Haemorrhagic disorders combined with soft tissue inflammation and infection may lead to severe bleeding complications before, during or after dental treatment. In selected cases, a combined therapeutic approach involving clinical therapies and systemic and local medication could improve the treatment outcomes and the patient’s quality of life. This clinical case report, presents for the first time a successful combined approach, completed in a 38-year-old male patient with severe type-B haemophilia in which an infected tooth was extracted, an immediate implant was inserted, bone grafting was performed and early implant loading was successfully applied. In addition to the clinical therapy, medication was provided orally, systemically and locally, thus preventing the haemorrhagic complications and improving the patient’s quality of life.
- oral and maxillofacial surgery
- haematology (incl blood transfusion)
- drug therapy related to surgery
- dentistry and oral medicine
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- oral and maxillofacial surgery
- haematology (incl blood transfusion)
- drug therapy related to surgery
- dentistry and oral medicine
Type-B haemophilia (Christmas disease) is originated by a deficiency in the factor IX (FIX) and is less prevalent (incidence 1:30 000 live male births) than type-A haemophilia (incidence 1:20 000 births).1
The risk of bleeding in patients with type-B haemophilia depends on the severity of the disease, which increases with the decrease in the percentage of FIX. Therefore, patients with mild type-B haemophilia possess between 5% and 25% of type FIX, patients with moderate type-B haemophilia possess between 1% and 5% of type FIX and patients with severe type-B haemophilia possess <1% of type FIX.2 Patients affected by severe type-B haemophilia exhibit frequent spontaneous bleeding in muscles and weight-bearing joints.2
The haemorrhagic complications of the patient with haemophilia can be worsened in the presence of nongenetic risk factors as associated infection, trauma or surgery, also besides, prolonged preventive replacement treatment can result in an immune reaction towards the administered antifibrinolytic factors.3 4
Furthermore, the quality of life of patients with haemophilia can be affected by the uncertainty of the chronic disease, the lack of adherence to medical and pharmacological prescriptions and the incidence of haemorrhagic episodes.5 Prophylactic approaches have demonstrated to reduce in 53% the incidence of haemorrhagic complications of patients with haemophilia, and if these appear, early interventions can reduce their adverse effects on the patient’s general health and quality of life.5–7
In 2013, the United Kingdom Haemophilia Centre Doctor’s Organisation Dental Working Party published updated consensus guidelines for the dental treatment of patients with haemophilia. This report presented an overview of the most common congenital bleeding disorders and also summarised the local haemostatic measures and agents used to control the haemorrhage and discussed the prevention and emergency treatment planning for patients with haemophilia. Furthermore, the authors highlighted the methodological limitations and the lack of robust data supporting surgical approaches for the treatment of patients with haemophilia.8
In regards to patients with haemophilia and dental implants, there are few descriptions of treatment approaches. Castellanos-Cosano et al described a clinical case of the oral implant rehabilitation of an HIV-positive patient with type-C hepatitis with severe type-A haemophilia. A 46-year-old male patient received five dental implants in the posterior region of his partially edentulous mandible after following a protocol with factor VIII replacement supplemented with oral antifibrinolytic therapy without postoperative complications.9 Gornitsky et al described a patient with type-A haemophilia with multiple surgical interventions for resolving ankylosis of the right temporomandibular joint followed by multiple extractions and dental implants placement. The patient received preoperatory and postoperatory treatment with factor VIII replacement concentrate and oral antifibrinolytic therapy without complications.10
However, there is a lack of references in the literature about dental implants inserted in patients with type-B haemophilia with infected postextraction sockets, in the aesthetic zone, and with simultaneous bone grafting and immediate temporary crown insertion.
This report provides for the first time, a protocol to reduce the haemorrhagic risk and to improve the quality of life of a patient with severe type-B haemophilia who presented with an infected hopeless upper central incisor. Through alternative local haemostatic measures (immediate implant placement, bone grafting with compression, collagen membranes and immediate temporisation), supplementation with local antifibrinolytics and premedication and postmedication (local and systemic), these goals were achieved.
