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Original Investigation |

Relationship of Serotonergic Antidepressants and Need for Blood Transfusion in Orthopedic Surgical Patients FREE

Kris L. L. Movig, PhD; Michiel W. H. E. Janssen, MD; Jan de Waal Malefijt, MD, PhD; Peter J. Kabel, MD, PhD; Hubert G. M. Leufkens, PhD; Antoine C. G. Egberts, PhD
[+] Author Affiliations

From the Hospital Pharmacy Midden-Brabant, St Elisabeth Hospital and TweeSteden Hospital, Tilburg, the Netherlands (Drs Movig and Egberts); Departments of Orthopaedic Surgery (Drs Janssen and de Waal Malefijt) and Medical Microbiology (Dr Kabel), St Elisabeth Hospital, Tilburg; and Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands (Drs Movig, Leufkens, and Egberts). The authors have no relevant financial interest in this article.


Arch Intern Med. 2003;163(19):2354-2358. doi:10.1001/archinte.163.19.2354.
Text Size: A A A
Published online

Background  Several reports of various bleeding problems associated with the use of serotonergic antidepressants have been published. However, no information concerning the effect of these drugs on perioperative blood loss and blood transfusion requirements during orthopedic surgery is available. The objective of this study was to determine the association between use of serotonergic antidepressants and perioperative blood loss and transfusion in orthopedic surgical patients.

Methods  A retrospective follow-up study, using routinely collected hospital and pharmacy data, was conducted among all orthopedic patients undergoing surgery from January 1, 1999, through December 31, 2000. The actual blood transfusion requirements and blood loss during surgery were assessed. Patients were divided into 3 groups for comparison: users of serotonergic antidepressants, users of nonserotonergic antidepressants, and nonusers of antidepressants. The Medical Ethics Committee approved the study protocol, and informed consent was obtained from all patients or their legal relatives.

Results  A total of 520 subjects with evaluable data participated in the study. The risk of blood transfusion almost quadrupled for the serotonergic antidepressant group as compared with the nonusers (adjusted odds ratio, 3.71; 95% confidence interval, 1.35-10.18). Patients using nonserotonergic antidepressants had no increased risk (odds ratio, 0.74; 95% confidence interval, 0.10-5.95).

Conclusions  Use of serotonergic antidepressants is associated with an increased risk of bleeding and subsequent need for blood transfusion during orthopedic surgery. The bleeding could be attributed to inhibition of serotonin-mediated platelet activation.

SELECTIVE SEROTONIN reuptake inhibitors, first introduced in the late 1980s, have become one of the most widely prescribed classes of drugs. They are frequently used in elderly patients to treat psychiatric diseases, such as depression and obsessive-compulsive disorders.1 It has been suggested that selective serotonin reuptake inhibitors have lower incidence and severity of side effects than the older antidepressants, such as monoamine oxidase inhibitors and tricyclics.2

Several reports have shown that the use of antidepressants, tricyclics as well as selective serotonin reuptake inhibitors, increases the risk of falls and related bone fractures among elderly people.3,4 The reasons for this increased risk are complex and may include sedation, orthostatic hypotension, and confusion.5 Of the patients who experience fractures while using antidepressants, many require joint arthroplastic surgery. There is as yet no information available concerning the effect of serotonergic antidepressants on perioperative blood loss, or the requirements for blood transfusion in orthopedic patients. Perioperative blood transfusion increases the risk of postoperative infections and mortality.6 In the past few years, however, there has been an increase in the number of case reports721 and studies2226 describing bleeding disorders (especially gastrointestinal) associated with the use of serotonergic antidepressants. These reports have raised concerns regarding the safety of serotonergic antidepressants in elderly patients undergoing orthopedic surgery. The objective of this study was to investigate the relationship between the serotonergic antidepressants and the need for blood transfusion during orthopedic surgery.

SETTING

The study was conducted in a large general teaching hospital (St Elisabeth Hospital) in Tilburg, the Netherlands. The study population consisted of all patients who received hip, knee, or spine implants during the period from January 1, 1999, through December 31, 2000. Patients were identified by means of a computerized database that contains information on all orthopedic operations performed within the study period. In the Tilburg region, all blood transfusion requirements and biochemical laboratory data from inpatients and outpatients are compiled into one database. The Medical Ethics Committee approved our study protocol, and we obtained informed consent for the use of medical records from all patients or their legal relatives.

