A case report of novel frameshift variant of protein S: Perioperative thrombosis triggers detection

• The patient was a case of perioperative thromboembolism. • Family history of pulmonary embolism and thrombophilic predisposition was examined. • A marked decrease in protein S activity was detected. • This could have been due to pathological factors, a thorough protein S examination including protein S specific activity was retested after the thromboembolism had resolved. • The patient and his father were novel protein S gene variants. A 53-year-old man underwent ileal resection to treat perforation caused by appendicitis. Ten days after the surgery, swelling appeared in his left lower extremity, his D-dimer level was found to be elevated, and a thrombus was found from his femoral to popliteal veins through ultrasonographic echography. A computed tomography angiogram of the chest revealed an embolism in the right pulmonary artery. The patient was referred to our department, where he was started on anticoagulation therapy and had a venous filter placed. His father had previously developed a pulmonary embolism, so the patient was therefore examined for thrombophilic predisposition. The results showed a significant decrease in protein S activity. Protein S activity, antigen, and specific activity levels were measured as part of a thorough examination of the protein after the thrombus had cleared—revealing decreased levels for all three parameters. Genetic testing revealed an abnormality in the patient’s protein S gene. The father was also found to have a similar genetic abnormality. To the best of our knowledge, this genetic abnormality was novel and had never been reported before in the literature. Protein S gene abnormality is the most common congenital type of predisposition to thrombophilia in the Japanese population, which is not the case in Caucasian ones. It is particularly important to measure not only protein S activity, but also its antigen levels, to confirm the specific activity level of protein S in patients with thrombophilia.