Update on Medically Compromised Patients for Oral Surgery: The Bleeders and the Non-healers

Causes of excessive bleeding

Post-operative bleeding has been attributed to various factors that can be broadly classified as local or systemic.¹ Systemic factors that increase the risk of bleeding include platelet disorders, clotting factor deficiencies, vascular disorders and fibrinolytic defects (Table 2).⁴ Disorders of haemostasis can also be classified according to the causative, underlying systemic disease (Table 3).

There are numerous drugs that predispose to excessive bleeding. Their mechanisms of action may impact on the function or number of platelets (Table 2) or on the action of individual clotting factors (Table 2 and Figure 1). There are also a number of herbs and dietary supplements such as St John's wort, echinacea, garlic, Gingko biloba and ginseng that inhibit platelet adhesion and aggregation or contain coumarins.⁶

In addition to systemic causes, post-extraction bleeding can be caused locally from soft tissue or bone. Soft tissue bleeding can result from laceration of blood vessels (arterial, venous or capillary). Bone bleeding may be from either nutrient canals or central vessels.¹ There have been reports of instances where massive post-extraction haemorrhage has resulted from the presence of an unknown arteriovenous malformation, although such incidents are, thankfully, very rare.⁷ Increased tissue vascularity, due to pre-existing inflammation or infection, and failure of the patient to follow post-operative instructions, have also been implicated in post-extraction bleeding.¹

Identifying patients at increased risk of bleeding

A thorough medical history is key to identifying patients at increased risk of bleeding and should be updated at every patient visit. In addition to identifying previously diagnosed systemic disease, a bleeding history is advisable, prior to undertaking invasive procedures. This can be a series of brief questions that elicit a history of excessive bleeding following trauma, surgery or parturition, easy bruising, menorrhagia or spontaneous epistaxis, particularly if medical or surgical intervention was required to arrest haemorrhage. Affirmative responses to these questions should alert the dentist to the need for haematological investigation.

A family history will identify patients who may have an inherited bleeding disorder. The drug history should include specific reference to both prescribed drugs and over-the-counter medications and dietary supplements that may potentiate bleeding.

On general examination, dentists should be vigilant for the presence of jaundice and other signs of chronic liver disease, as well as generalized purpura and ecchymosis. The presence of ecchymosis and haematomas of the oral mucosa suggests a coagulation defect, especially in the absence of trauma. Petechiae and prolonged bleeding from minor mucosal wounds suggest a problem with platelet number or function, or with blood vessel integrity.²

Although rare, arteriovenous malformations (AVMs) have the potential to cause massive haemorrhage during dento-alveolar surgery. Dentists may be alerted to their presence by spontaneous gingival bleeding, unexplained dental mobility or facial asymmetry in young patients (<20 years) and AVMs should be included in the differential diagnosis of radiographic, lytic lesions of the jaws.⁷

Management of patients at increased risk of bleeding

Patients with an inherited bleeding disorder should always be managed jointly with a haematologist and are, therefore, best referred to secondary care for invasive dental procedures.⁸ Those with underlying systemic disease, that increases bleeding risk, require haematological investigation prior to treatment, and any abnormal findings should be discussed with the patient's specialist physician.⁸

Patients at risk of thrombocytopenia require a full blood count (FBC) to check the platelet level. It has been cited that for patients with an isolated thrombocytopenia, it is safe to proceed with a limited amount of minor oral surgery, providing the platelet count is above 50 × 10⁹/L.² This platelet count is generally accepted as the lowest threshold for an otherwise healthy patient, undergoing elective and moderately invasive procedures in the hospital setting, although a recent systematic review suggests that evidence to support this figure is lacking.⁹

Patients at risk of a coagulation defect from systemic disease require a coagulation screen, comprising both the international normalized ratio (INR) and activated partial thromboplastin time (APTT), to assess both the intrinsic and extrinsic pathways of the coagulation cascade (Figure 2).⁸

The guideline that an INR <4.0 is safe for performing dental extractions only applies to patients who are taking warfarin. A raised INR or APTT, in any patient who is not taking anticoagulant medication, should be cause for concern. In this instance, invasive procedures should only be performed in secondary care following consultation with a medical specialist.

