Hemostatic Agents for the Management of Bleeding Risk Associated with Oral Anticoagulant Therapy Following Tooth Extraction: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Protocol and Eligibility Criteria
- (P) Type of participants: patients treated with oral anticoagulants
- (I) Type of interventions: dental extraction, either single or multiple
- (C) Comparison between interventions: any type of hemostatic measure compared with other treatments/placebo/no treatment
- (O) Type of outcome measures: bleeding control following dental extraction.
- Patients treated with oral anticoagulants
- Patients undergoing dental extractions
- One of the following study designs: observational studies, case-control studies, randomized controlled trials and interventional studies
- A minimum number of 10 participants in the study
- English language.
- Patients not treated with oral anticoagulants
- Patients undergoing oral surgical interventions other than tooth extraction
- One of the following study designs: systematic reviews and review articles, case reports and case series
- Less than 10 participants in the study
- Articles not written in English.
2.2. Literature Search
2.3. Study Selection and Data Collection
2.4. Quality Analysis and Risk of Bias Assessment
- Random sequence generation
- Allocation concealment
- Blinding of participants, personnel, and outcome assessors
- Incomplete outcome data handling
- Selective outcome reporting.
2.5. Synthesis of the Results
3. Results
3.1. Study Selection
3.2. Study Characteristics
3.3. Patients Treated with Warfarin
3.3.1. Intra-Alveolar Agents
3.3.2. Tranexamic Acid Mouthwashes
3.3.3. Platelet-Rich Fibrin
3.3.4. Comparison Studies
3.4. Patients Treated with DOACs
3.4.1. Tranexamic Acid
3.4.2. PRF
3.5. Risk of Bias in Interventional Studies
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Author | Setting, Funding | Study Design | Sample Size Number (% of Females), Mean Age, Number of Sites | Follow-Up | Oral Anticoagulant | Interventions | Study Conclusions |
---|---|---|---|---|---|---|---|
Al-Belasy et al., 2003 [29] | Dental Hospital, NR | CT | 40 patients (40% F), mean age 57.2 years, non specified umber of sites | 10 days | Warfarin | 1. Gelatin sponge 2. N-butyl-2-cyanoacrylate glue | Histoacryl glue reduced the occurrence of spontaneous bleeding |
Bajkin et al., 2014 [17] | Dental Hospital, NR | RCT | 90 patients (38% F), mean age 66.1 years, 121 sites | 5 days | Warfarin | 1. Suture 2. Gelatin sponge 3. Gauze compression | Gauze compression controlled bleeding in patients with INR ≤ 3.0 |
Blinder et al. 1999 [30] | Dental Hospital, NR | CT | 150 patients (42% F), age 35–93 years, 359 sites | 7 days | Warfarin | 1. Gelatin sponge and sutures 2. Gelatin sponge, sutures, and tranexamic acid mouthwash 3. Fibrin glue, gelatin sponge, and sutures | Resorbable gelatin sponge and sutures controlled bleeding following dental extractions |
Çakarer et al., 2013 [18] | Dental Hospital, NR | RCT | 25 patients (48% F), mean age 51.9 years, 32 sites | 7 days | Warfarin | 1. Gauze compression 2. Ankaferd Blood Stopper | Ankaferd Blood Stopper reduced bleeding in patients with INR ≤ 4.0 without interruption or reduction of the medication |
Carter & Goss 2003 [25] | Dental Hospital, Public funding | RCT | 85 patients (36% F), mean age 65.4 years, 152 sites | 7 days | Warfarin | 1. 4.8% tranexamic acid mouthwash for 2 days 2. 4.8% tranexamic acid for 5 days | Both administration protocols of 4.8% tranexamic acid mouthwash favored haemostasis in anticoagulated patients |
Carter et al., 2003 [31] | Dental Hospital, NR | RCT | 49 patients (36% F), mean age 65 years, 152 sites | 8 days | Warfarin | 1. 4.8% tranexamic acid solution 4 times a day for 7 days 2. Intra-alveolar autologous fibrin glue | Tranexamic acid mouthwash and autologous fibrin glue controlled postoperative bleeding |
da Silva et al., 2018 [32] | Dental Hospital, Public funding | RCT | 52 patients (53% F), mean age 61.9 years, 140 sites | 7 days | Warfarin | 1. Epsilon-aminocaproic acid mouthwash 2. No treatment | No differences in postoperative bleeding were observed between the study groups |
de Almeida Barros Mourão et al., 2019 [37] | Dental Hospital, NR | CT | 25 patients (56% F), mean age 72.44 years, 44 sites | 10 days | DOACs | PRF | PRF reduced bleeding |
