Syncopes are frequent in the paediatric population. Most are benign, but rare cases are caused by... more Syncopes are frequent in the paediatric population. Most are benign, but rare cases are caused by cardiac life-threatening diseases. Syncope units developed in the adult population have demonstrated improvement in evaluation and treatment, with a reduction in hospitalization. We report our experience of paediatric syncope management in a dedicated unit, and analyse the value of different elements in the identification of cardiac causes. This prospective study included 97 consecutive patients (mean age: 12.1±3.3 years) referred between January 2011 and June 2013 to a syncope unit with a paediatric cardiologist, a nurse, a physiotherapist and a psychologist. Patients were classified into diagnostic categories after an initial evaluation that included history, physical examination, electrocardiography, echocardiography and Holter monitoring. The most common diagnosis was neurocardiogenic syncope (n=69, 70.4%). Fifty-two cases (81.3%) had no or less recurrence after specific management that included physiotherapy and psychological support (follow-up: 11.5±5.4 months). Psychogenic pseudosyncopes affected 20 children (20.6%). Two patients had epileptic seizures. There were five cases of cardiac syncope (5.1%): two long QT syndromes and a catecholaminergic polymorphic ventricular tachycardia received beta-blockers; two atrioventricular complete blocks required pacemakers. One case was of indeterminate cause and received an insertable loop recorder after exhaustive investigations. Exercise-induced syncopes were significantly associated with cardiac origins (P=0.003), such as electrocardiographic abnormalities (P<0.001), whereas echocardiography was not contributive. Syncope units in the paediatric population may be useful in the diagnostic process, to help identify rare cardiac aetiologies, and could decrease recurrence through specific management.
Many factors have been shown to be involved in the development of hyperplasic lesions of vessels,... more Many factors have been shown to be involved in the development of hyperplasic lesions of vessels, but the role of extracellular nucleotides remains largely unknown. The presence of P2Y and P2X nucleotide receptors on arterial endothelial and smooth muscle cells suggests a potential role for nucleotides in the vessel pathophysiology. Although the role of P2X in physiology of vessels is
In recent years, the understanding of the molecular mechanisms involved in platelet production (m... more In recent years, the understanding of the molecular mechanisms involved in platelet production (megakaryopoiesis) has extremely increased, thanks to the study of genetic diseases causing inherited thrombocytopenia. Among the wide variety of transmembrane receptors covering the platelet membrane, αIIbβ3 integrin is the major one, allowing platelets to aggregate upon the occurrence of vascular breach. Platelet counts are usually normal in patients with αIIbβ3 deficiency, suggesting that its role for normal platelet production and morphology is very limited. However, recently, new clinical observations of genetic diseases provided evidence against this hypothesis, bringing new data on the role of αIIbβ3 integrin in defective megakaryopoiesis.
Platelet δ-storage pool disease (δ-SPD) is a platelet function disorder characterized by a reduct... more Platelet δ-storage pool disease (δ-SPD) is a platelet function disorder characterized by a reduction in the number or content of dense granules. Reports on δ-SPD are mostly limited to case presentations. We aimed to retrospectively describe a series of patients with δ-SPD to better characterize the disease. We studied 16 patients with congenital or acquired δ-SPD. Lumiaggregometry, α- and δ-granules content, platelet ultrastructure, αIIbβ3 integrin, and glycoprotein Ib (GPIb) activation were assessed. Most of the patients generally demonstrate mild to moderate bleeding diathesis. Platelet aggregation studies showed moderate abnormalities with variable profiles, while all the individuals had almost complete absence of adenosine triphosphate release. Mepacrine capture, CD63 expression, and study of dense granules by electron microscopy enabled to distinguish different subtypes of δ-SPD with quantitative or qualitative defect. Surprisingly, significantly decreased GPIb expression levels after platelet activation with thrombin receptor activating peptide 50 μM were found, suggesting that GPIb-impaired mobilization may represent an additional feature of the disorder. In conclusion, δ-SPD represents a complex disorder with various clinical and biological aspects, requiring a great deal of expertise to be properly diagnosed.
Inherited thrombocytopenia (IT) is a heterogeneous group of rare diseases that are often confused... more Inherited thrombocytopenia (IT) is a heterogeneous group of rare diseases that are often confused with immune thrombocytopenia (ITP). The objective of this study was to supply clinicobiological elements that allow a distinction to be drawn between IT and chronic ITP. We then compared 23 adult patients with IT and 9 patients with chronic ITP. Our study revealed six discriminating criteria: (i) an age of discovery <34 years: positive predictive value (PPV) = 88.2% [63.6; 98.5], (ii) a family history of thrombocytopenia: PPV = 100.0% [82.4; 100.0], (iii) a personal history of bleeding: PPV = 100% [76.8; 100.0], (iv) a mean platelet volume >11 fL: PPV = 93.3% [68.1; 99.8], (v) an excess of giant platelets on blood smear: 100.0% [76.8; 100.0], and (vi) a percentage >44% of platelets with a surface area >4 µm(2) in electron microscopy: PPV = 83.3% [58.6; 96.4]. If at least three of these criteria were combined, it was possible to distinguish IT from chronic ITP with 91.3% [72.0; 98.9] sensitivity and PPV = 100.0% [66.4; 100.0] specificity. The secondary objective of this study was to assess the prevalence of potential IT diagnosis in patients with chronic thrombocytopenia of uncertain origin. Applying our diagnostic approach to a series of 20 cases allowed us to estimate that 40% of them could be suffering from IT. Finally, our diagnostic approach may help to correctly distinguish IT from chronic ITP, particularly in the context of macrothrombocytopenia.
