A risk score for prediction of venous thromboembolism in gynecologic cancer: The Thrombogyn score

Abstract

Background Gynecologic cancers are associated with high rates of venous thromboembolism (VTE), which is exacerbated by pelvic surgery and chemotherapy. Objectives The aim of this study was to develop and validate a risk score for VTE in patients with gynecologic cancer and to test the predictive ability of the score following addition of procoagulant biomarker data. Patients and methods Clinical and laboratory variables were used to develop a risk score for the prediction of VTE in patients with gynecological cancer (n = 616), which was validated in a separate cohort of patients (n = 406). Endogenous thrombin potential and D‐dimer levels were determined in a subset (n = 290) of patients and used to produce an extended score in the validation cohort. Results Multivariable regression analysis identified BMI >30, hemoglobin <11.5 g/dL and chemotherapy as independent predictors of VTE, which formed the Thrombogyn score. Following competing risk regression analysis, subdistribution hazard ratios (SHRs), adjusted for cancer stage, were 8.16 (95% confidence interval [CI], 1.69‐43.77) in the high‐risk group (score = 2‐3) and 4.12 (95% CI, 0.85‐20.15) in the intermediate‐risk group (score = 1) compared with the low‐risk group (score = 0). SHRs for the validation cohort were 6.26 (95% CI, 1.24‐31.39) and 3.00 (95% CI, 0.67‐13.32), respectively. Cumulative incidence of VTE in the validation cohort high‐risk group was 10.34% (95% CI, 6.51‐16.41) per women‐years compared with 1.06% (95% CI, 0.26‐4.26) in the low‐risk group. Using the extended Thrombogyn score, adjusted SHRs were 16.83 (95% CI, 4.20‐67.37) in the high‐risk group with a cumulative incidence of 21.15% (95% CI, 10.32‐45.24). External validation of the score is required. Conclusions The Thrombogyn score identifies patients with gynecologic cancer at high and low risk of VTE. Addition of biomarker data improves the predictive power of the score.

Procoagulant activity in high grade serous ovarian cancer patients following neoadjuvant chemotherapy-The role of the activated protein C pathway

“…D-dimer levels were increased in our neoadjuvant and chemo naïve cohort compared with patients with benign disease with slightly lower levels in the neoadjuvant group. D-dimer is predictive of both preoperative and post-operative VTE [7,35]. The increased D-dimer levels observed reflects in vivo fibrin turnover which is associated with the prothrombotic phenotype of these patients.…”

“…In addition, ovarian cancer patients who experience a VTE during neoadjuvant chemotherapy having a longer mean time to surgery. Our group has shown that chemotherapy treatment is an independent risk factor for VTE in gynaecological cancer patients [7]. In a recent study, BMI, cancer stage and histological subtype were not found to be predictive of increased VTE risk in patients undergoing neoadjuvant chemotherapy, further highlighting the need for a greater understanding of the prothrombotic mechanisms involved in chemotherapy associated thrombosis [6].…”

“…The thrombin generation assay is a useful tool to investigate procoagulant activity and is a predictor of VTE in gynaecological and other cancers [7,17], however plasma thrombin generation assays are performed in the absence of cell surfaces, and therefore are not sensitive to membrane bound alterations in TM and EPCR. The thrombin generation assay can be modified to increase sensitivity to the aPC pathway using added TM [18].…”

Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?

“…Patients with metastatic cancer have global platelet hyperactivity, which could contribute to the risk of thrombosis [ 73 ]. Indeed, venous thromboembolisms (VTEs) are frequent complications in patients with cancer, with the incidence being high in pancreatic, brain, and gynaecological malignancies [ 74 – 76 ]. This hypercoagulable state is due to multiple factors including systemic inflammation and altered expression of circulating blood coagulation proteins such as fibrinogen, Tissue Factor (TF), Factor V (FV), FVII, FVIII, FIX and FX [ 77 , 78 ].…”

Extended thromboprophylaxis post gynaecological cancer surgery; the effect of weight adjusted and fixed dose LMWH (Tinzaparin)

“…Previous studies have reported that the incidence of postoperative VTE in gynaecological cancer patients is 5-6% in the 12 months following surgery (4,24,25). Based on a previously reported reduction in VTE of 60 % in patients undergoing abdominal surgery for cancer who received extended LMWH prophylaxis (8) and correcting for multiple (3) comparisons (30, 90 and 1 year post surgery), type 1 error is set at 0.016 and type II error is set at 0.2, a sample size of 1310 patients is required.…”