Response:W318 β1-tubulin and macrothrombocytopenia

Response:

We would like to thank Dr White for valuable comments on our study that reported the first human β1-tubulin mutation associated with congenital macrothrombocytopenia.¹  We have been working on congenital macrothrombocytopenia and analyzed more than 200 cases. We do not think that giant platelets from macrothrombocytopenia syndromes are necessarily larger than red blood cells. The mean platelet sizes determined as platelet diameters on peripheral blood smears in genetically confirmed Bernard-Soulier syndrome and MYH9 disorders²  were 5.3 (± 1.1) μm (n = 14) and 4.9 (± 1.1) μm (n = 81), respectively. These data are comparable with that of the patient in our study.¹  Because routine automated blood cell counting systems differentiate blood cells by their size and therefore do not recognize giant platelets as platelets, mean platelet volume (MPV) does not reflect actual platelet size. As is quite often the case, an automated counter did not generate MPV in the patient or the mother. We believe that the determination of platelet diameter on peripheral smear is a more reliable way to detect macrothrombocytopenia.

We admit that it is premature to make definite conclusions about how W318 β1-tubulin affects the normal platelet production and results in macrothrombocytopenia. This is mainly because the causative relationship between the mutation and giant platelets was not convincingly investigated in our work. To clarify this, we are planning to establish knockin cell models that equally express wild-type and mutant β1-tubulins identified in human¹  and canine³  macrothrombocytopenia.