Syncopes are frequent in the paediatric population. Most are benign, but rare cases are caused by... more Syncopes are frequent in the paediatric population. Most are benign, but rare cases are caused by cardiac life-threatening diseases. Syncope units developed in the adult population have demonstrated improvement in evaluation and treatment, with a reduction in hospitalization. We report our experience of paediatric syncope management in a dedicated unit, and analyse the value of different elements in the identification of cardiac causes. This prospective study included 97 consecutive patients (mean age: 12.1±3.3 years) referred between January 2011 and June 2013 to a syncope unit with a paediatric cardiologist, a nurse, a physiotherapist and a psychologist. Patients were classified into diagnostic categories after an initial evaluation that included history, physical examination, electrocardiography, echocardiography and Holter monitoring. The most common diagnosis was neurocardiogenic syncope (n=69, 70.4%). Fifty-two cases (81.3%) had no or less recurrence after specific management that included physiotherapy and psychological support (follow-up: 11.5±5.4 months). Psychogenic pseudosyncopes affected 20 children (20.6%). Two patients had epileptic seizures. There were five cases of cardiac syncope (5.1%): two long QT syndromes and a catecholaminergic polymorphic ventricular tachycardia received beta-blockers; two atrioventricular complete blocks required pacemakers. One case was of indeterminate cause and received an insertable loop recorder after exhaustive investigations. Exercise-induced syncopes were significantly associated with cardiac origins (P=0.003), such as electrocardiographic abnormalities (P<0.001), whereas echocardiography was not contributive. Syncope units in the paediatric population may be useful in the diagnostic process, to help identify rare cardiac aetiologies, and could decrease recurrence through specific management.
Many factors have been shown to be involved in the development of hyperplasic lesions of vessels,... more Many factors have been shown to be involved in the development of hyperplasic lesions of vessels, but the role of extracellular nucleotides remains largely unknown. The presence of P2Y and P2X nucleotide receptors on arterial endothelial and smooth muscle cells suggests a potential role for nucleotides in the vessel pathophysiology. Although the role of P2X in physiology of vessels is
In recent years, the understanding of the molecular mechanisms involved in platelet production (m... more In recent years, the understanding of the molecular mechanisms involved in platelet production (megakaryopoiesis) has extremely increased, thanks to the study of genetic diseases causing inherited thrombocytopenia. Among the wide variety of transmembrane receptors covering the platelet membrane, αIIbβ3 integrin is the major one, allowing platelets to aggregate upon the occurrence of vascular breach. Platelet counts are usually normal in patients with αIIbβ3 deficiency, suggesting that its role for normal platelet production and morphology is very limited. However, recently, new clinical observations of genetic diseases provided evidence against this hypothesis, bringing new data on the role of αIIbβ3 integrin in defective megakaryopoiesis.
Platelet δ-storage pool disease (δ-SPD) is a platelet function disorder characterized by a reduct... more Platelet δ-storage pool disease (δ-SPD) is a platelet function disorder characterized by a reduction in the number or content of dense granules. Reports on δ-SPD are mostly limited to case presentations. We aimed to retrospectively describe a series of patients with δ-SPD to better characterize the disease. We studied 16 patients with congenital or acquired δ-SPD. Lumiaggregometry, α- and δ-granules content, platelet ultrastructure, αIIbβ3 integrin, and glycoprotein Ib (GPIb) activation were assessed. Most of the patients generally demonstrate mild to moderate bleeding diathesis. Platelet aggregation studies showed moderate abnormalities with variable profiles, while all the individuals had almost complete absence of adenosine triphosphate release. Mepacrine capture, CD63 expression, and study of dense granules by electron microscopy enabled to distinguish different subtypes of δ-SPD with quantitative or qualitative defect. Surprisingly, significantly decreased GPIb expression levels after platelet activation with thrombin receptor activating peptide 50 μM were found, suggesting that GPIb-impaired mobilization may represent an additional feature of the disorder. In conclusion, δ-SPD represents a complex disorder with various clinical and biological aspects, requiring a great deal of expertise to be properly diagnosed.
Inherited thrombocytopenia (IT) is a heterogeneous group of rare diseases that are often confused... more Inherited thrombocytopenia (IT) is a heterogeneous group of rare diseases that are often confused with immune thrombocytopenia (ITP). The objective of this study was to supply clinicobiological elements that allow a distinction to be drawn between IT and chronic ITP. We then compared 23 adult patients with IT and 9 patients with chronic ITP. Our study revealed six discriminating criteria: (i) an age of discovery <34 years: positive predictive value (PPV) = 88.2% [63.6; 98.5], (ii) a family history of thrombocytopenia: PPV = 100.0% [82.4; 100.0], (iii) a personal history of bleeding: PPV = 100% [76.8; 100.0], (iv) a mean platelet volume >11 fL: PPV = 93.3% [68.1; 99.8], (v) an excess of giant platelets on blood smear: 100.0% [76.8; 100.0], and (vi) a percentage >44% of platelets with a surface area >4 µm(2) in electron microscopy: PPV = 83.3% [58.6; 96.4]. If at least three of these criteria were combined, it was possible to distinguish IT from chronic ITP with 91.3% [72.0; 98.9] sensitivity and PPV = 100.0% [66.4; 100.0] specificity. The secondary objective of this study was to assess the prevalence of potential IT diagnosis in patients with chronic thrombocytopenia of uncertain origin. Applying our diagnostic approach to a series of 20 cases allowed us to estimate that 40% of them could be suffering from IT. Finally, our diagnostic approach may help to correctly distinguish IT from chronic ITP, particularly in the context of macrothrombocytopenia.
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Papers by Xavier Pillois