D-dimer prognostic role in thromboembolism occurrence
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]
Overview
Elevated D-dimer levels is associated with an increased rate of subsequent occurrence of venous thromboembolism among medically ill patients in a wide variety of disease.[1]
Occurrence of VTE
- The predictive value of D-dimer for the occurrence of VTE has been investigated among 923 subjects from the LITE study which data is a combination of data from the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). VTE was defined as DVT confirmed by positive venogram, duplex, or Doppler ultrasound or PE confirmed by pulmonary angiography. One measurement of D-dimer was obtained from stored blood samples and data about the subjects were obtained from hospital medical records. Elevated levels of D-dimers have been shown to be associated with an increased incidence of VTE in general whether idiopathic or secondary to a non-cancer cause independently of the presence of the commonly inherited coagulopathies. According to this study, elevated levels of D-dimers were not associated with higher risk of cancer-related VTE; nevertheless, this finding might have been influenced by the fact that at the time of withdrawal of blood the subjects did not have cancer.[2] Following the publication of this article, this study has received criticism regarding several points. First of all, the prediction of the thrombotic risk based on the D-dimer level relied on the analysis of data that included only one measurement of the D-dimer level without taking into consideration the fluctuation that can occur in D-dimer levels across time. In addition, the cut off points for normal and abnormal D-dimer in the case of subjects with thrombophilia were the same as subjects without thrombophilia. And lastly, the critics addressed a concern regarding highly elevated levels of D-dimer in healthy individuals which raises the question that high D-dimer levels might be resulting from either high production or decreased clearance of D-dimers; therefore, it might be beneficial if future larger studies measure plasma/urine D-dimer ratio rather than plasma D-dimer alone. This is particularly important in order to differentiate healthy individuals from subjects with asymptomatic VTE.[3]
- The Vienna Cancer and Thrombosis Study (CATS) is a prospective observational study that aimed to investigate risk factors for VTE in cancer patients. Out of the enrolled subjects, 821 patients were evaluated for an association between their D-dimer levels and occurrence of VTE. The outcome of this study is the occurrence of objectively measured symptomatic or lethal VTE validated by duplex sonography or venography in the case of DVT and computed tomography or ventilation/perfusion lung scan in the case of PE. 5.7% of the patients developed VTE after 6 months, and by one year 7.9% of patients in total developed VTE. D-dimer levels were found to be significantly more elevated in patients who developed VTE compared to those who did not develop VTE; in fact, the hazard ratio of occurrence of VTE in patients having high levels of D-dimer was 2.2 (95% CI, 1.3 to 3.6; P =0.003) which significantly increased in multivariate analyses where elevated prothrombin fragment 1 and 2, age, gender, surgery, chemotherapy and radiotherapy were taken into consideration in addition to D-dimer. The results remained statistically significant after adjustment for tumor type, size and stage. Hence, D-dimer was found to be an independent risk factor for occurrence of VTE in cancer patients.[4]
- A recent publication in 2013 revealed that high levels of D-dimer are correlated with elevated risk of occurrence of VTE within 4 weeks in patients with recurrent malignant glioma during their treatment with bavacizumab (p<0.0001; sensitivity=89%).[5]
- A study was conducted in China on 458 patients whose mean age is 77 years and who were hospitalized for at least 3 days for either heart failure, respiratory failure, ischemic stroke, infection or recent surgery in order to evaluate whether elevated D-dimer levels more than 500 ng/ml is associated with high risk of occurrence of VTE in elderly patients hospitalized for acute illness. VTE events were defined as either asymptomatic DVT diagnosed by compression ultrasound at the enrollment day and three weeks afterwards or symptomatic VTE within 90 days of the enrollment. The results of this study were adjusted for gender, age, BMI, the acute medical disease and pre-existing comorbidities and they can be summarized as follow:
- A two year follow up in 142 patients with mechanical prosthetic heart valves revealed that D-dimer was a predictive factor of the occurrence of thromboembolic event. It is worth mentioning that patient who spent less than 75% of the time within the therapeutic INR had higher level of D-dimer P = 0.02).[7]
References
- ↑ Halaby R, Popma CJ, Cohen A, Chi G, Zacarkim MR, Romero G; et al. (2014). "D-Dimer elevation and adverse outcomes". J Thromb Thrombolysis. doi:10.1007/s11239-014-1101-6. PMID 25006010.
- ↑ Cushman M, Folsom AR, Wang L, Aleksic N, Rosamond WD, Tracy RP; et al. (2003). "Fibrin fragment D-dimer and the risk of future venous thrombosis". Blood. 101 (4): 1243–8. doi:10.1182/blood-2002-05-1416. PMID 12393393.
- ↑ "Fibrin fragment D-dimer and the risk of future venous thrombosis". Retrieved 28 April 2014.
- ↑ Ay C, Vormittag R, Dunkler D, Simanek R, Chiriac AL, Drach J; et al. (2009). "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. 27 (25): 4124–9. doi:10.1200/JCO.2008.21.7752. PMID 19636003.
- ↑ Misch M, Czabanka M, Dengler J, Stoffels M, Auf G, Vajkoczy P; et al. (2013). "D-dimer elevation and paresis predict thromboembolic events during bevacizumab therapy for recurrent malignant glioma". Anticancer Res. 33 (5): 2093–8. PMID 23645760.
- ↑ Fan J, Li X, Cheng Y, Yao C, Zhong N, Investigators Group (2011). "Measurement of D-dimer as aid in risk evaluation of VTE in elderly patients hospitalized for acute illness: a prospective, multicenter study in China". Clin Invest Med. 34 (2): E96–104. PMID 21463550.
- ↑ Giansante C, Fiotti N, Calabrese S, La Verde R, Pandullo C, Scardi S; et al. (1997). "D-dimer and anticoagulation in patients with mechanical prosthetic heart valves. A 2-year follow-up". Arterioscler Thromb Vasc Biol. 17 (7): 1320–4. PMID 9261262.