GPVI deficiency in a 17-year-old girl, congenital or acquired?

Introduction The diagnosis of the bleeding complications causes remains a very complicated part of the diagnostic process. In particular, distinguishing whether the disorder affects primary haemostasis or the plasma factor system can be very complicated, as can the question of whether it is a congenital or acquired condition. In our case report, we demonstrate inhibition of glycoprotein VI.

Glycoprotein VI (GPVI) is specifically expressed on megakaryocytes and platelets. It is a receptor for collagen-mediated platelet aggregation. GPVI deficiency is associated with bleeding manifestations. In congenital GPVI deficiency in Gray platelet syndrome (GPS), alpha-granules do not mature in platelets, the cause being a mutation in the NBEAL2 gene. GPS is manifested by mild macro-thrombocytopenia, platelet hypogranularity and reduced aggregation after collagen. The cause of acquired GPVI deficiency may be due to anti-GPVI autoantibodies that occur in association with autoimmune diseases such as autoimmune thyroiditis, autoimmune thrombocytopenia and systemic lupus erythematosus.

Method We report an unusual case of a young girl with sudden onset of moderate bleeding. The following tests were repeatedly performed: blood count, platelet count (PLT) and morphology, PFA-200, optical platelet aggregation, anti-platelet antibody ELISA, coagulation tests, platelet glycoprotein determination by flowcytometry. Genetic testing for congenital mutations was performed.

Results A 17-year-old girl presents to the pediatric hematology department for sudden onset of excessive bruising. The patient has autoimmune thyroiditis, otherwise healthy. 14 days ago she was vaccinated with Comirnaty Pfizer against Covid 19.

Her platelet count is decreased 113; 96; 108 x10⁹/L. On microscopy, we observe hypogranular macro-thrombocytes, PFA-200 COL-EPI>300s, COL-ADP 120s pathology is present, there is very reduced aggregation after collagen 2%, positive (+) anti-PLT, positive antinuclear antibody titer 1: 80, positive anti-TPO 62.88 kU/L, positive anti-TG 281 kU/L There is significantly decreased expression of GPVI 854 sABC. Coagulation tests are without pathology. Genetic testing did not show NBEAL2 mutation.

Over 1.5 years, PLT counts have gradually normalized, but some PLTs are still hypogranular, PFA200 pathology persists, and post-collagen aggregation is no longer normal. Clinical manifestations have diminished, however, extensive bruising still forms after insult.

Conclusion On the basis of the investigations performed, we excluded congenital Gray platelet syndrome as no NBEAL2 mutation was found. We are inclined towards acquired GPVI deficiency, which is described among others in autoimmune thyroiditis. We explain the reduced PLT count by vaccination with Comirnata Pfizer, which may cause autoimmune thrombocytopenia. In combination with the reduced PLT count and reduced GPVI expression, the patient may have developed significant bleeding manifestations. After normalization of PLT, the bleeding manifestations subsided.

Publication History

Article published online:
26 February 2024