Çiğdem ÖZDİLEKCAN, Tarkan ÖZDEMİR, Ümüs ÇİMEN, Melike BAHÇECİTAPAR

Kanserli hastalarda kan D-dimer değerlerinin pulmoner emboli tanısını öngörmedeki önemi

Amaç: Kanser hastaları artmış tromboz riskine sahiptirler. Tromboz biyobelirteçlerinden biri olan D-dimer’in malignite, major cerrahi, enfeksiyonlar ve gebelikte pulmoner emboli (PE) tanısında kullanılması önerilmemektedir, zira bu grup hastalarda gerçekte pulmoner emboli olmamasına rağmen değerler yüksek saptanmaktadır. Çalışmanın amacı, seçilen hasta grubunda D-dimer değerlerini klinik, demografik veriler ışığında değerlendirmek, D-dimer ölçüm değerlerinin kanserli hastalarda klinik karar mekanizmasındaki önemini ortaya koymaktır. Ayrıca kanserli hastalarda PE tanısını öngörmede bir eşik D-dimer değeri saptamaktır. Gereç ve Yöntem: Çalışma, tek merkezli kesitsel ve retrospektif hasta kayıtları göz önüne alınarak klinik demografik veriler eşliğinde yapıldı. D-dimer değeri 500 mcg/dl üzerinde pozitif sonuç olarak kabul edildi. Bulgular: Toplam 128 kesin PE tanılı hasta; kanser-vaka (n=44) ve kanser dışı hasta-kontrol (n=84) çalışmaya dahil edildi. Kontrol grubunun yaş ortalaması 61,30±13,24 (25-88) iken kanserli hasta grubunda yaş ortalaması 57,43±14,52 (22-84) bulundu. Kanserli hastaların dağılımında ilk üç sırayı akciğer, meme ve abdominal kanserler almaktaydı. Kanserli hastalar ile kontrol grubu hastalar arasında D-dimer seviyeleri bakımından istatistiksel olarak anlamlı bir farklılık bulundu (p<,001). D-dimer kontrol grubunda 1729,3±2272 mcg/dl iken kanser öyküsü olan hastalarda 3326,9±3162,2 mcg /dl olarak daha yüksek saptandı. Kanserli hasta grubunda D-dimer eşik değeri 1205 mcg /dl tespit edildi (sensitivite: %74, spesifite: %64). Bu değer, laboratuvar üst sınır değerimizin 2,41 katına karşılık gelmekteydi.Sonuç: Kan D-dimer değerleri kanserin eşlik ettiği olgularda klinik karar aşamasında oldukça değerli bir parametre olarak karşımıza çıkmaktadır. Kanser hastalarında farklı bir eşik değer saptadık ve bu durumun klinisyenlerin gelecekteki bakış açılarına rehberlik edebileceğini düşünmekteyiz.

Anahtar Kelimeler:

Kanser, D-dimer, eşik değer, pulmoner emboli

The utility of blood D-dimer levels predicting the diagnosis of pulmonary embolism in cancer patients

Aim: Cancer patients have increased risk of thrombosis. However, the use of D-dimer as a biomarker in malignancies, major surgery, infections and pregnancy was not recommended since D-dimer values were detected in high levels without PE. In this study, we aimed to evaluate the D-dimer values for the selected group of patients in the light of their clinical and demographic data and to reveal the utility of blood D-dimer measurements in cancer patients as a clinical decision rule. Also we aimed to define a new cut- off value for cancer patients who accurately diagnosed as pulmonary embolism.Material and Method: This single -center retrospective and cross-sectional study was based upon patients’ medical reports. The D-dimer values above 500 mcg/dl (>500 mcg/dl ) were considered as positive results.Results: One hundred twenty-eight patients (44 cancer patients (the case), 84 without cancer history (the control)) with accurate diagnosis of pulmonary embolism were included in the study. The mean blood level of D-dimer in the control group was 1729.3±2272.5 mcg/dl while the same parameters were calculated as 3326.9±3162.2 mcg/dl in the group with history of cancer indicating that the presence of malignancy caused a higher level of D-dimer levels. The most appropriate cut-off value in cancer patients was found as 1205 mcg /dl which had the sensitivity of 74%, specifity of 64%. This value corresponded to 2.41 times of the upper limits of the D-dimer value according to our laboratory results.Conclusion: For the diagnosis of PE the blood D-dimer values were absolutely a useful and a valuable parameter in cancer patients. We obtained a different cut-off value for D-Dimer in cancer patients which we think that will probably be a guidance for the future perspective of clinicians.

