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Biomedical subjects

C Kearon

Publications and source records attributed to C Kearon.

At least 19 recordsLinked to original sources
PubMed2005

Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis.

BACKGROUND: The post-thrombotic syndrome is a chronic, poorly understood complication of deep venous thrombosis (DVT). OBJECTIVES: To evaluate predictors of the post-thrombotic syndrome, including intensity of long-term anticoagulation, and to assess the impact of the post-thrombotic syndrome on quality of life. PATIENTS AND METHODS: The setting was 13 Canadian hospitals and one US hospital. One hundred and forty-five patients with an unprovoked episode of proximal DVT who were initially treated with 3 months of conventional-intensity warfarin [target International Normalized Ratio (INR) of 2.5] then participated in a trial comparing two intensities of long-term warfarin therapy (target INR 2.5 vs. INR 1.7). Post-thrombotic syndrome was assessed at the end of the trial using a validated clinical scale. Generic and venous disease-specific quality of life was compared in patients with and without the post-thrombotic syndrome. Multivariable regression analyses were performed to identify predictors of the post-thrombotic syndrome and of its severity. RESULTS: After an average follow-up of 2.2 years, the prevalence of post-thrombotic syndrome was 37% and of severe post-thrombotic syndrome was 4%. Quality of life was worse in patients with the post-thrombotic syndrome compared with patients who did not have it. The presence of factor (F)V Leiden or the prothrombin gene mutation was an independent predictor of both a lower risk (P = 0.006) and reduced severity (P = 0.045) of the post-thrombotic syndrome. Intensity of anticoagulation did not influence the risk of developing the post-thrombotic syndrome. CONCLUSIONS: The post-thrombotic syndrome is a frequent and burdensome complication of proximal DVT, even among patients maintained on long-term oral anticoagulation. While the presence of FV Leiden or prothrombin gene mutation appears to be associated with a reduced risk of post-thrombotic syndrome, this finding requires further evaluation in prospective studies.

Administration, Oral↗
PubMed2005

Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.

Summary. A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta-analyses. In the first step towards unified definitions of bleeding complications, the definition of major bleeding in non-surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities.

Anticoagulants↗
PubMed2005

Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the prevention of venous thromboembolism after total hip replacement.

BACKGROUND: Recombinant human soluble thrombomodulin (ART-123) is composed of the active, extracellular, domain of thrombomodulin. ART-123 binds to thrombin and this complex converts protein C into the natural anticoagulant activated protein C. This study was performed to identify an effective and safe dose of ART-123 for prevention of venous thromboembolism after elective, unilateral total hip replacement. METHODS AND RESULTS: An open-label, sequential, dose-ranging study was performed in which 312 patients received either 0.3 mg kg(-1) or 0.45 mg kg(-1) of ART-123, subcutaneously, 2-4 h after surgery (day 1). Those who received 0.3 mg kg(-1) were given a second dose of 0.3 mg kg(-1) on day 6, and the first 29 of these patients also used intermittent pneumatic compression devices. Those who received 0.45 mg kg(-1) were not given a second dose. Primary efficacy outcome was all deep vein thrombosis on mandatory bilateral venography performed on day 9 +/- 2 and symptomatic venous thromboembolism up to day 11. Primary safety outcome was major bleeding up to day 11. Among patients who did not use intermittent pneumatic compression, venous thromboembolism occurred in 3.4% of 116 evaluable patients in the 0.3 mg kg(-1) group and 0.9% of 111 patients in the 0.45 mg kg(-1) group. Major bleeding occurred in 1.4% of 139 patients in the 0.3 mg kg(-1) group and 6.3% of 144 patients in the 0.45 mg kg(-1) group. CONCLUSION: ART-123 is a highly effective antithrombotic agent that should be directly compared with current methods of prophylaxis in patients who have major orthopedic surgery.

Aged↗
PubMed2005

Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? A prospective case-control study.

