Lower D-dimer Levels Research Articles

Q.C.M.

Venous thromboembolism (VTE) is a serious complication of surgery, including gynecologic surgery. The plasma D-dimer test and proximal/distal vein compression ultrasonography are frequently used as an easy, preoperative VTE screening method. However, targeted patients for these two examinations have not been established.We retrospectively reviewed 380 gynecologic surgical patients who underwent preoperative VTE screening including the plasma D-dimer test and proximal/distal vein compression ultrasonography from March 2014 to February 2015. All patients underwent laparotomy or laparoscopy. In patients with a high risk of pulmonary thromboembolism, compression ultrasonography was substituted by or combined with contrast-enhanced computed tomography. With regard to D-dimer level, patients were divided to three groups: D-dimer level ≤0.5 μg/mL (group A), D-dimer level between 0.6 and 0.9 μg/mL (group B), and D-dimer level ≥ 1.0 μg/mL (group C).Twenty-seven cases had preoperatively detected VTE. Three patients in group B with benign disease were diagnosed with VTE before surgery. Among benign patients in group B, there was a significant difference in preoperative VTE occurrence between patients without risk factors (0/68 cases) and those with risk factors (3/54 cases). All 11 patients with benign disease having preoperative VTE had one or more risk factors.Even in benign cases with low preoperative D-dimer levels (0.6–0.9 μg/mL), an imaging test should be added when the patient has one or more VTE risk factors.

Influencia de los simbióticos en la disfunción multiorgánica: ensayo aleatorizado

Background and objectiveTo assess whether the administration of symbiotic preparations in patients with multi-organ failure (MOF) diminishes the evolution of the failure, the inflammatory response generated, the colonization pattern and the Intensive Care Unit (ICU) infectious illness. Patients and methodRandomized and controlled trial. All patients with MOF were included. Neutropenia and acute pancreatitis patients were excluded. A symbiotic (Simbiotic Drink®) was administered via enteral feeding during the first 7 days. Variables of interest were: Sequential Organ Failure Assessment (SOFA) score evolution, systemic concentrations of lactate, fibrinogen and D-dimer; skin and mucosa colonization and infectious disease register. ResultsEighty-nine patients were included; 46 in the symbiotic group (SG) and 43 in the control group (CG). There were 68.5% males, with a median age of 69 years. There were no significant differences in the patients’ fundamental characteristics (medical history, age, reason for admission, severity scores), nor in the length of ICU stay or in mortality. Comparing the SG with the CG, there were lower lactate levels on the second day, more fibrinogen levels on the days 5 and 7, and lower D-dimer levels on the day 7. Eight hundred and ninety-five cultures were performed for colonization assessment, with isolation of 528 microorganisms. No differences in microbiological resistance were found; there were more colonization in the SG by Candida in mucous membranes after the third day; this situation resolved after stopping symbiotic administration. Twenty-two patients suffered an infectious disease in ICU, 14 in SG (42.4%) and 19 in CG (57.6%). Although no differences were found in the microbiological pattern, there was a predominance of Candida spp. over other microorganisms (4 vs. 0 cases). ConclusionsThe symbiotic preparation Simbiotic Drink®, administered in MOF, results in differences to improve the early lactate levels and late fibrinogen/D-dimer levels as well as mucosa colonization by Candida. There were no differences in the ICU evolution.

Plazma D-dimer düzeyleri akciğer kanserinde prognoz için bir belirteç olabilir mi?

Plasma concentrations of circulatory markers of hemostatic activation which may be associated with tumor growth and dissemination have been shown to predict prognosis in malignancy. The present study was designed to investigate the prognostic value of plasma D-dimer level in lung cancer. Plasma levels of the D-dimer in 138 lung cancer patients [98 non-small cell lung cancer (NSCLC), 40 small cell lung cancer (SCLC)] were measured before the initiation of any therapy and each chemotherapy. There were 124 (89.9%) men and 14 (10.1%) women with a mean age of 62.8 years (range 38-84). There were no statistically significant differences among the histopathologic types for NSCLC patients. Stage IIIA NSCLC group had statistically significant higher D-dimer level than stages I-II and IV. D-dimer levels were increased significantly after 4 cycles of chemotherapy in progressive disease. The median survival times in NSCLC patients were 26.6 months (95% CI, 17.6-35.6) and 15.9 months (95% CI, 4.2-27.7; p= 0.037) respectively, for patients with a low D-dimer level (≤ 1.2 ng/L) and a high D-dimer level (> 1.2 ng/L).With the cox-regression analysis, the plasma level of D-dimer and tumour stage were identified as independent predictive factors of the survival. These results suggest that plasmalevel of D-dimer can act as a predictive factor of decreased survival and a poor response to the treatment in lung cancer.

