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Measurement of fibrin degradation products (FDPs) in plasma will include fibrinolytic breakdown products of both fibrinogen and cross-linked fibrin. Fibrinogen degradation products are generated in both secondary fibrinolysis (as in DIC) and in primary activation of the fibrinolytic pathway. Cross-linked fibrin degradation products are generated only in secondary fibrinolysis. The D-Dimer test offers a specific measurement of cross-linked fibrin degradation products. Increased levels of cross-linked fibrin degradation products are found in states of coagulation activation resulting in thrombin formation and subsequent secondary fibrinolysis. Increased levels of D-Dimer have been reported in the following situations: DIC, deep vein thrombosis (DVT), pulmonary embolism, surgery, cancer, and cirrhosis. D-Dimer is a useful test in the work-up of a patient with suspected DIC. The presence of increased D-Dimer levels differentiates DIC from primary fibrinolysis, where the level is not increased. The International Society of Thrombosis and Hemostasis (ISTH) recently proposed a scoring system for the diagnosis of disseminated intravascular coagulation (DIC) based on the presence of a predisposing clinical condition (eg sepsis, trauma), and assigning a score based on four laboratory parameters including decreased platelet count, elevated fibrin-related marker such as D-dimer, elevated protime (PT), and decreased fibrinogen. Algorithm for Diagnosis of Overt DIC 1. Patient must have an underlying disorder known to be associated with DIC 2. Score coagulation test results as follows:
If score < 5: may be compatible with non-overt (compensated) DIC, repeat testing in 1-2 days. Quantitative, rapid D-dimer assays have been widely utilized for several years, primarily for their high sensitivity in ruling out acute venous thromboembolism. D-dimer is a key component in the laboratory diagnosis of DIC, however little has been known about the performance of the newer D-dimer assays in the context of DIC diagnosis. A recent study evaluated the analytical performance of a quantitative D-dimer assay in hospitalized patients with suspected DIC (Am J Clin Pathol 2004; 122:178-184). D-dimer results were retrospectively analyzed in 241 hospitalized patients (134 women and 107 men aged 19-91 years) in whom D-dimer was ordered over a 12 month period. Medical records were reviewed for clinical and laboratory evidence consistent with DIC. The prevalence of DIC in this group was 22.4% (54/241 patients). The majority of those with DIC had sepsis or cancer. Patients with clinical DIC had a median D-dimer value of 21.7ug/mL (reference range 0-0.5ug/mL), while the median value in those without DIC was 2.7ug/mL. Using ROC curve analysis, a D-dimer cutoff of 8.2ug/mL optimized the sensitivity and specificity of the D-dimer assay for the diagnosis of DIC (sensitivity was 98%, specificity 86%, negative predictive value 99%, and positive predictive value 66%). The optimal D-dimer cutoff value (8.2ug/mL) was validated in a cohort of 286 additional patients. The high negative predictive value for D-dimer at this cutoff confirms the value of this assay in ruling out DIC. ROC curve analysis also showed that D-dimer had the best discriminatory value in the diagnosis of DIC of the four laboratory tests included in the ISTH scoring system. In the ISTH scoring system, a score of "3" (strong increase) should be assigned to a D-dimer value greater than 8.2 ug/mL. We would arbitrarily suggest that a score of 2 (moderate increase) be assigned to a D-dimer value greater than 4.0 ug/mL, but less than 8.2 ug/mL. The authors confirmed the relatively low specificity of D-dimer by demonstrating that D-dimer was elevated (>0.5 ug/dL) in 70% of 59 hospitalized patients without venous thromboembolism, cancer or DIC, and 90% of 27 patients with cancer and no evidence of venous thromboembolism or DIC. Use of the ISTH algorithm resulted in a higher specificity and positive predictive value for the diagnosis of DIC than use of the D-dimer result alone. In conclusion, a sensitive, rapid, quantitative D-dimer assay provides excellent sensitivity and negative predictive value for the diagnosis of DIC, optimized at a cutoff of 8.2ug/mL. Specificity and positive predictive value is improved by using the ISTH algorithm for DIC diagnosis. A 5mL blue-top tube is required. |
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