Patients taking antiplatelet drugs can be treated without interrupting these, using local measures for haemostasis, although prolonged bleeding should be anticipated in those receiving dual antiplatelet therapy, who may be best managed in secondary care.⁸ Warfarinized patients, with a stable INR which has tested <4.0 within 24 hours of treatment, may safely undergo routine extraction of up to three teeth or a single minor oral surgical procedure.⁸ Patients taking direct oral anticoagulants (DOACs) may be treated in the practice setting, closely following the current Scottish Dental Clinical Effectiveness Programme (SDCEP) guidance.¹⁰ Approximately 6% of patients taking DOACs may be expected to require specific intervention for persistent post-operative bleeding following minor oral surgery procedures.¹¹

Particular caution must be exercized with individuals who have multiple factors that may potentiate bleeding; for example patients with a systemic disease that may increase bleeding risk, who are also taking antiplatelets or anticoagulants, or those who are taking a combination of both antiplatelet and anticoagulant medications. In these circumstances, invasive procedures should only be performed in the hospital setting, following liaison with the appropriate medical specialists. The use of intravenous sedation with midazolam may be considered for patients with significantly elevated blood pressure, undergoing oral surgery procedures, as this aids intra-operative blood pressure control.¹²

For all patients at increased risk of bleeding, treatment should be performed in the morning and ideally at the beginning of the week, to allow time for them to return within standard working hours, should bleeding occur. If there is significant, pre-existing soft tissue inflammation, this may be reduced using chlorhexidine digluconate mouthwash in advance of treatment. The increased risk of bleeding should be clearly identified and recorded in accordance with the Local Safety Standard for Invasive Procedures (LocSSIP).¹³ Treatment should be carried out atraumatically, avoiding inferior dental blocks and raising of soft tissue flaps where possible. Multiple dental extractions may need to be staged over several visits. Local measures for haemostasis, such as packing with an absorbable haemostat and suturing of the socket, will reduce the risk of post-extraction bleeding and should be used routinely for all patients with an increased bleeding risk.⁸ A 5% tranexamic acid mouthwash may also be prescribed in secondary care, for use four times a day for 2–5 days post-operatively, in patients deemed to be at high risk of bleeding. This theoretically reduces the risk of post-surgical bleeding, due to its antifibrinolytic effect (Figure 3), although there is insufficient evidence to indicate any additional benefit when used in conjunction with other local haemostatic measures.¹⁰

All patients should be given comprehensive post-operative instructions with particular emphasis placed on avoiding early mouth rinsing, physical activity, hot drinks, alcohol and smoking, and dislodging the blood clot. Patients with an increased risk of bleeding should avoid taking non-steroidal anti-inflammatory drug (NSAID) analgesics, due to their antiplatelet effect. Safety netting involves ensuring the patient knows how to apply a gauze pressure pack, for 20 minutes, in the event of bleeding, and how to access urgent care if this measure is unsuccessful.

For those patients being treated in the hospital setting, with the highest bleeding risk, consideration can be given to constructing a preformed vacuum splint, worn for 48 hours to protect the extraction socket while the clot is stabilizing.¹⁴ For some patients, a prolonged period of post-operative observation or inpatient management may be necessary.⁸

Management of post-operative bleeding

Patients who report concerns about bleeding should be seen as a matter of urgency. If a large volume of blood loss is suspected, from the history or examination, or there is any evidence of haemodynamic instability, urgent hospital referral is required.

The patient's mouth should be gently cleaned, with suctioning and saline irrigation, and pressure applied at the site of bleeding with a damp gauze pack. The history of the acute bleed, medical and drug histories and any history of previous excessive bleeding can then be confirmed with the patient. Administration of local anaesthetic is beneficial due to the vasoconstriction effect. Any large, exophytic blood clots and previously placed sutures or haemostatic packs should be removed to determine the source and extent of bleeding underneath. Soft tissue bleeding can be arrested by suturing or judicious use of diathermy. Bone bleeding from a nutrient vessel can be managed using bone wax, or by gently crushing the trabeculae against the bleeding vessel using a blunt instrument. Generalized bleeding from an extraction socket can usually be successfully managed by irrigating the socket with tranexamic acid 500 mg/5 ml, packing with a haemostat, such as absorbable oxidized regenerated cellulose, and suturing of the socket. A gauze pressure pack, soaked in tranexamic acid, can then be applied. In the authors' experience, if a gauze pressure pack is unsuccessful, haemostasis can often be achieved by asking the patient to bite on a damp tea bag. This is presumably due to the astringent and anticoagulant effects of tannins¹⁵ and the ability of the loose tea within the bag to better conform to the morphology of the socket, so that a more even pressure is applied.

