Circulating intranuclear proteins may play a role in development of disseminated intravascular coagulation in individuals with acute leukemia

Intranuclear proteins, including high mobility group box 1 (HMGB1) and histone H3, released from inflammatory cells activate platelets and the coagulation systems, leading to development of disseminated intravascular coagulation (DIC) in individuals with sepsis. These observations prompted us to hypothesize that HMGB1 and histone H3 liberated from leukemia cells undergoing apoptosis after chemotherapy might play a role in development of DIC. To test this hypothesis, we prospectively measured plasma levels of coagulation markers and intranuclear proteins in patients with newly diagnosed acute leukemia (n = 17) before and after chemotherapy. Ten of 17 patients were diagnosed with DIC at the time of diagnosis of leukemia. Serum levels of HMGB1 and histone H3 were significantly higher in patients with DIC than in non-DIC patients. Of note, seven patients developed DIC or experienced exacerbation of coagulopathy after administration of anti-leukemic agents. Intriguingly, an increase in levels of HMGB1 and histone H3 were detected in five of seven patients. These findings suggest that intranuclear proteins spontaneously released from leukemia cells may play a role in development of leukemia-related DIC. Additionally, remission induction chemotherapy causes apoptosis of leukemia cells, leading to forced release of intranuclear proteins, which may exacerbate coagulopathy.