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PubMed1998

Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism.

In this review, we analyze data from randomized trials in which low molecular weight heparin was compared with unfractionated heparin, both to estimate the treatment effect of low molecular weight heparin in the initial treatment of venous thromboembolism and to evaluate the effect of the varied proportion of included cancer patients (6% to 22.7%) on the incidence of outcome events (recurrence of venous thromboembolism, bleeding, and mortality) and on the estimated treatment effect. Low molecular weight heparin has been extensively investigated in patients with deep vein thrombosis, but few trials have included patients with pulmonary embolism. The risk of recurrence of venous thromboembolism (odds ratio, 0.77; 95% CI, 0.56-1.04), major bleeding (odds ratio, 0.60; 95% CI, 0.38-0.95), and mortality (odds ratio, 0.72; 95% CI, 0.55-0.96) was less with low molecular weight heparins compared with unfractionated heparin. The proportion of cancer patients in these studies had a statistically significant effect on the incidence of recurrent venous thromboembolism (P = 0.03) and mortality (P = 0.002), but no influence on the estimated treatment effects of low molecular weight heparins. Low molecular weight heparin is effective and safe in the initial treatment of venous thromboembolism.

Anticoagulants↗
PubMed2000

Recurrent venous thromboembolism: diagnosis and management.

A diagnosis of recurrent venous thromboembolism is commonly suspected by physicians in the clinical setting. Many do not realize that recurrent venous thromboembolism may mimic the first venous thromboembolic event (VTE) and that only 20 to 30% of patients who have had a first VTE actually have objective recurrent thrombotic disease. Objective testing is necessary to prevent the misdiagnosis of thrombophilia in patients and the associated exposure to prolonged anticoagulant treatment that accompanies that diagnosis. In patients with clinically suspected recurrent venous thrombosis, compression ultrasonography in a new venous segment is the preferred diagnostic approach and contrast venography is an alternative test. There is insufficient evidence to know whether D-dimer testing is an effective approach to the diagnosis of thrombophilia. In patients with suspected recurrent pulmonary embolism, the diagnostic method should begin with ventilation/perfusion lung-imaging and a complementary pulmonary angiography when the results of initial tests are equivocal. Patients with recurrent venous thromboembolism should be treated with anticoagulants for longer than 6 months but the precise period depends on the patient's risk of bleeding as a result of the treatment. Finally, there is currently a lack of evidence that risk for recurrent VTE is increased in patients with a first episode of venous thromboembolism and heterozygous factor V Leiden mutation or the G2021OA prothrombin mutation.

Fibrin Fibrinogen Degradation Products↗
PubMed2006

The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?

The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.

Amino Acid Substitution↗
PubMed2004

Pentasaccharides in the prophylaxis and treatment of venous thromboembolism: a systematic review.

PURPOSE OF REVIEW: The aim of this review is to perform a critical analysis of all completed studies evaluating pentasaccharides-synthetically derived, selective inhibitors of activated factor X-in prophylaxis in major orthopedic surgery and the treatment of venous thromboembolism. RECENT FINDINGS: Venous thromboembolism is a disorder with considerable morbidity when left untreated. New antithrombotic agents have been developed that selectively inhibit components of the coagulation system, thereby avoiding the difficulties associated with current anticoagulants. The pentasaccharides fondaparinux and idraparinux are the first of a new class of synthetic selective inhibitors of activated factor X. Fondaparinux has been extensively investigated in two areas: orthopedic surgery and venous thromboembolism. It is clear from four thromboprophylaxis studies in major orthopedic surgery that fondaparinux is 50% more effective in reducing venous thromboembolism than enoxaparin. This superior efficacy led to an overall increase in major bleeding, which was however primarily due to more fondaparinux-treated patients with bleeding indexes of 2 or greater. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two groups. In the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, fondaparinux was equally effective as low molecular weight heparins and unfractionated heparin, respectively, without a different incidence in major bleeding in fondaparinux and comparator heparin groups. SUMMARY: Fondaparinux, one of the first of a new class of synthetic selective factor Xa inhibitors, is overall 50% more effective in reducing venous thromboembolism than enoxaparin in major orthopedic surgery, with an overall 1% increased rate of major bleeding, when compared with enoxaparin. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two treatment groups. Fondaparinux is equally effective as low molecular weight heparins and unfractionated heparin in the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, respectively. Finally, as with any new drug, fondaparinux should be used cautiously and only in patients who reflect the population of the clinical trials in which the drug was evaluated.

Clinical Trials as Topic↗
PubMed2003

Spinal Cord Injury Risk Assessment for Thromboembolism (SPIRATE Study).

OBJECTIVE: To identify risk factors for venous thromboembolism (VTE) during the rehabilitation phase of spinal cord injury. DESIGN: A comprehensive review of the charts of all patients admitted between 1992 and 1995 for rehabilitation after spinal cord injury. Only records including evidence for objective testing for thromboembolism were included. The analysis variables included type and location of spinal cord injury, American Spinal Injury Association classification, concomitant injuries, surgical procedures, complications, preexisting illnesses, and use of antithrombotic prophylaxis. Hierarchically optimal classification tree analysis was employed to develop a nonlinear model for predicting deep vein thrombosis. RESULTS: The analysis sample consisted of these 243 persons with acute spinal cord injury, 51 of whom had venous thromboembolism, and eight of whom died. A three-variable model emerged that identified patient groups differing in relative likelihood of experiencing deep vein thrombosis. The highest likelihood group were patients with cancer over the age of 35 yrs. Women between the ages of 36 and 58 yrs without cancer were also at increased risk, as were cancer-free men with flaccid paralysis. CONCLUSIONS: Venous thromboembolism is more likely to develop in spinal cord injury patients who are older, obese, and have flaccid paralysis or cancer. These patients should receive vigorous prophylaxis against venous thromboembolism.

