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Biomedical subjects

R D Hull

Publications and source records attributed to R D Hull.

At least 109 records · Page 6Linked to original sources

Treatment of venous thromboembolism with low molecular weight heparins.

The accumulating evidence indicates that certain LMW-heparins administered subcutaneously may replace classical intravenous heparin therapy. Certain of these subcutaneously administered LMW-heparins do not require monitoring. The simplified care offered by LMW-heparin therapy offers the possibility of transferring care from in the hospital to out of the hospital in uncomplicated patients with deep vein thrombosis. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient LMW-heparin therapy will likely prove to be highly cost-effective. It is uncertain at the present time whether the findings associated with an individual LMW-heparin preparation can be extrapolated to a different LMW-heparin. For this reason the findings of clinical trials apply only to the particular LMW-heparin evaluated and cannot be generalized to the LMW-heparins at large.

Double-Blind Method↗

Optimal therapeutic level of heparin therapy in patients with venous thrombosis.

BACKGROUND: Audits of heparin sodium therapy suggest that heparin administration is fraught with difficulty. The literature indicates that the current clinical practice of intuitive ordering of heparin results in inadequate therapy because of fear of bleeding. The importance of exceeding the lower limit of the therapeutic range has been strongly supported by findings of prospective clinical trials. Firm evidence indicates that failure to exceed the lower limit is associated with unacceptably high rates of recurrent venous thromboembolism. By comparison, evidence supporting the risk of exceeding the upper limit of the therapeutic range is weak. OBJECTIVES: The purposes of this study were (1) to validate prospectively an approach designed to minimize the proportion of patients receiving subtherapeutic doses of heparin and (2) to determine the effectiveness and safety of decreasing the heparin dosage infused on the basis of activated partial thromboplastin time (APTT) prolongation reflecting both heparin and warfarin sodium effects. METHODS: We performed a randomized double-blind study evaluating a prescriptive approach to heparin administration in patients receiving heparin or heparin with warfarin. Thromboembolic and bleeding complications were objectively documented. RESULTS: Only 1% and 2% of patients had subtherapeutic heparin levels for 24 hours or more in the heparin and combined groups, respectively. Recurrent venous thromboembolism occurred infrequently in both groups (7%). Sixty-nine (69%) of 99 patients receiving combined therapy had supratherapeutic values, compared with 24 (24%) of 100 receiving heparin; bleeding complications occurred in 9% and 12%, respectively. CONCLUSIONS: Our findings demonstrate that no association exists between supratherapeutic APTT responses and bleeding, which is in direct contrast to the observed association between subtherapeutic APTT responses and recurrent venous thromboembolism.

Double-Blind Method↗

Venous thromboembolic disease.

During the past year, the findings of several clinical trials have been published that have important implications for the care of patients with venous thromboembolism. These clinical trials have produced advances in the diagnosis and treatment of venous thrombosis and pulmonary embolism and in the prevention of venous thromboembolism in high-risk patients. In patients with clinically suspected pulmonary embolism, the value and limitations of ventilation-perfusion lung scanning have been established, and it is now accepted that objective tests for deep vein thrombosis have an important role. There have been important advances also in the diagnosis of deep vein thrombosis; these advances include the finding that impedance plethysmography is effective in pregnant symptomatic patients and the development of an objective technique for Doppler ultrasound. The optimal duration of initial intravenous heparin treatment of established thrombosis has been determined. In the prevention of venous thromboembolism, the effectiveness of sequential intermittent compression in patients having hip replacement has been established, and further data on the effectiveness of low-molecular-weight heparin in high-risk patients have become available.

Heparin↗

Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis.

It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin, with warfarin added on day 5 to 10 and continued for several months. We performed a randomized, double-blind trial comparing a shorter course of continuous intravenous heparin (5 days, with warfarin sodium begun on the first day) with the conventional 10-day course of heparin (with warfarin sodium begun on the fifth day) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography. The frequency of objectively documented recurrent venous thromboembolism was low and essentially the same in the two groups (7.1 percent in the short-course group vs. 7.0 percent in the long-course group). Because the observed difference between the groups was 0.1 percent in favor of the long-course group, it is unlikely (P less than 0.05) that a true difference in favor of this group would be greater than 7.5 percent; the difference could be as much as 7.3 percent in favor of the short-course group. Major bleeding episodes were infrequent, and the rate was similar in both groups. We conclude that a five-day course of heparin is as effective as a 10-day course in treating deep venous thrombosis. Furthermore, using the shorter course would permit earlier discharge from the hospital and thus offer substantial cost savings.

Acute Disease↗

Effectiveness of intermittent pneumatic leg compression for preventing deep vein thrombosis after total hip replacement.

A randomized trial was performed in consecutive patients undergoing total hip replacement to evaluate the effectiveness of sequential intermittent calf and thigh compression for preventing venous thrombosis compared with a control group given no prophylaxis. Both groups underwent case finding for deep vein thrombosis using combined fibrinogen I 125 leg scanning, impedance plethysmography, and venography. Deep vein thrombosis by venography was present in 77 (49%) of 158 control patients compared with 36 (24%) of 152 patients given intermittent compression. Proximal vein thrombosis was present in 42 controls (27%) compared with 22 patients (14%) given intermittent compression. Combined impedance plethysmography and leg scanning was insensitive in this patient group (sensitivity, 46%); venography was required to detect more than half the patients with venous thrombosis. Sequential intermittent leg compression clinically and statistically significantly reduced the frequency of both proximal vein and calf vein thrombosis. Case finding resulted in early detection and treatment of patients with venous thrombosis.

Female↗

Serial impedance plethysmography in pregnant patients with clinically suspected deep-vein thrombosis. Clinical validity of negative findings.

STUDY OBJECTIVE: To determine the safety of withholding anticoagulant therapy in pregnant patients with clinically suspected deep-vein thrombosis who have negative results by serial impedance plethysmography. DESIGN: Prospective study evaluating prognosis by long-term follow-up to 3 months postpartum in all patients. SETTING: University-affiliated community hospital and referral center. PATIENTS: One hundred fifty-two consecutive pregnant patients referred with clinically suspected deep-vein thrombosis. All patients completed the study. INTERVENTIONS: Anticoagulant therapy was withheld in 139 patients negative by serial impedance plethysmography, and the patients were followed long term. MEASUREMENTS AND MAIN RESULTS: None of 139 patients (0%; 95% CI, 0% to 2.6%) had symptomatic pulmonary embolism or recurrent venous thrombosis. CONCLUSIONS: The findings establish the safety of withholding anticoagulant therapy in pregnant patients who have negative results after serial impedance plethysmography. Sufficient patients were entered to provide narrow confidence intervals on the outcomes observed in patients with negative findings by impedance plethysmography. These findings are similar to those seen after venography in symptomatic patients. These data extend the role of non-invasive testing in patients with clinically suspected deep-vein thrombosis to the pregnant symptomatic patient.

Adolescent↗

Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism.

The objective of this study was to test the safety of withholding anticoagulant therapy in patients with clinically suspected pulmonary embolism who have normal perfusion lung scans, regardless of the clinical manifestations. Anticoagulant therapy was withheld or withdrawn in 515 consecutive patients except in patients in whom deep-vein thrombosis was detected. Only three of the 515 patients had symptomatic venous thromboembolism on follow-up. The frequency of symptomatic pulmonary embolism on follow-up was one of 515 patients. With knowledge of the normal findings by perfusion scanning, an alternative diagnosis was established in 367 of the 515 patients. Cause of symptoms remained uncertain in 148 patients. It is safe to withhold anticoagulant therapy in patients with suspected pulmonary embolism and normal perfusion scans, regardless of the clinical manifestations. The finding of a normal perfusion scan excludes the presence of clinically important pulmonary embolism and makes pulmonary angiography unnecessary.

Adolescent↗

A new noninvasive management strategy for patients with suspected pulmonary embolism.

Pulmonary embolism is associated strongly with proximal-vein thrombosis. We tested the hypothesis that recurrent venous thromboembolism is unlikely in the absence of proximal-vein thrombosis. We performed a prospective cohort study in 874 patients with suspected pulmonary embolism. On long-term follow-up of 371 patients with the following characteristics: (1) abnormal, non-high-probability lung scans, (2) off anticoagulant therapy, and (3) serial noninvasive test results negative for proximal-vein thrombosis, only 10 (2.7%; 95% confidence limits, 1.3% to 4.9%) had venous thromboembolism. By comparison, venous thromboembolism on follow-up occurred in 3 (1%) of 315 patients (95% confidence limits, 0.2% to 2.8%) with normal lung scans, and in 5 (7%) of 66 patients (95% confidence limits, 2.5% to 16.8%) with high-probability lung scans. Patients whose serial noninvasive test results were negative for proximal-vein thrombosis have a good prognosis without anticoagulant therapy.

