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Early drop in protein C and antithrombin III is a predictor for the development of venoocclusive disease in patients undergoing hematopoietic stem cell transplantation.

Venoocclusive disease (VOD) of the liver remains one of the major obstacles for patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT). Many factors have been associated with the development of VOD, including a hypercoagulable state secondary to a drop in protein C and antithrombin III (AT III). We conducted a prospective nonrandomized trial to try to determine whether the development of clinical VOD was associated with a drop in protein C, protein S, and AT III. A total of 42 patients undergoing high-dose chemotherapy and HSCT were enrolled in this study. Eleven patients underwent allogeneic bone marrow transplantation (BMT) following high-dose cyclophosphamide and fractionated total body irradiation (TBI). Thirty-one patients received autologous stem cell rescue following different preparative regimens. Measurements of protein C, protein S, and AT III levels were obtained prior to conditioning therapy and weekly thereafter for 2-3 weeks. A significant difference was noted in the mean levels of protein C on day 7 between those who developed VOD and those who did not (57.5 versus 72.1, p = 0.009). Similarly, there was a significant difference in the mean levels of AT III on days 7 and 14 between the two groups (day 7, 95.5 versus 80.6, p = 0.002; day 14, 99.6 versus 85.2, p = 0.01). The drop in protein S levels on days 7 and 14 was not statistically significant between the two groups. In conclusion, the degree of drop in protein C and AT III levels on day 7 was predictive for the development and severity of VOD.