Risk factors for post-extraction bleeding in patients with haemophilia: a retrospective cohort study

Open AccessPublished:October 11, 2020DOI:https://doi.org/10.1016/j.bjoms.2020.08.121

      Abstract

      Objective

      Many guidelines and studies describe haemostatic management protocols for haemophilia patients, but few have evaluated risk factors for post-extraction bleeding. This retrospective cohort study was performed to investigate risk factors for post-extraction bleeding among haemophilia patients.

      Material and methods

      We used medical records to identify haemophilia patients who underwent tooth extraction(s) between April 2006 and April 2019 in the Department of Oral and Maxillofacial Surgery at Nara Medical University Hospital. We conducted logistic regression analyses to identify risk/protective factors for post-extraction bleeding in procedures involving factor replacement therapy. Post-extraction bleeding was defined as bleeding that could not be stopped by biting down on gauze and required medical treatment between 30 min and 14 days after the extraction.

      Results

      A total of 151 extractions (84 interventions) in 55 patients fulfilled the inclusion criteria, with 130 extractions (72 interventions) in 48 patients with haemophilia A and 21 extractions (12 interventions) in 7 patients with haemophilia B. Post-extraction bleeding events were observed in 9 patients (16.3%), 10 interventions (11.9 %), and 12 extractions (7.9%). On average, post-extraction bleeding occurred six days after intervention and on the fifth post-operative day for extractions. Use of mouth splints significantly decreased the risk of post-extraction bleeding (odds ratio, 0.13; p = 0.01) in haemophilia patients receiving factor replacement therapy.

      Conclusion

      The use of mouth splints significantly decreased the risk of post-extraction bleeding in haemophilia patients. We will conduct a prospective study to investigate the optimal type of splint and splint-wearing period.

      Keywords

      INTRODUCTION

      Haemophilia is a common hereditary bleeding disorder. Haemophilia A, which affects approximately 1 in 5,000 men, is the most common form of this disorder. In comparison, haemophilia B is less common, affecting 1 in 30,000 men.
      • Bolton-Maggs P.H.
      • Pasi KJ.
      Haemophilias A and B.
      Haemophilia is defined as severe when plasma activity is less than 1%, moderate if it ranges between 1 and 5%, and mild if it is greater than 5%.

      White GC II, Rosendaal F., Aledort L.M., et al. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001;85:560.

      Patients with haemophilia are at a high risk of secondary bleeding during and after invasive dental procedures. Previous studies and current guidelines have described various haemostatic management protocols that use systemic and local haemostatic measures.

      HMcintyre H. Dental Extractions In Patients With Hemophilia Syndrome; A Method Of Local Management. Oral Surg Oral Med Oral Pathol. 1965;19:163-173.

      • Suwannuraks M.
      • Chuansumrit A.
      • Sriudomporn N.
      • et al.
      The use of fibrin glue as an operative sealant in dental extraction in bleeding disorder patients.
      • Zanon E.
      • Martinelli F.
      • Bacci C.
      • et al.
      Proposal of a standard approach to dental extraction in haemophilia patients. A case-control study with good results.
      • Piot B.
      • Sigaud-Fiks M.
      • Huet P.
      • et al.
      Management of dental extractions in patients with bleeding disorders.
      • Frachon X.
      • Pommereuil M.
      • Berthier A.M.
      • et al.
      Management options for dental extraction in hemophiliacs: a study of 55 extractions (2000-2002).
      • Franchini M.
      • Rossetti G.
      • Tagliaferri A.
      • et al.
      Dental procedures in adult patients with hereditary bleeding disorders: 10 years experience in three Italian Hemophilia Centers.

      Australian Haemophilia Centre Directors’ Organisation. Guideline for the management of patients with haemophilia undergoing surgical procedures. Available from URL: http://www.ahcdo.org.au/documents/item/13 (Accessed 8 July 2020).

      • Ak G.
      • Alpkılıç Başkırt E.
      • Kürklü E.
      • et al.
      The evaluation of fibrin sealants and tissue adhesives in oral surgery among patients with bleeding disorders.

      Edna Boliver, Susan Karp, Susan Peterson, et al. Canadian Association of Nurses in Hemophilia Care. DENTAL CARE FOR PEOPLE WITH BLEEDING DISORDERS. Available from URL: http://www.hemophilia.ca/files/Dental%20Care%202012%20EN%20-%20FINAL.pdf (Accessed 8 July 2020).