DESIGN

We investigated the risk of perioperative blood transfusion, in particular related to serotonergic antidepressants, in a group of orthopedic surgical patients in a nonconcurrent cohort study. Patients were excluded from the study if (1) no informed consent was obtained, (2) medical records were missing, and (3) drug prescription data were incomplete. The need for blood transfusion during surgery was used as a primary outcome variable. Furthermore, for all included patients, bleeding during operation, infusion requirements, and loss of drainage fluid were also noted. Drug prescription data for all hospitalized patients were obtained from community pharmacies. A strong pharmacy-patient liaison in the Netherlands ensures that the majority of patients are registered with the same pharmacy for the dispensing of their prescription drugs, guaranteeing optimal recording of drug use patterns.27 Data on morbidity and comorbidity and perioperative and postoperative information were obtained from medical records.

For the present study, we categorized antidepressants into 2 groups on the basis of their inhibitory properties of serotonin reuptake rather than chemical structure.28 The first group, serotonergic antidepressants, consisted of antidepressants, such as clomipramine hydrochloride, fluoxetine hydrochloride, fluvoxamine maleate, paroxetine, sertraline hydrochloride, and venlafaxine hydrochloride, that act mainly on the serotonergic system. Clomipramine and venlafaxine were included in the first group because both are known to be potent antagonists of the serotonin reuptake mechanism.28 The second group consisted of nonselective serotonergic-acting antidepressants.

The following covariates were studied as possible confounding factors: current use of aspirin, calcium-channel blockers, corticosteroids, iron supplements, nonsteroidal anti-inflammatory drugs (NSAIDs), vitamin K antagonists, and methotrexate. The confounding effects of concomitant diseases, such as diabetes mellitus, heart failure, hypertension, hepatic and renal diseases, and bleeding ulcers, were also considered.

DATA ANALYSIS

The association between exposure to serotonergic antidepressants compared with no exposure to any antidepressant and the need for blood transfusion was evaluated by means of logistic regression analysis. Patients who were given blood transfusion were compared with those who did not require a transfusion by means of logistic regression analysis. Odds ratios and 95% confidence intervals were estimated. The final model included age and sex and all univariate (P.10) associated risk factors.

Measurements of hemostasis, including perioperative blood loss, fluid infusion, and postoperative drainage, were determined for the serotonergic and nonserotonergic antidepressant groups. An analysis of variance with paired, 2-tailed t test was performed to assess the significance of differences in the mean of continuous variables between patient groups. Differences in proportions of categorical variables were tested for significance by a χ2 test. All statistical calculations were carried out with the SPSS statistical package (version 10.0; SPSS Inc, Chicago, Ill).

A total of 520 patients were included in the study. Although 685 suitable orthopedic procedures, corresponding to 643 patients, were recorded during the study period, lack of informed consent (16 patients) and missing (22) or incomplete (127) medical files were major reasons for exclusion (some patients had more than 1 reason for exclusion). There were no clinically important differences between included and excluded patients.

Table 1 summarizes the main baseline characteristics of all study patients. Female patients constituted 70% of the study population, and the mean age was 68 years. Fifty-nine patients (11%) required perioperative transfusion. The mean blood loss and fluid infusion volume during surgery were 1277 mL and 3016 mL, respectively, for patients who received transfusions as compared with 445 mL and 2309 mL for patients who did not receive transfusions. An average of 2.0 U (range, 1-6 U) of packed red blood cells was given to patients who required a transfusion. We found a significant association between the need for perioperative transfusion and the preoperative hemoglobin level (P = .007).

Table Graphic Jump LocationTable 1. General Characteristics of All Study Patients, Including Subgroups of Patients Requiring and Not Requiring Blood Transfusion During Surgery

Overall, 26 patients (5%) used serotonergic antidepressants before surgery: paroxetine (14 patients), fluoxetine (4), clomipramine (4), venlafaxine (2), fluvoxamine (1), and sertraline (1). Of these patients, 6 (23%) received perioperative blood transfusions (Table 2). Use of these antidepressants was significantly associated with increased blood loss during surgery (1019 mL for users vs 582 mL for nonusers; P = .001). Although the perioperative fluid requirements appeared to be unaffected, the postoperative drainage was slightly higher in the antidepressant group.