Any difficulty in achieving haemostasis with local measures, or repeated attendance due to bleeding, should prompt referral for haematological investigation and management in secondary care.

Normal wound healing process following minor oral surgery (MOS) procedures

Healing can be via primary or secondary intention. In healing via primary intention, there is no loss of tissue. All tissue is replaced in the same anatomical position or approximated to cover the underlying surgical site. Secondary intention healing occurs where there is incomplete coverage of the site with epithelialized tissue. Normal wound healing is an intricate process and involves a number of steps.^16,17

Delayed healing following MOS procedures

Healing following minor oral surgery is generally an uncomplicated process, but there are a number of aetiological factors that can contribute to delayed healing of intra-oral surgical sites. Initial presentation of a patient with symptoms of poor healing is usually to the primary care practitioner. It is, therefore, important to be aware of the aetiology and clinical signs and symptoms that require further investigation and appropriate referral for management.

Disturbed wound healing has a variety of clinical manifestations (Table 4).

Causes of delayed or non-healing

The disturbance of the normal physiological process of healing can be influenced by local or systemic factors. Local factors directly affect the surgical site. Systemic factors are related to medical conditions and medications that affect the patient's ability to heal (Table 5).

Identifying patients at increased risk of delayed or non-healing

A thorough history is important in identifying which patients are at increased risk of delayed or non-healing sites following surgery. The presenting complaint and symptom history can highlight symptoms of concern, such as altered sensation in the distribution of the inferior dental or infra-orbital nerves, which can be indicative of a more sinister cause. The history should include previous experience of delayed healing or dry socket.

The medical history is an integral part of identifying those at risk and should be updated at every visit. Important aspects to identify in the medical history include a history of malignancy, including oral cancer and treatment with radiotherapy to the head and neck region. This will provide information about the risk of osteoradionecrosis (ORN), trismus and fibrosis of tissue exposed to radiation.¹⁸ Oral metastasis from primary tumours, in particular lung, kidney, liver, prostate, breast, ovarian and colorectum, are rare but can manifest intra-orally as rapidly progressing swellings, with pain and paraesthesia. Patients undergoing current or maintenance oncology chemotherapeutic regimens are at risk of bone marrow suppression and resultant thrombocytopenia and neutropenia, which impair blood clotting and increase risk of infection, respectively.^8,18 Metastasis to the liver alters hepatic function and subsequent production of clotting factors, which increases bleeding tendency. Oncology patients, with skeletal metastasis or multiple myeloma, are prescribed regular intravenous bisphosphonates or denosumab for management of skeletal-related events, and are at risk of medication-related osteonecrosis of the jaw (MRONJ). A number of the new generation of novel targeted chemotherapies, used in the oncology setting, have been linked with MRONJ.^19,20 These novel agents and steroids are also used to treat autoimmune and inflammatory disorders. They target mediators involved in the inflammatory process and patients are at increased risk of post-operative infection. Liaison with the prescribing practitioner, for dose alteration prior to procedures, may be required. Long-term steroid therapy has a number of adverse effects, including osteoporosis. Clinicians should be aware that patients may be prescribed concomitant bisphosphonates for the prevention of this condition. Elderly patients have an impaired healing capacity and polypharmacy can frequently include a weekly oral bisphosphonate, annual intravenous bisphosphonate or 6-monthly denosumab subcutaneous injection for osteoporosis. Impaired wound healing is also well documented in diabetics, in whom defective collagen production and macrophage disruption prolong the inflammatory phase.¹⁷

The social history highlights oral cancer risk factors, for example tobacco use and excess alcohol consumption. Intravenous drug users may be exposed to viral hepatitis, which can have an adverse effect on liver function.

