D-dimer Cut-off Level Research Articles

Highlights of the American Society of Hematology Meeting 2013: hemostaseology

Venous thromboembolism is associated with substantial morbidity and mortality. Furthermore, the subsequently indicated anticoagulation treatment puts the patient at risk of possible bleeding complications. Therefore, improving treatment strategies as well as diagnostic approaches can optimize patient care. During the 55th Annual Meeting 2013 of the American Society of Hematology the Choosing Wisely® campaign was presented. An expert committee recommends against the test for thrombophilia after venous thromboembolism occurring in the setting of major transient risk factors to avoid over treatment in these patients. Other presentations focused on the use of the direct oral anticoagulants in patients with cancer-associated thromboembolism. However, specific studies comparing direct oral anticoagulants with the state-of the art treatment with low molecular heparins in cancer-associated thromboembolism are still missing. Finally, age-adjusted cut-off levels can increase the specificity of D-Dimer in older patients. Consequently, using clinical probability assessment in the combination with age-adjusted D-dimer cut-off levels may be associated with a larger number of patients in whom pulmonary embolism can be ruled out.

Predictive Value of Plasma d-Dimer Levels for Cancer-related Stroke: A 3-Year Retrospective Study

Cerebrovascular disease is the second leading cause of central nervous system pathology in cancer patients. Cancer-associated hypercoagulation plays an important role in cancer-related stroke. The present study aims to test whether plasma d-dimer levels could predict comorbid malignancy in patients with ischemic stroke. Five hundred sixteen stroke patients with measured d-dimer levels and who were consecutively admitted to our stroke center from 2009 to 2012 were included. Cancer status was determined by medical chart, and 59 patients were identified to have active cancer. An additional 48 cancer patients with stroke were identified from the hospital database. Several d-dimer cutoff levels were used to predict cancer-related stroke. Stroke patients with active cancer had significantly higher d-dimer levels than those without cancer (P < .001). The average d-dimer level in stroke patients without cancer was .66 ± 1.83 mg/L, whereas the levels for active cancer patients from the stroke center and hospital database were 5.70 ± 9.63 mg/L and 10.47 ± 12.31 mg/L, respectively. When using d-dimer of .55 mg/L or more and multiple territory infarctions as criteria, the specificity and positive predictive value (PPV) for cancer-related stroke were 99.7% and 92.9%, respectively. When using d-dimer of 5.5 mg/L or more as the cutoff value, the test had a high specificity and PPV regardless the brain magnetic resonance imaging (MRI) findings. Six stroke patients fitting our criteria were confirmed to have occult malignancy after comprehensive cancer survey. Extraordinary high d-dimer levels or combining d-dimer and MRI findings may be used as a screening tool to detect malignancy in stroke patients.

Influence of C‐reactive protein levels and age on the value of D‐dimer in diagnosing pulmonary embolism

Recently, the number of performed CT-angiographies to diagnose pulmonary embolism (PE) rised markedly, while the incidence of PE hardly increased. This low yield of CT-angiography leads to more patients exposed to radiation and higher costs. The diagnostic value of age, C-reactive protein (CRP) and D-dimer in PE was investigated. Additionally an age-adjusted D-dimer cutoff level [age-adjusted cutoff=age/100mg/L] was compared with the conventional cutoff level in diagnosing PE for patients ≥50yr. This observational study (2004-2007) included all consecutive patients suspected for PE presenting on the emergency department with a performed CT-angiography after measuring CRP and D-dimer levels. Of 4609 patients suspected for PE, 1164 patients underwent CT-angiography of whom 309 (26.5%) had PE. Correlation between CRP and D-dimer was 0.42 (P<0.001). D-dimer and age correlated positively (rs =0.33, P<0.001), but only in patients >50yr and independent of PE. Multivariate regression analysis showed significant contribution of age, D-dimer and age-adjusted D-dimer for diagnosing PE, but not for CRP. Using an age-adjusted D-dimer cutoff value increased specificity from 37% to 50%, whereas sensitivity declined from 96% to 90%. Applying this age-adjusted cutoff level in patients ≥70yr, specificity increased from 18% to 40%, while sensitivity decreased from 96% to 88%. In the prediction of PE, age and D-dimer levels are relevant, while CRP level is not. Using an age-adjusted D-dimer cutoff in older patients remarkably improves the specificity of D-dimer testing with a minor decline in sensitivity. This may increase the yield of CT-angiography in diagnosing PE.

