Glanzmann Thrombasthenia: Use of the Soft Splint with Tranexamic Acid Paste to Reduce Spontaneous Oral Bleeding

BACKGROUND

Glanzmann’s thrombasthenia (GT) (OMIM–#273800) was first described by Dr Eduard Glanzmann, a German pediatrician in 1918 as “Hereditary Haemorrhagic Thrombasthenia”.¹ It is a rare inherited autosomal recessive platelet disorder with an incidence of about 1 in 1,000,000.² High incidence rate is found to be in consanguineous populations like French Gypsies, Iraqi Jews, Jordanian Arabs, and South Indians where intermarriage is common.³ Both the genders are equally affected since the gene responsible for GT is carried on the long arm of chromosome 17 (17; q 21–22) one of the 22 pairs of autosomal chromosomes, in humans.⁴

Glanzmann thrombasthenia is a qualitative and/or a quantitative defect in the GP Ilb/IIIa glycoprotein complex.⁵ Diagnosis of GT usually occurs at a very early age due to spontaneous and unexplained bleeding. It is characterized by prolonged bleeding time, while platelet count, and morphology, as well as prothrombin time (PT) and partial thromboplastin time (PTT), remain unaffected.⁴ Key clinical features include purpura, epistaxis, gingival hemorrhage, and menorrhagia.⁶ For extraction of teeth or hemorrhage associated with loss of deciduous teeth, control of bleeding becomes a complex process. Antifibrinolytic agents, tranexamic acid had been broadly used in oral surgery. It blocks bleeding by inhibiting the degradation of the thrombus.⁷

Management of GT usually includes supportive measures and transfusions. However, repeated transfusions can lead to the development of self anti-GPIIb/IIIa antibodies making it ineffective and further complicating the treatment.⁵ Thus, the purpose of this report is to highlight the use of soft splint along with tranexamic acid paste to reduce the bleeding episodes in a 7-year-old female patient with spontaneous bleeding accompanying the eruption of teeth. The child also required multiple tooth extraction due to grossly decayed teeth. The patient was admitted to the casualty three times within 1 month due to bleeding from the oral cavity leading to hypovolemic shock owing to a severe fall in Hb levels. This case report also enlightens the need for awareness of such patients about the importance of oral hygiene maintenance and regular dental visit.

CASE DESCRIPTION

A 7-year-old female patient admitted to the pediatric intensive care unit (ICU) with a known medical history of GT was referred to a pediatric dentist for opinion and management for bleeding gums. The patient presented with a chief complaint of severe bleeding from the upper left back tooth region since the previous night. History of presenting illness revealed that the patient was apparently normal the previous day morning, after which spontaneous bleeding started by afternoon leading to severe blood loss and hypovolemic shock for which she was admitted to the ICU. Bleeding was continuous; there were no aggravating or relieving factors. Previous hospitalization history revealed she was admitted twice earlier within a period of 30 days, with a similar complaint of bleeding from the oral cavity leading to a significant decrease in the hemoglobin (Hb) levels. No dental treatment was performed in the earlier visits, as it was advised by the pediatrician to wait for a month for the complete recovery of the patient. The parent also gave a history of a similar episode of bleeding from gums, vomiting containing clots of blood 1 year back with decreased Hb level at the time of hospitalization. The patient was discharged without being referred to the dentist one year back. A family history of consanguineous marriage was present. On extraoral examination, purpuric spots were seen in the left leg along with crusting and bleeding from the lips. Intraoral examination revealed root stump in relation to 54, 65, dental caries in relation to 53, 74, 36, and mobile crown structure in relation to 75, 55. Spontaneous bleeding was evident from 54, 55, 21, 11, 12, 22, and 46 and the patient also had anterior tooth crossbite in relation to 11, 21 (Fig. 1). The provisional diagnosis was given as gingivitis and chronic irreversible pulpitis in relation to 55, 54, 65, 75.

