Laboratory characterization of leukemic cell procoagulants

Area of Science:

• Hematology
• Oncology
• Biochemistry

Background:

• Acute myeloid leukemias are associated with an increased risk of thrombotic disorders.
• Leukemic promyelocytes and monocytic leukemia cells may possess heightened procoagulant activity.

Purpose of the Study:

• To investigate the procoagulant activity of monocytic leukemia cells and their microparticles.
• To compare the thrombin generation potential of leukemic cells with normal human monocytes.

Main Methods:

• Assessed fibrin formation using a one-stage clotting assay.
• Performed thrombin generation tests (TGT) on isolated monocytes, leukemic cells, and microparticles using fluorimetric assays.
• Quantified phosphatidylserine (PS) expression and microparticle numbers via flow cytometry.

Main Results:

• All monocytic leukemia cell lines demonstrated significant procoagulant potential compared to normal monocytes.
• Leukemic cells exhibited shorter lagtime and time to peak in TGT (3.9-4.7 min and 9.9-10.3 min) versus monocytes (14.9 and 26.5 min).
• Leukemia cell-derived microparticles significantly shortened lagtime in TGT, indicating a procoagulant effect.

Conclusions:

• Investigated monocytic leukemia cell lines showed significant thrombin generation.
• This thrombin generation is mediated by procoagulants on leukemic cell surfaces and their derived microparticles.
• These findings highlight a mechanism contributing to the thrombotic risk in acute myeloid leukemia.