Imaging identifies the proximity of the teeth to anatomical structures (eg the maxillary sinus) and risk of an oro-antral communication, proximity to the inferior border or angle of the mandible and risk of fracture, size of the maxillary tuberosity, tooth morphology and complexity of the procedure. It is important for the operator to ensure good surgical technique, availability of equipment, including appropriate surgical handpieces with copious irrigation, and a suitable setting for the surgical procedure, to minimize the risk of post-operative infection. Underlying pathology can present as radiolucencies that can be indicative of cystic lesions or benign tumours, which require enucleation or biopsy. Florid cemento-osseous dysplasia can present as multiple radiopaque masses, throughout the jaws, associated with the teeth. Osteomyelitis can ensue following removal of a tooth in affected patients.

Management of patients at increased risk of delayed or non-healing

Patients who have been identified as being at risk of post-operative complications, such as oro-antral communication (OAC), fractures or retention of suspected cystic radiolucent lesions, and subsequent delayed healing, warrant referral to an oral surgery setting. Following the Montgomery ruling in 2015, informed consent should include the potential risks of the proposed treatment and of any alternative treatment options for the individual patient. Diagnostic imaging includes DPT and CBCT to aid surgical planning. For patients at risk of fractures, provision of a fracture kit may be required, or opting for a coronectomy can improve force distribution and reduce the need for extensive bone removal. For those at risk of tuberosity fracture, or with complex root morphology, planned sectioning of roots, operator experience and available splinting options should be considered.

For patients exposed to radiation of the head and neck region, minimizing invasive intra-oral surgical intervention, retention of teeth and dental health are important to reduce the risk of an ORN. There is some controversy around the prophylactic removal of molars prior to radiotherapy, and this has been noted as a cause for ORN, where the expedition of radiation therapy treatments exposes recent extraction sites to high-dose radiotherapy.²¹ The incidence of ORN following extractions is about 5%²² and the mandible is more frequently affected than the maxilla.²³ Referral to a hospital setting is recommended if a dental extraction is required. The dose and number of fractions are established. There is an increased risk of ORN for administered doses greater than 60 Gy. Intensity-modulated radiation therapy (IMRT) targets radiotherapy to the site of the tumour and reduces subsequent effects of post-operative fibrosis on the surrounding tissue. In 2004, Delanian et al suggested a new theory for the pathophysiology of ORN.²⁴ Trabecular bone is devitalized by radiation-induced endothelial damage, either directly or indirectly, via several harmful events triggered by reactive oxygen species. These cause an imbalance between tissue degradation and synthesis, generating hyalinization and fibrosis of the medullary spaces and radiation-induced scar tissue. Over the years there has been increasing interest in possible ways of preventing ORN with pentoxifylline and tocopherol (vitamin E), which work synergistically as potent anti-fibrotic agents. Evidence is growing for their use, and some units include prescription of 800 mg pentoxifylline and 1000 units tocopherol (vitamin E) daily,¹⁸ with oral antimicrobials and a chlorhexidine digluconate or hydrogen peroxide mouthwash, before and after planned dental extractions.

