Download PDF
Thromb Haemost 2020; 120(09): 1291-1299
DOI: 10.1055/s-0040-1713924
Cellular Haemostasis and Platelets

Plasma Serotonin is Elevated in Adult Patients with Sudden Sensorineural Hearing Loss

Ludovic Drouet
1   Anticoagulation Clinic (CREATIF), Hôpital Lariboisière, Paris, France
2   Université de Paris, Paris, France
,
Charlotte Hautefort
3   Department of Otorhinolaryngology, Hôpital Lariboisière, Paris, France
,
Hélène Vitaux
3   Department of Otorhinolaryngology, Hôpital Lariboisière, Paris, France
,
Romain Kania
2   Université de Paris, Paris, France
3   Department of Otorhinolaryngology, Hôpital Lariboisière, Paris, France
,
Jacques Callebert
2   Université de Paris, Paris, France
4   Department of Biochemistry, Hôpital Lariboisière, Paris, France
,
Alain Stepanian
5   Department of Biological Haematology, Hôpital Lariboisière, Paris, France
,
Virginie Siguret
2   Université de Paris, Paris, France
5   Department of Biological Haematology, Hôpital Lariboisière, Paris, France
6   Inserm UMR-S1140, Paris, France
,
Michael Eliezer
7   Department of Neuroradiology, Hôpital Lariboisière, Paris, France
,
Nicolas Vodovar
8   Inserm UMR-S 942, Paris, France
,
Jean-Marie Launay
2   Université de Paris, Paris, France
8   Inserm UMR-S 942, Paris, France
9   Centre for Biological Resources BB-0033-00064, Hôpital Lariboisière, Paris, France
› Author Affiliations Funding This work was funded by the Agence Nationale pour la Recherche (grant: ANR-16-CE16-0021-03) to J.M.L. and J.C.
› Further Information
    Permissions and Reprints

Abstract

Background The roles of thrombophilia and cardiovascular risk factors in sudden sensorineural hearing loss (SSNHL) remain controversial. Cochlear microthrombosis and vasospasm have been hypothesized as possible pathogenic mechanisms of SSNHL. This article investigates the circulating serotonin and homocysteine levels besides thrombophilia screening in patients with idiopathic SSNHL.

Methods A total of 133 SSNHL patients and age- and sex-matched controls were investigated (discovery cohort). Measurement included common inherited natural coagulation inhibitors, factor VIII, von Willebrand factor (VWF), antiphospholipid antibodies, homocysteine, and serotonin (whole blood, platelet, and plasma) levels, along with frequent relevant genetic variants. A validation cohort (128 SSNHL patients) was studied for homocysteine and serotonin levels.

Results and Conclusion In the discovery cohort, 58.6% of patients exhibited thrombophilia, of which most had a low to moderate titers of antiphospholipid antibodies and high levels of factor VIII/VWF. Twenty-seven patients (20%) had mild-to-moderate hyperhomocysteinemia or were homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Regarding serotonin, SSNHL patients had elevated whole blood levels that remained within the normal range and normal platelet content. However, approximately 90% patients of both cohorts had elevated plasma serotonin. Elevated plasma serotoninemia was accompanied by serotonylation of platelet rhoA protein. This study shows that increased plasma serotonin appears as a biomarker of SSNHL (specificity: ∼96%, sensitivity: ∼90%) and could participate in the pathophysiology of SSNHL.

Keywords

hearing loss - microvessels - plasma serotonin - thrombophilia

Authors' Contributions

L.D. and J.M.L. conceived and designed the study. C.H., H.V., M.E., R.K., and L.D. studied the patients. J.C., N.V., A.S., V.S., and J.M.L. performed laboratory measurements. N.V., L.D., A.S., V.S., and J.M.L. analyzed the data. N.V., R.K., L.D., and J.M.L. wrote the paper, and all authors approved the final version of the manuscript.