Should the cut-off value of D-dimer be elevated to exclude pulmonary embolism in acute exacerbation of COPD?

The aim of this study was to evaluate the D-dimer levels in patients with chronic obstructive pulmonary disease (COPD) exacerbation with and without pulmonary embolism (PE) and to attempt to define a new cut-off value for D-dimer to exclude the diagnosis of PE in patients with COPD exacerbation. This cross-sectional study was performed between the June 2012 and January 2013. The COPD patients who were admitted to the emergency department with acute exacerbation were consecutively included. D-dimer levels were measured upon admission. All patients underwent computed tomography angiography (CTA) and Doppler ultrasonography (US) of the lower extremities. A total of 148 patients were enrolled. Fifty-three patients (36%) who did not have PE had higher than normal (>0.5 pg/mL) D-dimer levels. The D-dimer levels of the COPD patients with PE were significantly higher than those of the patients without PE (2.38±2.80 vs. 1.06±1.51 pg/mL) (P<0.001). The cut-off value for D-dimer in diagnosing PE in the COPD patients was 0.95 pg/mL. The area under the receiver operating characteristic (ROC) curve was 0.752±0.040 (95% CI: 0.672-0.831) (P<0.001). This study showed that the D-dimer concentrations of COPD patients who are in the exacerbation period may be higher than normal, even without PE. The cut-off level for D-dimer was 0.95 pg/mL (sensitivity 70%, spesificity 71%) for the exclusion of PE in the patients with COPD exacerbation. The D-dimer cut-off value that is used to exclude PE in patients with acute exacerbation of COPD should be reevaluated to prevent the excessive use of further diagnostic procedures.

D-DIMER CUT-OFF ADJUSTED TO AGE PERFORMS BETTER FOR EXCLUSION OF PULMONARY EMBOLISM IN PATIENTS OVER 75 YEARS

Introduction: A D-dimer (DD) test improves the diagnosis of PE (PE) when combined with clinical scores. However, as DD levels increase physiologically with age, this testing has less specificity in older patients. Douma et al. (1). proposed the use of an age adjusted DD cut-off to increase the specificity of this test.Methods: We performed chart reviews of patients, older than 75 years, hospitalized for suspicion of PE in 2010-2011 (n = 165). PE was assessed with either pulmonary scintigraphy (PS, n = 64) and/or pulmonary computed tomography (PC, n = 101). We compared the specificity, sensitivity and false negatives rates of an age adjusted DD cut-off level (“ADC“ = (patient’s age × 0.01) μg/ml) with those of the conventional cut off level (“CDC”= 0.5 μg/ml).Results: PE was confirmed in 45 cases. In the 120 patients with no PE (negative PS or PC), 7 cases had CDC below cut-off levels, while 28 cases had an ADC below cut-off level. The use of the ADC thus increased the specificity (ADC: 23% vs CDC: 6%, p = 0.0001), and this was obtained without significant loss of sensitivity (ADC: 96% vs CDC: 98%, ns). Patients were clinically assessed with the revised Geneva scores. In the negative PE group, the number of patients classified with low, moderate or high clinical probability of PE were 31, 81 and 8, respectively. The percentage of patients with DD values below cut-off values was 4%, 0.8% and 0.8%, respectively using the CDC and 9%, 12% and 2.5% using the ADC.Conclusions: In this age group, the specificity of ADC was found superior to that of the CDC. The clinical use of the ADC might be associated with less useless diagnosis procedures, without significant increase in rate of diagnosis failure.

