Abstract
Background: The cancer is associated with a state of hypercoagulability, which may be the cause of venous thromboembolism (VTE), representing an undeniable cause of morbidity and mortality. Our study aimed to investigate the role of hypercoagulability markers (D-dimers, microparticles, and V Leiden mutation) in predicting cancer-associated VTE.
Methods: A prospective cohort study was conducted among cancer patients who will receive chemotherapy in the Medical Oncology and Hematology departments of the EHU of Oran, Algeria from February 2013 to May 2015, followed by an observation period of two years. First, we evaluated the risk of cancer-related VTE by hypercoagulability parameters (D-dimers, microparticles, V Leiden mutation). In the second step, we tested the predictive value of the Khorana risk score (KRS) of cancer-related VTE. Then, we developed and tested the predictive value of an expanded score based on the addition of predictive biomarkers to the KRS parameters.
Results: A total of 165 patients were included in our study whose median age was 62 years. More than half were males (52.7%). After an observation period of 2 years, ten patients (6.0%) developed a VTE. Among the criteria studied, only the D-dimers and the microparticles were predictive of VTE in cancer. The positive predictive value (PPV) of the KRS was 13.6%, and the negative predictive value (NPV) was 97.9%. After adding two predictive biomarkers (D-dimers and microparticles), the expanded score had a better predictive value with a PPV of 23.5% and a VPN of 98.6%.
Conclusion: The addition of hypercoagulability biomarkers (microparticles and D-dimers) to the routine clinical and biological parameters of the KRS enhances the predictive potential of VTE risk in cancer.
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References
- Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007 Mar ;5(3):632-4. doi: 10.1111/j.1538-7836.2007.02374. x.
- Sousou T, Khorana A. Identifying cancer patients at risk for venous thromboembolism. Hamostaseologie. 2009;29(1):121-4.
- Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005 Feb 9;293(6):715-22. doi: 10.1001/jama.293.6.715.
- Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost. 2002 Apr;87(4):575-9.
- Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006 Feb 27;166(4):458-64. doi: 10.1001/archinte.166.4.458.
- Mandalà M, Curigliano G, Bucciarelli P, Ferretti G, Mannucci PM, Colleoni M, et al. Factor V Leiden and G20210A prothrombin mutation and the risk of subclavian vein thrombosis in patients with breast cancer and a central venous catheter. Ann Oncol. 2004 Apr;15(4):590-3. doi: 10.1093/annonc/mdh146.
- Ay C, Vormittag R, Dunkler D, Simanek R, Chiriac AL, Drach J, et al. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol. 2009 Sep 1;27(25):4124-9. doi: 10.1200/JCO.2008.21.7752.
- Zwicker JI, Liebman HA, Neuberg D, Lacroix R, Bauer KA, Furie BC, Furie B. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res. 2009 Nov 15;15(22):6830-40. doi: 10.1158/1078-0432.CCR-09-0371.
- Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008 May 15;111(10):4902-7. doi: 10.1182/blood-2007-10-116327.
- Kakkar AK, Williamson RC. Prevention of venous thromboembolism in cancer patients. Semin Thromb Hemost. 1999;25(2):239-43. doi: 10.1055/s-2007-994925.
- Rasmussen MS, Jørgensen LN, Wille-Jørgensen P. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004318. doi: 10.1002/14651858.CD004318.pub2.
- Mandala M, Clerici M, Corradino I, Vitalini C, Colombini S, Torri V, et al. Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the 'SENDO experience'. Ann Oncol. 2012 Jun;23(6):1416-21. doi: 10.1093/annonc/mdr524.
- Moore RA, Adel N, Riedel E, Bhutani M, Feldman DR, Tabbara NE, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol. 2011 Sep 1;29(25):3466-73. doi: 10.1200/JCO.2011.35.5669.
- Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, Folsom AR. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004 Jul 1;117(1):19-25. doi: 10.1016/j.amjmed.2004.01.018.
- Khorana AA, Carrier M, Garcia DA, Lee AY. Guidance for the prevention and treatment of cancer-associated venous thromboembolism. J Thromb Thrombolysis. 2016 Jan;41(1):81-91. doi: 10.1007/s11239-015-1313-4.
- Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA Jr, Wheeler HB. Prevention of venous thromboembolism. Chest. 2001 Jan;119(1 Suppl):132S-175S. doi: 10.1378/chest.119.1_suppl.132s.
- Visuddho V, Subagjo A, Setyoningrum RA, Rosyid AN. Predictive accuracy of blood inflammatory markers on COVID-19 mortality. Journal of Ideas in Health 2021 ;4(4):623-629. DOI: 10.47108/jidhealth.vol4.iss4.196
- Zakai NA, Wright J, Cushman M. Risk factors for venous thrombosis in medical inpatients: validation of a thrombosis risk score. J Thromb Haemost. 2004 Dec;2(12):2156-61. doi: 10.1111/j.1538-7836.2004.00991. x.
- Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Somerfield MR, Falanga A; American Society of Clinical Oncology. Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. J Clin Oncol. 2015 Feb 20;33(6):654-6. doi: 10.1200/JCO.2014.59.7351.
- Mandalà M, Falanga A, Roila F, and ESMO Guidelines Working Group Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2011; 22(Suppl6):85–92.DOI:10.1093/annonc/mdr392.