Table Graphic Jump LocationTable 2. Comparison of Hematologic Measures of Patients Using a Serotonergic Antidepressant and All Other Patients Not Using a Serotonergic Antidepressant

The risk of blood transfusion almost quadrupled for the serotonergic antidepressant group as compared with the nonusers (adjusted odds ratio, 3.71; 95% confidence interval, 1.35-10.18) (Table 3). The use of comedications, NSAIDs, methotrexate, or iron supplements also increased the risk of perioperative blood transfusion. This increased risk was not found, however, for patients using nonserotonergic antidepressants, vitamin K antagonists, calcium-channel blockers, or corticosteroid treatment.

Table Graphic Jump LocationTable 3. Crude and Adjusted Odds Ratios for Blood Transfusion According to Age, Sex, Comedication, and Comorbidity

We found an association between serotonergic antidepressants and the need for blood transfusion among orthopedic surgical patients. In the present study, patients using serotonergic agents lost significantly more blood during orthopedic surgery than those not using any antidepressant. Evidence from case reports has indicated a possible link between serotonergic antidepressants and bleeding-related problems.721 Other studies have demonstrated that serotonergic antidepressants are associated with a substantially greater risk of major gastrointestinal bleeding,22 particularly in patients concomitantly taking NSAIDs.25 Recently, de Abajo et al25 reported a 3-fold increase in the risk of gastrointestinal bleeding in adult primary care patients. A large incidence study estimated an absolute risk of serotonergic antidepressant–induced gastrointestinal hemorrhages of 8 new hemorrhages per 1000 persons treated per year in elderly patients (65 years and older).22 There was no increased risk of intracranial bleeding among serotonergic antidepressant users.24

The main pharmacologic mechanism for the increased risk in prolonged bleeding may occur via a decrease in intraplatelet serotonin concentrations affecting platelet aggregation.29 Furthermore, decreased platelet serotonin and a concurrent increase in plasma serotonin levels have also been associated with surgical procedures.30 Thus, patients experiencing stress from surgical procedure are thought to be at higher risk for bleeding complications because of platelet impairment. The combination of these 2 effects may act synergistically to negatively influence hemostasis, resulting in an even higher bleeding risk. In this context, serotonergic antidepressants have recently been associated with decreased cardiovascular diseases, suggesting a thrombolytic mechanism of action.31

Aspirin and other NSAIDs cause prolonged bleeding by inhibiting prostaglandin endoperoxides and thromboxane A2 in platelets. The NSAIDs are widely used for painful osteoarthitis in orthopedic and rheumatology patients who subsequently require joint arthroplasty surgery. Robinson et al32 found that the risk of perioperative blood loss associated with NSAIDs doubled among patients undergoing total hip arthroplasty. Increased postoperative blood loss was also associated with NSAID use.33,34 Our present findings concerning NSAIDs concur with these studies. The use of calcium-channel blockers has been associated with a 2-fold increased risk of perioperative bleeding in hip surgical patients.35 In the present study, no elevated risk of perioperative blood transfusion was found for patients using calcium-channel blockers; they, however, experienced an increased need for postoperative blood transfusion requirements (data not shown). Ambulatory patients using intramuscular methotrexate are usually treated for rheumatoid arthritis. Although methotrexate itself is not known to be associated with an increased risk of bleeding, our finding confirms the findings of an earlier study of the need for perioperative blood transfusion in orthopedic patients with rheumatoid arthritis.36

As with other observational studies, our study may have been affected by bias and confounding, related to the effects of factors (other than the exposure of interest) on the risk of the outcome. However, we believe it is unlikely that any potential biases have significantly affected our results. First, information bias seems highly unlikely because bleeding complications during orthopedic procedures are not, in daily clinical practice, generally associated with serotonergic antidepressants. Serotonergic antidepressants are not mentioned in the orthopedic protocol as potentially dangerous for bleeding complication, unlike the recommendation for aspirin to be stopped 1 week before surgery. Thus, as expected, no association between this agent and the outcome in this study has been found. Referral bias is highly unlikely because of the seriousness of the orthopedic procedures and clinical events in question.