      Alok Srivastava, Andrew K. Brewer, Eveline P. Mauser-Bunschoten, et al. World Federation of Hemophilia. Guidelines for the management of hemophilia. 2nd edition. DOI: 10.1111/j.1365-2516.2012.02909.x. Available from URL: http://www1.wfh.org/publications/files/pdf-1472.pdf. (Accessed 8 July 2020).

      • Anderson J.A.
      • Brewer A.
      • Creagh D.
      • et al.
      Guidance on the dental management of patients with haemophilia and congenital bleeding disorders.
      • Peisker A.
      • Raschke G.F.
      • Schultze-Mosgau S.
      Management of dental extraction in patients with Haemophilia A and B: a report of 58 extractions.
      • Cocero N.
      • Pucci F.
      • Messina M.
      • et al.
      Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue.
      • Hsieh J.T.
      • Klein K.
      • Batstone M.
      Ten-year study of postoperative complications following dental extractions in patients with inherited bleeding disorders.
      Local haemostatic treatment can include the application of a mouth splint, and the use of absorbable haemostats such as oxidised cellulose and fibrin glue is recommended. However, few publications have evaluated risk factors for post-extraction bleeding among such patients. 16
      In the present study, we aimed to retrospectively evaluate the incidence of post-extraction bleeding and investigate risk factors for post-extraction bleeding among patients with haemophilia.

      Material and methods

       Patient recruitment

      We used medical records to identify patients with haemophilia who underwent tooth extraction(s) between April 2006 and April 2016 in the Department of Oral and Maxillofacial Surgery, Nara Medical University Hospital. The primary outcome was occurrence of post-extraction bleeding, which was defined as bleeding that could not be stopped by biting down on gauze and required medical treatment between 30 min and 14 days after the tooth extraction. Further variables included patient factors (such as sex and age), disease-related factors (such as the type and severity of haemophilia), and intervention-related factors (such as the number of teeth extracted, extraction methods, haemostatic measures, and prescription of nonsteroidal anti-inflammatory drugs [NSAIDs]). This study’s retrospective design was approval by the ethics committee of Nara Medical University, Nara, Japan (approval date: September 26, 2019; approval number: 2350) and the study was performed in accordance with the Declaration of Helsinki.

       Data analysis

      We conducted logistic regression analyses of risk factors for post-extraction bleeding in haemophilia patients undergoing factor replacement therapy. We excluded patients who were administered desmopressin (DDAVP) and bypassing therapy with factor (F) VIIa (FVIIa) or activated prothrombin complex concentrates (APCC). Continuous variables were compared by using the Student’s t-test, and dichotomous variables were compared by using the Mann-Whitney U test.
      We included explanatory variables with a significance level of P ≤ .20 in the univariate analyses in the multivariate model. P <  .05 denoted statistical significance. Goodness-of-fit of the logistic regression model was tested with the Hosmer-Lemeshow test, and potential multicollinearity was tested with the variance inflation factor. For statistical analyses, we used STATA (version 12, StataCorp, College Station, Texas).

       Basic principles for haemostatic management of tooth extraction in haemophilia patients at our institution

      At Nara Medical University Hospital, systematic haemostatic treatment is conducted as follows:
      • Screening for the presence of inhibitors (anti-FVIII or FIX antibodies) before any surgery.
      • Administration of oral anti-fibrinolytic agent at 20 mg/kg every 8 hours from 2 hours before tooth extraction and continuing for up to 7 days post-extraction.
      • Administration of coagulation factor concentrates about 1 hour before tooth extraction in order to increase the FVIII (or FIX) activity up to the normal level of 80–100 IU/dL.
      • Maintenance of a trough factor level (minimum factor level measured immediately before the next bolus injection) of 60–80 IU/dL for 3 days after surgery.
      • Administration of coagulation factor concentrates before suture removal to a peak level of 20–40 IU/dL.
      Meanwhile, local haemostatic treatment is administered as follows:
      • Filling of alveolar sockets with absorbable haemostats such as gelatine sponge, oxidised cellulose, and/or fibrin glue.
      • Application of a mouth splint for 7 days after tooth extraction, if not uncomfortable.

