Is the Platelet Involved in the Etiology of Neurocardiogenic Syncope?.

The purpose of this study was to evaluate platelet dysfunction as a mitigating factor of neurocardiogenic syncope. Neurocardiogenic, or vasovagal syncope as it is also known, is a condition that may lead to temporary loss of consciousness and posture. Commonly referred to as, “fainting,” or, “passing out”, it is the basis for 3% of emergency room visits and 6% of hospital admissions; it is thought to be caused primarily by a lack of blood flow to the brain. However, the pathogenesis of syncope is yet to be completely understood. Vasovagal syncope has been postulated to occur due to a sudden failure of the autonomic nervous system’s ability to maintain blood pressure and heart rate leading to insufficient cerebral perfusion. Subsequently, a cardiac “hyper-contractile” state is created, due to excessive venous pooling and diminished peripheral venous return that is thought to activate afferent mechanoreceptors, interpreted by the brain as hypertension causing a paradoxical reflex of bradycardia, resulting in a drop of peripheral vascular resistance. It has been postulated that an increase in serotonin (5HT) activity in the central nervous system acts as an inhibitor of sympathetic stimulation, preventing the symptoms of syncope. One of a number of pharmacologic approaches to the management of neurocardiogenic syncope is the use of selective serotonin reuptake inhibitors (SSRIs). Neurocardiogenic syncope has also been reported to be a low 5HT disorder. As the major storage pool of 5HT in the circulation is known to exist in platelet (PL)dense granules (DGs), it is possible that a PL dense granule storage pool deficiency (DG SPD) could be an important mediator of neurocardiogenic syncope. We commonly evaluate patients having undiagnosed bleeding symptoms for PL DG SPD. A total of 358 subjects having neurocardiogenic syncope have been evaluated because of a significant bleeding history. Eighty-two percent (293/358) of these patients have DG SPD, with an average of 2.27 ± 0.06 DG/PL (normal: 4–6 DG/PL). Interestingly, 98% (351/358) of these patients are female. Common bleeding symptoms included 53.8% with menorrhagia (189/351), 43.9% (157/358) with easy bruising, and 15.6% with epistaxsis (56/358). It has been reported in a study of 15 patients, that the PL 5HT concentration, determined by HPLC methodology, did not alter during episodes of syncope, suggesting that the serotonergic system does not play a role in the pathophysiology of vasovagal syncope. We are currently evaluating the 5HT concentration extracted from PLs of syncope patients by ELISA. To date, 10 such patients have been studied, having an average of 2.32 ± 0.26 DG/PL; their mean 5HT concentration is 202.13 ± 29.12 ng/10⁹ PL (normal range = 215–850 ng/10⁹ PL). Our preliminary results suggest that a significant number of patients having neurocardiogenic syncope have DG SPD and low concentrations of 5HT stored in these granules. These results may be attributed to the fact that all subjects included in our study presented with a history or symptom of bleeding. The mechanism of 5HT uptake by the platelet is independent of adenine nucleotide and calcium storage within DGs, thus the low 5HT levels found in the few cases described here may/may not be related to pathophysiology of neurocardiogenic syncope. A prospective study of neurocardiogenic syncope patients with/without bleeding histories or symptoms is planned to further evaluate the PL DG storage pool.