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

Abstract

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.

• Authors: H F S Negaard, P O Iversen, B Ostenstad, M C Mowinckel, P M Sandset
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 6 Issue 9 Pg. 1482-7 (Sep 2008) ISSN: 1538-7836 [Electronic] England
• PMID: 18573186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Activated Protein C Resistance (complications, therapy)
• Adult
• Aged
• Aged, 80 and over
• Female
• Hematologic Neoplasms (blood, complications)
• Humans
• Male
• Middle Aged