BACKGROUND: Although hormone replacement therapy (HRT) is associated with an increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs in users of combined estrogen-progestin HRT and estrogen-only HRT. METHODS: We prospectively studied postmenopausal women with suspected DVT in whom HRT use status was ascertained and who subsequently had objective diagnostic testing to confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there were no DVT risk factors, and controls were patients without DVT, in whom there were also no DVT risk factors. The risk of DVT was determined in users of estrogen-progestin HRT and estrogen-only HRT by comparing the prevalence of current HRT use in cases with idiopathic DVT and controls without DVT (reference group). Multivariable regression analysis was done to adjust for factors that might confound an association between HRT use and the risk of DVT. RESULTS: One thousand one hundred and sixty-eight postmenopausal women with suspected DVT were assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and no DVT risk factors were identified. Estrogen-only HRT was associated with an increased risk for DVT that was not statistically significant [odds ratio (OR) = 1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogen-progestin HRT was associated with a greater than 2-fold increased risk for DVT (OR = 2.70; 95% CI 1.44, 5.07). CONCLUSION: The risk of developing DVT may be higher in users of combined estrogen-progestin HRT than in users of estrogen-only HRT.

Aged↗
PubMed2004

Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin.

BACKGROUND: When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital. METHODS AND RESULTS: This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths. CONCLUSIONS: Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.

Anticoagulants↗
PubMed2004

Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor.

BACKGROUND: The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor. METHODS: In this double-blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow-up. RESULTS: Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) - 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient-year in those who received warfarin for 1 month and 3.2% per patient-year in those who received warfarin for 3 months (rate difference of 3.6% per patient-year; 95% CI - 3.8, 11.0). There were no major bleeds in either group. CONCLUSION: Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.

Adult↗
PubMed2004

Use of different D-dimer levels to exclude venous thromboembolism depending on clinical pretest probability.

Currently, the same D-dimer cut-off point is used to define a positive result for all patients with suspected venous thromboembolism, regardless of their pretest probability. However, use of a relatively high D-dimer cut-off point (lower sensitivity) for those with a low clinical pretest probability, and a low D-dimer cut-off point (higher sensitivity) for those with a high clinical pretest probability, may be preferable. To determine if using three different D-dimer cut-off points according to low, moderate or high clinical pretest probability has greater utility for exclusion of venous thromboembolism than using the same single D-dimer cut-off point in all patients. Data from a previously published study of 571 patients was used to identify the highest D-dimer cut-off point with a negative predictive value of at least 98% for the subgroup of patients with low and high pretest probability. The D-dimer cut-off point for those with moderate clinical pretest probability remained unchanged [0.5 fibrinogen equivalent units (FEU) microgram mL(-1)]. Accuracy of D-dimer testing for venous thromboembolism using three cut-off points vs. one cut-off point was than determined. D-dimer cut-off points of 0.2 and 2.1 FEU microgram mL(-1) were selected for the high and low pretest probability groups, respectively. When three pretest probability-specific cut-off points were used instead of the previously determined single D-dimer cut-off point (0.5 FEU microgram mL(-1)), sensitivity and negative predictive value were unchanged (95 and 98%, respectively), but specificity increased from 44.7 to 60.4% (P < 0.001). This resulted in exclusion of venous thromboembolism in 80 additional patients. Use of three pretest probability-specific D-dimer cut-off points rather than a single D-dimer cut-off point for all patients, has the potential to increase the utility of D-dimer testing for the diagnosis of venous thromboembolism.

Algorithms↗
PubMed2002

Decrease in sensitivity of D-dimer for acute venous thromboembolism after starting anticoagulant therapy.

