In vivo Platelet Activation Is Increased during Sleep in Patients with Obstructive Sleep Apnea Syndrome

Abstract

Background: Patients with obstructive sleep apnea syndrome (OSAS) have an increased risk of cardiovascular events including myocardial infarction and stroke. Objective: To determine whether in vivo platelet activation and the generation of procoagulant platelet-derived microparticles (PMP) are increased during sleep in patients with OSAS. Methods: In vivo platelet activation and PMP formation was determined using flow cytometry in 12 patients with untreated OSAS during and after sleep (4 and 7 a.m.). To study the effect of treatment with continuous positive airway pressure (CPAP), the measurements were repeated at the same time points after initiation of CPAP therapy. Healthy volunteers served as controls (n = 6). Results: Patients with OSAS had an increased percentage of platelets positive for the activation-dependent epitopes CD63 and CD62P during sleep (4 a.m.) compared to controls (4.8 ± 0.8 vs. 1.9 ± 0.4% for CD63, p < 0.01, and 2.0 ± 0.5 vs. 1.1 ± 0.3% for CD62P, p < 0.05). In OSAS patients, the amount of CD63- and CD62P-positive platelets was significantly elevated at 4 compared to 7 a.m. (4.8 ± 0.8 vs. 2.6 ± 0.4% for CD63 and 2.0 ± 0.5 vs. 1.1 ± 0.2% for CD62P, p < 0.05), but not in the control group. The levels of PMP were similar in patients with OSAS and controls at 4 and 7 a.m. After 1 night of CPAP therapy, there was a trend to reduced levels of CD63- and CD62P-positive platelets at 4 a.m. Conclusions: Patients with OSAS have increased in vivo platelet activation during sleep, which may contribute to the increased incidence of cardiovascular events in patients with OSAS.

P-Selectin- and CD63-Exposing Platelet Microparticles Reflect Platelet Activation in Peripheral Arterial Disease and Myocardial Infarction

“…Thus, discrepancies occur between exposure of P-selectin on platelets and the numbers of PMPs, which we have found in vitro and others in vivo (6,7,(12)(13)(14). These discrepancies may be attributed, at least in part, to the persistent release of MPs by megakaryocytes.…”

“…Because analysis of PMPs does not require fixation and can be applied to stored plasma samples, batchwise analysis of the in vivo platelet activation status is feasible. However, although several studies have confirmed concomitant changes in exposure of platelet Pselectin and circulating numbers of PMPs in vivo (10,11 ), others found discrepancies between both (6,7,(12)(13)(14), which may call into question the relevance of PMP numbers as a marker of platelet activation.…”

Effect of Continuous Positive Airway Pressure Treatment on Hemograms of Patients with Severe Obstructive Sleep Apnea in the Lack of Comorbidities

“…In several studies it has been shown that repetitive episodes of hypoxia and reoxygenation during sleep provoked platelet activation and/or systemic inflammation and platelet activation might lead to hypercoagulability and cardiovascular disease in OSAS [10,[16][17][18][19]. Platelets with high volume are metabolically and enzymatically more active and secrete more mediators [20,21].…”

Sleep related breathing disorders and cerebrovascular diseases

“…Aynı çalışmada, uyanma ve AHI indeksleri de PAC-1 ekspresyonu artışıyla ilişkili bulunmuştur. OSAS'lı hastaların uykuları sırasında plateletlerin aktivasyonuna bağımlı CD63 ve CD62P epitoplarının arttığı, bu artışın bir gece CPAP uygulanması sonrası düzeldiği gösterilmiştir (54).…”