The Diagnostic Value Of Two Age-Adjusted D-Dimer Cut-Offs In Senile Acute Pulmonary Embolism

ObjectiveWe investigated the diagnostic value of two age-adjusted D-dimer cut-offs in senile suspected acute pulmonary embolism and compared them with traditional clinical D-dimer cut-off(0.5mg/L) and two fixed(1.0mg/L and 1.5mg/L,which was approximately doubling and tripling the traditional cut-off) higher cut-offs. Validate whether the using of two age-adjusted strategies of D-dimer values or two fixed higher cut-offs would improve the specificity of identifying patients at risk for pulmonary embolism(PE) compared with traditional D –dimer cutoff value(0.5mg/L)in order to optimize inappropriate use of computed tomography pulmonary angiography(CTPA).MethodsCollected the basic information of consecutive inpatients presented to the radiology department of the first affiliated hospital of Nanchang university with suspected pulmonary embolism through the Picture Archiving and Communication Systems(PACS) from September 1, 2014 to August 1, 2015.Assessed the risk factors of suspected pulmonary embolism inpatients that meet our inclusion standard and gained the score of Wells. The diagnosis of PE in CTPA examination was made on the basis of the imaging guideline for pulmonary thromboembolism made by the Chinese medical association. D-dimer was measured with automatic Latex-enhanced immunoturbidimetric assay with Innovance DDIMER on the Sysmex coagulation system of CA7000 analyzer. The normal value of D-dimer was less than 0.5mg/L according with Chinese expert consensus on D-dimer test 2013. Sensitivity,Specificity, Positive Predictive Value(PPV) and Negative Predictive Value(NPV)were calculated for different D-dimer cutoff values. Receiver Operating Characteristic(ROC) curve was constructed with D-dimer values and the diagnosis of PE on the basis of CTPA results with the area under the ROC curve and 95%confidence interval.Results1 A total of 274 suspected pulmonary embolism inpatients evaluated by CTPA were included in our study population, 179 cases(65.3%) of men and 95 cases(34.7%) of women, with mean age 69.2±9.5 years VS 68.8±9.7years respectively and no statistical difference between them with P value of 0.7.61 cases of pulmonary embolism were identified by CTPA with an overall prevalence of confirmed PE of22.3%(40 men and 21 women).2 The mean value of D-dimer between male and female inpatients were 2.07±1.73mg/L VS 1.96 ± 1.6mg/L with no statistical difference. The concentration of D-dimer increased with age and was higher in PE+ inpatients than PE- inpatients with statistically significant difference(3.37±1.96mg/L VS 1.60±1.31mg/L,P?0.05).The plots of the D-dimer versus the age showed the best fit quadratic equation for D-dimer values for patients with and without PE(PE+:D-dimer =3.02-0.11× age+0.005×age2; PE-: D-dimer=7.54-0.15×age+0.001×age2). The splay in the curves showed widening in patients with age over 70 years between PE+ patients and PEpatients. The plasma concentration of D-dimer was statistically significantly higher in patients with age over 80 years than patients with age in 50-60 years(2.54 ± 1.90mg/L VS 1.57±1.39 mg/L,P=0.02). In the 213 patients with no PE(negative CTPA),40 cases, 54 cases, 53 cases, 78 cases and 101 cases had D-dimer concentration below cut-off in traditional cut-off group, yearly-adjusted cut-off group, decade adjusted cut-off group, doubling group and tripping group respectively.3 The Wells score was used to assess the clinical probability of pulmonary embolism of the 274 inpatients with the median score of 3.0 points and maximum score of 9.0 points. The score of PE + was higher than PE ? with statistically significant difference(3.8 points VS 2.5 points, P < 0.05). The prevalence of PE was9.5%(10/105), 7.5%(39/142),44.4%(12/27) in the low, moderate, and high probability groups, respectively.4 Compared with traditional cut-off, both yearly age-adjusted D-dimer cut-offand decade age-adjusted D-dimer cut-off increased the specificity of D-dimer for the exclusion of PE in senile patients(age 70 and more) with low and moderate probability, 23.6% VS 15.2% and 32.6% VS 15.2% respectively and 9 cases and 8cases had D-dimer concentration higher than traditional cutoff with negative CTPA results respectively, the false-negative rate was 0.7%. The specificity of decade age-adjusted cut-off was higher in patients with age over 70 years than patients with age below 70 years(34.9% VS 28.8%, P=0.03).5 In senile patients with low and moderate probability(aged 70 and more),the sensitivity, specificity, positive predictive value and negative predictive value of both two fixed higher D-dimer cut-off were:80%(60.9%-91.6%), 32.1%(23.5%-41.9%),25%(16.9%-35.0%),85%(69.5%-93.8%)and63.3%(43.3%-79.5%),44.8%(35.2%-54.8%),24.8%(15.9%-36.0%),81.0%(68.2%-89.7%) respectively, which both increased test specificity for excluding PE,while didn't maintained high sensitivity.Potentially avoided CTPA 20(14.3%) and 38(27.1%) for two fixed higher cut-off respectively.Conclusion1. For senile suspected pulmonary embolism patients with low and moderate probability, both the two kinds of age-adjusted D-dimer cut-offs improved the specificity of D-dimer for the exclusion of pulmonary embolism and decade age-adjusted D-dimer cut-off got higher specificity and without reducing sensitivity.2. Combined with clinical probability assessment, using fixed higher D-dimer cut-offs in elderly patients could reduce more inappropriate use of computed tomography pulmonary angiography(CTPA), however, the false negative rate might be higher because of the relatively low sensitivity.