D-dimer testing is useful for the exclusion of acute venous thromboembolism (VTE). Anticoagulant therapy is expected to reduce D-dimer levels in patients with thrombosis and, consequently, it may not be safe to use D-dimer levels to exclude VTE after anticoagulant therapy has been started. The objectives of this study were to estimate the decrease in D-dimer levels after 24 h of heparin therapy and, applying this estimate to the results of a recent study, to calculate the expected reduction in sensitivity. Using pre-defined criteria, we first performed a literature review to determine whether, and by how much, D-dimer levels decrease within 24 h of starting heparin therapy in patients with acute VTE. Using D-dimer levels that were measured in a prospective study of patients with confirmed deep vein thrombosis and/or pulmonary embolism as baselines, we then determined the change in sensitivity (and specificity) that would result from the fall in D-dimer levels that the literature review suggested would have occurred after 24 h of heparin therapy. On the basis of the literature review, we calculated that mean D-dimer levels decrease by 25%, 24 h after starting heparin therapy in patients with acute VTE. This 25% decrease in D-dimer levels resulted in a decrease in sensitivity from 95.6% (95% confidence interval, 90.0-98.6) to 89.4% (95% confidence interval, 83.7-95.1). There is a decrease in D-dimer levels in patients with acute VTE 24 h after starting heparin therapy that is expected to result in a clinically important drop in sensitivity.

Adult↗
PubMed2001

Management of suspected deep venous thrombosis in outpatients by using clinical assessment and D-dimer testing.

BACKGROUND: When deep venous thrombosis is suspected, objective testing is required to confirm or refute the diagnosis. OBJECTIVE: To determine whether the combination of a low clinical suspicion and a normal D -dimer result rules out deep venous thrombosis. DESIGN: Prospective cohort study. SETTING: Three tertiary care hospitals in Canada. PATIENTS: 445 outpatients with a suspected first episode of deep venous thrombosis. INTERVENTIONS: Patients were categorized as having low, moderate, or high pretest probability of thrombosis and underwent whole-blood D -dimer testing. Patients with a low pretest probability and a negative result on the D -dimer test had no further diagnostic testing and received no anticoagulant therapy. Additional diagnostic testing was done in all other patients. MEASUREMENTS: Venous thromboembolic events during 3-month follow-up. RESULTS: 177 (40%) patients had both a low pretest probability and a negative D -dimer result. One of these patients had deep venous thrombosis during follow-up (negative predictive value, 99.4% [95% CI, 96.9% to 100%]). CONCLUSION: The combination of a low pretest probability of deep venous thrombosis and a negative result on a whole-blood D -dimer test rules out deep venous thrombosis in a large proportion of symptomatic outpatients.

Ambulatory Care↗
PubMed2001

Duration of anticoagulation for venous thromboembolism.

The duration of oral anticoagulant therapy for venous thromboembolism (VTE) depends on the risk of recurrence if treatment is stopped and the risk of bleeding if treatment is continued. If the risk of recurrence is low (e.g., thrombosis provoked by a major reversible risk factor such as surgery), 3 months of treatment is usually adequate. If the risk of recurrence is high (unprovoked "idiopathic" VTE or associated with a non-reversible risk factor such as active cancer), 6 months or indefinite anticoagulant therapy is indicated. The presence of malignancy, an antiphospholipid antibody, and other selected thrombophilic states suggests more prolonged therapy, whereas isolated distal deep vein thrombosis, high risk of bleeding, and patient preference suggest a shorter course of treatment.

Anticoagulants↗
PubMed2001

A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism.

We compared three rapid D-dimer methods for the diagnosis of venous thromboembolism. Patients presenting to four teaching hospitals with the possible diagnosis of deep vein thrombosis or pulmonary embolism were investigated with a combination of clinical likelihood, D-dimer (SimpliRED) and initial non-invasive testing. Patients were assigned as being positive or negative for deep vein thrombosis or pulmonary embolism based on their three-month outcome and initial test results. The three D-dimer methods compared were: (a) Accuclot D-dimer (b) IL-Test D-dimer (c) SimpliRED D-dimer. Of 993 patients, 141 had objectively confirmed deep vein thrombosis or pulmonary embolism. The sensitivity of SimpliRED, Accuclot and IL-Test were 79, 90 and 87% respectively. All three D-dimer tests gave similar negative predictive values. The SimpliRED D-dimer was found to be less sensitive than the Accuclot or IL-Test. When combined with pre-test probability all three methods are probably acceptable for use in the diagnosis of venous thromboembolism.