A 38-year-old male patient with severe type-B haemophilia (FIX <1 IU/dL and normal range 70) presented to the private practice with oral bleeding and oral pain seeking for treatment.
The clinical evaluation showed a metal–ceramic crown with mobility, gum bleeding, apical abscess and inflammation around tooth No. 8. Both bleeding and pain increased with biting and palpation. Radiographical evaluation showed that tooth No. 8 also had a metallic post, horizontal fracture at the union of the middle and apical thirds of the root, and a radiolucent lesion affecting 50% of root length.
The patient reported that previous dental providers refused to complete his treatment because they were concerned with the haemorrhagic complications of the tooth extraction. Besides, the patient delayed the tooth extraction because he also was scared of the tooth extraction consequences.
After consultation with the patient’s haematologist, general dentist, prosthodontist and the oral surgeon, it was decided to proceed with the patient’s dental and implant treatment observing the following medication and therapeutic approaches:
Premedication (phase 1)
The immediate start of antibiotic therapy with Amoxicillin 875/Clavulanic acid 125 mg (Augmentin 875, GlaxoSmithKline, Madrid, Spain) for treating and reducing the infection. One capsule via oral every 8 hours was started 3 days before the surgery and maintained for 7 days postoperative.
The immediate start of pain treatment with Acetaminophen 500mg (Dolostop 500 mg, Kern Pharma, Barcelona, Spain) for pain control. One tablet via oral was started every 6 hours for 3 days.
Intravenous FIX (Grifols, Paret del Valles, Spain) replacement concentrate, 3000 IU to increase the percentages of FIX over 40%, Applied 1 day before the surgical procedure.
Tranexamic acid (TXA, 500 mg; Amchafibrin 500 mg, Meda Farma, Madrid, Spain) to provide systemic antifibrinolytic coverage. One tablet was started via oral every 8 hours 2 days before surgery and maintained for other 5 days postoperative.
Surgical procedures (phase 2)
Local infiltrative anaesthesia with Articaine chlorhydrate (Artinibsa 4%, Inibsa dental, Granollers, Spain).
A triangular flap with a mesial releasing incision was completed at the buccal area of tooth No. 7, followed by a intra-sulcular incision at the buccal, mesial and distal faces of tooth No. 9. The infected tooth No. 8 was extracted, and the infected soft and hard tissues were debrided carefully; afterwards, the area was irrigated profusely with saline. The socket depth was determined to be as 9 mm, measured with a periodontal probe.
The implant bed preparation was performed using tapered implant drills with a 4.1 mm diameter and 12 mm length (Straumann BLT, Basel, Switzerland), to achieve 3 mm of engagement at the apical area of the original socket depth.
Local haemostatic procedures
The bleeding coming from the implant bed preparation was controlled by the insertion of a titanium dental implant with a tapered body (Straumann BLT). The dimensions of the implant were 4.1 mm diameter and 12 mm length. The implant body occluded and compressed partially the bone at the apical zone, as well as the lingual wall, and two-thirds of the remaining buccal wall, thus reducing the bleeding. The primary stability was evaluated immediately after the implant insertion with a resonance frequency analysis device (Osstell, Gothenburg, Sweden). The recorded value reached an Implant Stability Quotient (ISQ) of 70 ISQ.
Residual bleeding coming from the remnants of the socket walls was controlled by filling the gap (space between the implant body and implant bed produced by the differences between the root anatomy and implant geometry) with a particulate bone graft (Bone Ceramic, Straumann, Basel, Switzerland) previously embedded in TXA11 12 (Amchafibrin, Meda Farma) and packed with 200g compression force with a bone condenser.13 The graft particles were condensed against the base and walls of the socket until the particles were compacted, stabilised and filled with a blood coagulum.14
The bleeding from the adjacent bone and the soft tissues was reduced by the insertion of a collagen membrane (Derma, Osteobiol, Italy) imbibed in TXA (Amchafibrin, Meda Farma) for 2 min. The membrane covered the osseous surface adjacent to the surgical area and also protected and provided additional stability to the graft particles.15 The membrane after insertion was compressed for 3 min and sutured to the lingual and buccal periosteum. Afterward, the flap was repositioned over the membrane and carefully stabilised by external sutures.
