Serious Bleeding Manifestations in Patients with Newly Diagnosed Acute Myeloid Leukemia: A Single Center Experience

Introduction

Acute myeloid leukemia (AML) is a malignant clonal disease characterized by the uncontrolled proliferation and failure of differentiation of myeloblast. These immature cells replace the hematopoietic system leading to cytopenias often including severe thrombocytopenia. This along with hyperleukocytosis, monocytic differentiation, infectious complications, fibrinolysis, disseminated intravascular coagulation, increased vascular permeability, due to abnormal signalling kinases and activation of metallopeptidase, contribute to the high risk of serious bleeding manifestations, associated with significant morbidity and mortality.

We aimed to describe the incidence and clinical impact of serios bleeding manifestations in patients with newly diagnosed AML.

Methodology

We retrospectively analyzed data from the clinical charts of newly diagnosed AML patients treated at our tertiary haematology centre, The National Center for Cancer Care and Research, Doha Qatar during the period of January 2017 to December 2021, Bleeding events were identified from patients' electronic notes and radiology imaging reports.

Result

During the five-year study period, a total of 214 patients were diagnosed and treated for AML. Among these, thirty -seven patients (17.2%) developed serios bleeding manifestations. Most of these patients were males (27/37, 82%). The median age was 48 years (range 27-78 years). Most of the patients were of Asian background (21, 64%). Hypertension was most common comorbidities with 17/37 (40%) of all patients, followed by diabetes at 13.5%. None of the patients had liver disease, renal disease or bleeding disorder prior to the study.

The initial laboratory investigations at diagnosis showed a mean hemoglobin (HB) level of 7.5 g/dL, a white blood cell (WBC) count of 52.8 x 10^3/µL, a platelet count of 84 x 10^3/µL, and a blast percentage of 59% in the peripheral blood. Based on cytogenetics, 4 patients (13%) were classified as high risk, and 6 patients (16%) had favorable cytogenetics. Mutation analysis revealed that 4 patients had an NPM1 positive mutation, and 7 patients had a FLT3-ITD mutation.

On examination, anisocoria was the most common finding at the time of bleeding (19%), while headache was the most frequent complaint, affecting around 35% of all patients. The most common site of bleeding was the brain, accounting for 87% of all cases. Of the brain bleeding cases, there were 15 cases of intracranial hemorrhage, 9 cases of subdural hematoma, 8 cases of subarachnoid hemorrhage, and 2 cases of cerebellar hemorrhage. The average size of brain bleeds was 13 mm.

At the time of bleeding the median of platelet counts was 40 x 10^3/µL, and WBC counts were 15 x 10^3/µL. Bleeding parameters, including INR, PT, PTT, and fibrinogen, were all within normal ranges.

The majority of patients (21) were treated conservatively, while 13 received medical supportive treatments, and 3 required surgical interventions. A total of 18 patients (48%) died, with 16 deaths occurring within 30 days and 2 within 60 days.

Conclusion

Acute bleeding events in patients with AML continue to be a serious complication. Patients who experience bleeding typically have low platelet counts and high WBC counts. The brain is the most frequent site of bleeding, and the associated mortality rate is very high. There is a pressing need for an accurate bleeding score to predict which patients are at higher risk. Meanwhile, all patients should be meticulously monitored and managed with regard to all factors contributing to bleeding complications.

No relevant conflicts of interest to declare.