Duplication of the prothrombin gene associated with a significant increase in thrombin generation

ABSTRACT

Background Prothrombin gene mutations can be associated with either a thrombotic or bleeding risk. Genomic studies and coagulation workup can provide valuable information to understand their clinical importance. Key Clinical Question We describe the case of a woman with a duplication of the whole prothrombin gene. Clinical Approach A 42-year-old woman presented for thrombophilia screening following a history of unprovoked arterial and superficial venous thrombotic episodes. Coagulation workup demonstrated a marked increase in prothrombin level and ex vivo thrombin generation. Genetic analysis revealed an at least 307.9 kb (maximum 366.7 kb) duplication: arr[ChRCh38]:11p11.2(46,455,533-46,763,446)x3, encompassing the whole prothrombin gene and six adjacent protein coding genes (HARBI1, ATG13, ARHGAP1, ZNF408 completely and AMBRA1 and CKAP5 partially involved). Conclusion The present case demonstrated duplication of the whole prothrombin gene associated with a significant hypercoagulable risk that has not been previously reported in the literature.