Protein S deficiency in a living liver donor

Abstract

Summary Protein S deficiency is a thrombophilia associated with increased risk of thromboembolic episodes in affected patients. Traditionally, protein S deficiency in a potential donor was considered an absolute contraindication to living donor liver transplantation, both due to the increased risk incurred by the thrombophilic donor as well as the risk of transmitting the thrombophilia to the liver recipient, as protein S is predominantly produced by the liver. We present the first successful case of living donor liver transplantation using a donor with asymptomatic protein S deficiency. Interestingly, whereas the donor continued to have protein S levels approximately 50% of normal, the recipient maintained normal levels of protein S post‐transplant, potentially due to compensation by extra‐hepatic protein S production. We discuss the prior literature of protein S deficiency acquired via liver transplantation, and we evaluate potential criteria by which the safety of transplants utilizing this pool of donors may be enhanced.

Evaluation of donor workups and exclusions in a single‐center experience of living donor liver transplantation

“…Nine potential donors with hypercoagulability risks were excluded in our series. Six cases were related to a low level of protein S or protein C. Kitchens et al reported a successful LT with a graft from a donor with low protein S level . Preservation of normal protein S level in the recipient and the intermediate deficiency state (>40%) were thought to be the reason of this success.…”

“…Six cases were related to a low level of protein S or protein C. Kitchens et al reported a successful LT with a graft from a donor with low protein S level. (29) Preservation of normal protein S level in the recipient and the intermediate deficiency state (>40%) were thought to be the reason of this success. They applied a strict protocol with venous thromboembolism prophylaxis and administration of 4 units of daily fresh frozen plasma until postoperative day 5.…”

Cardiovascular disease risk in patients receiving organ transplantation: a national cohort study

“…As complex and unpredictable in onset and severity, a few risk factors for venous thromboembolism after liver transplantation were identified, for example, prolonged immobilization, administration of excessive procoagulant factors, and peripherally inserted central catheter lines [14,15]. Other factors involved defects in the proteins that normally regulated anticoagulation, such as protein C, protein S, and antithrombin deficiency, transmitted from donors to recipients [29][30][31][32], and this can be missed Similarly, kidney and heart transplant recipients have been reported to be at risk of venous thromboembolism as mentioned previously [16,18,[33][34][35]. In heart transplant recipients, Elboudwarej et al [19] even demonstrated that lower extremity DVT posed a high risk of pulmonary embolism and death despite use of thromboprophylactic regimens.…”

“…As complex and unpredictable in onset and severity, a few risk factors for venous thromboembolism after liver transplantation were identified, for example, prolonged immobilization, administration of excessive procoagulant factors, and peripherally inserted central catheter lines . Other factors involved defects in the proteins that normally regulated anticoagulation, such as protein C, protein S, and antithrombin deficiency, transmitted from donors to recipients , and this can be missed preoperatively if donors were not screened for thrombophilic abnormalities.…”

Donor genetic variants as risk factors for thrombosis after liver transplantation: A genome-wide association study

“…The potential reason for a non-thrombotic phenotype in the latter report could be the compensation by extra-hepatic protein S production in the recipient. 42 This underscores the difficulty of thrombophilia screening, especially in the context of live liver donation.…”