Severe bleeding in a young patient with mild thrombocytopenia due to a novel mutation in growth factor inhibitor 1B

Introduction Inherited thrombocytopenia related to distinctive and clinically relevant bleeding disorder are rare diseases. Special diagnostic tools and intensive medical care are needed for these patients. Chronic thrombocytopenia is a disorder defined by low platelet count (<150.000 platelets/µl) caused by autoimmune platelet destructions or reduced platelet production by megakaryocytes. Growth factor inhibitor 1B (GFI1B) mutations have been reported to be related to thrombocytopenia and distinctive bleeding tendencies of patients.1,2 In mice, impaired erythropoiesis and thrombopoiesis were associated with GFI1B deficiency.3 A syndrome named bleeding disorder Platelet-Type 17 (BDPLT17) is rare but already reported on the Online Mendelian Inheritance in Man OMIM database.

Method We investigated global parameters of plasmatic coagulation, elisa assays, aggregometry of Born, lumi-aggregometry, flow cytometry, thrombelastografy and immunfluorescence microscopy. Genetic diagnostic has been introduced.[1] [2] [3]

Results A 27-years old woman presented to our department with suspected von Willebrand syndrome type 2B. The patient reported pronounced tendency to hematoma after minor traumas. Severe nose bleeds occurs monthly. The young woman reported also on prolonged hypermenorrhea, which was improved by oral contraception. During the removal of her wisdom teeth and a tonsillectomy, desmopressin was given to reduce bleeding tendencies. Moreover after small injuries, for example after a small mole removal on the back, severe and prolonged bleeding occured. The ISTH (International Society on Thrombosis and Haemostasis) Bleeding Score was abnormal (14 of 56 points).Thromboctyopenia (101.000 platelets/µl), which was already known, was confirmed in our tests. In vitro bleeding time was prolonged with collagen/epinephrine and in normal range with collagen/adenosine diphosphate (ADP). No quantitative or qualitative defect of the von Willebrand protein was detected. More importantly, in the aggregometry of Born no platelet aggregation was detected after induction with collagen, ADP and epinephrine in high and low concentration. Even arachidonic acid could not induce platelet aggregation. Aggregation after induction with TRAP-6 and ristocetin in concentration of 1.5 mg/ml was decreased. Adenosine triphosphate (ATP) release of platelets was decreased after adding ionophore in lumi-aggregometry. Giant platelets were detected by microscopy. Immature platelets were detected by elevated expression of CD34 by immunofluorescence microscopy and flow cytometry. Genetic diagnostic showed a heterozygous splice in intron 3 of the GFI1B gene.

Conclusion Inherited thrombocytopenia could cause low platelet count, platelets dysfunctions and severe bleeding in patients. Mutations in GFI1b are rare but already reported as being responsible for inherited thrombocytopenia. Immature giant platelets and platelet function disorders are the result of megakaryocytes dysfunction caused by the mutation in this transcription factor.

 

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Conflict of Interest

non

• References

• 1 Anguita E. ‘Transcription Factor GFI1B in Health and Disease’. JFront. Oncol 2017 7:54
• 2 Kurstjens R. et al 'Familial thrombopathic thrombocytopenia.'. Brit. J. Haemat 1968; 15: 305-317
• 3 Beauchemin H. et al ‘GFI1b controls integrin signaling-dependent cytoskeleton dynamics and organization in megakaryocytes’. Haematologica 2017; Volume 102 (03) 484-497

Publication History

Article published online:
20 February 2023