Eldibany et al., 2014 [33] | Dental Hospital, NR | RCT | 20 patients (45% F), mean age 46.5 years, non specified number of sites | 10 days | Warfarin | 1. PRF 2. HemCon Dental Dressing | PRF and HemCon Dental Dressing were both effective in reducing post-operative bleeding |
Halfpenny et al., 2001 [19] | Dental Hospital, NR | CT | 50 patients (52% F), mean age 65.6 years, non specified number of sites | 7 days | Warfarin | 1. Surgicel 2. Beriplast | Beriplast was as effective as Surgicel in preventing postextraction hemorrhage |
Harfoush et al., 2016 [27] | Dental Hospital, NR | CT | 50 patients (32% F), mean age 63 years, non specified number of sites | 1 day | Warfarin | 1. PRF 2. Gauze compression | Topical application of PRF reduced bleeding in patients taking warfarin |
Kumar et al., 2016 [20] | Dental Hospital, NR | RCT | 30 patients (40% F), age 30–50 years, non specified number of sites | 7 days | Warfarin | 1. HemCon Dental Dressing 2. Gauze compression | HemCon Dental Dressing shortened bleeding time and improved wound healing |
Malmquist et al., 2008 [21] | Dental Hospital, NR | RCT | 17 patients (53% F), mean age 25 years, 126 sites | 7 days | Warfarin | 1. HemCon Dental Dressing 2. No treatment | HemCon Dental Dressing improved wound healing |
Oberti et al., 2020 [34] | Private practice, NR | CT | 20 patients (30% F), mean age 54.3 years, 20 sites | 7 days | Warfarin | 1. Calcium sulphate (CaS) 2. Gauze soaked in tranexamic acid | Calcium sulphate was effective in controlling post-operative bleeding |
Ockerman et al., 2021 [38] | Dental Hospital, Public funding | RCT | 218 patients (33% F), mean age 73.75 years, 272 sites | 7 days | DOACs | 1. 10% tranexamic acid mouthwash 2. Placebo mouthwash | 10% tranexamic acid mouthwash did not reduce bleeding after dental extraction |
Okamoto et al., 2014 [22] | Dental Hospital, NR | RCT | 48 patients (41% F), mean age 67.79 years, non specified number of sites | 1 day | Warfarin | 1. Irradiatetion with blue-violet LED 2. Hemostatic gelatin sponge and LED irradiation 3. Hemostatic gelatin sponges | Hemostatic gelatin sponge and LED irradiation reduced postoperative bleeding |
Pippi et al., 2015 [35] | Dental Hospital, NR | CT | 25 patients (20% F), mean age 70.45 years, 50 sites | 5 days | Warfarin | 1. HemCon Dental Dressing 2. Collagen hemostatic sponge | HemCon Dental Dressing improved tissue healing |
Queiroz et al., 2018 [26] | Dental Hospital, Public funding | RCT | 37 patients (62% F), mean age 45.5 years, 37 sites | 7 days | Warfarin | 1. Saline 2. Tranexamic acid | Tranexamic acid controlled intermediate hemorrhage in the first 24 h post-op |
Sammartino et al., 2011 [28] | Dental Hospital, NR | CT | 50 patients (56% F), age 47–67 years, 168 sites | 7 days | Warfarin | PRF | PRF reduced post-operative bleeding |
Scarano et al., 2014 [23] | Dental Hospital, NR | RCT | 30 patients (73% F), mean age 54.6 years, 42 sites | 7 days | Warfarin | 1. Obliterative suture 2. Intra-alveolar calcium sulfate | Calcium sulfate controlled bleeding following dental extraction |
Soares et al., 2015 [36] | Dental Hospital, NR | RCT | 41 patients (33% F), mean age 51.1 years, 93 sites | 7 days | Warfarin | 1. Tranexamic acid 2. Gelatin sponge 3. Gauze compression | Compression with dry gauze without hemostatic agents was an effective hemostatic measure |
Svensson et al., 2013 [24] | Dental Hospital, NR | CT | 124 patients (44% F), mean age 71 years, 194 sites | 10 days | Warfarin | Hemostatic gelatin sponge/collagen fleece and sutures | Local hemostatics and sutures effectively controlled post-operative bleeding |
Authors | Study Design | Setting | Funding | Randomization | Allocation Conealment | Operators Blinding | Missing Outcome Data Reported | Missing Outcomes Were Balanced among Groups | Reasons for Dropout Clearly Specified | Selective Outcome Reporting | Therapist Experience | Statistical Method | Sample Size Estimation | Examiner Calibration |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Al-Belasy et al., 2003 [29] | CT | Dental Hospital | NR | NA | NA | NA | Unclear | Unclear | Unclear | Adequate | Unclear | Inadequate | Inadequate | Inadequate |
Bajkin et al., 2014 [17] | RCT | Dental Hospital | NR | Unclear | Unclear | Unclear | Adequate | Adequate | Adequate | Adequate | Unclear | Adequate | Inadequate | Inadequate |
Blinder et al. 1999 [30] | CT | Dental Hospital | NR | NA | NA | NA | Unclear | Unclear | Unclear | Adequate | Unclear | Inadequate | Inadequate | Inadequate |