Correlation between baseline plasma D-dimer levels and prognosis in patients with non-smal cell lung cancer

To investigate the correlation of baseline plasma D-dimer levels and clinicopathological features and tumor VEGF expression in non-small cell lung cancer(NSCLC) patients, and to evaluate the value of D-dimer in predicting survival time. A retrospective review of the clinicopathological data of 290 NSCLC patients confirmed pathologically in Tianjin Cancer Hospital from July 2007 to April 2009 was performed. The correlations between plasma baseline D-dimer levels and clinicopathological characteristics and progonosis were analyzed. For 290 NSCLC patients with low ( ≤ 0.3 µg/ml) and high (>0.3 µg/ml) D-dimer levels, the median survival times were 54.0 months and 46.2 months, respectively (P < 0.05), and for the patients with stages I, II, IIIA, IIIB and IV NSCLC, the median survival times were 58.1, 40.6, 26.7 and 23.5 months, respectively (P < 0.05). In the operable patients (stages I, II and IIIa) with low and high D-dimer levels, the median progression-free survivals (PFS) were 35.0 and 11.0 months, respectively (P < 0.05). Furthermore, the median PFSs were 57.2 months and 19.6 months, respectively, in these operable patients without and with lymph node metastasis (P < 0.05). High levels of baseline plasma D-dimer may indicate advanced disease stage, larger tumor size, lymph node metastasis and stronger tumor angiongenesis to some extent, and may be useful in prediction of survival time in NSCLC patients of different stages.

High plasma D-dimer level is associated with decreased survival in patients with lung cancer: a meta-analysis

An elevated plasma D-dimer level indicates the activation of coagulation and fibrinolysis. Several studies suggested that high level of plasma D-dimer was associated with the prognosis of lung cancer. In the present study, we performed a meta-analysis to evaluate the relationship between plasma D-dimer level and the prognosis of lung cancer based on larger sample size. We retrieved the literature, assessed and selected the data, and performed the statistical analysis according to the RevMan 5.0 guidelines. Literature-based searching was guided to gather data, and fixed-effects model was used to pool the hazard ratio according to the test of heterogeneity. A total of seven eligible studies including 1,377 lung cancer patients were analyzed. Survival time was significantly better in patients in the low D-dimer group than those in the high D-dimer group (hazard ratio for high D-dimer group = 1.12; 95% confidence interval 1.02 to 1.23). Patients with high levels of D-dimer have a poorer overall survival compared with those patients with low levels of D-dimer.

D-dimer and clinicoradiologic features in cerebral venous thrombosis

ObjectivesCerebral venous thrombosis (CVT) is a disease with varying clinical presentation and diagnosis presents many challenges in clinical practice. We investigated, whether D-dimer levels reflect clinical presentation, radiologic features, and outcome in CVT. MethodsWe included all consecutive patients with CVT treated in our hospital from 1987 to 2010 with D-dimer levels measured before initiation of anticoagulant treatment. D-dimer was categorized as low (<0.5mg/L), intermediate (0.6–2.0mg/L), and high (>2.0mg/L). Based on delay from symptom onset to hospital presentation mode of onset was categorized as acute (<2days), subacute (2–14days), or chronic (>14days). ResultsIn 71 patients included median level of D-dimer was 1.40mg/L (range 0.05–13.0mg/L). In 9 (12%) patients D-dimer was low, and of these, 7 presented with subacute and 2 with chronic mode of symptom duration. Elevated D-dimer levels were associated with thrombosis in multiple sinuses (P=0.044). Longer symptom duration was correlated with low D-dimer levels (P=0.010). ConclusionsIn clinical practice, low levels of D-dimer cannot rule out CVT in patients with subacute or chronic disease. High D-dimer levels correlate with greater thrombus extension and acute onset of symptoms.

