Impact of chemotherapy on activated protein C-dependent thrombin generation--association with VTE occurrence

Int J Cancer. 2013 Sep 1;133(5):1253-8. doi: 10.1002/ijc.28104. Epub 2013 Mar 16.

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.

Keywords: chemotherapy; thrombophilia; venous thromboembolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activated Protein C Resistance / etiology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Protein C / physiology*
  • Thrombin / biosynthesis*
  • Venous Thromboembolism / etiology*

Substances

  • Antineoplastic Agents
  • Protein C
  • Thrombin