Results
Ninety-three patients met inclusion criteria out of 144 records reviewed during the study period. Patients were 43% female, of varied races, 21.5% had a medical history (e.g. asthma), none with a personal history of bleeding and one patient had a family member with documented bleeding history (menorrhagia) – Table 1. A third of patients had bleeding symptoms upon presentation, which were most commonly bruising (80.6%) and petechiae (64.5%).
Patients were diagnosed (via peripheral blood flow and/or bone marrow studies) predominantly with ALL (82.7%). Of these, 82.9% had pre-B cell ALL and 17.1% had T-cell ALL. The remainder of diagnoses were AML (12.9%), APML (3.2%), biphenotypic leukemia (2.2%), and mature B cell leukemia (2.2%). All patients underwent a lumbar puncture (LP), bone marrow aspirate (and bone marrow biopsy for some patients) along with CVL placement for chemotherapy. One patient was diagnosed via fluid from a pleural effusion.
Two patients had minor bleeding (both WHO grade 2) noted at a procedure site. One patient had a bleed at the LP site (day 2 post-procedure), with normal PT/aPTT at presentation; bleeding was attributed to thrombocytopenia which resolved with a pressure bandage. The second patient had bleeding at the CVL site (day 1 post-procedure) and had presented with a PT of 13.9. This was not corrected initially, but patient was initiated on a course of vitamin K for the CVL site bleed.
Laboratory data are also presented in Table 1. The median age at diagnosis was 8 years (interquartile range [IQR] 3-12) with hematologic lab values as follows: white blood cell count (WBC) with leukocytosis (median 15.7; IQR 5.3-57.2), anemia with hemoglobin 8.1 (5.7-10.4), thrombocytopenia with platelets 64 (24-119), mildly prolonged prothrombin time (PT) at 13.2 (12.4-15.4), and normal partial thromboplastin time at 31 (27.4-33.6). Fibrinogen (343; 227-465) and D-dimer (834; 341-2869) were obtained in 37.6% and 22.5% of patients respectively, which were both elevated. Chemistries were obtained, most notably with an elevated LDH (637; 368-1218).
Prolonged PT was found in over half of patients (N=51, 54.8%) and only 5 had prolonged aPTT (5.4%). Of interest, 84.6% (11 of 13) patients with T cell leukemia had prolonged PT, along with 58.3% of patients with AML, and all 3 patients with APML. In our cohort, less than 27% of patients with prolonged PT/aPTT had factor levels obtained; of those, factor VII had the lowest activity with a median of 33.1% (19.4-50.5).
Varying blood products were administered for prophylaxis per institution guidelines prior to procedures (for hemoglobin <8 g/dL, platelets <10 K/uL, PT >15 s). Red blood cells (RBCs) were administered in 41.2% of patients, platelets in 52.9%, FFP in 7.8% and vitamin K in 21.6%.
Anemia and thrombocytopenia did not appear to correlate with prolonged PT (p=0.73 and p=0.18 respectively), nor with prolonged aPTT (p=0.52 and 0.42 respectively). Leukocytosis, however, showed significant correlation with elevated PT (p<0.001), but not aPTT (p=0.3) – Figure 1. This was also seen with elevated absolute neutrophil count with elevated PT (p<0.01), but not aPTT (p=0.5). Bleeding symptoms did not correlate with prolonged PT (p=0.83), prolonged aPTT (p=1) or anemia (p=0.06), but had significant correlation with thrombocytopenia (p=<0.0001) and elevated AST (p=0.05).