title: Impact of chemotherapy on activated protein C-dependent thrombin generation--association with VTE occurrence.
abstract: Chemotherapy has been associated with an increased risk of venous thromboembolism (VTE). However, the prevalence of coagulation abnormalities or VTE occurrence as a consequence of different anti-cancer agents or treatment schemes is largely uncharacterized. Thus, this study was aimed at analyzing the impact of different anticancer drugs on the prothrombotic status of cancer out-patients scheduled for chemotherapy. To this purpose, a mono-institutional study was prospectively conducted to monitor serial changes of activated protein C (APC) function in 505 consecutive cancer out-patients with primary or relapsing solid cancer at the start of a new chemotherapy regimen. The results obtained showed that age >65 years (p = 0.01), ECOG performance status (p = 0.01), platinum-based (p = 0.035) and fluoropyrimidine-based regimens (p = 0.008) were independent predictors of an acquired APC resistance during the first chemotherapy cycle. Multivariate model of Cox proportional hazards survival analysis demonstrated that a decline in APC functionality (HR = 2.4; p = 0.013) and platinum-based regimens (HR = 2.2; p = 0.042) were both capable of predicting the occurrence of a first VTE episode during chemotherapy. Indeed, 14% of patients with platinum-associated APC impairment had VTE over a 1-year follow-up, compared to 3% of patients treated with other regimens and in whom APC functionality remained stable (HR = 1.5; p = 0.003). We may, thus, conclude that use of platinum-based regimens is responsible for induction of an acquired thrombophilic condition and represents a predictor for VTE even after adjustment for other risk factors.
authors: Department of System Medicine, Medical Oncology, Tor Vergata Clinical Center, University of Rome Tor Vergata, Rome, Italy.
authors: Mario
authors: M
authors: Roselli
authors: Patrizia
authors: P
authors: Ferroni
authors: Silvia
authors: S
authors: Riondino
authors: Sabrina
authors: S
authors: Mariotti
authors: Anastasia
authors: A
authors: Laudisi
authors: Matteo
authors: M
authors: Vergati
authors: Francesco
authors: F
authors: Cavaliere
authors: Raffaele
authors: R
authors: Palmirotta
authors: Fiorella
authors: F
authors: Guadagni
mesh_terms: D020016:Activated Protein C Resistance / Q000209:etiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011486:Protein C / Q000502:physiology*; D013917:Thrombin / Q000096:biosynthesis*; D054556:Venous Thromboembolism / Q000209:etiology*
chemical_list: D000970:Antineoplastic Agents; D011486:Protein C; D013917:Thrombin
keywords: chemotherapy; thrombophilia; venous thromboembolism