Dalteparin Low Molecular Weight Heparin (LMWH) in ovarian cancer: A phase II randomized study

ObjectiveLow molecular weight heparin reduces the risk of venous thromboembolism (VTE) and may have antineoplastic effects by interfering with angiogenesis and with tumor growth and metastasis. A multicentre phase II randomized trial was done to evaluate the antineoplastic potential of dalteparin in ovarian cancer (OC). Materials and MethodsWomen with newly-diagnosed epithelial OC were randomized to receive standard chemotherapy (CT) and one of 3 doses of dalteparin (50IU/kg, 100IU/kg, or 150IU/kg) subcutaneously once daily during the first 3 of 6cycles of 3-weekly CT. Blood was drawn on day 1 of each cycle for CA125 and, in a substudy of randomized patients, for markers of coagulation activation and angiogenesis. The primary outcome was tumor response defined by ≥50% reduction in serum CA125 from baseline sustained for at least 28days. Patients were followed until the end of CT. ResultsThe study was terminated early due to poor recruitment. Seventy-seven women were evaluable for the primary outcome. A 50% drop in CA125 at the end of cycle 3 was seen in 85% of the 50IU/kg group, 92% of the100 IU/kg group, and 85% of the 150IU/kg group. There were no symptomatic VTE or major bleeding events while on dalteparin. Two patients experienced VTE several days after discontinuing study drug. Women on dalteparin had lower levels of D-dimer and thrombin-antithrombin, and higher levels of tissue factor pathway inhibitor, relative to baseline. ConclusionDalteparin is safe and well tolerated in women receiving CT for newly-diagnosed epithelial OC. A dose–response effect was not identified. The lack of control group precluded any inference on the antineoplastic effect of dalteparin.

Venous thromboembolism and coagulation activity in patients with immune thrombocytopenia treated with thrombopoietin receptor agonists

Venous thromboembolism and coagulation activity in patients with immune thrombocytopenia treated with thrombopoietin receptor agonists

D-dimers as a tumor marker in GIST: Can it reduce the frequency of CT scanning in patients receiving palliative imatinib?

119 Background: Treatment with palliative imatinib has improved outcomes in advanced GISTs, with a reported 2 year PFS of 50%. Guidelines suggest monitoring during imatinib by CT scan at 12 week intervals. There are no validated biomarkers to assist in disease evaluation. High d-dimer levels are associated with poor prognosis in several cancers and are predictive of disease progression during chemotherapy. In the diagnosis of venous thromboembolism, low D-dimer levels have a high negative predictive value (npv) for thrombosis. We investigated whether low d-dimers have a clinically useful npv for GIST progression. Methods: We retrospectively identified all patients treated with palliative Imatinib for GIST in a single tertiary referral centre using a systematic search of an electronic clinical database. Every 12 weeks during treatment patients were assessed by clinical evaluation, CT and a d-dimer measurement (HemosIL HS assay). The prognostic value of d-dimers was assessed by Cox regression. The clinical utility of d-dimers as a biomarker for radiological progression (rPD) was evaluated using radio operator curve (ROC) analysis. Results: 50 patients treated between Jan 2002 and June 2011 met criteria for inclusion. D-dimers were prognostic for progression free survival and overall survival, when analysed by level or over time (p &lt;0.05). Over 460 clinical observations with CT and d-dimer were analysed. Scans demonstrating rPD were associated with higher d-dimer levels and a rising trend (p &lt;0.05). D-dimer levels &lt;1000 had a npv for rPD of 85%. An asymptomatic patient with a d-dimer level &lt;1000 and a falling level over time was seen in 32% of observations, and had a npv for rPD of 92%. Conclusions: D-dimers may have a useful role in disease monitoring for GIST patients treated with palliative imatinib, particularly as a negative predictor of progression. This may reduce the burden of CT scanning in a useful percentage of patients but will require further validation.