Determination of the D-dimer cutoff level and its application in the diagnosis of venous thromboembolism in psychiatric patients

Determination of the D-dimer cutoff level and its application in the diagnosis of venous thromboembolism in psychiatric patients

Clinical features of patients with left atrial thrombus undergoing anticoagulant therapy

Left atrial (LA) thrombus was sometimes found by transesophageal echocardiography (TEE) in non-valvular atrial fibrillation (AF), even in the setting of continuous warfarin therapy. A D-dimer cutoff level of 0.50 μg/mL appears to be a useful marker to rule out venous vein thrombosis. This study analyzed the clinical features of patients with LA thrombi who received anticoagulant therapy and whether the D-dimer test is useful to exclude LA thrombus. Two hundred twenty-five consecutive patients with AF (149 with paroxysmal and 76 with persistent) were enrolled. All patients received continuous warfarin therapy with the prothrombin time-international normalized ratio (PT-INR) between 1.6 and 3.0 for more than 3 months and TEE was performed. LA thrombi were present in 23 and absent in 202 patients. Age, gender, and PT-INR (1.96 ± 0.59 vs. 1.98 ± 0.53) were not different between the two groups. Persistent AF (65 vs. 30%; p < 0.005), LA diameter (44 ± 5 vs. 40 ± 7 mm; p < 0.005), ejection fraction (57 ± 13 vs. 65 ± 9%; p < 0.005), brain natriuretic peptide levels (203 ± 209 vs. 105 ± 166 pg/mL; p < 0.05), D-dimer (0.55 ± 0.70 vs. 0.16 ± 0.20 μg/mL; p < 0.001), LA appendage flow velocity (33 ± 15 vs. 54 ± 19 cm/s; p < 0.001), CHADS(2) scores (2 ± 1 vs. 1 ± 1; p < 0.005), and CHA(2)DS(2)-VASc scores (3 ± 2 vs. 2 ± 1; p < 0.005) were significantly different in both groups. Although multivariate analysis showed that D-dimer and LA appendage flow velocity were significant independent predictors of LA thrombus, D-dimer levels below 0.5 μg/mL were found in 19 of 23 patients with LA thrombi. D-dimer levels below 0.5 μg/mL is not enough to rule out LA thrombus in AF patients with well-controlled anticoagulation.

Cerebral vein thrombosis: clinical manifestation and diagnosis

BackgroundCerebral venous thrombosis (CVT) is a disease with a wide spectrum of symptoms and severity. In this study we analysed the predictive value of clinical signs and symptoms and the contribution of D-dimer measurements for diagnosis.MethodsWe evaluated consecutive patients admitted with suspected CVT receiving non-invasive imaging. Symptoms and symptom combination as well as D-dimer levels were evaluated regarding their diagnostic value.Results239 patients were included in this study, 170 (71%) were females. In 39 patients (16%) a CVT was found. For identifying a CVT patients underwent either a venous CT-angiography or MR-angiography or both. No combination of symptoms either alone or together with the D-dimer measurements had a sensitivity and positive predictive value as well as negative predictive value and specificity high enough to serve as red flag. D-dimer testing produced rates of 9% false positive and of 24% false negative results. For D-dimer values a Receiver Operating Characteristic curve (ROC) and the area under the curve (AUC = 0.921; CI: 0.864 - 0.977) were calculated. An increase of sensitivity above 0.9 results in a relevant decrease in specificity; a sensitivity of 0.9 matches a specificity value of 0.9. This corresponds to a D-dimer cut-off level of 0.16 μg/ml.ConclusionImaging as performed by venous CT-angiography or MR-angiography has a 1 to 2 in 10 chance to detect CVT when typical symptoms are present. D-dimer measurements are of limited clinical value because of false positive and negative results.