Second, since all patients were sampled from a well-defined population, we believe that selection bias was not an important issue in this study. Because of the study's retrospective design, all information had been collected in the past; thus, recall bias is negligible. Data needed for end-point definition were electronically obtained from the hematological laboratory, which has highly secured procedures controlling and documenting blood transfusion requirements in our clinic. The medical record review was performed blinded to drug exposure. Prescription data from Dutch community pharmacies are virtually complete and have high agreement with the patients' adherence, so misclassification of antidepressant, or other drug, use is unlikely. If so, any selection bias or misclassification would have been nondifferential, underestimating the risks.

Although we controlled for several factors, confounding by indication cannot be excluded. There is evidence that depression itself might be associated with alterations in platelet serotonin levels, which may be further influenced by antidepressant treatment.37,38 In that case, depression itself may increase the bleeding risk.

The introduction of recombinant human erythropoietin into clinical orthopedic practice could decrease the allogeneic blood transfusion requirement, thus avoiding or minimizing transfusion-related complications.39 However, recombinant human erythropoietin was not used in orthopedic patients routinely in our hospital during the study period.

The present study provides new information. The association between serotonergic antidepressants and perioperative blood transfusion in orthopedic surgery could pose a potential health problem for elderly patients because of the widespread and increasing use of antidepressants. A relatively large number of patients may be exposed to this potential risk. Although increased bleeding is clinically important and should be considered for orthopedic patients using serotonergic antidepressants, it remains an uncommon adverse effect that should carefully be examined along with other information.

Corresponding author: Antoine C. G. Egberts, PhD, Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, PO Box 80082, 3508 TB Utrecht, the Netherlands (e-mail: A.C.G.Egberts@pharm.uu.nl).

Accepted for publication December 18, 2002.

We thank K. van Dongen and W. Wolters for providing clinical and laboratory data electronically and the staff members of the Hospital Admission Register Service of the St Elisabeth Hospital for their assistance in the data acquisition phase of this study. We are grateful to the pharmacists who provided medication data and to A. W. Lenderink, PharmD, for his critical comments on the concepts of the study protocol.

