Non-functional plateletsJanuary 14, 2019
Ramana (name changed), a 14-year-old boy, was brought to Dr. Kiran Kartheek Veeranki, a leading paediatrician practising at Sravani Hospital in Guntur, Andhra Pradesh with a bleeding nose and bleeding gums. The boy complained of spontaneous bleeding in the gums and from the nose, on and off, without any external trauma for the past 2 years. In addition, he also had a history of hematoma-like swellings at the site of intramuscular injections. In the past, he had been treated with fresh frozen plasma infusions at each bleeding instance, with temporary recovery. A thorough family history revealed that two of the boy’s siblings had died a few years ago; one sibling had died due to a bleeding manifestation which was not diagnosed, and the other had died of an infection. Since the family came from a small village, exhaustive testing was limited, and a detailed history was unavailable.
Several routine tests were carried out – Ramana showed no iron deficiency, platelet counts were normal, and interestingly, prothrombin time test was also within normal limits. Bone marrow biopsy was also performed and found to be normal. In spite of the lack of positive laboratory findings, Dr. Kiran still suspected the boy to be suffering from a platelet function disorder based on the symptoms and clinical presentation. To confirm this, he convinced Ramana’s family to opt for genetic testing. Even though the genetic testing costs were high for this family, it was the only available option for a confirmatory diagnosis. Ramana’s family were looking forward to finally reaching a diagnosis, especially since they had already lost two children.
Since Ramana had been routinely given fresh frozen plasma transfusions, Dr. Kiran first requested that the child should not be given any transfusions for at least 1 month before sending the boy’s blood sample for genetic testing for a platelet adhesion disorder panel. This was done to ensure that there was no contamination from donor plasma cells during genetic testing. The results of the genetic testing revealed a mutation in the ITGB3 gene, which encodes for the beta3 subunit of a protein, integrin alpha IIb/beta3 (αIIbβ3). This protein is present on the surface of platelets and key for platelet aggregation and formation of blot clots that promote wound healing. Mutations in either ITGB3 or ITGA2B, which codes for the alpha subunit of αIIbβ3, result in a platelet function disorder called Glanzmann thrombasthenia.
Glanzmann thrombasthenia is a rare autosomal recessive bleeding disorder associated with prolonged or spontaneous bleeding and or bruising. The severity of clinical symptoms can be extremely variable. Some incur only minimal bruising, while others have severe frequent hemorrhages. The site of bleeding is distinct. Purpura, epistaxis, gingival hemorrhage and menorrhagia, rather than gastrointestinal bleeding and hematuria.
While Glanzmann thrombasthenia is very rare — affecting only one in a million individuals worldwide — it is often found clustered amongst ethnic groups in which intermarriages are common. Ramana came from a family where intermarriages are rampant, and both his parents had a single copy of the ITGB3 mutation and are carriers for the disorder. Unfortunately for Ramana, he received two copies of the mutant gene, one from his father and the other from his mother, and consequently suffers from Glanzmann thrombasthenia.
There are no known cures for such platelet formation disorders. However, Glanzmann thrombasthenia has a good prognosis if the patient is provided with careful supportive care. Local hemostatic procedures, such as compression and gelatin sponges, followed by anti-fibrinolytic drugs or platelet transfusions work well for management of minor to moderate bleeding, as in this case. Recently, recombinant factor VIIa (rFVIIa) has been shown to be effective in treating and preventing hemorrhages in Glanzmann thrombasthenia patients. However, considering the economic status of the family, platelet transfusion was adjudged the most cost-effective treatment in this case. Ramana is currently undergoing platelet transfusions as and when needed and has been coping well with his condition for the past few months. He has been advised against contact sports and the use of aspirin and non-steroidal anti-inflammatory drugs as these affect platelet function. He has also been told to maintain good oral hygiene to avoid bleeding gums. These management concepts, while critical to avoid bleeding episodes, are not a cure for the disorder, which will continue to impact Ramana’s lifestyle until a suitable cure is found.