Prognostic Value of Plasma D-Dimer Levels in Lung Carcinoma

AIMS AND BACKGROUNDS: Plasma concentrations of several proteases of the coagulation system have been shown to predict prognosis in malignancy. The study was aimed to investigate the prognostic value of plasma D-dimer concentrations and some other coagulation factors in lung cancer. Between 2004 and 2008, 100 newly diagnosed lung cancer patients and 25 healthy individuals serving as the control group were evaluated. The patients had no history of coagulation system disorders or anticoagulant therapy. Plasma D-dimer concentrations, prothrombin time, activated partial thromboplastin time, international normalized ratio and blood counts of the patients were obtained. Patient age, lung cancer stage, tumor histology, therapy modalities (surgery, chemotherapy and radiotherapy), therapy outcomes and survival durations of the patients were determined. The median age of the patients (86 males/14 females) was 67 years, and 15% had stage 2, 26% had stage 3A, 24% had stage 3B, and 35% had stage 4 disease. Histologic subtypes were non-small cell carcinoma (87%) and small cell carcinoma (13%). The median D-dimer level of the patients was 1250 ng/dl, which was significantly higher than that of the control group. Survival duration was significantly higher in patients with low D-dimer levels (P <0.05). D-dimer plasma levels predicted survival independently of the clinical stage of disease, histologic tumor type and performance status of the patient (HR = 5.1; 95% confidence interval, 1.015-1.19, P = 0.013). Plasma D-dimer level was significantly higher in metastatic disease (P <0.01). The results suggest that D-dimer plasma levels might be useful to predict the clinical outcome and survival of patients with lung cancer.

Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

BackgroundIn cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR).MethodsWe performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB).Results160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant].We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events.ConclusionsProlonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.Current Controlled Trials numberISRCTN: ISRCTN84413719

Utilization and Yield of Chest Computed Tomographic Angiography Associated with Low Positive D-dimer Levels

BackgroundIt is unclear to what degree broadly applied D-dimer testing combined with a low threshold for imaging with even minimally positive results may be contributing to the utilization of chest computed tomographic angiography (CTA). Study ObjectivesTo determine what proportion of chest CTAs for suspected pulmonary embolism (PE) were performed in the setting of minimally elevated D-dimer levels, and to determine the prevalence of PE in those patients when stratified by clinical risk. MethodsRetrospective chart review of all patients who had chest CTA for the evaluation of suspected PE during the years 2002–2006 in a suburban community teaching hospital emergency department. ResultsThere were 1136 eligible patient visits, of which 353 (31.1%) were found to have D-dimer levels in the low positive range (0.5–0.99 μg/mL). Of these 353 patients, 9 (2.6%; 95% confidence interval [CI] 0.9–4.2%) were diagnosed with PE. There were also 109 patients (9.6%) who had normal D-dimer levels (<0.5 μg/mL). Two of these 109 (1.8%; 95% CI 0–4.2%) were diagnosed with PE. When stratified by the Pulmonary Embolism Rule-out Criteria, 99 of 353 patients with low positive D-dimer levels (28.0%; 95% CI 23.4–32.7%), and 14 of 109 with normal D-dimer levels (12.8%; 95% CI 6.6–19.1%) were classified as low risk, none of whom had PE. ConclusionsNearly one-third of all chest CTAs were done for patients with minimally elevated D-dimer levels, and another 9.6% for patients with normal D-dimer levels with very low yield. Further research to define clinical criteria identifying patients with minimal risk of PE despite low positive D-dimer levels represents an opportunity to improve both patient safety and utilization efficiency of chest CTA.

Changes in Inflammatory and Coagulation Biomarkers: A Randomized Comparison of Immediate versus Deferred Antiretroviral Therapy in Patients With HIV Infection

Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compared with those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. Stored specimens for 254 participants (126 drug conservation [DC] and 128 viral suppression [VS]) who were naïve to ART or off ART (6 months or longer) were analyzed for interleukin-6, high sensitivity C-reactive protein, and D-dimer at baseline and Months 2 and 6. At Month 6, 62% of the VS group had HIV RNA less than 400 copies/mL and median CD4 count was 190 cells/mm3 higher than for the DC group (590 versus 400 cells/mm3). Compared with DC, the VS group had 32% (95% confidence interval, 19%-43%) lower D-dimer levels at Month 6 (P < 0.001); differences were not significant for high sensitivity C-reactive protein or interleukin-6 levels. In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not interleukin-6 and high sensitivity C-reactive protein, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection.

