Platelet Delta Granule and Serotonin Concentrations Are Decreased in Patients with Postural Orthostatic Tachycardia Syndrome.

Abstract 2419

Poster Board II-396

Syncope is generally defined as a state of temporary, partial or complete, loss of consciousness (fainting) with spontaneous recovery. The basis for the phenomenon is complex and includes a variety of orthostatic intolerance conditions including neurocardiogenic syncope (NCS), postural orthostatic tachycardia syndrome (POTS), and other disorders affecting the autonomic nervous system. NCS patients and POTS patients can be differentiated with an upright tilt test because either bradycardia or tachycardia will occur with hypotension, respectively. Both are induced by the inability to maintain adequate systemic blood pressure. Though the two primary types of syncope are different in origin, both conditions are treated similarly. Recent reports suggest that syncope is a low serotonin (5HT) disorder and selective serotonin reuptake inhibitors (SSRIs) are a commonly prescribed treatment for both NCS and POTS patients. The major storage pool of serotonin, independent of the central nervous system, is contained in platelet dense granules (DG). Peripheral serotonin aids in vasoconstriction and blood clotting. Individuals prone to syncope may be deficient in serotonin. Insufficient peripheral serotonin may create conditions that lead to hypotension and excessive bleeding in an individual.

We previously reported that patients having episodes of syncope (Blood, 112(11):451, 2008) had statistically significant decreases of DG/PL, consistent with DG storage pool deficiency (δSPD), and PL 5HT concentrations when compared to control subjects. Our test subjects were screened by questionnaire to determine syncope and distinction between NCS and POTS was not considered. These patients had an average of 3.08 ± 0.52 DG/PL and a mean 5HT concentration of 248.40 ± 37.94 ng/10⁹ PL (PL 5HT normal range = 215-850 ng/10⁹ PL). Control subjects (n=24) had an average of 4.22 ± 0.12 DG/PL and a 5HT concentration of 666.54 ± 56.25; both values having a significant difference (p=.003 and p<.001) by a Mann-Whitney Rank Order test respectively. We now report the DG/PL and 5-HT values obtained exclusively from patients diagnosed with POTS by tilt-table assessment and compared with control subjects.

Patients for this study were obtained from our cardiology clinic and all were positive for POTS; they were not currently taking or were recently prescribed a SSRI for therapeutic management of their condition. Control subjects did not have syncope or history of bleeding. Peripheral blood was collected and PLs obtained via centrifugation to determine the mean DG/PL by electron microscopy and the mean 5HT concentration extracted from PLs using an ELISA technique. POTS patients (n=14) had a mean serotonin level of 326.6 ± 76.7 ng/10⁹ PL compared to 589.6 ± 56.3 ng/10⁹PL (p<0.004) for control subjects (n=21). POTS patients exhibited a mean of 2.6 ± 0.31 DG/PL compared to the control subject value of 4.16 ± 0.09 DG/PL (p<0.001). To date there is no significant difference in the number of PL DG or 5HT levels POTS patients compared to our previous evaluation of undefined syncope patients. These results support the hypothesis that syncope (NCS and POTS) may be the result of low peripheral serotonin levels. Our preliminary data demonstrates that POTS patients have low serotonin levels and δSPD when compared to control subjects. This study is ongoing to increase the total number of POTS patients enrolled as well as to recruit subjects diagnosed with NCS to determine whether a difference in DG and/or 5HT exists to explain either bradycardia or tachycardia as an early symptom in the development of hypotension.