Discussion
In our cohort of newly diagnosed pediatric leukemia patients, a third presented with bleeding symptoms, which correlated significantly with thrombocytopenia, but not with prolonged PT or aPTT. Interestingly, over half of patients presenting with a prolonged PT had significant correlation with leukocytosis. All patients with APL presented with elevated PT (which is consistent with published literature(4), along with most patients with T-cell ALL, which has been reported in adult T-cell patients(5).
The leukemic process can lead to the unregulated production of white blood cells with increased inflammation by release of cytokines and stress hormones(6). Hepatic dysfunction can also occur due to leukemic infiltration (as noted by increased bleeding symptoms correlating with elevated AST upon presentation), leading to deficiencies in coagulation factors synthesized by the liver. Factor VII was most notably affected due to its short half-life(7), contributing to a prolonged PT. However, bleeding in newly diagnosed leukemia patients is most likely related to thrombocytopenia as noted in our study, and not a prolonged PT. Thrombocytopenia is common in hematologic malignancies(8), with a platelet count below 10 K/uL leading to increased risk of hemorrhage(9).
Use of products such as FFP and vitamin-K prior to procedures in those with a prolonged PT is routinely practiced. With the finding of low factor VII levels in pediatric leukemia patients upon initial presentation, the use of targeted therapy with factor VII concentrate may be appropriate for major procedures such as lumbar punctures, to avoid administration of FFP with its complications such as fluid overload and allergic reactions. In inherited FVII deficiency, significant bleeding occurs with levels <10%, and whether this can be applied to acquired FVII deficiency is debated. Furthermore, the automated use of product replacement may not be indicated in the absence of significant bleeding associated with a prolonged PT and low FVII levels, which are likely related to leukocytosis than to a true coagulopathy. A previous study from our institution observed that low FVII levels do not predict peri-op bleeding even in the absence of intervention(10). In an adult study by Benlakhal et al(11), they recommended a FVII cut off of 10% in considering replacement therapy, irrespective of bleeding phenotype, for major surgeries (sensitivity of 87% and negative predictive value of 94% for 7% cutoff).
The limitations to this study are its retrospective design (with reliance on documentation for patient history) and incomplete patient workup in relation to abnormal laboratory values (such as prolonged PT and factor deficiencies). Nonetheless, the findings in our patients may enable tailoring the use of blood products based on significant bleeding symptoms and avoiding treating abnormal values in the absence of clinical bleeding.