Publication History

Received: 09 March 2020

Accepted: 28 May 2020

Article published online:
27 July 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

Comment to this article:

A Liaison between Sudden Sensorineural Hearing Loss and SARS-CoV-2 InfectionThromb Haemost 2020; 120(09): 1237-1239
DOI: 10.1055/s-0040-1714370

 

  • References

  • 1 Chau JK, Lin JR, Atashband S, Irvine RA, Westerberg BD. Systematic review of the evidence for the etiology of adult sudden sensorineural hearing loss. Laryngoscope 2010; 120 (05) 1011-1021
    PubMedGoogle Scholar
  • 2 Cunningham LL, Tucci DL. Hearing loss in adults. N Engl J Med 2017; 377 (25) 2465-2473
    CrossrefPubMedGoogle Scholar
  • 3 Stachler RJ, Chandrasekhar SS, Archer SM. , et al; American Academy of Otolaryngology-Head and Neck Surgery. Clinical practice guideline: sudden hearing loss. Otolaryngol Head Neck Surg 2012; 146 (03) S1-S35
    CrossrefPubMedGoogle Scholar
  • 4 Mom T, Gilain L, Avan P. Cochlear ischemia: from fundamental data to clinical hope [in French]. Ann Oto-Laryng Chir Cerv Fac 2008; 125 (06) 301-308
    PubMedGoogle Scholar
  • 5 Mosnier I, Stepanian A, Baron G. , et al. Cardiovascular and thromboembolic risk factors in idiopathic sudden sensorineural hearing loss: a case-control study. Audiol Neurotol 2011; 16 (01) 55-66
    CrossrefPubMedGoogle Scholar
  • 6 Cadoni G, Scipione S, Rocca B. , et al. Lack of association between inherited thrombophilic risk factors and idiopathic sudden sensorineural hearing loss in Italian patients. Ann Otol Rhinol Laryngol 2006; 115 (03) 195-200
    CrossrefPubMedGoogle Scholar
  • 7 Görür K, Tuncer U, Eskandari G, Ozcan C, Unal M, Ozsahinoglu C. The role of factor V Leiden and prothrombin G20210A mutations in sudden sensorineural hearing loss. Otol Neurotol 2005; 26 (04) 599-601
    CrossrefPubMedGoogle Scholar
  • 8 Marcucci R, Alessandrello Liotta A, Cellai AP. , et al. Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural hearing loss. J Thromb Haemost 2005; 3 (05) 929-934
    CrossrefPubMedGoogle Scholar
  • 9 Passamonti SM, Di Berardino F, Bucciarelli P. , et al. Risk factors for idiopathic sudden sensorineural hearing loss and their association with clinical outcome. Thromb Res 2015; 135 (03) 508-512
    CrossrefPubMedGoogle Scholar
  • 10 Fusconi M, Chistolini A, Angelosanto N. , et al. Role of genetic and acquired prothrombotic risk factors in genesis of sudden sensorineural hearing loss. Audiol Neurotol 2011; 16 (03) 185-190
    CrossrefPubMedGoogle Scholar
  • 11 Quaranta N, De Ceglie V, D'Elia A. Endothelial dysfunction in idiopathic sudden sensorineural hearing loss: a review. Audiology Res 2016; 6 (01) 151
    CrossrefPubMedGoogle Scholar
  • 12 Fasano T, Pertinhez TA, Tribi L. , et al. Laboratory assessment of sudden sensorineural hearing loss: a case-control study. Laryngoscope 2017; 127 (10) 2375-2381
    CrossrefPubMedGoogle Scholar
  • 13 Toubi E, Ben-David J, Kessel A, Halas K, Sabo E, Luntz M. Immune-mediated disorders associated with idiopathic sudden sensorineural hearing loss. Ann Otol Rhinol Laryngol 2004; 113 (06) 445-449
    CrossrefPubMedGoogle Scholar
  • 14 Heller U, Becker EW, Zenner HP, Berg PA. Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss [in German]. HNO 1998; 46 (06) 583-586
    CrossrefPubMedGoogle Scholar
  • 15 Agrup C, Luxon LM. Immune-mediated inner-ear disorders in neuro-otology. Curr Opin Neurol 2006; 19 (01) 26-32
    CrossrefPubMedGoogle Scholar
  • 16 Wiles NM, Hunt BJ, Callanan V, Chevretton EB. Sudden sensorineural hearing loss and antiphospholipid syndrome. Haematologica 2006; 91 (12) ECR46
    PubMedGoogle Scholar
  • 17 Eisenhut M. Evidence supporting the hypothesis that inflammation-induced vasospasm is involved in the pathogenesis of acquired sensorineural hearing loss. Int J Otolaryngol 2019; 2019: 4367240
    CrossrefPubMedGoogle Scholar