      RESULTS

       Case characteristics

      The characteristics of included cases are summarised in Table 1, Table 2, Table 3, according to patients, interventions, and extractions, respectively. A total of 151 extractions (84 interventions) in 55 patients fulfilled the inclusion criteria, with 130 extractions (72 interventions) in 48 patients with haemophilia A and 21 extractions (12 interventions) in 7 patients with haemophilia B. Of the 48 haemophilia A patients, 20 were classified as having severe disease, 15 were classified as having moderate disease, and 13 patients were classified as having mild disease. Of the 7 haemophilia B patients, 3 were classified as having severe disease, 2 were classified as having moderate disease, and 2 were classified as having mild disease. Five patients with inhibitors had 14 extractions in 8 interventions.
      Table 1Characteristics of 55 study patients.
      CharacteristicPatientsP values
      Male/female52/ 30.57
      Type of haemophilia (type A/type B) 48/ 70.26
      Type A mild (inhibitors)13 (1)-
      Type A moderate (inhibitors)15 (1)-
      Type A severe (inhibitors)20 (3)-
      Type B mild (inhibitors)2 (0)-
      Type B moderate (inhibitors)2 (0)-
      Type B severe (inhibitors)3 (0)-
      Interventions (mean number ± SD)1.5 ± 0.70.006
      Post-extraction bleeding (yes/no)9/ 46-
      SD, standard deviation; Tests for significant associations of post-extraction bleeding.
      Table 2Characteristics of patients according to 84 interventions
      CharacteristicInterventionsP values
      Male/female81/ 30.68
      Mean age ± SD29.5 ± 15.50.96
      Type of haemophilia (type A/type B) 72/ 120.19
      Severity (mild/moderate/severe)22/ 28/ 340.28
      Presence of inhibitors (yes/no)8/ 760.24
      Antifibrinolytic agent (yes/no)75/ 90.71
      Systemic haemostatic therapy (yes/no)84/ 0-
      Factor replacement therapy77-
      Factor VIII (plasma/recombinant)65 (52/ 13)-
      Factor IX (plasma/recombinant)12 (9/ 3)-
      Mean duration ± SD (days)2.6 ± 1.3-
        Mean peak value ± SD (%)           111 ± 31.1-
      DDAVP3-
      Bypassing therapy4-
      Mean number ± SD of teeth extracted1.7 ± 0.80.40
      Prescription of NSAIDs (yes/no)27/ 570.17
      Mean number ± SD of hospitalisation days7.2 ± 1.90.11
      Post-extraction bleeding (yes/no)10/ 74-
      Mean postoperative days ± SD6.0 ± 3.9-
      SD, standard deviation; DDAVP, desmopressin; NSAIDs, nonsteroidal anti-inflammatory drugs; Tests for significant associations of post-extraction bleeding
      Table 3Characteristics of patients according to 151 extractions performed
      CharacteristicExtractions      P values
      Male/female5/ 1460.65
      Mean age ± SD29.3 ± 16.40.86
      Type of haemophilia (type A/type B) 130/ 210.15
      Severity (mild/moderate/severe)37/ 49 / 650.21
      Presence of inhibitors (yes/no)14/ 1370.01
      Antifibrinolytic agent (yes/no)133/ 180.56
      Systemic haemostatic therapy (yes/no)151/ 0-
      Factor replacement therapy142-
      DDAVP3-
      Bypassing therapy6-
      Surgical extraction (yes/no)62/ 890.40
      Gingival incision (yes/no)62/ 890.40
      Bone removal (yes/no)27/ 1240.36
      Tooth separation (yes/no)39/ 1120.37
      Local haemostatic treatment (yes/no)151/ 0-
      Use of absorbable haemostats (yes/no)148/ 30.77
      Wound closure (primary/secondary)68/ 830.25
      Use of mouth splint (yes/no)139/ 120.05
      Prescription of NSAIDs (yes/no)43/ 1080.02
      Post-extraction bleeding (yes/no)12/ 139-
      Mean postoperative days ± SD5.3 ± 3.8-
      SD, standard deviatStblnion; DDAVP, desmopressin; NSAIDs, nonsteroidal anti-inflammatory drugs; Tests for significant associations of post-extraction bleeding.
      The mean age (± standard deviation [SD]) at the first time of tooth extraction was 31.2 ± 16.1 years. The mean number (± SD) of interventions per patient was 1.5 ± 0.7. The mean number (± SD) of teeth extracted per intervention was 1.7 ± 0.8. The average number (± SD) of hospitalisation days per intervention was 7.2 ± 1.9. Factor replacement therapy was performed in 77 interventions. Bypassing therapy was performed in 4 interventions for all 4 patients with high-responding inhibitors.
      Surgical procedures were performed in 62 of the 151 extractions (41.0%); bone removal was performed in 27 of the 62 surgical extractions. Some kind of local haemostatic treatment was performed in all extractions. Absorbable haemostats were used in all except three extractions (98.0%), and a mouth splint was used in 139 extractions (92.0%). Although mouth splints are of two types, full-coverage type covering all the teeth of the dental arch (Fig. S1) and partial-coverage type covering a part of the dental arch including extraction socket(s) (Fig. S2), we did not extract data on the type of splint used.
      Post-extraction bleeding events were observed in 9 of 55 patients (16.3%), 10 of 84 interventions (11.9%), and 12 of 151 extractions (7.9%). When we analysed the data per intervention, bleeding events were observed on the sixth post-operative day on average. When we analysed the data per extraction, bleeding events were observed on the fifth post-operative day on average. Among 12 extractions in 9 patients with post-extraction bleeding, 4 extractions (33.3%) were from 2 patients with inhibitors (22.2%) and the presence of inhibitors was significantly associated with post-extraction bleeding in an analysis per tooth extraction (P = .01).
      All bleeding could be stopped by haemostatic treatment, including compression with gauze, injection of local anaesthetics, use of absorbable haemostats, and/or application of mouth splints. No general complications were noted. The mean number (± SD) of teeth extracted per intervention was 2.0 ± 0.8 in the post-extraction bleeding group and 1.7 ± 0.8 in the non-post-extraction bleeding group. There was no significant association between post-extraction bleeding and the number of teeth extracted per intervention (P = .40).