Keywords:

Cancer, D-dimer, cut-off, pulmonary embolism,

PDF

___

1. Trousseau A. Phlegmasia Alba Dolens. Clinique medicale de l’Hotel-Dieu de Paris, London: New Syndeham Society. 1865; 3: 695–727.
2. Kuderer NM, Ortel TL, Francis CW. Impact of venous thromboembolism and anticoagulation on cancer and cancer survival. J Clin Oncol 2009; 27: 4902–11.
3. Zwicker JI, Furie BC, Furie B. Cancer‐associated thrombosis. Crit Rev Oncol Hematol 2007; 62: 126–36.
4. 4.Donnellan E, Kevane B, Bird BRH, et al. Cancer and venous thromboembolic disease: From molecular mechanisms to clinical management. Curr Oncol 2014; 21: 134–43.
5. Jeong J, Jeong MJ, Choi K, et al. Clinical outcomes of comorbid cancer patients with venous thromboembolism: A retrospective, single-center study in Korea. Medicine (Baltimore) 2019; 98: e17181.
6. 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; 5: 632-4.
7. Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-9.
8. Zhou YX, Yang ZM, Feng J, Shan YJ, Wang WL, Mei YQ. High plasma D-dimer level is associated with decreased survival in patients with lung cancer: A meta-analysis. Tumour Biol 2013; 34: 3701-4.
9. Kupp S, Pöss J. Importance of biomarkers in pulmonary embolism. Internist (Berl) 2019; 60: 571-7
10. Pabinger I, Thaler J, Ay C. Biomarkers for prediction of venous thromboembolism in cancer. Blood 2013; 122: 2011-8.
11. Qdaisat A, Wu CC, Yeung SJ. Normal D-dimer levels in cancer patients with radiologic evidence of pulmonary embolism. J Thromb Thrombolysis 2019; 48: 174-9.
12. Ge LP, Li J, Bao QL, Chen P, Jiang Q, Zhu LR. Prognostic and predictive value of plasma D-dimer in advanced non-small cell lung cancer patients undergoing first-line chemotherapy. Clin Transl Oncol 2015; 17: 57-64.
13. Qdaisat A, Yeung SJ, Variyam DE, et al. Evaluation of cancer patients with suspected pulmonary embolism: Performance of the American College of Physicians guideline. J Am Coll Radiol 2020; 17: 22-30.
14. Cosmi B, Legnani C, Cini M, Guazzaloca G, Palareti G. The role of D-dimer and residual venous obstruction in recurrence of venous thromboembolism after anticoagulation withdrawal in cancer patients. Haematologica 2005; 90: 713-5.
15. Stender MT, Frøkjaer JB, Larsen TB, Lundbye-Christensen S, Thorlacius-Ussing O. Preoperative plasma D-dimer is a predictor of postoperative deep venous thrombosis in colorectal cancer patients: A clinical, prospective cohort study with one-year follow-up. Dis Colon Rectum 2009; 52: 446-51.
16. Kodama J, Seki N, Masahiro S, et al. D-dimer level as a risk factor for postoperative venous thromboembolism in Japanese women with gynecologic cancer. Ann Oncol 2010; 21: 1651-6.
17. Ferroni P, Martini F, Portarena I, et al. Novel high-sensitive D-dimer determination predicts chemotherapy -associated venous thromboembolism in intermediate risk lung cancer patients. Clin Lung Cancer 2012; 13: 482-7.
18. Ay C, Vormittag R, Dunkler D, 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; 27: 4124-9.
19. Qdaisat A, Soud RA, Wu CC, et al. Poor performance of D-dimer in excluding venous thromboembolism among patients with lymphoma and leukemia. Haematologica 2019; 104: 265-8.
20. Dentali F, Ageno W, Pierfranceschi MG, et al. Prognostic relevance of an asymptomatic venous thromboembolism in patients with cancer. J Thromb Haemost 2011; 9: 1081-3.
21. Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood 2013; 122: 1712-23.
22. Armando Tripodi. D-Dimer Testing in Laboratory Practice Clinical Chemistry 2011; 57: 1256–62.
23. Froehling DA, Daniels PR, Swensen SJ, et al. Evaluation of a quantitative D-dimer latex immunoassay for acute pulmonary embolism diagnosed by computed tomographic angiography. Mayo Clin Proc 2007; 82: 556–60.