Abstract
We describe an 11-year-old girl with a mild bleeding disorder since early childhood. The disorder was characterized by a prolonged bleeding time, and the patient's platelets showed defective aggregation responses to thromboxane A2 (TXA2) mimetic U46619 and arachidonic acid. In contrast, the platelets showed normal responses to thrombin and Ca ionophore A23187. When the platelet TXA2 receptor was examined with the [3H]-labeled TXA2 agonist U46619, the equilibrium dissociation rate constants (kd) and the maximal concentration of binding sites (Bmax) of the patient's platelets were within normal ranges. Normal GTPase activity was also induced in the patient's platelets by stimulation with U46619, however, inositol 1,4,5-triphosphate (IP3) formation was not induced by U46619. These results suggests that the patient's platelets had a defect in phospholipase C activation beyond TXA2 receptors.
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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Adenosine Diphosphate / pharmacology
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Blood Platelet Disorders / blood*
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Blood Platelets / drug effects
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Blood Platelets / physiology*
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Calcimycin / pharmacology
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Child
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Female
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GTP Phosphohydrolases / blood
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GTP-Binding Proteins / metabolism*
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Humans
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In Vitro Techniques
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Inositol 1,4,5-Trisphosphate / blood*
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Kinetics
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Platelet Aggregation / drug effects
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Prostaglandin Endoperoxides, Synthetic / pharmacology
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Receptors, Thromboxane / physiology*
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Signal Transduction*
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Thrombin / pharmacology
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Thromboxane A2 / analogs & derivatives
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Thromboxane A2 / pharmacology
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Type C Phospholipases / blood
Substances
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Prostaglandin Endoperoxides, Synthetic
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Receptors, Thromboxane
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Calcimycin
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Thromboxane A2
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Adenosine Diphosphate
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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Inositol 1,4,5-Trisphosphate
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Type C Phospholipases
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Thrombin
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GTP Phosphohydrolases
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GTP-Binding Proteins