Table of Contents  
Year : 2016  |  Volume : 9  |  Issue : 3  |  Page : 449-451

Management of perioperative bleeding associated with the use of selective serotonin reuptake inhibitors

1 Department of Pharmacology, Clinical Pharmacology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Anaesthesia and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission12-Apr-2016
Date of Acceptance17-May-2016
Date of Web Publication31-Aug-2016

Correspondence Address:
Lobna A Saleh
Department of Pharmacology, Clinical Pharmacology Unit, Faculty of Medicine, Ain Shams University, Abbassia, Cairo 11535
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1687-7934.189567

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Increased bleeding tendency is associated with the use of selective serotonin reuptake inhibitors. In this study, we report a case of perioperative bleeding in patient on selective serotonin reuptake inhibitors. The management options for such cases are discussed.

Keywords: selective serotonin reuptake inhibitors, bleeding tendency, paroxetine, perioperative bleeding

How to cite this article:
Saleh LA, Hassan AN, Sobhy A. Management of perioperative bleeding associated with the use of selective serotonin reuptake inhibitors. Ain-Shams J Anaesthesiol 2016;9:449-51

How to cite this URL:
Saleh LA, Hassan AN, Sobhy A. Management of perioperative bleeding associated with the use of selective serotonin reuptake inhibitors. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Oct 22];9:449-51. Available from:

  Case presentation Top

A female patient aged 48 years was admitted to the ICU for postoperative care because of intraoperative bleeding during total abdominal hysterectomy. The patient was known to be diabetic and on oral hypoglycemics; she was also suffering from generalized anxiety disorder [was on paroxetine 20 mg and selective serotonin reuptake inhibitors (SSRIs) for 3 months]. The patient’s laboratory analysis on admission showed the following parameters − hemoglobin 11.2 g%, prothrombin time 14.3, partial thromboplastin time 34.6, international normalized ratio 1.2, and platelets 220 000 (all within the normal range)

During the surgery, the patient lost excessive amounts of blood (unexplained by the surgery), and the blood oozed to the surgical field. Intraoperative complete blood count showed hemoglobin levels of 7.5 g% and platelets of 188 000. Resuscitation was initiated, and blood product replacement was carried out. The patients remained in the ICU until she received a total of 3 U packed red blood cells+2 U fresh frozen plasma.

Pharmacotherapy problems

  1. Is there a correlation between SSRI and increased bleeding tendency; if so, what is the mechanism involved and how do we manage it?
  2. Are there any recommendations to stop such drugs in the perioperative period?


A Medline search was performed using the following search details: (‘Serotonin Uptake Inhibitors’[Mesh] AND ‘Blood Coagulation Disorders’[Mesh]; OR ((‘Serotonin Uptake Inhibitors’[Mesh]) AND ‘Hemorrhage’[Mesh]; OR (((‘Serotonin Uptake Inhibitors’[Mesh])) AND ‘Blood Transfusion’[Mesh].

The following filters were activated: Humans, English, Guidelines, RCTs, Case Report, and Systematic Reviews.

  Discussion Top

Perioperative blood transfusions increase the relative risk of postoperative infections and are associated with significant morbidity and mortality [1]. A vital indication for blood transfusions is major perioperative blood loss [2]. The amount of perioperative blood loss can be negatively influenced by the use of drugs that increase bleeding tendency [3]. Increased bleeding tendency is associated with the use of SSRIs. These reports are mainly from observational, retrospective studies that do not prove causality [4],[5],[6].

Antidepressant medications are commonly used for many psychiatric illnesses including major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, obsessive compulsive disorder, bulimia nervosa, post-traumatic stress disorder, premenstrual dysphoric disorder, borderline personality disorder, and nicotine dependence [7].

Several studies have shown that the use of SSRIs is associated with an increased risk of gastrointestinal bleeding [8],[9]. Moreover, many studies have addressed the association between SSRI use and perioperative blood loss [10].

Over the years, numerous case reports and case–control studies have suggested that SSRI use is associated with an increased risk of bleeding. The bleeding pattern varied from minor bleeding to spontaneous gastrointestinal bleeding and excessive perioperative hemorrhage [11]. One study showed that SSRI users who underwent orthopedic surgery had nearly a four-fold increased risk of requiring blood transfusion [12]. In addition, large population-based, case–control studies have consistently shown an increased incidence of upper gastrointestinal bleeding associated with SSRI use, especially when comedicated with NSAIDs and aspirin [13]. In 2014, a retrospective study on SSRI users undergoing hip surgery showed that they had an increased risk for blood transfusion during hospitalization. The study considered SSRI use as a potential risk indicator for increased blood loss in patients admitted for hip surgery [6].

The underlying pathophysiological mechanisms of increased bleeding tendency after SSRIs use have been previously studied, and significant changes in platelet function related to SSRI use are consistently reported, such as prolongation of platelet function assay (PFA) closure time and a decrease in plasma β-thromboglobulin and plasma platelet factor 4 [14],[15]. Furthermore, SSRIs decrease the reuptake of serotonin, thereby increasing serotonin levels in the synapses of the central nervous system promptly, and after prolonged exposure they also induce a gradual downregulation and desensitization of serotonin autoreceptor activity in serotonergic cell bodies and terminals. These changes are considered to be linked to the improvement of depression with SSRIs. Serotonin transported into platelets is released from platelets in response to vascular injury, which in turn triggers vasoconstriction and platelet aggregation. As SSRIs inhibit the activity of serotonin reuptake transporters of the platelets, they lower the amount of serotonin available in the platelets. Therefore, serotonin depletion leads to suboptimal initiation of the coagulation cascade and causes prolongation of bleeding [16].

