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.