Increased acquired activated protein C resistance in unselected patients with hematological malignancies.
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.


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.
Department of Hematology, Ullevål University Hospital Trust, Oslo, Norway. negaard@medisin.uio.no
H F S
HF
Negaard
P O
PO
Iversen
B
B
Ostenstad
M C
MC
Mowinckel
P M
PM
Sandset
D020016:Activated Protein C Resistance / Q000150:complications* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged