Safety of withholding anticoagulation in pregnant women with suspected deep vein thrombosis following negative serial compression ultrasound and iliac vein imaging

Background:

Compression ultrasonography performed serially over a 7-day period is recommended for the diagnosis of deep vein thrombosis in symptomatic pregnant women, but whether this approach is safe is unknown. We evaluated the safety of withholding anticoagulation from pregnant women with suspected deep vein thrombosis following negative serial compression ultrasonography and iliac vein imaging.

Methods:

Consecutive pregnant women who presented with suspected deep vein thrombosis underwent compression ultrasonography and Doppler imaging of the iliac vein of the symptomatic leg(s). Women whose initial test results were negative underwent serial testing on 2 occasions over the next 7 days. Women not diagnosed with deep vein thrombosis were followed for a minimum of 3 months for the development of symptomatic deep vein thrombosis or pulmonary embolism.

Results:

In total, 221 pregnant women presented with suspected deep vein thrombosis. Deep vein thrombosis was diagnosed in 16 (7.2%) women by initial compression ultrasonography and Doppler studies; none were identified as having deep vein thrombosis on serial testing. One patient with normal serial testing had a pulmonary embolism diagnosed 7 weeks later. The overall prevalence of deep vein thrombosis was 7.7% (17/221); of these, 65% (11/17) of cases were isolated to the iliofemoral veins and 12% (2/17) were isolated iliac deep vein thromboses. The incidence of venous thromboembolism during follow-up was 0.49% (95% confidence interval [CI] 0.09%–2.71%). The sensitivity of serial compression ultrasonography with Doppler imaging was 94.1% (95% CI 69.2%–99.7%), the negative predictive value was 99.5% (95% CI 96.9%–100%), and the negative likelihood ratio was 0.068 (95% CI 0.01–0.39).

Interpretation:

Serial compression ultrasonography with Doppler imaging of the iliac vein performed over a 7-day period excludes deep-vein thrombosis in symptomatic pregnant women.Over the last 2 decades, venous compression ultrasonography has become the imaging test of choice for diagnosing deep vein thrombosis in the lower extremities of men and nonpregnant women.^1–4 Although this test is highly sensitive (about 97%) for deep vein thrombosis involving the femoral and popliteal veins, compression ultrasonography is less sensitive for the detection of isolated deep vein thrombosis in the calf.⁵ Because proximal propagation of isolated calf deep vein thrombosis occurs in about 20% of cases, serial compression ultrasonography performed over a 7-day period is recommended to definitely exclude such thromboses if the results of the initial compression ultrasound are negative.⁶The use of serial compression ultrasonography in symptomatic men and nonpregnant women has been validated in prospective studies,^1,7 suggesting that withholding anticoagulation from symptomatic patients whose serial compression ultrasound results are negative is safe, with less than 2% of patients subsequently being diagnosed with deep vein thrombosis.^1,7,8 Although the use of serial compression ultrasonography has not been validated in pregnant women, this strategy is also advocated for symptomatic pregnant women.⁹The appeal of using compression ultrasonography for diagnosing deep vein thrombosis in pregnant women is obvious: it is noninvasive, widely available and does not expose the fetus to ionizing radiation. However, generalizing results from studies involving men and nonpregnant women to pregnant women is problematic because of differences in clinical presentation and anatomic distribution of deep vein thromboses.¹⁰ Compared with men and nonpregnant women, pregnant women more often present with very proximal deep vein thrombosis (including isolated iliac vein deep vein thrombosis); isolated distal calf deep vein thromboses are infrequent.¹⁰ In a recent review of the literature, we found that 62% of all deep vein thromboses in symptomatic pregnant women were in the iliofemoral veins, 17% were in the iliac vein alone, and 6% were in the calf veins.¹⁰ In contrast, in the general population, more than 80% of deep vein thromboses involved calf veins, and iliofemoral deep vein thromboses or isolated iliac veins are uncommon (< 5%).^1–4Physiologic changes associated with pregnancy might affect blood flow patterns and normal compressibility of the proximal veins, thereby affecting the diagnostic accuracy of compression ultrasonograpy. This technique cannot be used to detect isolated deep vein thromboses in the iliac vein; these veins are not compressible because of their intrapelvic location. Whether Doppler studies are sensitive for detecting deep vein thromboses in these high proximal veins (i.e., iliac veins) has not been well studied, but data suggest that this method of detection compares favourably to compression ultrasonography in men and nonpregnant women for proximal deep vein thromboses.¹¹ The use of Doppler imaging in pregnant women for the purpose of detecting iliac vein deep vein thromboses has been reported in the literature,^12,13 but it has not been adequately evaluated.Currently, the standard practice of diagnosing deep vein thrombosis in symptomatic pregnant women is by compression ultrasonography. If the results of the compression ultrasound are negative, Doppler imaging of the iliac vein (with or without vagal manoeuvres) is recommended, particularly for women with a high clinical probability of deep vein thrombosis in the iliac vein.^9,12,13 This diagnostic approach is advocated despite the absence of any prospective studies validating its use. In this study, we evaluated the diagnostic accuracy of serial compression ultrasonography and Doppler imaging of the iliac veins over a 7-day period among symptomatic pregnant women.     

