H. Heijboer

Acenocoumarol and Heparin Compared with Acenocoumarol Alone in the Initial Treatment of Proximal-Vein Thrombosis

BACKGROUNDnIn most countries, heparin is used in the initial treatment of patients with deep-vein thrombosis. Well-designed studies establishing the efficacy of heparin therapy are lacking, however. Treatment with acenocoumarol alone, according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin, is considered an effective alternative in some countries.nnnMETHODSnIn a randomized, double-blind study we compared the efficacy and safety of continuous intravenous heparin plus acenocoumarol with the efficacy and safety of acenocoumarol alone in the initial treatment of outpatients with proximal-vein thrombosis. The principal study end point was a confirmed symptomatic extension or recurrence of venous thromboembolism during six months of follow-up. In addition, we assessed asymptomatic extension or pulmonary embolism by repeating venography and lung scanning after the first week of treatment. The incidence of major bleeding was determined during three months of follow-up.nnnRESULTSnThe study was terminated early by the Data Safety and Monitoring Committee because of an excess of symptomatic events in the group that received acenocoumarol alone (in 12 of 60 patients [20 percent], as compared with 4 of 60 patients [6.7 percent] in the combined-therapy group by intention-to-treat analysis; P = 0.058). Asymptomatic extension of venous thrombosis was observed in 39.6 percent of the patients in the acenocoumarol group and in 8.2 percent of patients treated with heparin plus acenocoumarol (P < 0.001). Major bleeding complications were infrequent and comparable in the two groups.nnnCONCLUSIONSnPatients with proximal-vein thrombosis require initial treatment with full-dose heparin, which can safely be combined with acenocoumarol therapy.

Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis.

BACKGROUNDnIsolated deficiencies of antithrombin III, protein C, protein S, and plasminogen have been implicated as a cause of deep-vein thrombosis. It is assumed that patients with recurrent, familial, or juvenile thrombosis are very likely to have such a deficiency.nnnMETHODSnWe studied the prevalence of isolated deficiencies of these proteins in 277 consecutive outpatients with venographically proved acute deep-vein thrombosis, as compared with 138 age-matched and sex-matched controls without deep-vein thrombosis, and calculated the positive predictive value of a history of recurrent, familial, or juvenile venous thromboembolism for the presence of such a deficiency.nnnRESULTSnThe overall prevalence of deficiencies of any of these proteins in the patients with venous thrombosis was 8.3 percent (23 of 277 patients) (95 percent confidence interval, 5.4 to 12.4), as compared with 2.2 percent in the controls (3 of 138 subjects) (95 percent confidence interval, 0.5 to 6.1; P less than 0.05 for the comparison between groups). The positive predictive values for the presence of an isolated protein deficiency in patients with recurrent, familial, or juvenile deep-vein thrombosis, defined as the proportion of patients with the clinical finding who had a deficiency of one or more of the proteins, were 9, 16, and 12 percent, respectively.nnnCONCLUSIONSnThe cause of acute venous thrombosis in most outpatients (91.7 percent) cannot be explained by abnormalities of coagulation-inhibiting and fibrinolytic proteins. The information obtained from the medical history concerning recurrent or familial venous thrombosis or the onset of the disease at a young age is not useful for the identification of patients with protein deficiencies.

A Comparison of Real-Time Compression Ultrasonography with Impedance Plethysmography for the Diagnosis of Deep-Vein Thrombosis in Symptomatic Outpatients

BACKGROUNDnImpedance plethysmography performed serially over a one-week period has been shown to be an effective diagnostic strategy for patients with clinically suspected acute deep-vein thrombosis. Compression ultrasonography has a high sensitivity and specificity for the detection of proximal-vein thrombosis. The clinical value of repeated ultrasonography in the management of symptomatic deep-vein thrombosis is unknown.nnnMETHODSnWe conducted a randomized trial in 985 consecutive outpatients with clinically suspected deep-vein thrombosis to compare the diagnostic value of serial impedance plethysmography (494 patients) and serial compression ultrasonography (491 patients). We compared the positive predictive values of both tests for the diagnosis of venous thrombosis, using contrast venography as a reference. The frequencies of venous thromboembolism during a six-month follow-up period were also compared in patients with repeatedly normal results in order to evaluate the safety of withholding anticoagulant therapy from such patients.nnnRESULTSnThe positive predictive value of an abnormal ultrasonogram was 94 percent (95 percent confidence interval, 87 to 98 percent), whereas the predictive value of impedance plethysmography was 83 percent (95 percent confidence interval, 75 to 90 percent) (P = 0.02). In patients with repeatedly normal results, the incidence of venous thromboembolism during the six-month follow-up period was 1.5 percent (95 percent confidence interval, 0.5 to 3.3 percent) for serial compression ultrasonography, as compared with 2.5 percent (95 percent confidence interval, 1.2 to 4.6 percent) for serial impedance plethysmography.nnnCONCLUSIONSnIn making the diagnosis of deep-vein thrombosis in symptomatic outpatients, serial compression ultrasonography is preferable to impedance plethysmography, in view of its superior performance in detecting venous thrombosis.

Clinical Utility of Real-Time Compression Ultrasonography for Diagnostic Management of Patients with Recurrent Venous Thrombosis

In the diagnostic management of patients with clinically suspected recurrent deep-vein thrombosis (DVT), there are potential limitations to all available diagnostic techniques. Since venous abnormalities may persist for some time after an acute thrombosis, the usefulness of compression ultrasonography (US) for the detection of recurrent DVT may be jeopardized. We determined the rate of normalization of an abnormal compression US test of the popliteal and the common femoral veins in patients after a first episode of proximal DVT. In a cohort of 60 consecutive patients, the test result was normalized in only 29, 44, 54, and 60% of patients at 3, 6, 9, and 12 months, respectively. The investigation shows that for the detection of recurrent DVT of the leg, real-time compression US (using the single criterion of compression of the common femoral and popliteal vein) is of limited value. Future studies need to be performed, using more subtle interpretation of the compression US result, by quantifying the extent of residual thrombus, which may increase the usefulness of this test in patients with recurrent symptoms.