L-asparaginase is a chemotherapeutic agent commonly used in the treatment of both adult and pediatric acute lymphoblastic leukemia (ALL). A major complication is thrombosis, resulting from reduced synthesis of proteins such as antithrombin III. Hypofibrinogenemia, also a side effect, may be a marker of thrombosis and decreased protein synthesis. A retrospective chart review of identically treated patients revealed 9 thrombotic events among 93 patients (10%), 6 (7%) occurring during treatment cycles including L-asparaginase. Twelve (13%) patients had fibrinogen levels <50 mg/dL. Of these, 3 (25%) suffered a thrombotic event. This results in a specificity of 90% and a relative risk of 10 (P = 0.014). Therefore, a fibrinogen <50 mg/dL may serve as a marker for a hypercoagulable state in ALL patients receiving L-asparaginase.