Çakarer et al., 2013 [18] | RCT | Dental Hospital | NR | Inadequate | Inadequate | Inadequate | Unclear | Unclear | Unclear | Adequate | Unclear | Unclear | Inadequate | Inadequate |
Carter & Goss 2003 [25] | RCT | Dental Hospital | Public funding | Adequate | Adequate | Unclear | Unclear | Unclear | Unclear | Adequate | Unclear | Unclear | Inadequate | Inadequate |
Carter et al., 2003 [31] | RCT | Dental Hospital | NR | Inadequate | Inadequate | Inadequate | Inadequate | Unclear | Unclear | Adequate | Unclear | Inadequate | Inadequate | Inadequate |
da Silva et al., 2018 [32] | RCT | Dental Hospital | Public funding | Adequate | Adequate | Adequate | Unclear | Unclear | Unclear | Adequate | Unclear | Adequate | Inadequate | Inadequate |
de Almeida Barros Mourão et al., 2019 [37] | CT | Dental Hospital | NR | NA | NA | NA | Unclear | Unclear | Unclear | Adequate | Adequate | Inadequate | Inadequate | Inadequate |
Eldibany et al., 2014 [33] | RCT | Dental Hospital | NR | Inadequate | Inadequate | Inadequate | Inadequate | Unclear | Unclear | Adequate | Unclear | Inadequate | Inadequate | Inadequate |
Halfpenny et al., 2001 [19] | CT | Dental Hospital | NR | NA | NA | NA | Unclear | Unclear | Unclear | Adequate | Unclear | Inadequate | Inadequate | Inadequate |
Harfoush et al., 2016 [27] | CT | Dental Hospital | NR | NA | NA | NA | Unclear | Unclear | Unclear | Unclear | Unclear | Adequate | Inadequate | Inadequate |
Kumar et al., 2016 [20] | RCT | Dental Hospital | NR | Adequate | Adequate | Adequate | Unclear | Unclear | Unclear | Unclear | Unclear | Adequate | Adequate | Inadequate |
Malmquist et al., 2008 [21] | RCT | Dental Hospital | Industry | Inadequate | Inadequate | Inadequate | Unclear | Unclear | Unclear | Adequate | Unclear | Unclear | Inadequate | Inadequate |
Oberti et al., 2020 [34] | CT | Private practice | NR | NA | NA | NA | Unclear | Unclear | Unclear | Inadequate | Inadequate | Inadequate | Inadequate | Inadequate |
Ockerman et al., 2021 [38] | RCT | Dental Hospital | Public funding | Adequate | Adequate | Adequate | Adequate | Adequate | Adequate | Adequate | Unclear | Adequate | Adequate | Unclear |
Okamoto et al., 2014 [22] | RCT | Dental Hospital | NR | Inadequate | Inadequate | Inadequate | Unclear | Unclear | Unclear | Adequate | Unclear | Adequate | Inadequate | Inadequate |
Pippi et al., 2015 [35] | CT | Dental Hospital | NR | Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Adequate | Unclear | Adequate | Adequate | Unclear |
Queiroz et al., 2018 [26] | RCT | Dental Hospital | NR | Adequate | Adequate | Adequate | Adequate | Adequate | Adequate | Adequate | Adequate | Adequate | Adequate | Unclear |
Sammartino et al., 2011 [28] | CT | Dental Hospital | NR | NA | NA | NA | Unclear | Unclear | Unclear | Adequate | Unclear | Adequate | Inadequate | Inadequate |
Scarano et al., 2014 [23] | RCT | Dental Hospital | NR | Inadequate | Inadequate | Adequate | Unclear | Unclear | Unclear | Adequate | Unclear | Adequate | Inadequate | Inadequate |
Soares et al., 2015 [36] | RCT | Dental Hospital | NR | Unclear | Unclear | Adequate | Unclear | Unclear | Unclear | Adequate | Unclear | Adequate | Adequate | Unclear |
Svensson et al., 2013 [24] | CT | Dental Hospital | NR | NA | NA | NA | Unclear | Unclear | Unclear | Adequate | Unclear | Inadequate | Inadequate | Inadequate |
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Nisi, M.; Carli, E.; Gennai, S.; Gulia, F.; Izzetti, R. Hemostatic Agents for the Management of Bleeding Risk Associated with Oral Anticoagulant Therapy Following Tooth Extraction: A Systematic Review. Appl. Sci. 2022, 12, 11017. https://doi.org/10.3390/app122111017
Nisi M, Carli E, Gennai S, Gulia F, Izzetti R. Hemostatic Agents for the Management of Bleeding Risk Associated with Oral Anticoagulant Therapy Following Tooth Extraction: A Systematic Review. Applied Sciences. 2022; 12(21):11017. https://doi.org/10.3390/app122111017
Chicago/Turabian StyleNisi, Marco, Elisabetta Carli, Stefano Gennai, Francesco Gulia, and Rossana Izzetti. 2022. "Hemostatic Agents for the Management of Bleeding Risk Associated with Oral Anticoagulant Therapy Following Tooth Extraction: A Systematic Review" Applied Sciences 12, no. 21: 11017. https://doi.org/10.3390/app122111017
APA StyleNisi, M., Carli, E., Gennai, S., Gulia, F., & Izzetti, R. (2022). Hemostatic Agents for the Management of Bleeding Risk Associated with Oral Anticoagulant Therapy Following Tooth Extraction: A Systematic Review. Applied Sciences, 12(21), 11017. https://doi.org/10.3390/app122111017