       Risk factors for post-extraction bleeding in tooth extractions involving factor replacement therapy

      To investigate risk factors for post-extraction bleeding in haemophilia patients receiving factor replacement therapy, logistic regression analyses were conducted with data for 142 extractions. For statistical analysis, duration of factor replacement therapy was dichotomised as ≥3 days and <3 days. In the univariate analyses (Table 4), use of mouth splints was significantly associated with lack of post-extraction bleeding (P = .01). Factors correlating with post-extraction bleeding (P < .20) included bone removal (P = .14), tooth separation (P = .12).
      Table 4Risk factors for post-extraction bleeding in patients receiving factor replacement therapy
      UnivariateMultivariate
                    Odds ratios (95% CI)P valuesOdds ratios (95% CI) P values
      Sex (male/female)----
      Age1.00

      (0.95-1.04)
      0.99--
      Type of haemophilia (type A vs type B)----
      Severity of haemophilia0.57

      (0.23-1.41)
      0.22--
      Antifibrinolytic agent (yes/ no)1.01

      (0.11-8.78)
      0.98--
      Duration of factor replacement therapy (≥3 days vs <3 days)1.16

      (0.27-4.83)
      0.83--
      Gingival incision (yes/no)1.48

      (0.35-6.17)
      0.59--
      Bone removal (yes/no)3.22

      (0.71-14.5)
      0.141.71

      (0.21-13.6)
      0.61
      Tooth separation (yes/no)3.18

      (0.75-13.4)
      0.121.62

      (0.21-12.0)
      0.63
      Use of absorbable haemostats (yes/no)----
      Wound closure (primary/secondary)0.76

      (0.17-3.32)
      0.71--
      Use of mouth splint (yes/no)0.10

      (0.02-0.52)
      0.010.13

      (0.02-0.69)
      0.01
      Prescription of NSAIDs (yes/no)1.83

      (0.41-8.10)
      0.43--
      Explanatory variables with a significance level of P < 0.2 in the univariate analyses were included in the multivariate model. NSAIDs, nonsteroidal anti-inflammatory drugs; CI, confidence interval.
      Subsequently, use of mouth splints, bone removal, and tooth separation were entered into the multivariate analysis, which was used to identify predictive factors for post-extraction bleeding. Use of mouth splints significantly decreased the risk of post-extraction bleeding (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.02–0.69; P =  .01). In our study cohort, other factors such as age, severity of haemophilia, duration of factor replacement therapy, gingival incision, bone removal, tooth separation, use of absorbable haemostats, wound closure, and prescription of NSAIDs were not significantly associated with post-extraction bleeding.