A cross-sectional study comparing D-Dimer levels from first trimester to day 2 post partum in low risk pregnancies

D-Dimer measurement is a highly recognised test to exclude venous thromboembolism (VTE). However, during pregnancy D-Dimer levels increase significantly, making diagnosis of VTE using the recommended non-pregnancy cut-off point ineffectual.The...

Therapeutic Significance of a D-dimer Cut-off Level of &gt;3 g/ml in Colorectal Cancer Patients Treated with Standard Chemotherapy plus Bevacizumab

The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy. The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months. Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 µg/ml. The appropriate D-dimer cut-off level was 3 µg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 µg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 µg/ml, only one patient developed a venous thromboembolism. A D-dimer cut-off level of 3 µg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy.

Clinical decision rule and D-dimer have lower clinical utility to exclude pulmonary embolism in cancer patients

Patients with malignancy frequently present with clinically suspected pulmonary embolism (PE). However, the safe and efficient combination of a clinical decision rule (CDR) and D-dimer test to rule out PE performs less well in patients with malignancy. We examined potential explanations and analysed whether elevating the D-dimer cut-off could improve the clinical utility. We used data on consecutive patients with suspected PE included in a multicenter management study. The performance of the Wells CDR and the D-dimer test was compared between patients with and without malignancy and multivariable analysis was used to compare the weights of the CDR variables. Furthermore, we combined the CDR (cut-off ≤4) with different D-dimer cut-off levels for the exclusion of PE. Of 3,306 patients with suspected PE, 475 (14%) had cancer. The Wells rule variables were less diagnostic in cancer patients. Increasing the D-dimer cut-off level to 700 μg/l for all ages or using an age-dependent cut-off resulted in an increase in the proportion of patients in whom PE could be excluded from 8.4% to 13% and 12%, respectively. The corresponding false-negative rates were 1.6% (95% confidence interval 0.3-8.7%) and 0.0% (0.0-6.3%). The Wells CDR and D-dimer perform less well in patients with suspected PE if they have cancer. Individual variables in the Wells rule are less diagnostic in cancer patients than in non-cancer patients with suspected PE. A CDR combined with an age-dependent D-dimer cut-off shows a modest improvement of the strategy in cancer patients.

D-Dimer and Prothrombin Fragment 1 + 2 Predict Venous Thromboembolism in Patients With Cancer: Results From the Vienna Cancer and Thrombosis Study

Venous thromboembolism (VTE) is a well-recognized complication of cancer. Laboratory parameters might be useful to assess the VTE risk in patients with cancer. The aim of this study was to investigate D-dimer and prothrombin fragment 1 + 2 (F 1 + 2), which reflect activation of blood coagulation and fibrinolysis, for prediction of cancer-associated VTE. In a prospective, observational, cohort study of 821 patients with newly diagnosed cancer or progression of disease who did not recently receive chemotherapy, radiotherapy, or surgery were enrolled and followed for a median of 501 days (interquartile range, 255 to 731 days). The malignancies in these patients were as follows: breast (n = 132), lung (n = 119), stomach (n = 35), lower gastrointestinal tract (n = 106), pancreas (n = 46), kidney (n = 22), and prostate (n = 101) cancers; high-grade glioma (n = 102); malignant lymphoma (n = 94); multiple myeloma (n = 17); and other tumor types (n = 47). The study end point was occurrence of objectively confirmed symptomatic or fatal VTE. VTE occurred in 62 patients (7.6%). The cutoff level for elevated D-dimer and elevated F 1 + 2 was set at the 75th percentile of the total study population. In multivariable analysis that included elevated D-dimer, elevated F 1 + 2, age, sex, surgery, chemotherapy, and radiotherapy, the hazard ratios (HRs) of VTE in patients with elevated D-dimer (HR, 1.8; 95% CI, 1.0 to 3.2; P = .048) and elevated F 1 + 2 (HR, 2.0; 95% CI, 1.2 to 3.6; P = .015) were statistically significantly increased. The cumulative probability of developing VTE after 6 months was highest in patients with both elevated D-dimer and elevated F 1 + 2 (15.2%) compared with patients with nonelevated D-dimer and nonelevated F 1 + 2 (5.0%; P < .001). High D-dimer and F 1 + 2 levels independently predict occurrence of VTE in patients with cancer.

