Disseminated intravascular coagulation (DIC) has been reported in 8-25% of acute lymphoblastic leukemia (ALL). Coagulopathy may accompany leukemia at diagnosis and during the induction phase and negatively impact prognosis. However, recognizing coagulopathy during this period can be challenging due to the accompanying bone marrow failure. Furthermore, distinguishing between asparaginase-associated hypofibrinogenemia and disseminated intravascular coagulation is challenging in clinical practice. It is important to determine which patients are at clinical risk and how they should be managed.

Fifty patients with ALL followed at our center, diagnosed between 16.August.2019 and 17.June.2025 were retrospectively evaluated. The relationship between the patients' coagulation parameters and clinical data at diagnosis and during the induction period was investigated.

The median age at diagnosis was 39 (18-79), and the majority of the patients were male (31/19). Nine of the patients had T-ALL, 17 had Ph-positive B-ALL, and 24 had Ph-negative B-ALL. The median follow-up duration was 15.3 (0.2-71.9) months. At the time of diagnosis, mild hypofibrinogenemia (<200 mg/dL) was detected in 8 (17%) and severe hypofibrinogenemia (<100 mg/dL) was detected in 2 (4%) patients. During the induction phase, mild hypofibrinogenemia was detected in 36 (72%) and severe hypofibrinogenemia was detected in 11 (22%) patients. No statistically significant association was found between mild or severe hypofibrinogenemia at diagnosis and induction phase with age, gender, and ALL subtype. Fibrinogen level at diagnosis was lower in patients who developed mild hypofibrinogenemia at induction phase compared to those who did not (median 278 vs. 453) (p=0.004). In patients who received an asparaginase-containing induction regimen, both mild hypofibrinogenemia (92.9% vs. 63.9%) and severe hypofibrinogenemia (42.9% vs. 13.9%) were observed more frequently at induction phase (p=0.039 and p=0.036, respectively). In patients with mild hypofibrinogenemia at induction, the requirement for cryoprecipitate or fresh frozen plasma (FFP) was higher than in patients with normal fibrinogen levels (55.6% vs. 21.4%, p=0.030). D-dimer levels at diagnosis were higher in Ph-positive B-ALL than in Ph-negative B-ALL (median 15 vs. 4.3; p=0.030). D-dimer levels at induction phase were also higher in patients requiring cryoprecipitate or FFP (median 14.6 vs. 7.1; p=0.07). Early mortality (in the first 30 days) was 1 (2%), and was not associated with bleeding or thrombosis. No statistically significant association was found between age, gender, disease subtype, fibrinogen and D-dimer levels at diagnosis and induction phase, asparaginase use, or cryoprecipitate or FFP requirement and overall survival.

In this study, we demonstrated that hypofibrinogenemia, while observed at diagnosis of ALL, is particularly prevalent during the induction phase. Hypofibrinogenemia at induction phase is determined by the fibrinogen levels at diagnosis and the use of asparaginase-containing regimens. Following, consumption of the blood products containing coagulation factors determined by the hypofibrinogenemia at induction phase. Although coagulopathy increased the frequency of blood product use, it was observed that it did not negatively impact patient survival. Clinical guidelines should be reviewed for newly diagnosed ALL patients with and without asparaginase use and updated based on large-scale studies.