Procoagulant activity in gynaecological cancer patients; the effect of surgery and chemotherapy

Thromb Res. 2016 Mar:139:135-41. doi: 10.1016/j.thromres.2016.01.027. Epub 2016 Feb 2.

Abstract

Background: Gynaecological cancers are associated with high rates of venous thromboembolism (VTE). Studies on ambulatory cancer patients do not support thromboprophylaxis during chemotherapy. Approximately 6-7% of gynaecological cancer patients suffer a postoperative VTE despite Low Molecular Weight Heparin prophylaxis (LMWH). Large cancer studies have shown that Calibrated Automated Thrombogram (CAT) and Microparticles (MP) assays may be useful in predicting VTE but data on gynaecological cancer patients is scarce.

Objective: Our objective was to identify whether the CAT assay and MP functional assays have potential as biomarkers predictive of VTE in gynaecological cancer patients.

Patients and methods: Gynaecological cancer patients were investigated before surgery (n=146) and at 5, 14 and 42days post-surgery (n=78). Fourteen additional patients were investigated before chemotherapy and after 3 and 6 cycles of therapy. Thrombin generation was measured before and after addition of thrombomodulin.

Results: Patients with clear cell cancer (CCC) of the ovary and patients with endometrial cancer had higher ETP and peak thrombin compared with patients with benign disease. Patients who developed VTE (n=8) following surgery had enhanced thrombin generation prior to surgery which persisted during the post-operative period despite LMWH prophylaxis. Both neoadjuvant and adjuvant chemotherapy showed increased thrombin generation following addition of thrombomodulin. There were no differences in MP levels during the study.

Conclusions: CAT assay shows potential as a promising biomarker for the prediction of VTE in gynaecological cancer patients. The identification of high risk patients combined with individualised LMWH prophylaxis might reduce VTE in this high risk group.

Keywords: Anti-neoplastic agents; Low molecular weight heparin; Ovarian neoplasms; Thrombin; Venous thromboembolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Blood Coagulation / drug effects
  • Blood Coagulation Tests
  • Cell-Derived Microparticles / metabolism
  • Chemotherapy, Adjuvant
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / complications*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / surgery*
  • Endometrium / surgery
  • Female
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / complications*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / surgery*
  • Ovary / surgery
  • Thrombin / analysis
  • Thrombin / metabolism
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / complications*
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / prevention & control

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Heparin, Low-Molecular-Weight
  • Thrombin