D-dimer Testing and Venous Thromboembolism

With its high sensitivity and negative predictive value, D-dimer (DD) testing has gained a role in the diagnostic work-up of suspected venous thromboembolism (VTE) for the exclusion of the disease, potentially reducing the need for imaging tests. The diagnostic yield of DD testing is affected not only by the choice of the appropriate assay for its measurement, but also by patient characteristics. As a consequence, its clinical usefulness for the exclusion of suspected VTE should be carefully evaluated in special clinical settings. There is increasing evidence that DD testing after anticoagulation withdrawal for a first unprovoked VTE episode may be useful to identify patients at higher risk of recurrence, and may help clinicians with the decision of whether to continue or stop anticoagulant treatment. However, further studies are needed to establish the optimal timing of DD testing and the best DD cut-off level that predicts recurrence, and to develop a clinical prediction rule for recurrent VTE.

Predictive Value of D-Dimer Levels for Venous Thromboembolism in Cancer Patients: Results from the Vienna Cancer and Thrombosis Study (CATS)

Venous thromboembolism (VTE) is a frequent complication of cancer, which represents a major cause of morbidity and mortality in cancer patients. Laboratory parameters with a predictive value for VTE could help to assign a patient to a high or low risk group. D-Dimer is a global indicator of coagulation activation and fibrinolysis and is frequently elevated in cancer patients, even without thrombosis. The measurement of D-dimer levels is a widely applied test in the diagnostic work-up of patients with suspected VTE. Prospective observational studies have shown that D-dimer levels have a predictive value for the risk of recurrence in non-cancer patients after the discontinuation of oral anticoagulant treatment. Whether testing for D-Dimer at diagnosis of cancer would be useful for prediction of cancer-associated thrombosis, is not elucidated because up to now appropriately designed prospective studies have not yet been carried out. Therefore, we have assessed D-Dimer levels in cancer patients as risk predictor for VTE and provide a report from the ongoing prospective observational CATS, which was initiated in October 2003. Patients with newly diagnosed cancer or progression of disease that had neither chemotherapy within the last three months, nor radiotherapy nor surgery within the last two weeks were recruited and followed prospectively. Occurrence of VTE and information on the patients' anti-cancer-treatment within the follow up period were recorded. Observation ended with occurrence of VTE, death or after 2 years. VTE has always been confirmed by imaging. D-Dimer levels were measured with a D-Dimer latex agglutination assay. Kaplan Meier and Cox regression analysis were applied for statistical calculation. Data on 821 patients with cancer (370 women/451 men, median age [IQR]: 62 [53–68] yrs) were available for analyses. Patients were followed for a median observation time of 454 days. Main tumour entities were malignancies of the breast (n=132), lung (n=119), upper (n=35) and lower gastrointestinal tract (n=106), pancreas (n=46), kidney (n=22) and prostate (n=101). Furthermore, 102 patients had high-grade glioma, 94 lymphomas, 17 multiple myeloma and 47 other tumour types. During the observation period VTE occurred in 62 patients (24 female/38 male, median age [IQR]: 60 [50–66] yrs). Elevated levels of D-Dimer (cut-off level 1.44 μg/ml, representing the 75th percentile of the total study population) [hazard ratio (HR): 2.4, 95% CI 1.4–4.0], surgery [HR: 2.3, 95% CI 1.0–5.3] and radiotherapy [HR: 2.3, 95% CI 1.2–4.4] were statistically significant risk factors for VTE in multivariate analysis including D-Dimer, age, sex, surgery, chemotherapy and radiotherapy. The cumulative probability of developing VTE after 6 months was 11.2 % in patients with D-Dimer levels above and 4.2 % in those below the 75th percentile (p=0.003). In conclusion, cancer patients with elevated D-Dimer levels have an approximately 3-fold increased risk for future occurrence of VTE. High levels of D-Dimer independently predict VTE in these patients and D-Dimer measurement at diagnosis of cancer would help identify patients at increased risk for VTE.