      DISCUSSION

      For patients with moderate and severe haemophilia A and B undergoing invasive dental procedures, coagulation factor replacement therapy is recommended to prevent postoperative bleeding.

      Australian Haemophilia Centre Directors’ Organisation. Guideline for the management of patients with haemophilia undergoing surgical procedures. Available from URL: http://www.ahcdo.org.au/documents/item/13 (Accessed 8 July 2020).

      Alok Srivastava, Andrew K. Brewer, Eveline P. Mauser-Bunschoten, et al. World Federation of Hemophilia. Guidelines for the management of hemophilia. 2nd edition. DOI: 10.1111/j.1365-2516.2012.02909.x. Available from URL: http://www1.wfh.org/publications/files/pdf-1472.pdf. (Accessed 8 July 2020).

      • Anderson J.A.
      • Brewer A.
      • Creagh D.
      • et al.
      Guidance on the dental management of patients with haemophilia and congenital bleeding disorders.
      Local haemostatic treatment includes application of mouth splints, and the use of absorbable haemostats such as oxidised cellulose and fibrin glue is recommended.

      HMcintyre H. Dental Extractions In Patients With Hemophilia Syndrome; A Method Of Local Management. Oral Surg Oral Med Oral Pathol. 1965;19:163-173.

      • Suwannuraks M.
      • Chuansumrit A.
      • Sriudomporn N.
      • et al.
      The use of fibrin glue as an operative sealant in dental extraction in bleeding disorder patients.

      Australian Haemophilia Centre Directors’ Organisation. Guideline for the management of patients with haemophilia undergoing surgical procedures. Available from URL: http://www.ahcdo.org.au/documents/item/13 (Accessed 8 July 2020).

      • Ak G.
      • Alpkılıç Başkırt E.
      • Kürklü E.
      • et al.
      The evaluation of fibrin sealants and tissue adhesives in oral surgery among patients with bleeding disorders.
      ,

      Alok Srivastava, Andrew K. Brewer, Eveline P. Mauser-Bunschoten, et al. World Federation of Hemophilia. Guidelines for the management of hemophilia. 2nd edition. DOI: 10.1111/j.1365-2516.2012.02909.x. Available from URL: http://www1.wfh.org/publications/files/pdf-1472.pdf. (Accessed 8 July 2020).

      • Anderson J.A.
      • Brewer A.
      • Creagh D.
      • et al.
      Guidance on the dental management of patients with haemophilia and congenital bleeding disorders.
      However, post-operative bleeding can occasionally occur despite appropriate systemic and local haemostatic management. Moreover, our clinical experience has highlighted the challenges of haemostatic management of haemophilia patients undergoing tooth extraction. Therefore, we retrospectively evaluated the incidence of post-extraction bleeding and evaluated the risk factors of post-extraction bleeding among haemophilia patients.
      The incidence of post-extraction bleeding per intervention and per tooth extraction was 11.9% and 7.9%, respectively. These findings are in accordance with previously reported figures, which range from 1.9% to 31.5%.
      • Piot B.
      • Sigaud-Fiks M.
      • Huet P.
      • et al.
      Management of dental extractions in patients with bleeding disorders.
      • Frachon X.
      • Pommereuil M.
      • Berthier A.M.
      • et al.
      Management options for dental extraction in hemophiliacs: a study of 55 extractions (2000-2002).
      • Ak G.
      • Alpkılıç Başkırt E.
      • Kürklü E.
      • et al.
      The evaluation of fibrin sealants and tissue adhesives in oral surgery among patients with bleeding disorders.
      • Peisker A.
      • Raschke G.F.
      • Schultze-Mosgau S.
      Management of dental extraction in patients with Haemophilia A and B: a report of 58 extractions.
      ,
      • Cocero N.
      • Pucci F.
      • Messina M.
      • et al.
      Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue.
      However, the discrepancy between reported values may relate to the use of different definitions of post-extraction bleeding. A retrospective study using the same definition for post-extraction bleeding as in this study reported that the incidence of post-extraction bleeding for patients receiving anticoagulants and those not receiving anticoagulants was no more than 11% and 0.9%, respectively. 17 These results suggest that even if we perform tooth extraction in haemophilia patients with careful systemic and local haemostatic management, post-extraction bleeding occurs much more frequently than in patients without bleeding disorders. We suggest that there is a need to revise the haemostatic management of tooth extraction in haemophilia patients to reduce the frequency of post-extraction bleeding.
      Our multivariate logistic regression analysis revealed that use of mouth splints significantly decreased the risk of post-extraction bleeding in haemophilia patients. Previous literature and guidelines have recommended the use of mouth splints in haemophilia patients

