title: Procoagulant activity in gynaecological cancer patients; the effect of surgery and chemotherapy.
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.
  
  
  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.
authors.affiliation: Department of Gynaecology Oncology, St James's Hospital, Dublin 8, Ireland. Electronic address: ferasabusaadeh@dubgyn.org.
authors.forename: F
authors.initials: F
authors.lastname: Abu Saadeh
authors.affiliation: Trinity College Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Langhe
authors.affiliation: Department of Gynaecology Oncology, St James's Hospital, Dublin 8, Ireland.
authors.forename: D M
authors.initials: DM
authors.lastname: Galvin
authors.affiliation: Trinity College Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
authors.forename: S A
authors.initials: SA
authors.lastname: O Toole
authors.affiliation: Department of Medical Oncology, St James's Hospital, Dublin 8, Ireland.
authors.forename: D M
authors.initials: DM
authors.lastname: O'Donnell
authors.affiliation: Department of Gynaecology Oncology, St James's Hospital, Dublin 8, Ireland; Trinity College Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
authors.forename: N
authors.initials: N
authors.lastname: Gleeson
authors.affiliation: Trinity College Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
authors.forename: L A
authors.initials: LA
authors.lastname: Norris
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D055252:Cell-Derived Microparticles / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D016889:Endometrial Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000601:surgery*; D004717:Endometrium / Q000601:surgery; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000601:surgery*; D010053:Ovary / Q000601:surgery; D013917:Thrombin / Q000032:analysis / Q000378:metabolism; D054556:Venous Thromboembolism / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D006495:Heparin, Low-Molecular-Weight; D013917:Thrombin
keywords: Anti-neoplastic agents; Low molecular weight heparin; Ovarian neoplasms; Thrombin; Venous thromboembolism