SSRIs affect platelet aggregation, which can be measured by a PFA. The PFA measures both platelet adhesion and aggregation (primary hemostasis) [17]. SSRIs do not affect other bleeding parameters including the international ratio, partial thromboplastin time, or prothrombin time, which measures the enzymatic cascade leading to a fibrin clot. Alterations of the PFA in patients taking SSRIs compared with those on a nonserotonergic antidepressant have been demonstrated [18]. Mago et al. [19] suggested that PFA should be evaluated before elective surgery in patients on SSRIs, although no data are present to define the benefits of this test in the presurgical setting.

Perioperative continuation of SSRIs is associated with increased blood loss. However, anesthesiologists should consider the increased risk of bleeding in combination with other patient or surgery factors, including the use of antiplatelet drugs such as clopidogrel or NSAIDs, pre-existing bleeding disorders, or intracranial surgery. Planned discontinuation of SSRIs 2 weeks before the operation in patients with high risk of bleeding or shifting to an antidepressant that does not inhibit or less potently inhibits serotonin reuptake (e.g. bupropion or mirtazapine) or obtaining a PFA can be considered.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Shander A, Spence RK, Adams D, Shore-Lesserson L, Walawander CA. Timing and incidence of postoperative infections associated with blood transfusion: analysis of 1489 orthopedic and cardiac surgery patients. Surg Infect (Larchmt) 2009;10:277–283.  Back to cited text no. 1
Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, de Robertis E, Filipescu DC et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013;30:270–382.  Back to cited text no. 2
Radovanovic I, Queally J, Bahari S, Sproule J, McElwain J. Anticoagulant use and its effect on bleeding and complications in total knee arthroplasty. Acta Orthop Belg 2012;78:187–191.  Back to cited text no. 3
De Abajo FJ, García-Rodríguez LA. Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents. Arch Gen Psychiatry 2008;65:795–803.  Back to cited text no. 4
Vidal X, Ibáñez L, Vendrell L, Conforti A, Laporte JR, Spanish-Italian Collaborative Group for the Epidemiology of Gastrointestinal Bleeding. Risk of upper gastrointestinal bleeding and the degree of serotonin reuptake inhibition by antidepressants: a case-control study. Drug Saf 2008;31:159–168.  Back to cited text no. 5
Schutte HJ, Jansen S, Schafroth MU, Goslings JC, van der Velde N, de Rooij SE. SSRIs increase risk of blood transfusion in patients admitted for hip surgery. PLoS One 2014;9:e95906.  Back to cited text no. 6
Schatzberg AF. New indications for antidepressants. J Clin Psychiatry 2000;61(Suppl 11):9–17.  Back to cited text no. 7
De Abajo FJ, Rodríguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ 1999;319:1106–1109.  Back to cited text no. 8
Serebruany VL. Selective serotonin reuptake inhibitors and increased bleeding risk: are we missing something? Am J Med 2006;119:113–116.  Back to cited text no. 9
Singh I, Achuthan S, Chakrabarti A, Rajagopalan S, Srinivasan A, Hota D. Influence of pre-operative use of serotonergic antidepressants (SADs) on the risk of bleeding in patients undergoing different surgical interventions: a meta-analysis. Pharmacoepidemiol Drug Saf 2015;24:237–245  Back to cited text no. 10
Barbui C, Andretta M, de Vitis G, Rossi E, D’Arienzo F, Mezzalira L et al. Antidepressant drug prescription and risk of abnormal bleeding: a case-control study. J Clin Psychopharmacol 2009;29:33–38.  Back to cited text no. 11
Movig KL, Janssen MW, de Waal Malefijt J, Kabel PJ, Leufkens HG, Egberts AC Relationship of serotonergic antidepressants and need for blood transfusion in orthopedic surgical patients. Arch Intern Med 2003;163:2354–2358.  Back to cited text no. 12
Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2008;27:31–40.  Back to cited text no. 13
De Abajo FJ. Effects of selective serotonin reuptake inhibitors on platelet function: mechanisms, clinical outcomes and implications for use in elderly patients. Drugs Aging 2011;28:345–367.  Back to cited text no. 14
Abdelmalik N, Ruhé HG, Barwari K, van den Dool EJ, Meijers JC, Middeldorp S et al. Effect of the selective serotonin reuptake inhibitor paroxetine on platelet function is modified by a SLC6A4 serotonin transporter polymorphism. J Thromb Haemost 2008;6:2168–2174.  Back to cited text no. 15
Bismuth-Evenzal Y, Gonopolsky Y, Gurwitz D, Iancu I, Weizman A, Rehavi M. Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs. J Affect Disord 2012;136:99–103.  Back to cited text no. 16
McCloskey DJ, Postolache TT, Vittone BJ, Nghiem KL, Monsale JL, Wesley RA, Rick ME. Selective serotonin reuptake inhibitors: measurement of effect on platelet function. Transl Res 2008;151:168–172.  Back to cited text no. 17
Morel-Kopp MC, McLean L, Chen Q, Tofler GH, Tennant C, Maddison V, Ward CM. The association of depression with platelet activation: evidence for a treatment effect. J Thromb Haemost 2009;7:573–581.  Back to cited text no. 18
Mago R, Mahajan R, Thase ME. Medically serious adverse effects of newer antidepressants. Curr Psychiatry Rep 2008;10:249–257.  Back to cited text no. 19


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