      HMcintyre H. Dental Extractions In Patients With Hemophilia Syndrome; A Method Of Local Management. Oral Surg Oral Med Oral Pathol. 1965;19:163-173.

      • Suwannuraks M.
      • Chuansumrit A.
      • Sriudomporn N.
      • et al.
      The use of fibrin glue as an operative sealant in dental extraction in bleeding disorder patients.
      • Ak G.
      • Alpkılıç Başkırt E.
      • Kürklü E.
      • et al.
      The evaluation of fibrin sealants and tissue adhesives in oral surgery among patients with bleeding disorders.
      • Anderson J.A.
      • Brewer A.
      • Creagh D.
      • et al.
      Guidance on the dental management of patients with haemophilia and congenital bleeding disorders.
      and patients on antithrombotic therapy,
      • Japanese society of Oral and Maxillofacial Surgeons
      Japanese Society of Gerodontology, Japanese Society of Dentistry for medically compromised patient. Guidelines for patients on antithrombotic therapy requiring dental extraction. Tokyo: Gakujutsush Corporation.
      because it prevents the tongue from scratching the inside of the extraction socket and protects the blood clot beneath it. However, we believe our study is the first to have used statistical methods to support the preventive effect of mouth splints for post-extraction bleeding in haemophilia patients.
      Mouth splints are of two types, full-coverage and partial-coverage. However, we could not examine which type of splint was more useful, as this was a retrospective study. Therefore, we will investigate which type of splints provides a more preventive effect for post-extraction bleeding in haemophilia patients. Additionally, as the splint-wearing period varies between institutions, we will investigate the optimal splint-wearing period for individual patients. Guidance from the United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO) recommends the use of mouth splints for 48 hours after tooth extraction in haemophilia patients with inhibitors. 13 In our protocol, the mouth splint-wearing period is set at 7 days, but patients are instructed to remove and brush their teeth and splints after every meal to maintain a healthy periodontium during this period. Considering that, on average, post-extraction bleeding occurred around the sixth post-operative day, we are confident that a splint-wearing period of 7 days is appropriate; however, we think that it may be better to recommend a splint-wearing period in accordance with individual patient factors, disease-related factors, and intervention-related factors on a case-by-case basis.
      Although teeth extractions are conducted as outpatient procedures in some institutions,
      • Zanon E.
      • Martinelli F.
      • Bacci C.
      • et al.
      Proposal of a standard approach to dental extraction in haemophilia patients. A case-control study with good results.
      • Cocero N.
      • Pucci F.
      • Messina M.
      • et al.
      Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue.
      at our institution all haemophilia patients were hospitalised to undergo tooth extractions, with a hospitalisation of 7.2 days. We believe that hospitalisation enables better haematological monitoring of patients and immediate intervention for haemorrhagic complications. Nonetheless, for minimising medical cost and ensuring patient convenience, it is better to keep the hospitalisation period short. Incidentally, both the Australian Haemophilia Centre Directors’ Organisation and UKHCDO propose that haemophilia patients should stay at least overnight at the hospital after tooth extraction.

      Australian Haemophilia Centre Directors’ Organisation. Guideline for the management of patients with haemophilia undergoing surgical procedures. Available from URL: http://www.ahcdo.org.au/documents/item/13 (Accessed 8 July 2020).