DISCUSSION

Glanzmann thrombasthenia is a rare inherited platelet disorder that occurs due to the mutation of glycoprotein (GP) IIb–IIIa that is present on the surface of platelets.¹ The primary target area of this glycoprotein is fibrinogen, which is responsible for platelet aggregation. Thus, this condition manifests as defective platelet aggregation and decreased or absence of clot retraction, while the platelet count and morphology remain normal⁸ as observed in our case. Platelet aggregation and flow cytometry are the most important diagnostic test for this condition. In GT, platelet does not aggregate to adenosine diphosphate (ADP), thrombin, epinephrine, collagen, and arachidonic acid as these depend on fibrinogen attachment to the platelet for aggregation.³ Flow cytometry helps in detecting the quantity of the GP IIb–IIIa complex based on which GT can be classified by George et al.⁹ into three types. While GT type (I and II) have some amount of GP IIb–IIIa, patients could still have severe recurrent hemorrhagic episodes while patients with type III (inactive GP IIb–IIa) may have mild clinical manifestations. This makes both the test and classification indecisive in diagnosing the severity of the condition.⁹ The bleeding conditions are clearly defined which include purpura, epistaxis, gingival hemorrhage, and menorrhagia. Gingival hemorrhage is usually associated with poor oral hygiene and is not present in patients with regular dental visits. Although it is said to be rarely associated with major acute blood loss,⁹ it is contrary to our case report where the child suffered from acute blood loss, leading to hypovolemic shock due to poor oral hygiene. Spontaneous oral bleeding could also be associated with severely decayed teeth and eruption of permanent teeth⁹ which were contributing factors in this case leading to severe fall in Hb level. Gastrointestinal hemorrhage, hematuria, and hemarthroses have also been reported in the literature although not positive in our case.⁹

The differential diagnosis for this condition includes other bleeding disorders like Bernard–Soulier syndrome, a disorder of adhesion.⁸ The presence of normal platelet size and ristocetin-induced aggregation rules out the above syndrome.⁸ Similarly, thrombocytopenia is eliminated by normal platelet count while the presence of normal clotting factors excludes the other clotting disorders like hemophilia and Von Willebrand’s disease.⁸ Since, our case was diagnosed at 1 year of age, no test was performed at the time of admission.

Management is provided by supportive care and most importantly by hemostatic measures along with platelet transfusions.⁹ Definitive treatment is by hematopoietic transplantation (HSBT) from the siblings,¹⁰ however, due to the increased risk associated with the procedure, it is recommended only in cases of severe hemorrhage or development of autoimmunization.¹¹ Bleeding in GT is usually unpredictable⁹ and hence platelet transfusions before any invasive procedure is indicated even if minimal bleeding is expected and advised until wound healing is incomplete. Thus, platelet transfusions were performed before and after restorative procedures in our case. Traditionally after extraction, bleeding is controlled by three methods, antifibrinolytic drugs, hemostatic agents, and physical barriers. Spontaneous bleeding is usually treated by oral prophylaxis and maintenance of meticulous oral hygiene^2,5,6 which was followed in our case as well. Drugs that affect the platelet function like non-steroidal anti-inflammatory drugs (NSAID) and aspirin are contraindicated⁹ thereby, paracetamol^7,12 was used as an analgesic after extraction in our case. Tramadol⁴ is also considered an ideal analgesic that can be used safely in GT patients with severe pain.

The antifibrinolytic agents recommended for bleeding disorders are Epsilon aminocaproic acid (EACA),⁴ tranexamic acid,¹³ and desmopressin.¹⁴ Desmopressin has been tested as a therapeutic measure for GT, but due to a lack of clinical evidence in the literature, it was not used in our case.¹⁴ Tranexamic acid is a derivative of amino acid lysine. It acts primarily by blocking the lysine binding sites on plasminogen molecules. This in turn inhibits the formation of plasmin that interferes with fibrinolysis, thereby preventing the breaking down of the clot.¹⁵ Mannucci and Levi¹⁶ proved that tranexamic acid was ten times more potent than EACA. Thus, tranexamic acid was used in our case. Preoperatively, tranexamic acid mouth wash was prepared freshly and used two days before the procedure as recommended by Nuvvula et al.¹⁷ to decrease the episodes of spontaneous bleeding. After the extraction procedure, tranexamic acid was crushed and mixed with saline, and placed on a gauze piece. It was held on to the socket for 10 minutes. Coetzee¹⁸ had recommended the same procedure for a duration of 30 minutes, but due to multiple extractions in different sites, we had placed tranexamic acid only for 10 minutes. Tranexamic acid was also effectively used postoperatively and as a home remedy to stop bleeding by placing it on the splint in the area of bleeding. The commonly advocated hemostatic agents are microfibrillar collagen,¹⁹ resorbable oxidized cellulose,^4,7 and gel foam soaked in topical thrombin.⁹ In our case, resorbable oxidized cellulose (Ab foam gel) was placed inside the sockets after extraction to achieve hemostasis.