Fibrin Fibrinogen Degradation Products↗
PubMed2001

Noninvasive diagnosis of deep vein thrombosis in postoperative patients.

The accuracy of noninvasive testing for the diagnosis of deep vein thrombosis (DVT) generally is less in asymptomatic patients than it is in those with symptoms suggestive of thrombosis. This is because asymptomatic DVT often is confined to the distal veins and, when it involves the proximal veins, the thrombi usually are smaller than in symptomatic patients with proximal thrombosis. Because the positive predictive value of noninvasive tests for asymptomatic DVT generally is 80% or less, abnormal results should be confirmed by venography. There are two main reasons why asymptomatic DVT is sought in the postoperative period: (1) to identify the need for full-dose anticoagulant therapy to prevent symptomatic episodes of venous thromboembolism (VTE), including fatal pulmonary embolism (this represents a form of secondary prophylaxis), and (2) to use this outcome as a surrogate for episodes of clinically important VTE in studies that are designed to evaluate methods of venous thrombosis prophylaxis. In relation to the first of these indications, evidence suggests that routine surveillance of high-risk patients to detect asymptomatic postoperative DVT does not result in improved clinical outcomes in patients who received appropriate VTE prophylaxis. In relation to the second indication, there is concern that asymptomatic VTE may not be a reliable surrogate for clinically important VTE, particularly if the effectiveness of different antithrombotic agents is being compared. Coupled with the comparatively low accuracy of noninvasive testing for asymptomatic DVT, this suggests that the results of such testing are unsuitable for the evaluation of new methods of prophylaxis in clinical trials.

Diagnostic Imaging↗
PubMed2001

Natural history of venous thromboembolism.

Most deep vein thromboses (DVTs) start in the calf; however, thrombi that remain confined to the calf rarely cause leg symptoms or are associated with symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins, and subsequently cause PE, increases with the severity of the initiating prothrombotic stimulus and if this stimulus persists. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Treated proximal DVTs resolve slowly, and half of patients still have detectable thrombi after a year. About 10% of patients with symptomatic DVT develop severe postthrombotic syndrome within 5 years. This is more likely to occur if there has been an ipsilateral recurrent DVT. About 10% of PEs are rapidly fatal. Of PEs that are diagnosed before death, about 50% are associated right ventricular dysfunction, a finding that is associated with a high short-term mortality. There is about 50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. After a course of treatment, the risk of recurrent thrombosis is higher in patients without a reversible risk factor and in those with certain biochemical abnormalities, including antiphospholipid antibodies, hyperhomocysteinemia, and homozygous factor V Leiden.

Arterial Occlusive Diseases↗
PubMed2001

Epidemiology of venous thromboembolism.

The annual incidence of diagnosed venous thromboembolism (VTE) is 1 to 2 events per 1000 of the general population. VTE is very uncommon before age 20 years and, after 40 years of age, the incidence about doubles with each decade. Over half of episodes of VTE are deep vein thrombosis (DVT), and three quarters are first episodes. The incidence of VTE is similar in men and women and lower in Asians than it is in Caucasians or Africans. Hereditary risk factors include the factor V Leiden mutation; the G20210A prothrombin gene mutation; and deficiencies of protein C, protein S, and antithrombin. Hyperhomocysteinemia and elevated levels of factors I, VIII and XI, which may be hereditary and/or acquired, are also risk factors. Acquired risk factors include malignancy, hospitalization, surgery, venous trauma, immobilization, estrogen therapy, pregnancy, and the antiphospholipid antibodies. Risk factors for a first episode of VTE are generally also risk factors for recurrence, although the associated relative risk for thrombosis may differ for a first and subsequent event.

Age Factors↗