      • Anderson J.A.
      • Brewer A.
      • Creagh D.
      • et al.
      Guidance on the dental management of patients with haemophilia and congenital bleeding disorders.
      Currently, we are examining the effects of shortening the hospitalisation period, while considering whether the patient’s place of living allows easy access to our institution.
      Our study is subject to some limitations. Firstly, this was a small-scale retrospective study and the data were obtained at a single facility. Secondly, we performed the multivariate analysis for risk factors of post-extraction bleeding per tooth extraction and not per intervention, which increases the possibility of bias because patients could be counted multiple times. However, we were especially concerned with the relationship between post-extraction bleeding and intervention-related factors (type of extraction procedure and local haemostatic measures). Intervention-related factors vary depending on each tooth even within the same intervention during which multiple teeth are extracted. Previous studies investigating the risk of post-extraction bleeding have not reported a significant correlation between the number of extracted teeth and post-extraction bleeding.
      • Hsieh J.T.
      • Klein K.
      • Batstone M.
      Ten-year study of postoperative complications following dental extractions in patients with inherited bleeding disorders.
      • Yagyuu T.
      • Kawakami M.
      • Ueyama Y.
      • et al.
      Risks of postextraction bleeding after receiving direct oral anticoagulants or warfarin: a retrospective cohort study.
      • Campbell J.H.
      • Alvarado F.
      • Murray R.A.
      Anticoagulation and minor oral surgery: should the anticoagulation regimen be altered?.
      • Evans I.L.
      • Sayers M.S.
      • Gibbons A.J.
      • et al.
      Can warfarin be continued during dental extraction? Results of a randomized controlled trial.
      • Sacco R.
      • Sacco M.
      • Carpenedo M.
      • et al.
      Oral surgery in patients on oral anticoagulant therapy: a randomized comparison of different intensity targets.
      • Garcia D.A.
      • Regan S.
      • Henault L.E.
      • et al.
      Risk of thromboembolism with short-term interruption of warfarin therapy.
      • Kataoka T.
      • Hoshi K.
      • Ando T.
      Is the HAS-BLED score useful in predicting post-extraction bleeding in patients taking warfarin? A retrospective cohort study.
      Furthermore, when we analysed the data per intervention and per extraction, similar incidence rates of post-extraction bleeding events were observed (10 of 84 interventions [11.9%] and 12 of 151 extractions [7.9%], respectively). Moreover, when we analysed data per intervention in patients receiving factor replacement therapy, the mean number (± SD) of teeth extracted per intervention was 2.0 ± 0.9 in the post-extraction bleeding group and 1.8 ± 0.8 in the group without post-extraction bleeding. There was no significant association between post-extraction bleeding and the number of teeth extracted per intervention (P = .57). These data suggest that any bias from the per-tooth analyses likely had a minimal effect on our findings.

       Conclusions

      In this retrospective cohort study of 151 extractions in 84 interventions among 55 haemophilia patients, we reported that the incidences of post-extraction bleeding per intervention and per tooth extraction were 11.9% and 7.9%, respectively. Moreover, the use of mouth splints significantly decreased the risk of post-extraction bleeding. In future, we will conduct a prospective study to investigate the optimal type of splint and splint-wearing period to improve haemostatic management of tooth extraction in haemophilia patients.

      Ethics statement/confirmation of patients’ permission

      Institutional approval was obtained for the study. Patient consent is not required.

      Conflict of Interest

      Keiji Nogami receives grants and personal fees from Chugai Pharmaceutical Co., Shire, and Novo Nordisk, Bioverativ, Bayer. Koji Yada teaches a course endowed by Shire Japan Co. Ltd. The other authors have no conflict to declare.

      Appendix A. Supplementary data

      References

        • Bolton-Maggs P.H.
        • Pasi KJ.
        Haemophilias A and B.
        Lancet. 2003; 361: 1801-1809
      1. White GC II, Rosendaal F., Aledort L.M., et al. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001;85:560.

      2. HMcintyre H. Dental Extractions In Patients With Hemophilia Syndrome; A Method Of Local Management. Oral Surg Oral Med Oral Pathol. 1965;19:163-173.