Acrylic splints^20,21 and soft splints^8,9,22 can be used as physical barriers to preserve the blood clot in its position and reduce bleeding. Due to the presence of clasp in acrylic splints that could irritate, the soft splint was used in this case. As per the evidence stated in the literature, soft splint has been used widely to act as a physical barrier after any surgical procedures in patients with GT.^8,9,22 Therefore, we developed this novel technique of using a paste of tranexamic acid (500 mg tablet powdered with mortar and pestle and mixed with saline)²³ to reduce the spontaneous bleeding, postoperatively. The patient was instructed to apply the paste on the soft splint in the area where spontaneous bleeding was occurring then place the splint intraorally and leave it in place for 30 minutes¹⁸ followings which they were advised to remove the soft splint and swallow the remaining paste. In our case report, it was noted that the patient continued to have spontaneous gingival bleeding from areas other than the extraction socket even after oral prophylaxis which could be due to the eruption of permanent teeth. This perhaps would have led to the patient requiring multiple transfusions. According to the literature, it was found that multiple transfusions could lead to the development of alloimmunization which is noted in 30 to 70% of the cases.²⁴ This is due to the development of self anti-GP IIb–IIIa antibodies⁵ which can be detected by complement fixation, ELISA, and flow cytometry,^25–28 leading to massive bleeding. This could further complicate the treatment as it makes transfusions ineffective. A case report by Ghosh et al.²⁹ performed a full mouth extraction for a patient with GT to avoid repeated transfusions, where spontaneous bleeding continued to occur even after oral prophylaxis leading to severe fall in hemoglobulin level which was similar to our case. Considering the young age of the patient, mixed dentition stage, and effects of repeated transfusions, a novel technique of using a paste of tranexamic acid did seem to reduce bleeding from the oral cavity, thus avoiding repeated transfusions.

As a home remedy measure, the patient was taught how to prepare the paste and place it on the splint. This was done as a precautionary measure, as chances of spontaneous bleeding were high due to the extraction of multiple teeth and eruption of permanent teeth. According to the guidelines,³⁰ the recommended dosage for tranexamic acid (orally) is 15 to 25 mg/kg, 3 to 4 times a day with a maximum dose of 1.5 g. Thus, the patient was advised not to use more than two tablets per day. Soft splints also have the added advantage of snugly fitting on the teeth and hence do not induce bleeding.⁹ Follow-up was done every month, and the patient gave a history of using this technique of soft splint with tranexamic acid paste twice in the first 2 months. Seven months follow-up revealed no history of any need for hospitalization.

CONCLUSION

This case report paves a way for further research to prove if this novel technique could act as an effective treatment option to stop spontaneous bleeding from the oral cavity in patients with GT. Also, as the patient was in the mixed dentition phase, soft splint aided both as a physical barrier to achieve hemostasis during extraction and during the shedding of deciduous teeth. However, the need for repeated splint fabrication is still questionable as this patient is in the mixed dentition phase.

CLINICAL SIGNIFICANCE

Due to the severity of the condition, a multidisciplinary team approach is needed comprising of pediatrician, hematologist, and pediatric dentist for effective management. Maintenance of good oral hygiene and regular dental visits could have prevented this child from requiring multiple transfusions. Hence, it is the need of the hour to create awareness among pediatricians, hematologists, and other healthcare providers about the importance of emphasizing regular dental visits to all patients with severe medical conditions. The authors also recommend that the usage of this technique could reduce bleeding in patients with other bleeding disorders.

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