Special care dentistry: part 1. dental management of patients with inherited bleeding disorders

Clinical manifestations of inherited bleeding disorders

Ecchymoses are bruises due to larger extravasations of blood and can measure greater than 1 cm. Inherited coagulation defects, such as haemophilia, usually present as ecchymoses where bleeds occur in muscle (haematoma) or in joints (haemarthrosis – Figure 2). Recurrent bleeds in joints in severe haemophiliacs can cause joint deformity, and some severely affected haemophiliacs may have had joint replacement surgery.⁷

Marfans syndrome

This is an autosomal inherited connective tissue disorder with skeletal, ocular, cardiac and dermatological malformations.⁸ Prevalence is 2–3 per 10,000 and affects both sexes equally. It is the most common genetic connective tissue disorder. There is usually great variation in the phenotype within families with the same genetic condition. The diagnosis for Marfans syndrome is usually clinical. The following are affected:

The condition can be asymptomatic, although patients are usually longer and thinner than average. Fingers and toes are also usually long and thin and patients may not be aware of a bleeding problem.

Osler–Weber–Rendu syndrome

This is also known as Hereditary Haemorrhagic Telangiectasia (HHT/HHT1).

This is a hereditary condition due to a gene mutation. It is inherited as an autosomal dominant trait with a high penetrance, as 97% of people affected exhibit symptoms.⁹ The prevalence is between 1 in 5000 and 1 in 8000 of the population. There is vascular dysplasia leading to a telangiectasia (small dilated blood vesssels) and arteriovenous malformations in the skin, mucosa (which can be evident on extra-oral examination) and viscera. Interestingly, the condition usually first presents in adolescence. Most people (62%) are diagnosed by the age of 16, with over 90% of cases presenting with recurrent epistaxis. The nasal mucosa, lips and tongue usually develop mucocutaneous lesions which are sharply demarcated red-papular, macular or spider-like lesions and could help to alert a clinician about problems if invasive procedures were carried out. These lesions can also occur in the conjunctiva, upper respiratory tract, gastrointestinal tract, bronchi, brain and the liver. Cutaneous telangiectasia does not present until adult life. Investigations include capillary microscopy, computerized tomography (CT), magnetic resonance imaging (MRI) and angiography. The differential diagnosis is von Willebrand's disease.

Ehlers-Danlos syndrome

This is a rare autosomal dominant condition which occurs in 1 in 5000 live births. There is disruption of proteins leading to fragile connective tissue and causes laxity of joints or ligaments, as well as fragile skin.¹⁰ It usually presents as ready bruising (due to abnormal bleeding), dissecting aortic aneurysm (at an early age), joint laxity and hyperplasticity of skin. Diagnosis is usually based upon the clinical presentation.

Dental management for vascular disorders

Vascular disorders rarely cause bleeding problems and can be managed in primary care. However, it is important to aid haemostasis by using thorough local measures such as applying pressure, suturing, using haemostatic agents and delivering routine post-operative instructions, both verbally and in writing.

Inherited qualitative platelet abnormalities

In inherited qualitative platelet abnormalities, the platelet count, which is taken as part of a Full Blood Count (FBC) test, is normal but the bleeding time is prolonged, as it is platelet function that is impaired (Table 1).

von Willebrand's disease

Haemophilia A

Haemophilia A has a prevalence of 1 in 10,000 people and is inherited as a sex–linked recessive trait and therefore affects males.^7,14 However, spontaneous mutations may still occur as 150 point mutations have been characterized. In a third of cases there is no family history. Although females are carriers of the condition, they may still exhibit symptoms of haemophilia and may require haemaotological management through a Haemophilia Reference Centre prior to any invasive dental procedures requiring surgery or extractions, depending on their Factor VIII levels. It is also important to know that haemophilia can also be acquired in later life, but this is extremely rare.

In haemophilia, the diagnostic laboratory findings can be summarized as a prolonged activated partial thromboplastin time (APTT), normal bleeding time and low Factor VIIIc levels (Table 1).