Treatment of deep vein thrombosis with streptokinase.

From September 1962 to May 1972 145 patients with acute or subacute deep vein thrombosis confirmed by phlebography were treated with streptokinase. During the same period 42 patients considered unfit for thrombolytic therapy were treated with herapin and oral anticoagulants. The results, assessed by repeat phlebography, in 93 of the patients treated with streptokinase were compared with those in 42 patients treated with heparin. The age, sex, and severity of occlusion were roughly similar in both groups. Streptokinase treatment was successful in 42 per cent, partially successful in 25 per cent, and unsuccessful in 32 per cent of the 93 patients compared with none, 10 per cent, and 88 percent respectively in the 42 patients treated with heparin. Streptokinase was more effective when the thrombus was in proximal rather than calf veins. Thrombi of more than six days old were readily lysed. Plasma fibrinogen levels were below 0-8 g/1 (80 mg/100 ml) in nearly all patients successfully treated. The incidence of pulmonary embolism was no greater with streptokinase than with heparin treatment. Only prolonged follow-up would show whether thrombolytic treatment would be effective in preventing late complications of deep vein thrombosis such as chronic venous insufficiency.     

After-exercise thermography and prediction of deep vein thrombosis.

A total of 112 patients participated in a prospective study of after-exercise thermography as a screening method for predicting risk of postoperative deep venous thrombosis. The fibrinogen-uptake test was used to detect thrombosis after elective surgery. The incidence of the complication showed no significant difference between patients who had had positive and those who had had negative thermograms. Thermography does not seem to be useful for predicting risk of postoperative thrombosis.     

Fibrinogen uptake scanning for diagnosis of deep vein thrombosis: a plea for standardization.

From an examination of the factors affecting the diagnostic accuracy of the 125I-fibrinogen test for detecting deep vein thrombosis it is concluded that there is a greater possibility of error if postoperative counts are referred to the preoperative baseline rather than counts made immediately after operation. A method is proposed for reducing other errors caused by instrument mishandling.     

Measurement of fibrinogen-fibrin-related antigen in serum as aid to diagnosis of deep vein thrombosis in outpatients.

A study of serum levels of fibrinogen-fibrin-related antigen (F.R.-antigen) in outpatients presenting with clinical features suggesting deep vein thrombosis was undertaken. A raised serum level of this antigen (greater than 12 mg/1) is strong evidence in favour of the diagnosis of deep vein thrombosis. It is virtually conclusive evidence if other known causes of a raised level of the antigen are absent. On the other hand, a normal serum level of F.R.-antigen does not exclude even extensive thrombosis, and other objective techniques are required to substantiate the diagnosis.