Isolated Anterior Cerebral Artery Territory Infarction: Dissection as an Etiological Mechanism

Background: Intracranial arterial lesions are important causes of ischemic stroke, particularly in the Asian population. Of the intracranial lesions, the etiology of isolated anterior cerebral artery (ACA) territory infarction is not fully elucidated. The purpose of this study was to determine the etiological and clinical characteristics of patients with isolated ACA territory infarction, especially those with ACA dissection. Methods: Of 3,115 consecutive patients with acute ischemic stroke, 42 patients (1.3%, 30 men, 38–88 years old) having an isolated ACA territory infarction were studied. Infarcts were principally verified by diffusion-weighted MRI, and vascular lesions were identified by MRA, CTA, or digital subtraction angiography. Three-dimensional rotational angiography was performed if needed. Results: Eighteen patients (43%) were diagnosed as having ACA dissection. The stroke subtypes of the other 24 patients included cardioembolism for 6 patients and large-artery atherosclerosis for 8. Patients with dissection were younger (p < 0.001) and heavier (p = 0.026), less commonly had heart disease (p = 0.002) and previous stroke (p = 0.002), and had lower initial systolic blood pressure (p = 0.029) and lower levels of D-dimer (p = 0.041) than patients without dissection. Stroke onset more commonly followed physical exertion (p = 0.013) and headache (p = 0.041) in patients with dissection than in patients without dissection. At hospital discharge, the modified Rankin scale score was lower in patients with dissection than in patients without dissection (p = 0.005). Conclusions: Arterial dissection was the most common vascular lesion underlying an isolated ACA territory infarction in our Japanese cohort. Patients with ACA dissection had unique baseline characteristics and unique conditions at stroke onset.

D-Dimers Predict Stroke Subtype when Assessed Early

Background:Early classification of ischemic stroke subtype is important for secondary stroke prevention and may guide further investigations. Methods: Levels of coagulation activation [fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT)] and fibrinolysis activation [plasmin-α2-antiplasmin complex (PAP), D-dimers] markers were measured in 98 consecutive patients with a first-ever acute ischemic stroke admitted within 12 h after symptom onset. Results: Median age was 67 years and 44% were women. Median time from symptom onset to blood sampling was 4 h. Stroke subtype was classified as ‘cardioembolic’ (54%), ‘large-artery atherosclerosis’ (11%), ‘small-vessel disease’ (5%), ‘other determined’ (9%) or ‘undetermined etiology’ (20%). Patients with cardioembolic stroke suffered more often from coronary artery disease than patients with other stroke etiologies (40 vs. 22%, p = 0.019). There were no differences in age, sex, stroke severity, time to blood sampling, frequency of hypertension, diabetes mellitus or current smoking. D-dimers (medians) were higher in patients with cardioembolic strokes than in those with other etiologies (615 vs. 322 μg/l, p < 0.001). No differences in F1+2, FPA, TAT or PAP levels were found. After multivariate analysis, higher D-dimer levels remained independently associated with cardioembolic stroke (p = 0.022). When measured within 6 h, D-dimers below 300 μg/l excluded cardioembolic stroke with a sensitivity of 100% and a specificity of 52%. Conclusions: Low D-dimer levels in the first few hours make a cardioembolic stroke unlikely, and may be useful to guide further investigations. Other coagulation markers were not useful in differentiating between different stroke etiologies.

Computed Tomography Angiography in Patients Evaluated for Acute Pulmonary Embolism with Low Serum D-dimer Levels: A Prospective Study

Pulmonary computed tomography angiography (CTA) and the Wells criteria both have interobserver variability in the assessment of pulmonary embolism (PE). Quantitative D-dimer assay findings have been shown to have a high negative predictive value in patients with low pretest probability of PE. Evaluate roles for clinical probability and CTA in Emergency Department (ED) patients suspected of acute PE but having a low serum D-dimer level. Prospective observational study of ED patients with possible PE who underwent pulmonary CTA and had D-dimer levels </=1.0 mug/mL. Clinical probability of PE determined by ED physicians using standard published criteria; pulmonary CTAs read by initial and study radiologists kept unaware of D-dimer results. In 16 months, 744 patients underwent pulmonary CTA, with 347 study participants who had a D-dimer level </= 1.0 mug/mL. In one participant, CTA showed a PE that was agreed on by both the initial and study radiologists. In six participants, the initial findings were reported as positive for PE but were not interpreted as positive by the study radiologist. In none of these participants was PE diagnosed on the basis of clinical probability, of findings on ancillary studies and three-month follow-up examination, or by another radiologist, unaware of findings, acting as a tiebreaker. Pulmonary CTA findings positive for acute embolism should be viewed with caution, especially if the suspected PE is in a distal segmental or subsegmental artery in a patient with a serum D-dimer level of </=1.0 mug/mL. Furthermore, the Wells criteria may be of limited additional value in this group of patients with low D-dimer levels because most will have low or intermediate clinical probability of PE.