Haemophilia presents as bleeding into muscle or joints (Figure 2). In severe cases, where haemarthrosis is recurrent, joint deformity may necessitate joint replacement. More seriously, a cerebral bleed after a mild injury can lead to fatal complications. In some cases, post extraction haemorrhage can lead to a diagnosis of haemophilia. Initially, vascular and platelet responses of the haemostatic process operate and bleeding stops, but then there is oozing from the extraction site due to absence of clotting factor. Bleeding into the larynx or pharynx after inferior dental nerve block administration can obstruct the airway with fatal consequences.⁷

Hepatitis/HIV

Treatment with contaminated plasma products before 1990 resulted in increased rates of Hepatitis B and C viruses, as well as HIV. The World Federation of Haemophilia¹⁸ conducted a global survey and found that, while 31% of haemophiliacs died from bleeding episodes, a further 20% died from AIDS-related illness and 13% from liver disease. Stigma-associated with blood-borne viruses is a well recognized barrier to care for these patients, despite clinicians being advised to follow universal infection control guidelines.

Problems of Hepatitis C and HIV with regards to dental management include:

Therefore, patients who have moderate to severe haemophilia, with complications from co-infection, are best managed in a specialist setting, depending on dental treatment required.

Inhibitors

Inhibitors are auto-antibodies to Factor VIII. Their development remains a major complication in the management of Haemophilia A and has an impact on success as well as the cost of treatment.¹⁹ Inhibitors are more likely to develop in people with severe haemophilia. Both environmental and genetic factors have been implicated in playing a role in inhibitor development.^20,21

It is vital to ask the patient when taking a history if the patient has inhibitors and, if so, to find out how the patient was dentally managed previously. The haematologist must always be consulted and patients with inhibitors must be treated with caution when carrying out surgical treatment, including administering inferior dental nerve block injections. Traumatic procedures must be avoided unless absolutely necessary.

In patients requiring invasive treatment, Human Factor VIII Inhibitor Bypassing Fractions (FEIBA) can be administered intravenously prior to treatment. These bypassing fractions work by activating Factor X directly, thus bypassing the intrinsic pathway of the clotting cascade altogether. Unfortunately, these products can cause uncontrolled coagulation leading to thromboses. An alternative is to administer 1000,000 units of activated Factor VIIa (Novoseven) which directly acts on the surface of platelets. Using additional haemostatic adjuncts, such as Tisseel (a highly concentrated combination of fibrinogen, thrombin and Factor XIII, which crosslinks the clot), together with topical tranexamic acid, helps to stabilize the clot post-operatively. These products are not readily available in primary care and therefore these patients are usually best managed in a hospital setting. Platelets may also be administered to aid haemostasis. Patients with inhibitors require careful post-operative follow-up care.

Mobility

Access and mobility problems may exist as a result of joint deformity, which is common in severe haemophiliacs. This is due to recurrent bleeds into joints (haemarthrosis – Figure 2) and is a main reason why some haemophiliacs give themselves Factor cover at home prophylactically. It is not uncommon for some haemophiliacs to have prosthetic joint replacements. Joint problems can restrict mobility and therefore clinicians need to be aware of how best to accommodate this group of patients (Figure 2).

vCJD if blood transfusions have been received

It is known that batches of products to treat Haemophilia/von Willebrand's disease have been made from the blood of donors who have been diagnosed later with vCJD.²² People who have received British blood products between 1980 and 2001 are at risk. There has been a recent identification of CJD in a patient with haemophilia where Factor VII concentrates from human plasma have been implicated as a likely cause. Fortunately, dentistry is classified as a low risk procedure and universal infection control precautions apply.

Prevention

Prevention should be started as early as possible in childshood when the teeth begin to erupt. Early prevention will help to reduce the need for dental treatment in the future and hence the need for repeated cover, which is not only uncomfortable for the patient, but is also costly, and repeated cover can lead to the formation of inhibitors, especially in younger patients. It is important to institute the use of fluorides from childhood, fissure sealants/preventive resin restorations and to emphasize the importance of sugar restriction, good oral hygiene and regular check-ups from an early age. An orthodontic assessment should also be carried out at an early stage to predict any future problems, such as overcrowding, which might be avoided. It is vital that patients discharged from paediatric dental services are seamlessly transferred to adult special care services for continuity of care.

