Protein C deficiency following hematopoietic stem cell transplantation: Optimization of intravenous vitamin K dose

Patients undergoing hematopoietic stem cell transplantation (HSCT) are dependent on iv vitamin K supplementation to prevent deficiency. Vitamin K deficiency may contribute to the development of a hypercoagulable state by limiting hepatic synthesis of fully functional carboxylated anticoagulant protein C (PC). The ratio of PC antigen (CAg) to PC measured in a clot-based functional assay (CFx) reflects the degree to which PC is carboxylated. The 133 patients undergoing HSCT received vitamin K 10 mg per week (low dose, 101 patients) or 5 mg per day (high dose, 32 patients) iv as their sole exogenous source of vitamin K. CAg and CFx were assayed before HSCT preparative regimen and again 14 days later. CAg and CFx fell significantly in both groups from day 0 to day 14 but there were no differences between the low-dose and high-dose vitamin K groups. For both groups, CAg correlated strongly with CFx at day 14 (p =0.0001). At day 14, the CAg/CFx ratio for the low-dose group was significantly greater than for the high-dose group (1.26 ± 0.4 vs 1.09 ± 0.1, p < 0.0002), suggesting that low-dose patients had a higher proportion of incompletely carboxylated PC. The CAg/CFx ratio at day 14 correlated with serum albumin for the high-dose group (p = 0.05), but not the low-dose group (p = 0.09), suggesting that the change in ratio in the low-dose group was not simply due to a lack of protein synthesis. The data suggest that the decrease in PC after HSCT occurs independently of vitamin K dose, but patients receiving daily vitamin K have less dysfunctional PC (lower CAg/CFx ratio) and therefore may have less risk of hypercoagulability. Although we did not assess the effect of other doses of vitamin K, we suggest that vitamin K 5 mg iv daily following HSCT is an appropriate dose in the HSCT setting.