Adult↗

Heparin therapy for venous thrombosis and pulmonary embolism.

Intravenous heparin is the initial treatment of choice for most patients with acute pulmonary embolism or proximal deep vein thrombosis. The primary objective of initial heparin therapy in such patients is to prevent recurrent venous thromboembolism. The efficacy of intravenous heparin for this purpose has been established by randomized clinical trials in patients with pulmonary embolism, and more recently, in patients with proximal vein thrombosis. Heparin is given as an initial intravenous bolus of 5000 units, followed by a maintenance dose of 30,000-40,000 units per 24 h by continuous intravenous infusion. A recent randomized trial in patients with proximal vein thrombosis indicates that failure to achieve an adequate anticoagulant response (APTT greater than 1.5 times control) is associated with a high risk (25%) of recurrent venous thromboembolism. Intravenous heparin administered in doses that prolong the activated partial thromboplastin time (APTT) to 1.5 or more times the control value is highly effective, and associated with a low frequency (2%) of recurrent venous thromboembolism. Heparin is continued for 7-10 days, overlapped with warfarin sodium during the last 4-5 days. Multiple randomized clinical trials indicate that this approach is highly effective. An alternative approach is to commence heparin and oral anticoagulants together at the time of diagnosis, and to discontinue heparin on the fourth or fifth day. A recent randomized trial in patients with submassive venous thrombosis or pulmonary embolism suggests that 4-5 days of initial heparin therapy is effective and safe, but this approach must be evaluated by further randomized trials before it is recommended for patients with extensive proximal vein thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin↗

Pulmonary embolism in outpatients with pleuritic chest pain.

Pleuritic chest pain is a frequent complaint in patients coming to the emergency room, but the proportion of such patients with pulmonary embolism is uncertain. In a prospective study, we evaluated the diagnostic outcomes in 173 consecutive patients who came to the emergency room with pleuritic chest pain. Pulmonary embolism, as demonstrated by angiography or autopsy, was present in 36 (21%). The need for objective testing is clearly indicated by our finding that the sensitivity (85%) and specificity (37%) of predetermined clinical variables for pulmonary embolism were insufficient to allow a definitive treatment decision. Optimal sensitivity and specificity are obtained by using pulmonary angiography in combination with lung scanning. The proportion of patients requiring angiography is substantially reduced, from 43% to 26%, without significant loss of accuracy, if ventilation imaging and impedance plethysmography are used together with perfusion scanning.

Adult↗

Double-blind randomised trial of Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke.

In a double-blind, randomised trial Org 10172 low-molecular-weight (LMW) heparinoid was compared with placebo in the prevention of deep-vein thrombosis in patients with acute thrombotic stroke. Prophylaxis was started within 7 days of the onset of stroke with a loading dose of 1000 anti-factor-Xa units intravenously followed by a fixed dose of 750 anti-factor-Xa units twice a day subcutaneously; it was continued for 14 days or until hospital discharge, if earlier. 50 patients were randomised to receive Org 10172 and 25 to receive placebo. All patients underwent surveillance with I125-fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became positive. Venous thrombosis occurred in 2 of 50 patients (4.0%) given Org 10172 and 7 of 25 patients (28.0%) given placebo (p = 0.005); the corresponding rates of proximal-vein thrombosis were 0% and 16%, respectively (p = 0.01). There was one major haemorrhage in the Org 10172 group and one minor bleed in the placebo group.

Acute Disease↗

Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis.

We performed a randomized double-blind trial comparing continuous intravenous heparin with intermittent subcutaneous heparin in the initial treatment of 115 patients with acute proximal deep-vein thrombosis. Intermittent subcutaneous heparin as administered in this trial was inferior to continuous intravenous heparin in preventing recurrent venous thromboembolism. The subcutaneous heparin regimen induced an initial anticoagulant response below the target therapeutic range in the majority of patients and resulted in a high frequency of recurrent venous thromboembolism (11 of 57 patients, 19.3 percent), which was virtually confined to patients with a subtherapeutic anticoagulant response. In contrast, continuous intravenous heparin induced a therapeutic anticoagulant response in the majority of patients and a low frequency of recurrent events (3 of 58 patients, 5.2 percent; P = 0.024); the recurrences were limited to patients with an initial subtherapeutic anticoagulant response. The results of this trial establish the efficacy of intravenous heparin in the treatment of proximal venous thrombosis and suggest a relation between the effectiveness of heparin and the levels of anticoagulation achieved; such a relation could explain the observed failure of the subcutaneous regimen.

Acute Disease↗