Pain and anxiety control

Anxiety and drug dependence have been mentioned as one of the main barriers to managing patients with congenital bleeding disorders. Means of control include:

Conservation and fixed prosthodontics

Katz and Terezhalmy²⁹ stated that certain precautions, such as application of rubber dam and careful placement of the clamp avoiding soft tissue trauma, as well as careful placement of matrix band, can minimize bleeding. High-speed suction should be used with caution to avoid mucosal trauma. Conservative extension of gingival margins and supragingival crown preparations should be considered, where appropriate. Tranexamic acid can be used topically to control any local bleeding. Non-metal impression trays can minimize soft tissue trauma. Fissure sealants should be considered at an early stage as part of the prevention regime. Trauma from a saliva ejector can be avoided by placing gauze beneath it.²⁸ The authors recommend considering the use of more acceptable pain-free restorative techniques, such as using atraumatic restorative technique (ART) or air abrasion/Carisolv™ gel, where appropriate.³⁰ Any sharp-edged restorations or dentures must be smoothed.

All patients requiring endodontic treatment should be appropriately covered for their bleeding severity and the proposed procedure. The main concern is to avoid instrumentation through the apex. Using an apex locator can reduce this. Intrapulpal anaesthesia can also help to reduce the risk of bleeding.

Periodontology

In mild haemophiliacs, scaling can usually be carried out without problems using tranexamic acid, depending on their oral hygiene and the extent of pocketing. It is possible to scale tooth by tooth in mild haemophiliacs. If in doubt advice should be sought from the haematologist. In moderate haemophiliacs, DDAVP as well as tranexamic acid might be required, if oral hygiene is poor and pockets are deep (>3 mm). Severe haemophiliacs may require Factor cover and tranexamic acid cover. Any additional treatment, such as conservation, should also be carried out at the same visit to avoid the need for repeat cover. Oraqix non-injectable anaesthetic gel, with a 2.5% Lidocaine and 2.5% prilocaine formulation, for placement with a blunt-ended needle tip into periodontal pockets prior to scaling, is a viable alternative to using local anaesthesia Any periodontal surgery would require appropriate cover, depending on the severity of the condition. A level of Factor VIII at 50–75% is necessary.

Orthodontic treatment

There is no contra-indication to having orthodontic treatment. However, care must be taken with any sharp edges to orthodontic appliances as these can induce bleeding.

Exodontia/dento-alveolar surgery/maxillofacial surgery

Extractions must be carefully planned, with appropriate special tests and radiographs having been taken at the outset to identify any other problems. When staging extractions, it is important to weigh up the risk of repeated cover and managing bleeding risk. Repeated recombinant cover has been implicated in developing inhibitors. Factor VIII levels should be 50–75%^14,29 for dental extractions or dento-alveolar surgery, which the haematologist will prescribe according to the dental treatment plan. Lingual tissues should be left undisturbed to prevent blood from tracking down the mediastinum. Local measures must be implemented with minimal trauma. Good wound cleaning and placing resorbable sutures, such as Vicryl, help to reduce the risk of further bleeding on removal as they help to stabilize the gum flap. Post-operative bleeding causing blood to track down the mediastinum is usually an indication of inadequate cover. Topical tranexamic acid can be placed into the socket to aid haemostasis. Haemostatic agents, such as Gelfoam and Instat, which are of bovine origin and contain collagen, can be used. Surgicel is of synthetic origin and mainly consists of cellulose but should be used with caution owing to its acidic pH, which can irritate the socket. Fibrin sealant, which mainly consists of fibrinogen and thrombin, can provide rapid haemostasis, as well as tissue sealing and adhesion. Owing to a concern regarding vCJD, recombinant fibrin glues are becoming more readily available.

Patients should be instructed to have a soft diet for a week following surgery. Antimicrobials are only indicated where there is a risk of infection inducing secondary haemorrhage due to enhanced fibrinolysis. The patient should be warned against any swelling, dysphagia or hoarseness, indicating haematoma formation and risk to the airway. It is important to consider compounding factors such as delayed healing, increased risk of infection and prolonged bleeding due to thrombocytopenia in some patients with HIV disease.

When planning maxillofacial surgery, Factor VIII replacement is necessary for ALL haemophiliacs at a level of 75–100% one hour post-operatively.¹⁴ Tests in addition to Full Blood Count and haemostatic screening include specific antibody tests, fibrinogen estimation, viral screen and liver function tests. Blood is grouped and cross-matched in case of an emergency.

Post-operative pain management should exclude antiplatelet analgesic drugs such as aspirin. Paracetamol or combination drugs with codeine/paracetamol may be a suitable alternative, although care should be taken when prescribing opioids for pain management after conscious sedation owing to the enhanced sedative effects following treatment on the same day.