To provide additional stability to the collagen membrane, a titanium abutment was screwed to the implant through an orifice perforated previously in the membrane and secured with 20 Ncm torque. The flap edges were repositioned carefully to obtain primary closure around the titanium abutment. Silk 4–0 sutures were used.
Local compression with a gauze imbibed in TXA (Amchafibrin, Meda Farma) was applied for 3 min over the surgical area.
A temporary composite crown was fabricated with a wide emergence profile and was adjusted to the titanium abutment. Thus, providing additional protection to the soft tissues with the contours of the wide emergence profile of the crown. The occlusal contacts were relieved until there was no contact during centric occlusion or excursive contacts with the opposite teeth.
After the adjustments of the temporary crown, a second compression procedure with a gauze imbibed in TXA (Amchafibrin, Meda Farma) was applied for an additional 5 min.
Postoperative radiograph was obtained for the evaluation of the implant position and graft distribution within the surgical area (figures 1A, B, C and D).
Postoperative medication (phase 3)
Intravenous FIX (Grifols, Paret del Valles, Spain) replacement concentrate, 3000 IU every 24 hours during 2 days.
Mouth rinses with a TXA solution (Amchafibrin 500 mg, Meda Farma), every 6 hours for 2 days after the surgery.
TXA 500 mg (Amchafibrin 500 mg, Meda Farma) one tablet via oral every 6 hours after the surgery and until 7 days were completed.
Acetaminophen 500 mg (Dolostop 500 mg, Kern Pharma) for the control of the postoperative pain. One tablet via oral every 6 hours for 2 days
The patient received general postoperatory recommendations to reduce trauma and irritation to the surgical area (soft foods, intake of cold foods and drinks, maintenance of oral hygiene with a surgical toothbrush and extraoral ice).
Outcome and follow-up
The sutures were removed after 1 week. The patient reported a normal healing without pain, inflammation or haemorrhagic events. No infection or inflammation was observed.
After 4 months of healing time, the temporary crown was removed, the secondary implant stability was confirmed by resonance frequency analysis (ISQ value of 75) and radiographs were obtained for the evaluation of adjacent bone.
Impressions were taken, and a definitive implant supported metal–ceramic crown was fabricated and inserted. The patient was able to keep the aesthetics and phonetics during the whole time from the moment of the extraction to the insertion of the definitive restoration satisfactorily, thus improving his quality of life (figure 2A, B and C).
Follow-up visits showed a clinical stable gingival margin, probing depths remained stable and radiographical evaluation did not show changes at the crestal bone level after 1-year follow-up.
The haemorrhage management options for patients with haemophilia who are going to receive dental treatment are variable and depend on the type of haemophilia, severity of the disease, the specific procedure that is going to be completed (invasive/noninvasive), the patient’s health condition (presence of pain, active haemorrhage) and aggravating factors (infection, resistance to the replacement therapy).16 The goals of these different preventive and therapeutic approaches for patients with haemophilia are to provide haemostasis during the period of bleeding risk and until the wound is fully healed. However, there is no sufficient evidence about the most effective treatment to prevent bleeding in patients with severe type-B haemophilia who need dental surgical procedures.16
In relation to teeth extraction in patients with type-B haemophilia, different approaches for the prevention of haemorrhagic episodes have been presented. Zanon et al 17 recommended preoperative intravenous replacement factors 1 hour prior to tooth extractions and 20 mg/kg of TXA in 100 mL of saline solution, fibrin sponges as local haemostatic measure and postoperative oral antifibrinolytics the following 7 days.17 18 Hewson et al achieved haemostasis in patients with type-B haemophilia undergoing third molar extractions using a single preoperative dose of FIX replacement followed by intraoperative 5% TXA solution applied locally, oxidised cellulose sponges placed in the surgical defect and flap closure with monofilament sutures.18
Cakr et al 19 administered 12 hours preoperative TXA 10 mg/kg +1 hour preoperative FIX replacement 50– 60 IU/dL followed by 5–7 days TXA 30–40 mg/kg 3–4 times a day and FIX replacement after 8–12 hours. In addition to local haemostatic procedures and proper wound management in patients who underwent teeth extractions.19 20Peisker et al reported appropriate bleeding control after third molar extraction in a female patient with severe haemophilia type-B by using defined preoperative and postoperative FIX replacement and local haemostatic measures of collagen fleece, fibrin glue, primary suture and TXA solution.20
Givol et al 21 presented patient’s data from 20 years of experience with patients receiving oral surgery procedures and showed that the best approaches for the prevention of bleeding episodes in patients with haemophilia were those that received a combined approach including systemic therapy, local haemostatic procedures and fibrin glue and were related to the procedure-related risk and the patient’s calculated haematological risk for bleeding.21
Just two articles in the literature described the bleeding control in patients with type-A haemophilia receiving dental implants.
