Endodontic management of a patient with Bernard-Soulier syndrome.

Bernard-Soulier syndrome is a rare inherited disorder with giant platelets, thrombocytopenia and a prolonged bleeding time. These abnormalities are caused by genetic defects of the glycoprotein Ib/IX/V complex that constitutes the von Willebrand factor receptor on the platelet surface. We are documenting a 30-year-old female patient reported with a chief complaint of swelling in relation to right maxillary canine for 5 days. The primary treatment remains platelet transfusion. Root canal treatment was performed following platelet rich plasma transfusion. As the tooth was necrotic and had a periapical pathology post-operative bleeding was absent. The root canal treatment was uneventful and the patient was asymptomatic. Optimum oral hygiene practices were emphasized to avoid dental diseases.

INTRODUCTION

Bernard-Soulier syndrome (BSS) was first recognized by two French hematologists, Jean Bernard and Jean Pierre Soulier in the year 1948 in a young male patient who has prolonged bleeding time, mild to moderate thrombocytopenia and very large platelets.[1] It is known by other names such as hemorrhagiparous thrombocytic dystrophy, congenital hemorrhagiparous thrombocytic dystrophy and giant platelet syndrome. This syndrome is extremely rare as only ˜100 cases have been reported in published articles, mostly in the populations of Japan, Europe and North America. Prevalence has been estimated at <1/1,000,000.[2] In India the reported cases are 27 until date.[3] The mode of inheritance is usually autosomal recessive with autosomal dominant pattern seen in isolated cases.

The disorder is caused by a deficiency in glycoprotein (GP) Ib/IX/V,[4] which is a protein found on the surface of platelets. The GPIb-IX-V complex is composed of 4 transmembrane polypeptide subunits, disulfide-linked alpha and beta subunits of the GPIb and the noncovalently associated subunits GPIX and GPV[5] [Figure 1]. The gene of each of the subunits has been cloned and their chromosomal locations are identified as follows: GPIb-alpha gene (chromosome 17),[6] GPIb-beta gene (22q11.2),[7] GPIX gene (3q21),[8] and GPV gene (3q29).[9] This protein is essential to the aggregation of platelets around injured blood vessels via a receptor to the von Willebrand factor (vWF) residing on the GPIb-alpha subunits This complex is involved in hemostasis. BSS can occur due to a defect in any of the subunits of the GPIb/IX/V complex. The majority of cases are due to defect in the GPIb-alpha subunit. The defect in GPIb-alpha subunit can be grouped as either qualitative or quantitative. The definitive diagnosis of BSS is made by identifying isolated defective ristocetin-induced agglutination when placed in an aggregometer. The diagnosis may be confirmed biochemically or by genotyping. Neutrophil inclusions are absent in peripheral smear in BSS.[10] Four different features of BSS may contribute to the hemorrhagic diathesis: Thrombocytopenia, abnormal platelet interaction with vWF, abnormal platelet interaction with thrombin and abnormal platelet coagulant activity.

Figure 1

Platelet glycoprotein Ib-V-IX complex (courtesy of François Lanza Université Louis Pasteur, Strasbourg, France)

Oral health care providers must be aware of the impact of bleeding disorders. In BSS patients, even the routine dental treatment cause a life-threatening situation; hence, they must be given special care. There are no documented cases of root canal treatment performed in patient with BSS. Provided herein is a case report of a female patient who presented to our department with BSS.

CASE REPORT

The present case report is about a 30-year-old female patient who reported with a chief complaint of swelling in relation to right maxillary canine for 5 days. Dental examination revealed a right maxillary canine with a deep carious lesion. The patient also gave history of episodic swelling in the involved tooth. Clinical diagnosis was pulpal necrosis with periapical abscess and sinus discharge. The patient gave a history of BSS which was diagnosed at the age of 5 years. Her parents, siblings and her children were free of BSS symptoms.

Medical management prior to dental treatment

Patient with BSS usually requires platelet concentrate supplement prior to dental invasive procedures and tranexamic acid to control bleeding post-operatively. The referring physician from Department of Hematology instructed us to give 1 unit of platelet rich plasma and Iron dextran for thrombocytopenia and anemia. The patient showed allergy to Iron dextran after a test dose so further infusion was given with Iron sucrose (4 ampules). There was a significant increase in hemoglobin level and platelet count [Table 1].