Oncology patients under current chemotherapeutic regimens are myelosuppressed, and liaison with the oncology team is required, prior to any invasive dental procedures. Only emergency procedures should be considered, and these should be carried out in a hospital setting. The oncology team will advise on the frequency of cycles, optimal timing for treatment, the need for antimicrobial prophylaxis and haematological support. The effects on the bone marrow usually begin around 7–14 days after each treatment. Blood counts are at their lowest at this stage, which is called a nadir. They usually return to normal between days 21 and 28.²⁵ Treatment is usually recommended at this time, or towards the end of a cycle. An FBC is required no longer than 1 day prior to an invasive dental procedure, to assess platelet and neutrophil counts. Some hospital units advise platelet levels should be at least 50 × 10⁹/L and neutrophil counts above 1.0 × 10⁹/L for a limited amount of invasive dental treatment. However, RCS guidelines recommend platelet counts should be >60 x 10⁹/L18 for oncology patients prescribed chemotherapy treatments. This threshold of thrombocytopenia differs from that, in an otherwise healthy patient, mentioned previously. A liver profile and coagulation screen (INR and APTT) are additionally required in cases of metastasis to the liver, because hepatic dysfunction can have an adverse effect on coagulation, as well as causing thrombocytopenia. The increased risks should be clearly identified and recorded, in accordance with the LocSSIP,¹³ and correspondence from oncology teams included in the patient records. Local haemostatic measures, oral antimicrobial prophylaxis and an antimicrobial mouthwash are recommended post-operatively. Comprehensive post-operative instructions should be given, with particular emphasis on when and where to seek help for an acute infection, to prevent a neutropenic sepsis. Bone marrow changes are present until 4 weeks after completion of chemotherapy treatment.¹⁸ Patients may be due for preventive and adjunctive regimens, which can include bisphosphonates, denosumab and anti-angiogenic maintenance therapies. Primary care practitioners have an important role in providing maintenance of oral health for these patients during and after treatment.

For patients at risk of MRONJ, stratification of risk is based on the type, dose and administration route of anti-resorptive medication. Patients with high cumulative doses and long duration of nitrogen containing IV bisphosphonates, denosumab or anti-angiogenic medications, in a cancer setting and with a previous diagnosis of MRONJ, are considered to be at higher risk of developing MRONJ.^27,28,29,30 Dento-alveolar treatment in these patients has been reported as the main local risk factor.^27,28,29 However, there is a growing body of evidence, which suggests that existing dental or periodontal infection, rather than extraction, might, in fact, represent the main local risk factor.³⁰ Referral to an oral surgery or maxillofacial unit should be considered, if an extraction is indicated and all other treatment alternatives have been explored.²⁸ The risks and benefits of surgery are included in the consent, and the risk of MRONJ is documented on the LocSSIP form. Suggested interventions for the prevention of MRONJ include oral antimicrobials, antimicrobial mouthwash, administered before and after surgery, and insertion of plasma rich in growth factor (PRGF) into the post-extraction socket.¹⁸ Extractions should be carried out with minimal trauma, in a surgical setting, and some groups recommend smoothing of sharp bone edges, alveolectomy, flap mobilization and primary, tension-free closure of the socket, so that all bone is covered.³⁰ Patients should be closely monitored post-operatively, and avoid wearing dentures that are in contact with the surgical site, until healing is complete. Evidence for interruption to anti-resorptive treatments, or ‘drug holidays’, is weak, although the effects of denosumab are reversed faster on suspension of treatment, than those of bisphosphonates which remain bound to bone for many years. Any cessation of medication should be discussed with the patient's medical team. The National Institute for Health and Care Excellence (NICE) has incorporated an adjuvant IV bisphosphonate as part of treatment for early and locally advanced breast cancer.²⁶ Patients being treated for osteoporosis or other non-malignant bone disease can be prescribed low-dose IV regimens of bisphosphonates quarterly or annually, a weekly oral bisphosphonate, or subcutaneous denosumab injection 6-monthly. Patients who have used oral bisphosphonates for less than 4²⁷ or 5²⁸ years, with no concomitant steroids or immunosuppressants, are at a lower risk of MRONJ, and any extractions or bone-impacting procedures can be treated in a practice setting, as recommended by SDCEP guidance.²⁸

Management of patients with non-healing sockets

Patients who report concerns regarding delayed healing, following a dento-alveolar procedure, should be seen promptly. A thorough history will highlight symptoms and aspects of the medical history of concern. The area being examined should be handled gently. Significant post-operative discomfort may require local anaesthetic for symptom relief and examination of the area.

A dry socket (alveolar osteitis), although not a causative factor, is a common presentation of poor wound healing following a dento-alveolar procedure. The patient will present with a dull throbbing pain, usually 2–5 days post-operatively. Clinically, there will be absence of a blood clot, a bad taste and malodour will be apparent, and there will be food debris in the socket. A medicated dressing is placed in the socket, which usually provides symptom relief, and appropriate analgesia is prescribed.