The first was performed at the lower jaw of a patient with partial edentulism who received five dental implants. A premedication protocol started the night before the surgical procedure with 1 g of TXA (via oral) every 6 hours and replacement FVIII 3000 UI (intravenous) 15 min before the procedure followed by a postoperative regimen with FVIII replacement 2000 UI (intravenous) 12 hours after surgery, FVIII replacement 3000 UI (intravenous) 24 hours after surgery and FVIII replacement 2000 UI (intravenous) 48 hours after surgery plus 1 g of TXA (via oral) every 6 hours for additional 5–7 days; in addition, pain control medication and antibiotics were provided to the patient.9
The second, used premedication with 2500 UI of FVIII 1 hour before the procedure and TXA, 2.5 g, 8 hours before the procedure; 12 hours postoperative, the patient received 1000 units of FVIII and TXA every 8 hours for 10 days. The surgery involved teeth extraction and five immediate implants at the lower jaw in four staged surgeries protocol to reduce the risk of bleeding.10
However, as per authors knowledge, there is no available information about the treatment approaches to control the bleeding in patients with severe type-B haemophilia who need a tooth extraction, immediate dental implant placement, bone grafting and immediate temporisation at the upper anterior aesthetic region of the maxilla.
In this clinical report, preoperative FIX replacement as well as oral antifibrinolytics was prescribed based on the severity of the patient with type-B haemophilia (FIX <1 IU/dL) and following the recommendations of the haematologist and according to the 2013 ‘Guidance on the dental management of patients with haemophilia and congenital bleeding disorders’.8 In addition, pain control was established with nonsteroidal anti-inflammatory drugs to avoid the increased risk of bleeding coming from platelets aggregation inhibition,22 and antibiotic therapy was started to reduce the infection.23
Currently, haemophilia type-B is managed using FIX replacement therapy which can be completed with plasma-derived or recombinant factors.24 As per the International Society of Thrombosis and Homeostasis, there are five treatment protocols25: episodic (replacement therapy administered at the time of clinically evident bleeding), primary prophylaxis (regular, replacement therapy in the absence of documented joint disease, initiated before age 3 years), secondary prophylaxis (regular, replacement therapy initiated after two or more large joint bleeds, but before joint disease confirmation), tertiary prophylaxis (regular replacement started after the onset of joint disease) and intermittent prophylaxis (replacement therapy during periods <45 weeks/year).
There is a general agreement that the prophylactic FIX replacement therapy for patients with type B haemophilia should be initiated early in the patient’s life.26 However, many adult patients do not adhere to their prescribed regimens and to long-term protocols.27 28
For these patients not adherent to regular replacement therapy, an episodic/on-demand treatment might reduce the bleeding complications of surgical procedures. Therefore, to obtain the benefits of the FIX therapy, the patient of this case report was treated with on-demand FIX treatment until the surgical areas were fully healed and minimal risk of bleeding from the surgical procedure was confirmed.