Table 1

Complete blood examination of the patient was performed before and after platelet rich plasma transfusion

After the consent obtained from the referral doctor and written consent from the patient root canal treatment was planned for the syndromic patient. A pre-operative radiograph was obtained, which showed periapical radiolucency in relation to maxillary right canine [Figure 2]. After detailed clinical and radiographic examination, the right maxillary canine was prepared for non-surgical endodontic therapy. The tooth was isolated with a rubber dam and a conventional endodontic access opening was made [Figure 3]. The working length of canal was estimated by means of an electronic apex locator (Root ZX; Morita, Tokyo, Japan) and then confirmed by a radiograph. The canals were initially instrumented with #15 nickel titanium files (Dentsply Maillefer) under irrigation with 5% sodium hypochlorite and 17% ethylenediaminetetraacetic acid. Coronal flaring was carried out by using gates glidden burs. Cleaning and shaping of the canals was done by using hand nickel titanium ProTaper file system (Dentsply Maillefer, Ballaigues, Switzerland) with a crown-down technique. The canals were obturated with AH plus resin sealer (Dentsply Maillefer, Ballaigues, Switzerland) and Gutta-percha points using lateral Products, St. Paul, MN). Amoxyllin and acetaminophen were given for the patient for 5 days. The patient was recalled after a period of 1 week and was found asymptomatic. We placed a porcelain fused to metal crown for the root canal treated tooth [Figure 4]. There was substantial reduction in the periapical radiolucency after 1 year follow-up.

Figure 2

Pre-operative intra oral periapical view showing periapical radiolucency in relation to upper right canine tooth

Figure 3

Rubber dam isolation done in the upper right canine tooth

Figure 4

Post-operative radiograph showing reduction of periapical radiolucency after 1 year following

DISCUSSION

The management of patients with bleeding disorders depends on the severity of the condition and the invasiveness of the planned dental procedure. The patients require transfusion in most cases. The benefits of receiving the transfusions must be evaluated against the risks of exposure. Repeated exposure to blood products raises concern for alloimmunization and platelet refractoriness. Factor VIIa can also be used as alternative drug regimen, but at times needs to be supplemented with platelet transfusion. This can result in a reduction in the perioperative use of blood products. However, it should be noted that factor VIIa may result in an increased risk of thromboembolic events.-[11] When platelet transfusion is planned, human leukocyte antigen matching should take place if possible. Desmopressin administration have been shown to shorten the bleeding time in some patients. As a rather simple genetic defect, BSS could be a candidate for future gene replacement therapy using virally transduced megakaryocyte progenitors.

In patients with BSS, nerve-block anesthetic injections are contraindicated unless there is no better alternative and prophylaxis is provided, as the anesthetic solution is deposited in a highly vascularized area, which carries a risk of hematoma formation.[12] Anesthetic infiltration and intraligamentary anesthesia are potential alternatives to nerve block in many cases. An anesthetic with a vasoconstrictor should compaction technique. The access cavity was then restored with posterior composite filling (P60; 3M Dental be used when possible. Alternative techniques, including sedation with diazepam or nitrous oxide-oxygen analgesia, can be employed to reduce or eliminate the need for anesthesia. The patients require infusion of 1 bottle platelet rich plasma prior to procedure and tranexamic acid post-operatively. In our case, we did not require local anesthetic infiltration since the tooth was non-vital. As no much bleeding was contemplated post-operatively, as the tooth was non-vital, we did not give tranexamic in our case. Care should be taken to avoid injuring the gingiva while placing rubber dam clamps, matrices and wedges, alternately widgets may be placed. A rubber dam should be used to prevent laceration of soft-tissues by the cutting instruments. Saliva ejectors and high-speed suction can injure the mucosa in the floor of the mouth and cause hematoma or ecchymosis; thus, they should be used carefully. A gauze piece may be placed below the saliva ejector to prevent trauma to the delicate tissues in the floor of mouth. Endodontic therapy is preferred over extraction whenever possible in these patients. Endodontic therapy does not usually pose any significant risk of bleeding and can be performed routinely.[13] Preventive and restorative dentistry are of particular importance to BSS patient since early dental treatment minimizes the need for later oral surgery. Every restoration in a BSS risk of a potential extraction. Care should be taken when prescribing drugs in BSS patients. Non-steroidal anti-inflammatory drug are contraindicated and the patient may be given acetaminophen 650 mg thrice daily. Post-operative antibiotics were advised as this will reduce the late bleeding which is due to the infection. The finish line for crown preparations for BSS patients should be preferably supragingival, so as to reduce the chances of gingival bleeding. Observation time is required for patients with bleeding disorders, it could be hours for those patients with a mild bleeding tendency whilst those with more severe conditions may require supervision overnight in hospital.[14]

CONCLUSION

The endodontic treatment in patients with BSS requires an interdisciplinary approach involving an endodontist and a physician. Adequate precautions need to be taken to prevent potential problems of hemorrhage. Drugs with antiplatelet activity are usually contraindicated. Nerve blocks must be avoided. These patients need to be educated about the disease and the need to avoid trauma. Optimum oral hygiene practices should be emphasized to avoid dental diseases.