytochemical pathology of platelets in male members of a family with X-linked GATA-1 G208S macrothrombocytoenia. A large proportion of their circulating platelets were hypogranular macrothrombocytes, resembling cells from patients with the Gray Platelet Syndrome. However, most of the GATA-1 macrothrombocytes contained some alpha granules, and a small number had as many as are present in normal platelets. GATA-1 macrothrombocytes also contained tubular inclusions formed from elements of the dense tubular system wrapped around each other like scrolls. Many macrothrombocytes contained flat tubular membrane sheets connected to channels of the open canalicular system, platelets in platelets and platelets attached to platelets forming very large macrothrombocytes. The present study has examined one obligate and three potential female carriers in this family. Thin sections of their platelets examined in the electron microscope revealed features consistent with the pathology observed in male family members. Most of their platelets were normal-sized, discoid cells containing the usual complement of alpha and delta storage organelles and channels of the dense tubular system and OCS. However, a significant number of giant platelets containing the usual frequency of alpha and delta granules and hypogranular and agranular giant platelets were observed. The frequency of the macrothrombocytes varied in each of the four women studied, but were present in all. The ability of their platelets to bind multimers of vWF, in contrast to male family members, did not differ from normal controls. Near normal as well as normal platelet counts and the ability of their platelets to bind vWF multimers may protect them from the serious bleeding problems of males with the X-linked GATA-1 G208S mutation. Our findings indicate that obligate female carriers of the GATA-1 gene can be detected by examination of their platelets in the electron microscope and distinguished from the pathology of other giant platelet disorders.