Platelet spherocytosis: a new bleeding disorder.
The present study evaluated a child with thrombocytopenia and a rare congenital bleeding disorder associated with platelet spherocytosis. Differential interference phase contrast microscopy (DIC) revealed that his platelets were spherical in form. Examination of thin sections in the electron microscope showed that his platelets were nearly devoid of microtubules (MT) and microtubule coils (MTC) that support the discoid shape in 100% of normal platelets. Immunofluorescence with a monoclonal antibody to tubulin, the precursor protein of MT, revealed bright rings in normal cells and diffuse fluorescence of patient platelets. The brightness of the fluorescence emitted by patient platelets was comparable to the diffuse fluorescence of normal platelets after chilling to dissolve intact MT, suggesting normal and patient cells contained comparable amounts of tubulin. Exposure of patient platelets to Taxol, an agent that stabilizes and induces MT, caused MT formation in 82% of patient platelets and MTC development in 11%, resulting in their conversion to discs. Glycoproteins GPIIb/IIIa and GPIb were present on patient platelets, and the cells contained normal numbers of dense bodies, ruling out storage pool disease. The patient's platelets adhered to and spread normally on glass but failed to undergo rapid, irreversible aggregation when stirred with agents that produced a complete response in normal discoid platelets, even when the patient's platelets were concentrated. The poor response of spherical platelets was associated with failure to become irregular and extend long filopodia. Thus, the spherical shape of patient platelets may contribute to the thrombocytopenia and to the clinical bleeding symptoms.
Departments of Laboratory Medicine & Pathology, University of Minnesota Medical School, 420 Delaware Street SE, Mayo Mail Code 490, Minneapolis, MN 55455, USA. white003@tc.umn.edu
James G
JG
White
Pedro A
PA
de Alarcon
D000293:Adolescent; D000911:Antibodies, Monoclonal; D001760:Bleeding Time; D001778:Blood Coagulation Disorders / Q000473:pathology / Q000503:physiopathology*; D001791:Blood Platelet Disorders / Q000473:pathology / Q000503:physiopathology*; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D017239:Paclitaxel / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis / Q000276:immunology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis / Q000276:immunology; D013917:Thrombin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D013917:Thrombin; D017239:Paclitaxel