PS is a vitamin K-dependent protein produced in the liver and augments the effect of PC to inhibit activated coagulation factors V and VIII. Hence, PS acts as an anticoagulant factor . The PS activity level is affected by hepatic or renal disorders, vitamin K antagonist (warfarin), chronic infection, pregnancy, disseminated intravascular coagulopathy, and other conditions, all of which results in acquired PS deficiency . The incidence of PS deficiency in patients undergoing cardiac surgery reportedly ranges from 0.03 to 0.13% . Because of this rarity, little evidence is available regarding avoidance of thromboembolism in patients with PS deficiency who undergo cardiac surgery.
Prophylactic anticoagulation therapy is recommended for PS deficiency patients exposed to surgery . CPB may trigger consumptive coagulopathy because the blood is in contact with the surface of its circuit . Thus, PS deficiency patients who undergo cardiac surgery involving CPB have a significantly increased risk of thrombosis. However, heparin must be discontinued intraoperatively to avoid hemorrhagic complications, necessitating other anticoagulants during the period of heparin cessation.
No purified form of PS is available for clinical use. FFP is the only agent that can enhance the level of PS . Hsu and Despotis  described two patients with PS deficiency who underwent CABG, and FFP was transfused as the priming fluid of CPB. Balan  transfused FFP during the pre-bypass period and added more FFP for CPB priming. Neither of these reports focused on transfusing FFP during the period of heparin cessation. In these cases, FFP was not administered after protamine, increasing the potential risk of thrombosis. Our case is unique in that FFP was administered at pre-bypass and after protamine, while targeting two heparin cessation periods.
We did not measure the plasma PS level perioperatively because we assume that measurement of this parameter is problematic. First, it takes approximately 2 to 4 days to measure the PS level in our institution, making it difficult to adjust the volume of FFP while monitoring the PS level in real time intraoperatively. Second, approximately 60% of PS antigen is bound to C4b-binding protein (C4bBP) . Acute inflammation triggered by CPB can result in an increase of C4bBP, which may lead to a reduction in free PS antigen by increasing its binding to C4bBP [1, 4]. In that case, a low level of free PS antigen does not necessarily indicate a shortage of FFP volume. Third, in our institution, the results of both PS activity and antigen are shown as a percent, whereas the cut-off value of the PS level shown as a percent for identification of the risk of thrombosis has not been fully elucidated. Lijfering and Pintao [7, 8] described the cut-off value of the free PS antigen level, but their data are presented in units of U/dL. The difference in units makes it difficult for us to refer to their data. Finally, Haubelt  described a wide variety of PS values contained in FFP, resulting in various increases in the plasma PS level after FFP infusion. Therefore, even if the cut-off value of PS is clarified, the volume of FFP needed to achieve an adequate PS level above the cut-off value would be difficult to predict.
The thrombin generation assay (TGA) (Technoclone GmbH, Vienna, Austria) evaluates procoagulant-induced thrombin generation and anticoagulant-induced thrombin decay . The peak height, which represents the highest thrombin concentration, rises in a hypercoagulable state and falls in a hypocoagulable state. Heger  reported that the peak height decreased as the plasma PS level increased. Based on this finding, the TGA may be beneficial in that it can help to identify the real-time effect of FFP administration on PS level and clarify the most appropriate times and volume of FFP administration in PS deficiency patients. Unfortunately, application of the TGA is limited to laboratories in Japan. Although the clotting time, one of the parameters of rotational thromboelastometry (ROTEM; Pentapharm GmbH, Munich, Germany), had correlation with the PS level , its clinical usefulness for PS deficiency patients is not well known.
Patients with PS deficiency have historically received warfarin as an anticoagulant therapy . However, warfarin decreases the PS level and potentially induces a hypercoagulable state, resulting in skin necrosis . Xa inhibitors have been considered as potential alternative drugs . Martinelli  described that skin necrosis disappeared after warfarin was altered to rivaroxaban. Little available evidence shows that Xa inhibitors are safer than warfarin with respect to skin necrosis .
Villacorta  reported a case of intraoperative graft thrombosis in a patient with PS deficiency after administration of protamine. The author recommended the use of a lower dose of protamine to avoid thrombosis. Our patient was administered 3 mg/kg of protamine, the typically administered dose, and no graft occlusion occurred. This outcome indicates that administration of FFP to augment the PS level may have a beneficial effect on avoiding graft thrombosis after protamine infusion.