Lubberts, S. (2013) Chemotherapy-induced hypercoagulability and thromboembolic events in patients with metastatic testicular cancer. thesis, Medicine.
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Abstract
Introduction: The majority of patients with disseminated testicular cancer can be cured with 3 or 4 courses of combination chemotherapy consisting of bleomycin, etoposide and cisplatin (BEP). Because of this good prognosis, focus shifts to adverse effects of this treatment. Venous thromboembolism and arterial thromboembolism (VTE and ATE) during and after chemotherapy are reported with incidences up to 15%. This hypercoagulability is thought to be caused by presence of cancer and administration of chemotherapy. Low molecular weight heparin (LMWH) reduces incidence of VTE, but incidence is too low to justify prophylaxis in most patients starting with chemotherapy. With better identification of high risk patients it becomes possible to decrease morbidity from thromboembolisms in this young group of testicular cancer survivors. Aim of this study: The influence of BEP-chemotherapy on coagulation was investigated. We also investigated which coagulation biomarkers are predictors for thromboembolic events and we combined predictive value with the clinical Khorana score. Methods: 74 metastatic testicular cancer patients were included in this prospective cohort study with a median age of 31 (range: 18-46) years at start of chemotherapy. Patients received 3 or 4 BEP-courses. The Khorana score was assessed from clinical information retrieved from digital patient files. The following coagulation biomarkers were measured in citrate plasma: von Willebrand factor (vWF), fibrinogen, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) , soluble P-selectin (sP-selectin), coagulation factor VIII (FVIII) and D-dimer. Samples were derived at baseline, the last day of the third BEP-course (day 56) and 1 month after finishing chemotherapy. Outcomes were symptomatic VTE or ATE or asymptomatic VTE or ATE discovered on staging CT-scans. Results: 8 patients (10,8%) developed an event during or after chemotherapy, 4 had VTE and 4 had ATE. Median duration from start of chemotherapy until development of VTE was 82 days (range: 32-278) and for ATE 85 days (range: 69-435). Patients with ATE had a higher age (median: 44 years (29-45)) than patients without TE (median: 31 years (18-46)). vWF, fibrinogen, FVIII, D-dimer and PAI-1 levels increased during chemotherapy. This hypercoagulability normalized to baseline coagulant activity afterwards, except for FVIII and vWF levels. We found elevated FVIII (> 150%) as predictor with a positive predictive value (PPV) of 50% (95% CI: 14-86%) and a HR for TE of 4,7 (95% CI: 1-22) corrected for age at start of chemotherapy. Khorana-score had no predictive value. At day 56 FVIII (>150%), vWF (>150%) and D-dimer (>1440 ng/ml) were more frequently elevated in patients with TE, although HR’s were non-significant. Large change between baseline and day 56 in both vWF (∆ > 86,5%) and D-dimer (∆ > 935 ng/ml) levels had a PPV of 44,4% (95% CI: 15-77%) and a HR for TE of 7,0 (95% CI: 2-33). Furthermore, hypercoagulability correlated with tumor markers and recurrence of cancer. Conclusions: BEP-courses induce hypercoagulability in metastatic testicular cancer patients. Elevated FVIII before start of chemotherapy and increases in D-dimer and vWF levels during chemotherapy are associated with an increased risk of developing both ATE and VTE. This study suggests that baseline FVIII is a promising predictor for future TE’s in testicular cancer patients.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Kamphuisen, Prof. dr. P.W. |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:07 |
| Last Modified: | 25 Jun 2020 11:07 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2665 |
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