Jeffrey S. Ginsberg

Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded.

Background D-dimer testing to rule out deep vein thrombosis is less useful in older patients because of a lower specificity. An age-adjusted D-dimer cut-off value increased the proportion of older patients (>50 years) in whom pulmonary embolism could be excluded. We retrospectively validated the efficacy of this cut-off combined with clinical probability for the exclusion of deep vein thrombosis. Design and Methods Five management study cohorts of 2818 consecutive outpatients with suspected deep vein thrombosis were used. Patients with non-high or unlikely probability of deep vein thrombosis were included in the analysis; four different D-dimer tests were used. The proportion of patients with a normal D-dimer test and the failure rates were calculated using the conventional (500 μg/L) and the age-adjusted D-dimer cut-off (patients age x 10 μg/L in patients >50 years). Results In 1672 patients with non-high probability, deep vein thrombosis could be excluded in 850 (51%) patients with the age-adjusted cut-off value versus 707 (42%) patients with the conventional cut-off value. The failure rates were 7 (0.8; 95% confidence interval 0.3-1.7%) for the age-adjusted cut-off value and 5 (0.7%, 0.2-1.6%) for the conventional cut-off value. The absolute increase in patients in whom deep vein thrombosis could be ruled out using the age-adjusted cut-off value was largest in patients >70 years: 19% among patients with non-high probability. Conclusions The age-adjusted cut-off of the D-dimer combined with clinical probability greatly increases the proportion of older patients in whom deep vein thrombosis can be safely excluded.

Diagnosis of deep vein thrombosis and pulmonary embolism in pregnancy

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality. Because unrecognized and untreated pulmonary embolism (PE) can result in maternal mortality, physician vigilance for this disease should remain high. The diagnosis of both PE and deep vein thrombosis (DVT) in the pregnant patient, as in the nonpregnant patient, requires the use of accurate objective imaging. However, unlike the nonpregnant population, there is a paucity of trials evaluating the safety and accuracy of objective testing for PE or DVT diagnosis in pregnant patients--likely because of concerns surrounding the use of ionizing radiation associated with diagnostic tests during pregnancy. Regardless of extrapolating results from studies in the nonpregnant population, the use of compression leg ultrasound and ventilation-perfusion (VQ) scanning during pregnancy is central to the diagnosis of DVT and PE, respectively. Data on the utility of structured clinical models or D-dimer testing for the diagnosis of DVT or PE during pregnancy is currently unavailable. Future research is urgently needed to validate the use of current approaches and perhaps define safer and more accurate strategies to reduce maternal morbidity from this disease.

Low-dose warfarin in rehabilitating stroke survivors

BACKGROUND Patients undergoing rehabilitation after thromboembolic stroke have a relatively high incidence of venous thromboembolism (VTE). Warfarin, with a target international normalized ratio (INR) of 2.0-3.0 is effective for the prevention of VTE. However, because stroke is a major risk factor for bleeding with warfarin, a less intense regimen (target INR < 2.0), might safely prevent VTE in stroke rehabilitation patients. METHODS This study was a randomized, double-blind, placebo-controlled trial of 2 mg of warfarin in patients undergoing rehabilitation following completed stroke. The major efficacy endpoint was symptomatic, objectively proven VTE or asymptomatic VTE detected by monthly duplex ultrasonography (DU) of the proximal leg veins or mandatory bilateral contrast venography performed at the end of the study. The major safety endpoint was bleeding. RESULTS There were 475 patients screened for enrollment, 355 had one or more exclusion criterion, and 17 had previously undetected proximal DVT on admission. Of the 103 eligible and consenting patients, 56 received warfarin and 47 received placebo. Of the randomized patients, 88 had successful venography (47 warfarin and 41 placebo). In the warfarin group, three (8%) patients had DVT and one (2%) had proximal DVT whereas in the placebo group, seven (20%) had DVT and five (13%) had proximal DVT. The risk ratio for any DVT in warfarin-treated patients relative to placebo-treated patients was 0.39 (95% confidence interval (CI), 0.13-1.37). For proximal DVT, the risk ratio was 0.17 (95% CI, 0.01-1.4). No patients suffered major bleeding. CONCLUSIONS A fixed dose of 2 mg of warfarin per day in patients undergoing stroke rehabilitation is safe and associated with a relative risk reduction of about 80% in the incidence of proximal DVT and 60% in overall DVT.

Evaluation of the Combination of a Bedside D-Dimer Assay and Enzyme-Linked Immunosorbent Soluble Fibrin Assay in Patients with Suspected Venous Thromboembolism

The objectives of the study were to determine whether the combination of a negative SimpliRED D-dimer assay and a low soluble fibrin result reliably excludes venous thromboembolism, and whether patients with proven venous thromboembolism and a normal SimpliRED D-dimer have evidence of impaired fibrinolysis. The study was a retrospective analysis of a cohort of 262 consecutive patients, 94 patients presenting with suspected deep venous thrombosis and 168 with suspected pulmonary embolism. Fifty-nine patients (22.5%) were classified as venous thromboembolism-positive, 27 with pulmonary embolism, and 32 with deep venous thrombosis. One hundred and fourteen patients (43.5%) had SimpliRED D-dimer and a soluble fibrin result of less than or equal to 2.0 microg/ml; the negative predictive value was 98.2% (95% confidence interval: 93.8-99.8%), and the likelihood ratio was 0.06. Eight patients with proven venous thromboembolism had a negative SimpliRED D-dimer; all had elevated ELISA D-dimer levels and six had elevated soluble fibrin levels. This suggests that patients with venous thromboembolism and a normal SimpliRED result do not have impaired fibrinolysis as a cause of their false-negative result. This study suggests that the combination of SimpliRED and soluble fibrin can be used to exclude venous thromboembolism in over 40% of patients who present with a clinical suspicion of deep venous thrombosis or pulmonary embolism and that the small group of patients with venous thromboembolism and a normal SimpliRED do not have impaired fibrinolysis.

Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism

Venous thrombosis is a common disease. As the mean age of the population increases, so does the incidence of venous thromboembolism. Anticoagulant therapy is equally effective in young and older patients, and can reduce substantially the associated morbidity and mortality. When considering long-term oral anticoagulant therapy in older patients, however, careful ongoing evaluation is imperative to ensure that the risk of bleeding does not outweigh the antithrombotic benefits.

Evaluation of the Bleeding Effects of Antithrombotic Drugs

Heparin and the vitamin K antagonists are effective for the prevention and treatment of both venous and arterial thromboembolism. The major side effect of both groups of anticoagulants is bleeding and the purpose of this review is to review the hemorrhagic effects of heparin and oral anticoagulants. The mechanisms of bleeding for both groups of anticoagulants will first be discussed, and then the incidence of bleeding in the major clinical situations for which these drugs are indicated will be discussed. Some of the clinical and laboratory features that have been associated with bleeding over the last few years will be discussed and then, briefly, the management of patients who bleed while being treated with anticoagulants will be discussed. For the purposes of this review, bleeding that is intracranial, retroperitoneal, intraocular or bleeding that causes death, hospitalization or transfusion will be classified as major. All other clinically overt bleeding will be classified as minor.