Qualitative platelet alterations in may - hegglin anomaly

Introduction: May - Hegglin anomaly is an autosomal dominant mutation in the MYH9 gene that disrupts the dynamics of the cytoskeleton in megakaryocytes. Megakaryocyte dysfunction entails a violation of thrombocytopoiesis, which is manifested by macrothrombocytopenia, sometimes associated with bleeding. Aim: to study the structure and function of platelets in the family members with documented May - Hegglin anomaly. Patients and methods. The proband, her sister and their mother who all had a heterozygous mutation R1933X in the MYH9 gene were examined. The examination included complete blood count, peripheral blood microscopy, platelet flow cytometry, blood clot contraction kinetics, scanning and transmission electron microscopy of platelets. The control group included 10 healthy donors. Results. In the proband and her sister the degree of contraction of blood clots was reduced. Unstimulated platelets displayed overexpression of P-selectin and active alpha IIb beta 3 integrin. After TRAP-induced stimulation the proportion of platelets expressing P-selectin in the patients was below normal, indicating partial platelet refractoriness. Electron microscopy of the unstimulated platelets revealed macrothrombocytosis and multiple filopodia, as well as enlargement of the open canalicular system. Conclusion. The May - Hegglin anomaly caused by a heterozygous mutation R1933X in the MYH9 gene is accompanied by thrombocytopenia associated with structural and functional platelet defects. Partial platelet refractoriness and contractile dysfunction can impair the retraction of hemostatic clots, predisposing patients with MYH9-related disorders to bleeding.