Egberts  ACLeufkens  HGHofman  AHoes  AW Incidence of antidepressant drug use in older adults and association with chronic diseases: the Rotterdam Study. Int Clin Psychopharmacol. 1997;12217- 223
PubMed Link to Article
Mourilhe  PStokes  PE Risks and benefits of selective serotonin reuptake inhibitors in the treatment of depression. Drug Saf. 1998;1857- 82
PubMed Link to Article
Liu  BAnderson  GMittmann  NTo  TAxcell  TShear  N Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet. 1998;3511303- 1307
PubMed Link to Article
Thapa  PBGideon  PCost  TWMilam  ABRay  WA Antidepressants and the risk of falls among nursing home residents. N Engl J Med. 1998;339875- 882
PubMed Link to Article
Pacher  PUngvari  Z Selective serotonin-reuptake inhibitor antidepressants increase the risk of falls and hip fractures in elderly people by inhibiting cardiovascular ion channels. Med Hypotheses. 2001;57469- 471
PubMed Link to Article
Dodd  RY Current viral risks of blood and blood products. Ann Med. 2000;32469- 474
PubMed Link to Article
Vandel  PVandel  SKantelip  JP SSRI-induced bleeding: two case reports. Therapie. 2001;56445- 447
PubMed
Lake  MBBirmaher  BWassick  SMathos  KYelovich  AK Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol. 2000;1035- 38
PubMed Link to Article
Cooper  TAValcour  VGGibbons  RBO'Brien-Falls  K Spontaneous ecchymoses due to paroxetine administration. Am J Med. 1998;104197- 198
PubMed Link to Article
Tielens  JA Vitamin C for paroxetine- and fluvoxamine-associated bleeding. Am J Psychiatry. 1997;154883- 884
PubMed
Leung  MShore  R Fluvoxamine-associated bleeding. Can J Psychiatry. 1996;41604- 605
PubMed
Wilmshurst  PTKumar  AV Subhyaloid haemorrhage with fluoxetine [letter]. Eye. 1996;10141
PubMed Link to Article
Calhoun  JWCalhoun  DD Prolonged bleeding time in a patient treated with sertraline [letter]. Am J Psychiatry. 1996;153443
PubMed
Pai  VBKelly  MW Bruising associated with the use of fluoxetine. Ann Pharmacother. 1996;30786- 788
PubMed
Ottervanger  JPStricker  BHHuls  JWeeda  JN Bleeding attributed to the intake of paroxetine. Am J Psychiatry. 1994;151781- 782
PubMed
Ottervanger  JPvan den Bemt  PMde Koning  GHStricker  BH Risk of hemorrhage with the use of fluoxetine (Prozac) or fluvoxamine (Fevarin). Ned Tijdschr Geneeskd. 1993;137259- 261
PubMed
Gunzberger  DWMartinez  D Adverse vascular effects associated with fluoxetine [letter]. Am J Psychiatry. 1992;1491751
PubMed
Aranth  JLindberg  C Bleeding, a side effect of fluoxetine [letter]. Am J Psychiatry. 1992;149412
PubMed
Yaryura-Tobias  JAKirschen  HNinan  PMosberg  HJ Fluoxetine and bleeding in obsessive-compulsive disorder [letter]. Am J Psychiatry. 1991;148949
PubMed
Evans  TGBuys  SSRodgers  GM Acquired abnormalities of platelet function [letter]. N Engl J Med. 1991;3241671
Link to Article
Humphries  JEWheby  MSVandenBerg  SR Fluoxetine and the bleeding time. Arch Pathol Lab Med. 1990;114727- 728
PubMed
van Walraven  CMamdani  MMWells  PSWilliams  JI Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ. 2001;323655- 658
PubMed Link to Article
Layton  DClark  DWPearce  GLShakir  SA Is there an association between selective serotonin reuptake inhibitors and risk of abnormal bleeding? results from a cohort study based on prescription event monitoring in England. Eur J Clin Pharmacol 2001;57167- 176