        • Suwannuraks M.
        • Chuansumrit A.
        • Sriudomporn N.
        • et al.
        The use of fibrin glue as an operative sealant in dental extraction in bleeding disorder patients.
        Haemophilia. 1999; 5: 106-108
        • Zanon E.
        • Martinelli F.
        • Bacci C.
        • et al.
        Proposal of a standard approach to dental extraction in haemophilia patients. A case-control study with good results.
        Haemophilia. 2000; 6: 533-536
        • Piot B.
        • Sigaud-Fiks M.
        • Huet P.
        • et al.
        Management of dental extractions in patients with bleeding disorders.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002; 93: 247-250
        • Frachon X.
        • Pommereuil M.
        • Berthier A.M.
        • et al.
        Management options for dental extraction in hemophiliacs: a study of 55 extractions (2000-2002).
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005; 99: 270-275
        • Franchini M.
        • Rossetti G.
        • Tagliaferri A.
        • et al.
        Dental procedures in adult patients with hereditary bleeding disorders: 10 years experience in three Italian Hemophilia Centers.
        Haemophilia. 2005; 11: 504-509
      3. Australian Haemophilia Centre Directors’ Organisation. Guideline for the management of patients with haemophilia undergoing surgical procedures. Available from URL: http://www.ahcdo.org.au/documents/item/13 (Accessed 8 July 2020).

        • Ak G.
        • Alpkılıç Başkırt E.
        • Kürklü E.
        • et al.
        The evaluation of fibrin sealants and tissue adhesives in oral surgery among patients with bleeding disorders.
        Turk J Haematol. 2012; 29: 40-47
      4. Edna Boliver, Susan Karp, Susan Peterson, et al. Canadian Association of Nurses in Hemophilia Care. DENTAL CARE FOR PEOPLE WITH BLEEDING DISORDERS. Available from URL: http://www.hemophilia.ca/files/Dental%20Care%202012%20EN%20-%20FINAL.pdf (Accessed 8 July 2020).

      5. Alok Srivastava, Andrew K. Brewer, Eveline P. Mauser-Bunschoten, et al. World Federation of Hemophilia. Guidelines for the management of hemophilia. 2nd edition. DOI: 10.1111/j.1365-2516.2012.02909.x. Available from URL: http://www1.wfh.org/publications/files/pdf-1472.pdf. (Accessed 8 July 2020).

        • Anderson J.A.
        • Brewer A.
        • Creagh D.
        • et al.
        Guidance on the dental management of patients with haemophilia and congenital bleeding disorders.
        Br Dent J. 2013; 215: 497-504
        • Peisker A.
        • Raschke G.F.
        • Schultze-Mosgau S.
        Management of dental extraction in patients with Haemophilia A and B: a report of 58 extractions.
        Med Oral Patol Oral Cir Bucal. 2014; 19: e55-e60
        • Cocero N.
        • Pucci F.
        • Messina M.
        • et al.
        Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue.
        Blood Transfus. 2015; 13: 287-294
        • Hsieh J.T.
        • Klein K.
        • Batstone M.
        Ten-year study of postoperative complications following dental extractions in patients with inherited bleeding disorders.
        Int J Oral Maxillofac Surg. 2017; 46: 1147-1150
        • Yagyuu T.
        • Kawakami M.
        • Ueyama Y.
        • et al.
        Risks of postextraction bleeding after receiving direct oral anticoagulants or warfarin: a retrospective cohort study.
        BMJ Open. 2017; 7e015952
        • Japanese society of Oral and Maxillofacial Surgeons
        Japanese Society of Gerodontology, Japanese Society of Dentistry for medically compromised patient. Guidelines for patients on antithrombotic therapy requiring dental extraction. Tokyo: Gakujutsush Corporation.
        2015
        • Campbell J.H.
        • Alvarado F.
        • Murray R.A.
        Anticoagulation and minor oral surgery: should the anticoagulation regimen be altered?.
        J Oral Maxillofac Surg. 2000; 58: 131-135
        • Evans I.L.
        • Sayers M.S.
        • Gibbons A.J.
        • et al.
        Can warfarin be continued during dental extraction? Results of a randomized controlled trial.
        Br J Oral Maxillofac Surg. 2002; 40: 248-252
        • Sacco R.
        • Sacco M.
        • Carpenedo M.
        • et al.
        Oral surgery in patients on oral anticoagulant therapy: a randomized comparison of different intensity targets.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 104: e18-e21
        • Garcia D.A.
        • Regan S.
        • Henault L.E.
        • et al.
        Risk of thromboembolism with short-term interruption of warfarin therapy.
        Arch Intern Med. 2008; 168: 63-69
        • Kataoka T.
        • Hoshi K.
        • Ando T.
        Is the HAS-BLED score useful in predicting post-extraction bleeding in patients taking warfarin? A retrospective cohort study.
        BMJ Open. 2016; 6e010471