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

Prothrombin gene mutations can be associated with either a thrombotic or a bleeding risk. Genomic studies and coagulation workup can provide valuable information to better understand their clinical importance. We describe the case of a woman with a duplication of the entire prothrombin gene. 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 levels and ex vivo thrombin generation. Genetic analysis revealed a duplication of at least 307.9 kb (maximum 366.7 kb): arr[ChRCh38]:11p11.2(46,455,533-46,763,446)x3, encompassing the entire prothrombin gene and 6 adjacent protein-coding genes (HARBI1, ATG13, ARHGAP1, and ZNF408 completely involved, and AMBRA1 and CKAP5 partially involved). The present case demonstrated duplication of the entire prothrombin gene, associated with a significant hypercoagulable risk, a finding not previously reported in the literature.