PubMed Link to Article
de Abajo  FJJick  HDerby  LJick  SSchmitz  S Intracranial haemorrhage and use of selective serotonin reuptake inhibitors. Br J Clin Pharmacol. 2000;5043- 47
PubMed Link to Article
de Abajo  FJRodriguez  LAMontero  D Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ. 1999;3191106- 1109
PubMed Link to Article
Alderman  CPSeshadri  PBen-Tovim  DI Effects of serotonin reuptake inhibitors on hemostasis. Ann Pharmacother. 1996;301232- 1234
PubMed
Lau  HSde Boer  ABeuning  KSPorsius  A Validation of pharmacy records in drug exposure assessment. J Clin Epidemiol. 1997;50619- 625
PubMed Link to Article
Tatsumi  MGroshan  KBlakely  RDRichelson  E Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997;340249- 258
PubMed Link to Article
Li  NWallen  NHLadjevardi  MHjemdahl  P Effects of serotonin on platelet activation in whole blood. Blood Coagul Fibrinolysis. 1997;8517- 523
PubMed Link to Article
Naesh  OHindberg  IBruun  AB Decreased reuptake of serotonin in human platelets after surgery. Clin Physiol. 2001;2139- 43
PubMed Link to Article
Sauer  WHBerlin  JAKimmel  SE Selective serotonin reuptake inhibitors and myocardial infarction. Circulation. 2001;1041894- 1898
PubMed Link to Article
Robinson  CMChristie  JMalcolm-Smith  N Nonsteroidal antiinflammatory drugs, perioperative blood loss, and transfusion requirements in elective hip arthroplasty. J Arthroplasty. 1993;8607- 610
PubMed Link to Article
Connelly  CSPanush  RS Should nonsteroidal anti-inflammatory drugs be stopped before elective surgery? Arch Intern Med. 1991;1511963- 1966
PubMed Link to Article
Fauno  PPetersen  KDHusted  SE Increased blood loss after preoperative NSAID: retrospective study of 186 hip arthroplasties. Acta Orthop Scand. 1993;64522- 524
PubMed Link to Article
Zuccala  GPahor  MLandi  F  et al.  Use of calcium antagonists and need for perioperative transfusion in older patients with hip fracture: observational study. BMJ. 1997;314643- 644
PubMed Link to Article
Bierbaum  BECallaghan  JJGalante  JORubash  HETooms  REWelch  RB An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am. 1999;812- 10
PubMed
Owens  MJNemeroff  CB Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem. 1994;40288- 295
PubMed
Bakish  DCavazzoni  PChudzik  JRavindran  AHrdina  PD Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder. Biol Psychiatry. 1997;41184- 190
PubMed Link to Article
Tamir  LFradin  ZFridlander  M  et al.  Recombinant human erythropoietin reduces allogeneic blood transfusion requirements in patients undergoing major orthopedic surgery. Haematologia. 2000;30193- 201
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. General Characteristics of All Study Patients, Including Subgroups of Patients Requiring and Not Requiring Blood Transfusion During Surgery
Table Graphic Jump LocationTable 2. Comparison of Hematologic Measures of Patients Using a Serotonergic Antidepressant and All Other Patients Not Using a Serotonergic Antidepressant
Table Graphic Jump LocationTable 3. Crude and Adjusted Odds Ratios for Blood Transfusion According to Age, Sex, Comedication, and Comorbidity