Prediction of left atrial appendage thrombi in non-valvular atrial fibrillation

There is little knowledge about the predictors of left atrial appendage (LAA) thrombi in non-valvular atrial fibrillation (NVAF). We investigated the ability of D-dimer to predict LAA thrombi. In this study, 925 patients with NVAF were enrolled. At the time of transoesophageal echocardiography (TEE), D-dimer levels were measured simultaneously. Significant independent predictors of LAA thrombi were the presence of congestive heart failure [odds ratio (OR) 3.10, 95% confidence interval (CI) 1.77-5.50, P < 0.0001), a history of recent embolic events (OR 3.39, 95% CI 1.90-6.04, P < 0.0001), and D-dimer levels (OR 97.6, 95% CI 17.3-595.8, P < 0.0001). Receiver operating characteristic analysis yielded an optimal cutoff value of 1.15 microg/mL for D-dimer to detect LAA thrombi. LAA thrombi were detected in 21.8% of patients with higher D-dimer values, whereas it was detected in only 3.1% of patients with lower D-dimer values. D-dimer cutoff level of 1.15 microg/mL had a negative predictive value of 97% for identifying LAA thrombi. In patients with NVAF, D-dimer may be helpful for predicting the absence of LAA thrombi. D-dimer level was clinically useful to guide the management of patients with NVAF, especially for those complicated with congestive heart failure and/or recent embolic events.

Rapid D-dimer test combined a clinical model for deep vein thrombosis. Validation with ultrasonography and clinical follow-up in 383 patients.

An optimal approach to the diagnosis of deep vein thrombosis (DVT) in lower limbs in the emergency department is still unknown. In this prospective cohort study, we aimed to evaluate the accuracy of the widely available plasma D-dimer test (VIDAS) and establish the usefulness of combining D-dimer testing with a clinical model to reduce the need for serial ultra-sonographies and improve the diagnostic strategy of DVT. We performed a cohort study in 383 consecutive outpatients referred to the emergency department of Hospital La Princesa, with clinical suspicion of DVT. The patients were stratified into three pre-test probability categories using an explicit clinical model (Wells score), and underwent a quantitative automated ELISA D-dimer assay (VIDAS D-Dimer bioMérieux). Patients were managed according to the diagnostic strategy based on clinical probability and compression ultrasonography (CU). Patients for whom DVT was considered a high pre-test probability with negative ultrasonographic findings in the initial CU, returned the following week for repeat ultrasonography. All patients with DVT excluded did not receive anticoagulant therapy, and were followed up for three months to monitor the development of venous thromboembolic complications. DVT was confirmed in 102 patients (26.6%): 95 in the initial test, four in the second test, and three who developed venous thromboembolic complications in the three-month follow-up period. The calculated D-dimer cut-off level was 1 micro g/ml. One hundred patients (98%) with DVT had positive D-dimer. D-dimer had a sensitivity of 98% and a negative predictive value of 98.6%. Among the high-probability patients with positive D-dimer tests and initial negative CU, 9.75% had DVT on repeat CU at one week. The study results suggest that the addition of VIDAS D-dimer to this diagnostic algorithm could improve the management of patients with suspected DVT in daily practice. A diagnostic approach of DVT based on D-dimer (cut-off > or =1 microg/ml) as the first diagnostic tool for the exclusion of DVT, and the clinical probability model as the tool that identifies those patients requiring a second ultrasonography is useful and suitable for daily medical practice.