O0014 ASSESMENT OF DISEASE-SEVERITY SCORING SYSTEMS FOR SEPTIC PATIENTS IN DEPARTMENTS OF INTERNAL MEDICINE

ultrasound. Only 22.5% of patients sent for imaging were positive for DVT. In low risk patients who had been sent for imaging (n=97), a D-Dimer threshold of 1.0 (Table 1) yielded a sensitivity of 95%, specificity of 47.4%, positive predictive value of 32% and negative predictive value of 97.4% for DVT. By adjusting D-Dimer thresholds in the low risk population, the projected sensitivities were calculated (Figure 2). Increasing D-Dimer thresholds up to 2.2 did not compromise sensitivity, but reduced the number of patients sent for imaging by 29%. In the high or indeterminate risk group, a D-Dimer level of 1 yielded sensitivities of 78.9% and 86.4% respectively (Figure 3). Throughout the 6 month period, no patients returned with a missed case of DVT. Discussion and conclusion: In high or unknown risk patients, a low D-Dimer level alone is insufficient to exclude DVT. In low risk patients, D-Dimer thresholds of 1.0, even up to 2.2, offers sufficient sensitivity (95%) to discharge patients without the need for imaging. Longer term data is required before a higher cut-off can be determined and safely applied. Our results highlight the importance of risk stratification in DVT assessment and suggest that our algorithm is a safe and effective method in reducing the number of patients sent for imaging.

Predicting thrombosis in systemic lupus erythematosus

Biomarkers that reliably identify or even predict disease manifestations in systemic lupus erythematosus (SLE) are needed. In a recent issue of the Clinical Journal of the American Society of Nephrology, Wu and colleagues reported on the predictive value of routine D-dimer measurements for future thromboembolic events in patients enrolled in the Ohio SLE study, a unique prospective, longitudinal evaluation of individuals with recurrently active SLE. As in other disease settings, low D-dimer levels (<0.5 microg/ml) excluded clotting at a given time point and identified a zero risk of future clotting events. Conversely, 42% of patients with a high D-dimer level (>2.0 microg/ml) subsequently experienced a clinically relevant clotting event, in some cases in the absence of antiphospholipid antibodies or lupus anticoagulant. This Practice Point commentary considers whether the D-dimer assay will remain simply a tool to rule out thrombosis in symptomatic patients with SLE or whether it could eventually be used to initiate preventive anticoagulation in asymptomatic patients.