References

Egberts  ACLeufkens  HGHofman  AHoes  AW Incidence of antidepressant drug use in older adults and association with chronic diseases: the Rotterdam Study. Int Clin Psychopharmacol. 1997;12217- 223
PubMed Link to Article
Mourilhe  PStokes  PE Risks and benefits of selective serotonin reuptake inhibitors in the treatment of depression. Drug Saf. 1998;1857- 82
PubMed Link to Article
Liu  BAnderson  GMittmann  NTo  TAxcell  TShear  N Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet. 1998;3511303- 1307
PubMed Link to Article
Thapa  PBGideon  PCost  TWMilam  ABRay  WA Antidepressants and the risk of falls among nursing home residents. N Engl J Med. 1998;339875- 882
PubMed Link to Article
Pacher  PUngvari  Z Selective serotonin-reuptake inhibitor antidepressants increase the risk of falls and hip fractures in elderly people by inhibiting cardiovascular ion channels. Med Hypotheses. 2001;57469- 471
PubMed Link to Article
Dodd  RY Current viral risks of blood and blood products. Ann Med. 2000;32469- 474
PubMed Link to Article
Vandel  PVandel  SKantelip  JP SSRI-induced bleeding: two case reports. Therapie. 2001;56445- 447
PubMed
Lake  MBBirmaher  BWassick  SMathos  KYelovich  AK Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol. 2000;1035- 38
PubMed Link to Article
Cooper  TAValcour  VGGibbons  RBO'Brien-Falls  K Spontaneous ecchymoses due to paroxetine administration. Am J Med. 1998;104197- 198
PubMed Link to Article
Tielens  JA Vitamin C for paroxetine- and fluvoxamine-associated bleeding. Am J Psychiatry. 1997;154883- 884
PubMed
Leung  MShore  R Fluvoxamine-associated bleeding. Can J Psychiatry. 1996;41604- 605
PubMed
Wilmshurst  PTKumar  AV Subhyaloid haemorrhage with fluoxetine [letter]. Eye. 1996;10141
PubMed Link to Article
Calhoun  JWCalhoun  DD Prolonged bleeding time in a patient treated with sertraline [letter]. Am J Psychiatry. 1996;153443
PubMed
Pai  VBKelly  MW Bruising associated with the use of fluoxetine. Ann Pharmacother. 1996;30786- 788
PubMed
Ottervanger  JPStricker  BHHuls  JWeeda  JN Bleeding attributed to the intake of paroxetine. Am J Psychiatry. 1994;151781- 782
PubMed
Ottervanger  JPvan den Bemt  PMde Koning  GHStricker  BH Risk of hemorrhage with the use of fluoxetine (Prozac) or fluvoxamine (Fevarin). Ned Tijdschr Geneeskd. 1993;137259- 261
PubMed
Gunzberger  DWMartinez  D Adverse vascular effects associated with fluoxetine [letter]. Am J Psychiatry. 1992;1491751
PubMed
Aranth  JLindberg  C Bleeding, a side effect of fluoxetine [letter]. Am J Psychiatry. 1992;149412
PubMed
Yaryura-Tobias  JAKirschen  HNinan  PMosberg  HJ Fluoxetine and bleeding in obsessive-compulsive disorder [letter]. Am J Psychiatry. 1991;148949
PubMed
Evans  TGBuys  SSRodgers  GM Acquired abnormalities of platelet function [letter]. N Engl J Med. 1991;3241671
Link to Article
Humphries  JEWheby  MSVandenBerg  SR Fluoxetine and the bleeding time. Arch Pathol Lab Med. 1990;114727- 728
PubMed
van Walraven  CMamdani  MMWells  PSWilliams  JI Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ. 2001;323655- 658
PubMed Link to Article
Layton  DClark  DWPearce  GLShakir  SA Is there an association between selective serotonin reuptake inhibitors and risk of abnormal bleeding? results from a cohort study based on prescription event monitoring in England. Eur J Clin Pharmacol 2001;57167- 176
PubMed Link to Article
de Abajo  FJJick  HDerby  LJick  SSchmitz  S Intracranial haemorrhage and use of selective serotonin reuptake inhibitors. Br J Clin Pharmacol. 2000;5043- 47
PubMed Link to Article
de Abajo  FJRodriguez  LAMontero  D Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ. 1999;3191106- 1109
PubMed Link to Article
Alderman  CPSeshadri  PBen-Tovim  DI Effects of serotonin reuptake inhibitors on hemostasis. Ann Pharmacother. 1996;301232- 1234
PubMed
Lau  HSde Boer  ABeuning  KSPorsius  A Validation of pharmacy records in drug exposure assessment. J Clin Epidemiol. 1997;50619- 625
PubMed Link to Article
Tatsumi  MGroshan  KBlakely  RDRichelson  E Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997;340249- 258
PubMed Link to Article
Li  NWallen  NHLadjevardi  MHjemdahl  P Effects of serotonin on platelet activation in whole blood. Blood Coagul Fibrinolysis. 1997;8517- 523
PubMed Link to Article
Naesh  OHindberg  IBruun  AB Decreased reuptake of serotonin in human platelets after surgery. Clin Physiol. 2001;2139- 43
PubMed Link to Article
Sauer  WHBerlin  JAKimmel  SE Selective serotonin reuptake inhibitors and myocardial infarction. Circulation. 2001;1041894- 1898
PubMed Link to Article
Robinson  CMChristie  JMalcolm-Smith  N Nonsteroidal antiinflammatory drugs, perioperative blood loss, and transfusion requirements in elective hip arthroplasty. J Arthroplasty. 1993;8607- 610
PubMed Link to Article
Connelly  CSPanush  RS Should nonsteroidal anti-inflammatory drugs be stopped before elective surgery? Arch Intern Med. 1991;1511963- 1966
PubMed Link to Article
Fauno  PPetersen  KDHusted  SE Increased blood loss after preoperative NSAID: retrospective study of 186 hip arthroplasties. Acta Orthop Scand. 1993;64522- 524
PubMed Link to Article
Zuccala  GPahor  MLandi  F  et al.  Use of calcium antagonists and need for perioperative transfusion in older patients with hip fracture: observational study. BMJ. 1997;314643- 644
PubMed Link to Article
Bierbaum  BECallaghan  JJGalante  JORubash  HETooms  REWelch  RB An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am. 1999;812- 10
PubMed
Owens  MJNemeroff  CB Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem. 1994;40288- 295
PubMed
Bakish  DCavazzoni  PChudzik  JRavindran  AHrdina  PD Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder. Biol Psychiatry. 1997;41184- 190
PubMed Link to Article
Tamir  LFradin  ZFridlander  M  et al.  Recombinant human erythropoietin reduces allogeneic blood transfusion requirements in patients undergoing major orthopedic surgery. Haematologia. 2000;30193- 201
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