β1-tubulin gene mutation platelets are not macrothrombocytes

To the editor:

The brief report by Kunishima et al¹  describing a mutation of the β1 tubulin gene affecting microtubule assembly is of interest, but data presented do not support association of the genetic defect with macrothrombocytopenia. The authors stated both the male propositus and his mother had prominent appearance of giant platelets on peripheral blood smears, and provided light (Figure 1A¹ ) and electron micrographs (Figure 1B¹ ) to support that finding. The patient platelet in Figure 1A¹  has damaged peripheral cytoplasm that may make it appear larger than a normal cell, but, more important, the platelet is significantly smaller than any red blood cell in the same field. No discoid platelets from the control or patient are present in the electron micrographs (Figure 1B¹ ). As a result, it is difficult to be certain there is any real size difference between patient and control platelets. Surely the authors must be aware that giant platelets from all of the known macrothrombocytopenias are larger than red blood cells, and many exceed the size of lymphocytes, monocytes, and neutrophils.²  It might have been helpful if the authors had provided the mean platelet volumes of the mother and child.

The immunofluorescence studies raise 2 questions. Patient and control microtubule coils in the report's Figure 2A¹  are similar in size and appear to be perfect coils. If the patients had complete platelet microtubule coils, those coils should be many times the diameter of control coils. More important, giant platelets from the known inherited macrothrombocytopenias rarely have complete microtubule coils lying just under the surface membrane. Rather, the giant platelets are spherical in form, and their microtubules are often organized in a manner resembling balls of yarn.³  The studies of the mutation in the present study are of interest. However, the statement “W318 β1 tubulin may interfere with normal platelet production, resulting in macrothrombocytopenia”¹  is not supported by the data presented.