Glanzmann’s thrombasthenia: prevention of bleeding compli- cations using microfibrillar collagen and oral stints

Glanzmann "s thrombasthenia is a rare coagulation disorder characterized by impaired platelet function during hemostasis. The management of bleeding in individuals with the disease is difficult because treatment options are few and in many instances only partially effective. The management of a patient with Glanzmann "s thrombasthenia who had unremitting gingival hemorrhage is described. A microfibrillar collagen used in combination with oral splint therapy resulted in an immediate improvement in the patient’s overall condition. transfusions are capable of managing acute hemorrhage, but carry the potential for stimulating the production of antibodies which suppress the effectiveness of further platelet therapy. 6 Hemorrhage has been controlled during oral surgery without the infusion of blood or blood products using a microfibrillar collagen preparation as a local hemostatic agent, v We describe the successful use of this latter approach in .combination with oral stint therapy in a patient with GT who had unremitting gingival hemorrhage. The thrombasthenias are a group of rare coagulation disorders characterized by mucosal surface bleeding from the gingiva, nose, vagina, and anus. Laboratory investigations demonstrate a normal platelet count, but a prolonged bleeding.time, poor clot retraction, and absence of platelet aggregation. The pathophysiologic process involves a failure to form the primary hemostatic plug with abnormalities of both primary and secondary platelet aggregation phenomena. 1 In Glanzmann’s thrombasthenia (GT) platelets are of normal size, morphology, and number but have decreased amount of two specific membrane glycoproteins which may be related to impaired platelet function during hemostasis.2-4 The disease is considered to be inherited according to an autosomal recessive pattern with equal incidence in both sexes, little or no bleeding in parents, and evidence of consanguinity in_a number of reported cases. ~ Currently, there is no specific treatment for GT. Oral iron supplements and packed red blood cell transfusions are used in patients with chronic hemorrhage. Palliative measures to control bleeding are at best only occasionally effective. Epsilon-aminocaproic acid, a commonly used drug in the treatment of a number of bleeding disorders because of its antifibrinolytic action on the blood clot, has no scientific rationale in treatment because GT is a platelet defect affecting the primary platelet plug and not the fibrin deposition mechanism. Platelet Case Report Medical Evaluation A 12-year-old, 75-pound caucasian male was referred to the Pediatric Dental Center by the Department of Pediatrics. The medical assessment indicated chronic gingival bleeding and iron deficiency anemia secondary to GT. The medical history revealed that GT had been suspected since the patient was less than one year of age, but the diagnosis of GT had not been confirmed by laboratory studies until age 10 when polyacrylamide gel analysis of platelet surface proteins became available. 6 The diagnostic criteria for GT are listed in Figure 1. The patient had periodic episodes of epistaxis and oral hemorrhage since early childhood; this usually required hospitalization and treatment for severe anemia secondary to the chronic bleeding. Blood loss had been managed with whole blood,, ptatelet transfusions, and iron supplements. Also, packed red blood cell transfusions had been given unsuccessfully to maintain a hemoglobin greater than 10 g/dl. Dental Evaluation A dental evaluation consisting of a visual and radiographic examination revealed the patient to have a transitional dentition. The teeth were well aligned and the arches well occluded. Carious lesions were found in the occlusal surfaces of the four first permanent molars and the lingual surface of the maxillary left permanent cenPEDIATRIC DENTISTRY:Volume 4, Number 4 343 DIAGNOSTIC CRITERIA FOR PRESENT ~ 50G LANZMANN’S THROMBASTH ENIA LITERATURE CASE ~ Prolonged Bleeding Time + + °°-40" Abnormal Clot Retraction -+ Platelet Aggregation i the Presence of: ~ Collagen -~ 20" Epinephrine ADP Ristocetin + + o 10 Normal Platelet Count & Morphology + + Normal Prothrombin Time & Partial Thromboplastin Time + + Consanguinity/Autosomal Recessive + + Radioisotopic Analysis of Olatelet Surface Glycoproteins on Polyacrylamide Gel + + Figure 1. Diagnostic criteria for Glanzmann’s thrombasthenia. traI incisor. The mandibular second primary molars exhibited considerable root resorption and mobility. The maxillary second primary molars had moderate roDt resorption but the teeth were not yet mobile. Oral soft and hard tissues were otherwise healthy. The child’s oral hygiene was poor and the gingival tissues were erythematous and edematous. Continuous gingival marginal hemorrhage was found in the maxillary and mandibular left posterior quadrants and slight marginal bleeding was evident around the remainder of the dentition. During the three months prior to the dental examination the patient required eight to 12 units (1600-2400 cc) packed red blood cells every week for the management of anemia resulting from oral hemorrhage (Figure 2). Treatment Subsequent to the dental evaluation, a consultation with the patient’s pediatric hematologist resulted in a recommendation for dental treatment. The hematologist advised against local anesthetic injection because of the patient’s compromised hemostatic mechanism. On the day of the dental appointment, the patient received two units (400 cc) of packed red blood cells, raising his hemoglobin from eight to 10 g/dl. One hour prior to treatment a syrup containing meperidine (50 mg) and promethazine (25 rag) was given orally. During the dental procedure a mixture of 40°7o nitrous oxide/ 60% oxygen was administered. The teeth were isolated carefully with rubber dam, and restored with amalgam. Teeth were cleaned thoroughly with hand instruments, and maxillary and mandibular alginate impressions for study models were made. An acidulated phosphate fluoride gel (1.23% F ion) was applied to the teeth using styrofoam trays. At the completion of treatment, the patient was allowed to breathe 100% oxygen for five minutes and was then observed for one hour. At a 24hour postoperative appointment, gingival bleeding was evident but no worse than prior to treatment. Maxillary and mandibular soft, custom-adapted acrylic stints (mouthguards), fabricated from the study models, were inserted 24 hours after completion of the Figure 2. Units of packed red blood cells necessary preand postoperatively for the management of patient’s anemia secondary to oral hemorrhage. restorative procedure (Figure 3). A microfibrillar bovine collagen ~ was placed on the tissue surface of the stints prior to placement. Moderate pressure was used to hold the mouthguards in place until bleeding had ceased. After an observation period to ensure that hemorrhage had stopped, the amalgams were polished carefully. The patient and parents were given oral hygiene counseling which stressed extremely gentle but thorough removal of oral plaque and debris. They were instructed to wear the mouthguards initially without the collagen whenever gingival bleeding was encountered and to use the collagen with the stints only if hemorrhage persisted. The patient reported using the stints without collagen for spontaneous hemorrhage approximately once a week over a 17-month postoperative evaluation period. With the oral stint therapy and improved oral hygiene, continuous gingival bleeding was reduced to only periodic episodes (Figure 2). The patient was not hospitalized for his disease during the postoperative period and the need for transfusions was substantially reduced. Postoperative bleeding episodes were associated with the patient’s loss of the stints and the exfoliation of primary teeth, and were treated successfully with new stints in combination with the collagen.