Venous Thromboembolism Events and Prophylaxis in Patients with Acute Myeloid Leukemia
Authors: Reed Daniel R , Nicolais Maria C , Orellana-Noia Victor M. , Minkin Samantha J , Morris Amy L , Maitland Hillary S. , Keng Michael K 
Published: October 2019

Abstract
Introduction: Thrombotic events are a frequent complication in patients with malignancy due to increased tissue factor expression and activation of hemostatic mechanisms by both host cells and cancer tissues. Patients with acute myeloid leukemia (AML) are at risk of venous thromboembolism (VTE) not only because of their malignancy but also because of prolonged hospitalizations, immobility, and the need for central venous access. Profound thrombocytopenia is an expected complication, due to myelosuppressive chemotherapy as well as from underlying marrow-infiltrative disease. This results in difficult prophylactic and treatment decisions where providers must carefully balance the risk of thrombosis and bleeding. There are no published consensus guidelines regarding appropriate use of prophylaxis in patients with leukemia.
Methods: A retrospective chart review was completed on AML patients receiving induction or consolidation chemotherapy or treatment for relapsed disease admitted to the University of Virginia from October 2011 through September 2017. Patients with acute promyelocytic leukemia were excluded. Clinical data from 142 patients over a total of 667 hospital admissions were reviewed. The following data was collected: demographics (including age, sex, and race), clotting events, clot location, type of line placed, treatment of clot, and bleeding events. Bleeding events were defined according to International Thrombosis and Hemostasis criteria. χ2 analysis was performed to compare categorical values.
Results: Twenty-nine of 142 (20.4%) AML patients were diagnosed with VTE. None of the patients had a prior history of clot or diagnosis of clotting disorder. Thrombosis occurred more commonly during induction therapy, 13 of the 29 events (45%), compared to other stages in their treatment (p value=0.37). Of the thromboses occurring during induction, 14 clotting events (48%) were central line associated, 4% (5/125) of thrombosis occurred in peripherally inserted central lines, 10% (5/51) in temporary internal jugular central lines and 2% (4/165) in tunneled central lines (p value=0.99).
The average platelet count at the time of clot was 61 K/µl. Most patients were not on prophylaxis at the time of their clotting event (93.1% vs 6.9%; p value= <0.001). The majority of patients (19 of 29; 65.5%) were treated with therapeutic anticoagulation with heparin or low molecular weight heparin; 4 of 29 (13.8%) patients received temporary inferior vena cava filters. For those patients with a line-associated VTE, 9 of the 14 (64%) had the line removed. There was no statistically significant difference in the incidence of VTE in patient ages less than 60 years versus in older patients (55% vs 44.8%; p value=0.75).
Patients who received therapeutic anticoagulation had a comparable rate of bleeding compared to patients who were not on anticoagulation (31.6% vs 40.8%; p value= 0.44). Patients who were treated for VTE (n=19) had 2 major bleeds and 4 clinically relevant non-major bleeds. Patients who did not receive treatment for their VTE event (n=10) had 1 major bleed and 3 minor bleeding events.
Conclusion: Our study identified a 20.4% incidence of VTE in AML patients, occurring more frequently during induction chemotherapy and in patients without prior thrombotic history.The clots were most commonly catheter associated and the highest rate of clot occurred with temporary internal jugular lines. Importantly, we found that when patients were treated with anticoagulation, their incidence of bleed did not exceed the general incidence of bleeding (43%) seen during the time period of the analysis. Average platelet count at VTE diagnosis was 61 K/µL, which is above most institutions' thresholds for use of pharmacologic VTE prophylaxis including patients with acute leukemia. Given that only two patients in our study were receiving prophylaxis at the time of VTE and that bleeding rates were similar with full therapeutic anticoagulation, this suggests prophylaxis is important, safe, and is potentially neglected in patients with acute leukemia. This highlights an area of potential improvement in decreasing VTE in patients that can safely receive prophylaxis and is the basis for future prospective safety trials exploring the use of prophylaxis in this patient population.

Disclosures
No relevant conflicts of interest to declare.