The surgical procedure was performed with extreme caution to reduce the trauma to other areas that may increase the risk of bleeding. A full-thickness flap was extended to the next adjacent teeth medially and distally, one small release incision and one peri-sulcular incision allowed the access and debridement of the existing infected tissues, evaluation of the buccal wall integrity, measurement of the bone defect and reduction of the flap tension. The tooth extraction was performed with periotomes and the implant bed preparation was extended 3 mm apically to achieve implant stability. A 4.1 mm diameter implant with 12 mm length facilitated the haemostasis of the apical bone and the middle and apical thirds around the implant body. Graft particles were embedded in TXA to stabilise the fibrin clot and to create a more stable and malleable grafting paste11 12; afterward, the graft was compressed to provide additional haemostasis, stabilise the graft particles by reducing the voids between particles and to facilitate the fibrin clot contact with all the surfaces.13 14
Finally, a collagen membrane embedded in TXA solution was used for defect closure, particle stability and additional bleeding reduction around the grafted area.15 16 Proper sutures were performed with 4–0 silk sutures to obtain primary closure of the wound. The insertion of the temporary abutment and the temporary crown with a wide profile conferred additional stability to the membrane and the graft particles and protected the surgical area from trauma. The presence of enough primary stability to apply immediate loading was confirmed with the initial resonance frequency analysis (>60 ISQ).
Local TXA in combination with graft particles and with the collagen membrane was used as coadjutants for bleeding prevention. The use of local TXA as an antifibrinolytic drug has shown evidence of postoperative bleeding reduction following dental extractions,29 and this was explained by the minimal haemorrhage suffered by patients with haemophilia who received dental extractions given the maintenance of the inhibition of fibrinolysis some hours after single mouth rinses with 5% TXA solution.30 TXA can inhibit plasminogen, and therefore inhibits fibrin degradation, which results in minimal systemic absorption and can limit postsurgical bleeding without systemic effects.31 32
It is not clear which haemostatic approaches must be used in patients with bleeding disorders who are going to oral surgery procedures. For example, sutures, gazes and matrices (gauze pressure, oxidised cellulose soaked in TXA, TXA-soaked gauze); sponges and foams (haemostatic sponge, gelatin sponge, fibrin sponge, collagen sponge, TXA-soaked sponge); glues and adhesives (fibrin glue, histoacryl glue); mouthwashes and solutions (epsilon aminocaproic acid mouthwash, TXA mouthwash, TXA irrigation); wax and bone grafting materials (calcium sulfate) have been reported.33 In relation to dental implant surgeries in patients with severe type-B haemophilia, these methods are assumed similar and had been even less studied.
In this clinical case, it was decided to continue with postoperative medication to minimise the risk of bleeding until the surgical area was completely healed. The FIX replacement was maintained just for 2 days after the surgery to maintain more than 40% of plasmatic levels of the FIX and to reduce the risk of immune reactions that potentially might be induced by the continued delivery of replacement FIX therapy.3 4 Postoperative TXA was continued for five more days until the wound was healed. Thus, postoperative local bleeding was controlled.8 34
The patient was able to speak, eat and socialise during the whole treatment period without haemorrhagic, functional or aesthetic complications, thus improving his quality of life.
Case reports involving dental implants in patients with severe type-B haemophilia are very scarce. The treatment is usually delayed given the lack of information about potential therapeutic options, and the patient’s and dentist’s fear of complications.
A combined approach with the following three phases might be considered in selected cases:
Factor IX (FIX) replacement, systemic antifibrinolytics as well as pain and infection control, if required.
atraumatic surgery, tooth extraction, debridement, local haemostasis with the insertion of a dental implant, bone graft, collagen membrane, implant abutment, temporary crown and local antifibrinolytics.
FIX replacement continuation, systemic and local antifibrinolytics with proper postoperative care.
The communication between the haematologist, general dentist, oral surgeon and prosthodontics and patient compliance is crucial for the success of the treatment.
Contributors All the authors participated in the conception, design, analysis and interpretation of data (JLCG, GER, RAD-R). Drafting the article and revising it critically for important intellectual content (JLCG, GER, RAD-R). Final approval of the version published (JLCG, GER, RAD-R). Agreement to be accountable for the article and to ensure that all questions regarding the accuracy or integrity of the article are investigated and resolved (JLCG, GER, RAD-R).
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Patient consent for publication Not required.