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.
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: Patrizia Ferroni; Francesca Martini; Ilaria Portarena; Italia Grenga; Silvia Riondino; Francesca La Farina; Anastasia Laudisi; Fiorella Guadagni; Mario Roselli Journal: Support Care Cancer Date: 2012-02-10 Impact factor: 3.603
Authors: Mari Tinholt; Marte Kathrine Viken; Anders Erik Dahm; Hans Kristian Moen Vollan; Kristine Kleivi Sahlberg; Oystein Garred; Anne-Lise Børresen-Dale; Anne Flem Jacobsen; Vessela Kristensen; Ida Bukholm; Rolf Kåresen; Ellen Schlichting; Grethe Skretting; Benedicte Alexandra Lie; Per Morten Sandset; Nina Iversen Journal: BMC Cancer Date: 2014-11-19 Impact factor: 4.430