  • 18 Da Prada M, Picotti GB. Content and subcellular localization of catecholamines and 5-hydroxytryptamine in human and animal blood platelets: monoamine distribution between platelets and plasma. Br J Pharmacol 1979; 65 (04) 653-662
    CrossrefPubMedGoogle Scholar
  • 19 Vulliamy P, Gillespie S, Armstrong PC, Allan HE, Warner TD, Brohi K. Histone H4 induces platelet ballooning and microparticle release during trauma hemorrhage. Proc Natl Acad Sci U S A 2019; 116 (35) 17444-17449
    CrossrefPubMedGoogle Scholar
  • 20 Watts SW. Oh, the places you'll go! My many colored serotonin (apologies to Dr. Seuss). Am J Physiol Heart Circ Physiol 2016; 311 (05) H1225-H1233
    CrossrefPubMedGoogle Scholar
  • 21 Guilluy C, Rolli-Derkinderen M, Tharaux PL, Melino G, Pacaud P, Loirand G. Transglutaminase-dependent RhoA activation and depletion by serotonin in vascular smooth muscle cells. J Biol Chem 2007; 282 (05) 2918-2928
    CrossrefPubMedGoogle Scholar
  • 22 Miyakis S, Lockshin MD, Atsumi T. , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
    CrossrefPubMedGoogle Scholar
  • 23 Eliezer M, Verillaud B, Guichard JP. , et al. Labyrinthine infarction caused by vertebral artery dissection: consideration based on MRI. J Neurol 2019; 266 (10) 2575-2577
    CrossrefPubMedGoogle Scholar
  • 24 Gao Z, Chi FL. The clinical value of three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging in patients with idiopathic sudden sensorineural hearing loss: a meta-analysis. Otol Neurotol 2014; 35 (10) 1730-1735
    CrossrefPubMedGoogle Scholar
  • 25 Le Brocq M, Leslie SJ, Milliken P, Megson IL. Endothelial dysfunction: from molecular mechanisms to measurement, clinical implications, and therapeutic opportunities. Antioxid Redox Signal 2008; 10 (09) 1631-1674
    CrossrefPubMedGoogle Scholar
  • 26 Brand T, Anderson GM. The measurement of platelet-poor plasma serotonin: a systematic review of prior reports and recommendations for improved analysis. Clin Chem 2011; 57 (10) 1376-1386
    CrossrefPubMedGoogle Scholar
  • 27 Hirowatari Y, Hara K, Shimura Y, Takahashi H. Serotonin levels in platelet-poor plasma and whole blood from healthy subjects: relationship with lipid markers and coronary heart disease risk score. J Atheroscler Thromb 2011; 18 (10) 874-882
    CrossrefPubMedGoogle Scholar
  • 28 Odaka Y, Takahashi J, Tsuburaya R. , et al. Plasma concentration of serotonin is a novel biomarker for coronary microvascular dysfunction in patients with suspected angina and unobstructive coronary arteries. Eur Heart J 2017; 38 (07) 489-496
    PubMedGoogle Scholar
  • 29 Guilluy C, Eddahibi S, Agard C. , et al. RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling. Am J Respir Crit Care Med 2009; 179 (12) 1151-1158
    CrossrefPubMedGoogle Scholar
  • 30 Kéreveur A, Callebert J, Humbert M. , et al. High plasma serotonin levels in primary pulmonary hypertension. Effect of long-term epoprostenol (prostacyclin) therapy. Arterioscler Thromb Vasc Biol 2000; 20 (10) 2233-2239
    CrossrefPubMedGoogle Scholar
  • 31 Walther DJ, Peter JU, Winter S. , et al. Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release. Cell 2003; 115 (07) 851-862
    CrossrefPubMedGoogle Scholar
  • 32 Watts SW, Priestley JR, Thompson JM. Serotonylation of vascular proteins important to contraction. PLoS One 2009; 4 (05) e5682
    CrossrefPubMedGoogle Scholar
  • 33 Kim SY, Lim JS, Sim S, Choi HG. Sudden sensorineural hearing loss predicts ischemic stroke: a longitudinal follow-up study. Otol Neurotol 2018; 39 (08) 964-969
    CrossrefPubMedGoogle Scholar
  • 34 Hansen-Schwartz J, Ansar S, Edvinsson L. Cerebral vasoconstriction after subarachnoid hemorrhage--role of changes in vascular receptor phenotype. Front Biosci 2008; 13: 2160-2164
    CrossrefPubMedGoogle Scholar
  • 35 Hasni Ebou M, Singh-Estivalet A, Launay JM. , et al. Glucocorticoids inhibit basal and hormone-induced serotonin synthesis in pancreatic beta cells. PLoS One 2016; 11 (02) e0149343
    CrossrefPubMedGoogle Scholar