Summary
We report a family with inherited macrothrombocytopenia and characteristic large membrane
complexes in the platelets. Two affected subjects had platelet counts of 40 and 65X109/L respectively as assessed by contrast phase microscopy. Ultrastructural studies
revealed giant spheroid platelets with characteristic large membrane complexes and/or
giant vacuoles containing platelet organelles. Immunohistochemical studies of actin
and tubulin showed a disorganization of the microtubule and actin systems. These abnormalities
were absent in leukocytes, indicating a platelet-specific cytoskeleton disorder.
Platelet autoantibodies were repeatedly absent. Nevertheless, in the peripheral blood
we observed several figures of platelet phagocytosis by macrophages and neutrophils.
The in vitro aggregometric response of platelets to ADP, collagen, thrombin, ristocetin was present,
but shape change was absent. The urinary excretion of thromboxane A2 metabolites of
the affected subjects were approximately 2 standard deviations above control values,
in spite of a reduced maximal biosynthetic capacity of thromboxane from giant platelets
assessed in vitro during whole blood clotting.
This inherited platelet disorder shows structural and functional features which allow
to distinguish it from other syndromes associated with giant platelets. We also propose
to include ultrastructural and cytoskeletal studies in the diagnosis as well as in
the classification of inherited giant platelet disorders.
Key words
Macrothrombocytopenia - actin - tubulin - platelet ultrastructure - platelet - function
- thromboxane
