BACKGROUND AND OBJECTIVES: May-Hegglin anomaly (MHA) and Sebastian syndrome (SBS) are inherited macrothrombocytopenias with D hle-like bodies in leukocytes. MHA-SBS are due to mutations of the gene (MYH9) for the heavy chain of non-muscle myosin IIA (NMMHC-IIA), the only myosin II expressed in platelets. The bleeding tendency is often more severe than expected on the basis of platelet count, but no abnormality of platelet function has been identified. To characterize platelet abnormalities deriving from MYH9 mutations better, we studied surface glycoproteins (GPs) in platelets from MHA-SBS patients. DESIGN AND METHODS: Eight patients from 4 unrelated families were studied. Platelet surface GPs were studied by flow cytometry in both the whole platelet population and subpopulations of platelets identified according to their size. RESULTS: Flow cytometry identified a defect of the GPIb/IX/V complex in the whole platelet population in 7 of 8 patients. Moreover, in all patients the subpopulation of large platelets had defective expression of this complex. INTERPRETATION AND CONCLUSIONS: These findings indicate that MYH9 mutations may be responsible for reduced surface expression of GPIb/IX/V. This defect could contribute to the bleeding tendency of these patients. The identification of a GPIb/IX/V defect in MHA-SBS platelets raises the question of the differential diagnosis from heterozygous Bernard-Soulier syndrome.

Defective expression of GPIb/IX/V complex in platelets from patients with May-Hegglin anomaly and Sebastian syndrome

SAVOIA A.;
2002-01-01

Abstract

BACKGROUND AND OBJECTIVES: May-Hegglin anomaly (MHA) and Sebastian syndrome (SBS) are inherited macrothrombocytopenias with D hle-like bodies in leukocytes. MHA-SBS are due to mutations of the gene (MYH9) for the heavy chain of non-muscle myosin IIA (NMMHC-IIA), the only myosin II expressed in platelets. The bleeding tendency is often more severe than expected on the basis of platelet count, but no abnormality of platelet function has been identified. To characterize platelet abnormalities deriving from MYH9 mutations better, we studied surface glycoproteins (GPs) in platelets from MHA-SBS patients. DESIGN AND METHODS: Eight patients from 4 unrelated families were studied. Platelet surface GPs were studied by flow cytometry in both the whole platelet population and subpopulations of platelets identified according to their size. RESULTS: Flow cytometry identified a defect of the GPIb/IX/V complex in the whole platelet population in 7 of 8 patients. Moreover, in all patients the subpopulation of large platelets had defective expression of this complex. INTERPRETATION AND CONCLUSIONS: These findings indicate that MYH9 mutations may be responsible for reduced surface expression of GPIb/IX/V. This defect could contribute to the bleeding tendency of these patients. The identification of a GPIb/IX/V defect in MHA-SBS platelets raises the question of the differential diagnosis from heterozygous Bernard-Soulier syndrome.
Piastrinopenie ereditarie
Complesso GPIb/IX/V
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1064371
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