Comparison of three activated protein C resistance tests in the risk assessment of venous thrombosis in non-carriers of the factor V Leiden mutation.

Activated protein C resistance (APCR), measured using the original assay described by Dahlbäck, is a risk factor for venous thrombosis independent of the factor V Leiden (FVL) mutation. This assay is based on the activated partial thromboplastin time (APTT) after plasma exposure to activated protein C (APC). As this assay was sensitive to numerous interferences, new assays have been developed for FVL screening. The objectives of the study were to investigate the association of second generation assays for APCR with venous thrombosis in FVL non-carriers. One hundred ninety-seven subjects with a history of venous thrombosis and 211 controls were explored using 3 APCR assays, the original APTT-based assay (test A), an APTT-based assay with factor V depleted plasma pre-dilution (test B) and a direct factor X activation-based assay with the same pre-dilution (test C). We found that subjects with results in the lowest quartile of the APTT-based assays are at increased risk, compared to those in the highest quartile (test A Odds Ratio = 6.39; 95% CI 3.23-12.63; test B OR = 2.72; 95% CI 1.50-4.94). There was no significant risk increase associated with test C results. After adjusting for FVIII levels, the ORs of tests A and B were similar (test A OR = 3.22; 95% CI 1.47-7.08; test B OR = 3.10; 95% CI 1.54-6.21). In conclusion, APTT-based assays, but not direct factor X activation-based assays, effectively detect the risk for venous thrombosis independent of FVL. Pre-dilution in factor V depleted plasma is an effective way to directly assess the risk independent of FVIII levels.

Diagnostic management of pulmonary embolism using clinical assessment, plasma D-dimer assay, complete lower limb venous ultrasound and helical computed tomography of pulmonary arteries. A multicentre clinical outcome study.

The objective of the study was to assess the clinical validity of a non-invasive diagnostic strategy for acute pulmonary embolism using clinical assessment combined with both ELISA D-dimer and complete lower limb ultrasound (US) examination of proximal and distal veins, before single-detector helical computed tomography (CT) of pulmonary arteries. We expected the strategy to have a high diagnostic exclusion power and to safely decrease the number of CT scans. This prospective, multicenter outcome study included 274 consecutive outpatients. All underwent a priori clinical probability, D-dimer and bilateral complete lower limb US assessments. Only patients with a high clinical probability and both tests negative, or positive D-dimer and negative US assessments, underwent CT. This was deemed necessary in 114 patients (42%). At baseline, venous thromboembolism (VTE) was detected in 110 patients (40%), either by US showing proximal (n=65) or distal (n=36) thrombosis, or by CT (n=9). Anticoagulant was withheld in the remaining patients with negative results in both D-dimer and US but a non-high clinical probability (n=59), or in both US and CT (n=90), or with negative US (n=6) and inadequate CT (n=9). All patients underwent a three-month clinical follow-up. VTE occurred in one patient with inadequate CT, yielding an incidence of 0.6% [95% confidence interval: 0.1-3.4]. No patient died from VTE or had major bleeding. Using clinical probability, ELISA D-dimer and complete US before helical CT is a safe strategy resulting in a substantial reduction in CT scans.

Diagnostic performance of complete lower limb venous ultrasound in patients with clinically suspected acute pulmonary embolism.

A limited ultrasound (US) confined to the popliteal and femoral veins is usually performed to detect deep vein thrombosis (DVT) in patients with clinically suspected acute pulmonary embolism (PE). Our objective was to assess the diagnostic accuracy of complete lower limb US examining both the proximal and distal veins in this setting. In this prospective study, 210 consecutive patients were included. Complete US was performed by independent operators and compared blindly with a reference strategy combining clinical probability, ventilation perfusion scan and pulmonary angiography to a three-month clinical follow-up. Simultaneously, VIDAS D-dimer (DD) assay and helical computed tomography (HCT) of the lungs were assessed independently and blindly. PE was present in 74 patients (35%). Complete US detected DVT in 91 patients (43%), proximal in 51 and distal in 40. Sensitivity and specificity with a 0.95 confidence interval were respectively 0.93 [0.85 - 0.97] and 0.84 [0.77 - 0.89]. Limited US detected DVT in only 46 patients (22%). Sensitivity and specificity were respectively 0.55 [0.44 - 0.66] and 0.96 [0.92 - 0.98]. For DD they were 0.92 [0.83 - 0.96] and 0.24 [0.17 - 0.32] and for HCT 0.84 [0.73 - 0.90] and 0.87 [0.80 - 0.92]. Complete lower limb US has higher sensitivity and capacity to exclude PE than limited US, but a slightly lower specificity. Complete US results also compared favourably with those of HCT and DD. The utility of including this method in diagnostic strategies for PE needs to be assessed in cost-effectiveness analysis and in outcome studies.

Comparison of the diagnostic performance of three soluble fibrin monomer tests and a D-dimer assay in patients with clinically suspected deep vein thrombosis of the lower limbs.

We assessed three soluble fibrin monomer (SFM) assays in 231 in and out-patients with clinically suspected deep-vein thrombosis. Thrombosis was confirmed or excluded by complete lower-limb ultrasound. SFM assay were less accurate than VIDAS D-dimer and in patients with small thrombosis or under anticoagulation. Specificity was lower for a similar sensitivity.

Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin.

The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (+/- SD) dose of 0.06 +/- 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy.