Related Experiment Video
Updated: Jul 4, 2026
Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
Published on: June 17, 2022
Increased acquired activated protein C resistance in unselected patients with hematological malignancies
H F S Negaard1, P O Iversen, B Ostenstad
1Department of Hematology, Ullevål University Hospital Trust, Oslo, Norway. negaard@medisin.uio.no
Background:
We have previously found that activation of coagulation in patients with various hematological malignancies was apparently not initiated by tissue factor (TF). Acquired activated protein C (APC) resistance may be another mechanism responsible for such hypercoagulation, and has been demonstrated in patients with solid tumors, but not in patients with hematological malignancy.
Objective:
To investigate acquired APC resistance in a hypercoagulable cohort of patients with hematological malignancies.
Patients/Methods:
Blood samples from 93 patients with acute myeloid leukemia (AML), chronic lymphatic leukemia, multiple myeloma, or non-Hodgkin's lymphoma, were analyzed before start and after completion of cancer therapy. APC resistance was measured using calibrated automated thrombography. The APC sensitivity ratio (APC-SR) was calculated as the ratio of the endogenous thrombin potential (ETP) determined in plasma probed with either APC or buffer.
Results:
Untreated patients were found to have higher APC-SR than healthy controls, and patients with AML had higher APC-SR as compared to the other diagnoses, both findings being consistent with acquired APC resistance. The acquired APC resistance was partly ameliorated with cancer treatment. Decreased levels of protein S and TF pathway inhibitor were inversely correlated to APC resistance.
Conclusions:
APC resistance may contribute to the hypercoagulable state in hematological malignancies.