D-Dimer Test Is Less Informative in Older Patients

Jane Salodof MacNeil is a senior editor with Elsevier Global Medical News. ATLANTA — Elderly people have much higher rates of venous thromboembolism than younger people do. They also tend to have elevated levels of D-dimer—which can make D-dimer testing less useful in predicting the risk of recurring blood clots when patients are aged 65 and older. The relationship between exponentially increasing venous thromboembolism (VTE) rates in the elderly and rising D-dimer levels presents a diagnostic dilemma, according to speakers at a symposium on how thrombosis in the elderly presents “a public health and scientific problem of unrecognized dimensions.” “Older age reduces the clinical usefulness of D-dimer testing. … We probably need age-adjusted cutoffs in older people,” Dr. Kenneth A. Bauer, a professor of medicine at Harvard Medical School, Boston, said during the special session at the annual meeting of the American Society of Hematology. “We really do need more work done in D-dimer, though it is the most promising of the markers that we see in predicting recurrence risk,” said Dr. Bauer, who is also chief of the hematology section at the Veterans Affairs Boston Healthcare System and director of thrombosis research at Beth Israel Deaconess Medical Center, Boston. VTE is three times more common in people aged 65 years and older, compared with those aged 45–64 years, reported Dr. Mary Cushman of the University of Vermont, Burlington. When VTE patients are stratified by age, 70% are 60 years and older. Just why VTE incidence increases with age is not clear, said Dr. Cushman. Despite limited data, she said, the evidence to date makes clear that the impact is also high in the elderly, with rates of death, recurrence, post-thrombotic syndrome, and treatment complications rising with each decade of life. The elderly “are more likely to fail treatment than those under age 65,” she said. In healthy elderly individuals, however, researchers have found high levels of many coagulation activation markers, including D-dimer, a fibrin degradation product released when blood clots. “D-dimer really is a composite of thrombin activation and then plasma dissolution of the fibrin that is normally formed. There are low levels of D-dimer that we measured in normal healthy people,” Dr. Bauer said. The fact that D-dimer is heterogeneous has led to issues in using and standardizing D-dimer assays, he noted, contrasting it with other coagulation markers that are discrete polypeptides with defined molecular weights. “D-dimer is a physiological variable and can vary over time,” Dr. Bauer said, discussing a study of centenarians conducted in Italy (Blood 1995;85:3144–9). Investigators compared 25 healthy centenarians with two control groups of healthy people aged 18–50 years and 51–69 years. Each of these groups was also made up of 25 people. The healthy centenarians showed laboratory signs of coagulation activation, including high levels of proteins that can predict cardiovascular disease in middle-aged people. Notably, the D-dimer concentrations were highly elevated in the centenarians: 323 ng/mL, compared with 29 ng/mL in the younger control group and 50 ng/mL in the middle group. That healthy centenarians have significantly higher levels of D-dimer suggests that increased D-dimer “is not necessarily a bad thing. It is consistent with long life,” Dr. Bauer commented. While many coagulation activation markers increase with age, he focused on D-dimer because it has the potential to stratify recurrence risk in patients after treatment for their first idiopathic VTE and thereby identify who would benefit from extended anticoagulation. Among several studies showing higher recurrence risk in patients with elevated D-dimer levels, he highlighted a multicenter investigation conducted in Italy (N. Engl. J. Med. 2006;355:1780–9). In that study, D-dimer levels were tested 1 month after anticoagulation was stopped in patients who had a first unprovoked deep vein thrombosis or pulmonary embolism. Patients with normal levels did not resume therapy. Those with “abnormal” D-dimer levels were randomly assigned to resuming or staying off treatment. Of the patients with elevated D-dimer levels, 74% were aged 65 years and older. At a median follow-up of 1.4 years, 10.7% of untreated patients with abnormal D-dimer levels had a recurrence, compared with 4.4% of those with normal levels (hazard ratio 2.27). When untreated patients were stratified by age, Dr. Bauer said the risk of recurrence was less in the elderly; they had a hazard ratio of 1.63, compared with 4.40 for those younger than age 65. Among patients with normal D-dimer levels, however, he said recurrence was higher in the elderly. In an interview immediately after the session, he cautioned against taking an alarmist stance when elderly patients present with high D-dimer levels. “We are getting a lot of elderly referred because they have chronically elevated D-dimers with no history of thrombosis,” he said. “One needs to be aware that [this is] probably something that goes along with age.”

High Plasma d-dimer Level is Associated with Decreased Survival in Patients with Lung Cancer

Aims An elevated plasma d-dimer level indicates the activation of coagulation and fibrinolysis. In the present study, we investigated the association of pre-treatment haemostatic parameters ( d-dimer, fibrinogen and prothrombin fragment 1+2) with clinicopathological parameters and outcome in patients with lung cancer. Materials and methods Plasma levels of d-dimer and other parameters were measured in 78 evaluable patients with lung cancer (60 non-small cell lung cancers, 18 small cell lung cancers). At diagnosis, 35 patients (44.9%) were locally advanced stage (IIIA/B) and 43 patients (55.1%) had metastatic disease (IV). Multivariate statistical analysis was carried out using Cox's proportional hazards model. The receiver operating characteristic curve was used to determine the cut-off values for d-dimer, fibrinogen and prothrombin fragment 1+2. Results The median survival for all patients was 264 days (95% confidence interval 200–328 days). A significant association between the plasma levels of d-dimer and the response to chemotherapy was observed ( P = 0.03). With the univariate analysis, tumour stage, pre-treatment plasma levels of d-dimer, fibrinogen, platelet count, lactate dehydrogenase concentration and Karnofsky performance status were predictive for survival. With the multivariate analysis ( P ≤ 0.1), the plasma level of d-dimer ( P < 0.001), tumour stage ( P = 0.01) and Karnofsky performance status ( P = 0.02) were identified as independent predictive factors. The median survival times were 405 days (95% confidence interval 165–644 days) and 207 days (95% confidence interval 146–267 days, P < 0.001), respectively, for patients with a low d-dimer level (≤0.65 μg/ml) and a high d-dimer level (>0.65 μg/ml). Conclusions Elevated plasma levels of d-dimer in patients with lung cancer are associated with decreased survival and a poor response to treatment. Pre-treatment for the d-dimer level may be useful in the prediction of survival and the response to treatment.