Infection can present from a few days to a few weeks post-operatively, with increasing swelling, trismus, erythema, pyrexia and malaise. Management with systemic, broad-spectrum antimicrobials is required, and may be supplemented with antibiotics that target Gram-negative anaerobes. Concern regarding airway compromise should prompt urgent referral to hospital for IV antibiotics, incision and drainage, and removal of the source of infection.

Granuloma formation overlying the socket may be indicative of small fragments of socket bone that exfoliate or tooth remnants that work their way through the mucosa following an extraction. Plain films will confirm the presence of bone or tooth spicules, which can be treated with curettage or reflection of overlying tissues and removal of fragments.

Exophytic mucosal growth or a local soft tissue mass with enlarged, fixed, regional cervical lymph nodes, can indicate malignancy, such as squamous cell carcinoma (SCC), lymphoma or distant metastasis. Radiographic signs of malignancy include atrophy of the cortical lamina, osteolytic defects, ragged socket outline or loss of support of adjacent teeth at later stages. Patients require referral to the appropriate oral and maxillofacial unit via the suspected cancer pathway, and are seen within 2 weeks.

The course of treatment for exposure of the maxillary sinus during a procedure is determined by the size of the defect. For small defects, absorbable oxidized cellulose can be placed at the base of the socket and an oro-antral regimen followed to include prevention of pressure increase in the sinus (ie avoidance of sneezing or nose blowing), antibiotics and a nasal decongestant for 7 days. For larger defects, closure with a buccal advancement flap, or construction of an obturator, minimizes the risk of sinusitis developing.

Fracture of the maxillary tuberosity can occur on extraction of an upper wisdom tooth, frequently causing a tear in the palatal mucosa. It is important to ensure that the tooth and bone are carefully dissected from the attached mucosa, so that the soft tissue can be realigned over the defect and sutured. Supplemental local anaesthesia is usually required, as removal of the tuberosity causes significant discomfort for the patient. A flexible splint is rarely effective and access for rapid construction of a vacuum/pressure-formed splint may be necessary, to allow healing and surgical removal in the future.

Currently, there is no standardized protocol for the management of ORN. CBCT imaging reveals the extent of necrosis, evidence of sequestrum formation and pathological fractures and provides an imaging baseline for monitoring disease. There is a developing evidence base for the synergistic effects of 800 mg pentoxifylline and 1000 units tocopherol (vitamin E) daily,¹⁸ as a possible way of managing ORN. For symptomatic ORN, broad-spectrum, high-dose systemic antimicrobials are prescribed, for example amoxicillin with clavulanic acid, in addition to chlorhexidine digluconate mouthwash. Surgical intervention includes sequestrectomy, with sampling for histopathology to confirm non-malignancy, and microbiology for culture and sensitivity, to determine optimal antimicrobial therapy. Late-stage or chronic disease, with invasion into adjacent anatomical sites, may require resection with microvascular reconstruction.

The main goal of therapy for patients with MRONJ is preservation of quality of life (QoL), while supporting oncology or osteoporosis treatment, by controlling pain and secondary infection and preventing further development of necrosis. The American Association of Oral and Maxillofacial Surgeons (AAOMS) has previously recommended a stage-specific management approach²⁷ and an updated position paper on management strategies is being finalized. Pain and infection can be managed with a conservative approach, which includes maintenance of optimal oral hygiene, analgesia, antibacterial mouthwash and systemic antimicrobials. The microbes involved have been shown to be sensitive to penicillin. Alternatives for penicillin-allergic patients include the quinolones, clindamycin, doxycycline, erythromycin and metronidazole. Conservative management can be a good option for patients unwilling to undergo invasive procedures or when their condition does not allow for further surgery. Overall consideration should be given to the goals of surgery, the oncology prognosis, quality of life during recovery, risk of failure and complications. The European Task Force on MRONJ has highlighted a number of controversial aspects of current knowledge and practice relating to MRONJ, including definition and classification, risk factors and management. More recent studies have reported successful outcomes with early surgical interventions, including sequestrectomy and debridement with tension-free closure, resection and reconstruction, removal of teeth within necrotic bone and the use of PRGF.