Adult↗
PubMed2006

Protein C and protein S levels can be accurately determined within 24 hours of diagnosis of acute venous thromboembolism.

In the 50% of cases of acute idiopathic venous thromboembolism, laboratory testing for inherited causes is often performed. Most physicians are under the impression that assays for protein C and protein S should not be measured at the time of diagnosis because of a high false positive rate. We performed a prospective cohort study from two outpatient thromboembolism clinics on consecutive patients with an objectively confirmed diagnosis of first acute idiopathic venous thromboembolism. Assays for protein C and protein S were performed prior to the initiation of oral anticoagulation therapy and within 24 h of diagnosis of venous thromboembolism. Abnormal results were repeated when patients discontinued oral anticoagulant therapy. Of 253 patients tested for both protein C and protein S, 229 (91%; 95% confidence interval 87-94%) were negative and 484 of 508 (95%) tests were normal. Of the 24 initial abnormal results, 21 were repeated and 10 (48%; 95% confidence interval 26-70%) were still abnormal. Overall, 97.8% of initial protein C and protein S results were accurate. If protein C and protein S are measured at the time of diagnosis of acute venous thromboembolism, the majority of the results will be normal and false positives are uncommon.

Acute Disease↗
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↗
PubMed2004

Challenges in the prevention of venous thromboembolism in the elderly.

Aging itself is a risk factor for venous thromboembolism, and the prevalence in the elderly of additional risk factors (e.g. cancer, orthopedic surgery, immobility) increase its intrinsic risk. Many in the medical community are reluctant to prescribe anticoagulation (for primary and secondary prevention of venous thromboembolism) to their geriatric patients for the fear that bleeding complications may outweigh the benefits. A thorough analysis of the data support the concept that the under-use of heparin in primary prevention in the elderly is more related to medical beliefs than to facts. The risk of bleeding due to oral anticoagulants (secondary prevention) is greatly reduced by keeping the International Normalized Ratio (INR) values within therapeutic ranges and carefully avoiding conditions/drugs that may interfere with such treatment. The oral direct thrombin inhibitor ximelagatran has been studied for primary (hip and knee replacement surgery) and for secondary prophylaxis of venous thromboembolism, and for acute venous thromboembolism treatment. The selective factor Xa inhibitor fondaparinux has been approved for primary prophylaxis of venous thromboembolism in hip and knee replacement surgery and in hip fracture surgery. Studies on the latter drugs, where most of the patients were > 65 years of age, further show that the fear of bleeding complications due to anticoagulation in the elderly is largely unjustified.

Age Factors↗
PubMed1999

Thromboembolic complications of cardiac radiofrequency catheter ablation: a review of the reported incidence, pathogenesis and current research directions.

INTRODUCTION: Radiofrequency catheter ablation (RFCA) has become established as an effective therapy for the treatment of many cardiac tachyarrhythmias. The principle limitation of conventional RFCA continues to be the risk of thromboembolism. This risk is of particular concern for the ongoing development of the catheter maze procedure for the treatment of atrial fibrillation, which currently involves the creation of extensive linear lesions in the left atrium. METHODS AND RESULTS: A Medline search of the literature over the last ten years was performed. Focused review of the reported thromboembolic complications of RFCA indicates an overall incidence of 0.6%. However, the risk is increased when ablation is performed in the left heart (1.8% to 2%) and for ventricular tachycardia (2.8%). It is of concern that intravenous heparin and the use of temperature feedback to control radiofrequency current do not eliminate the risk of thromboembolic events. CONCLUSION: The thromboembolic complications of RFCA are not eliminated by the treatment of intravenous herapin and mode of temperature control during ablation. Potential approaches to further reduce the risk of thromboembolism include the adjunctive administration of specific inhibitors of platelet activation and aggregation, intraprocedural intracardiac echocardiography, irrigated radiofrequency ablation, and cryoablation catheter systems.

Anticoagulants↗
PubMed1969

Investigation of relation between use of oral contraceptives and thromboembolic disease. A further report.

The results of a previous study of the use of oral contraceptives by married women discharged from hospital with a diagnosis of thromboembolic disease in the years 1964-6 were reported by us last year. The present paper adds results relating to patients discharged during 1967 and a few data, that could not be sought previously, for patients discharged with cerebral or coronary thrombosis from three of the hospitals in the earlier period.Of 84 patients with deep-vein thrombosis or pulmonary embolism 42 (50%) had used oral contraceptives during the month preceding the onset of their illness, while only 23 of the 168 controls (14%) had done so. No differences in risk were found either for the types of preparation or for the duration of use. After allowance for age and height, the patients with venous thromboembolism were about 10 lb. (4,535 g.) heavier than the control patients, irrespective of whether they were using oral contraceptives or not. No appreciable difference was found between the smoking habits of patients with and without venous thromboembolism treated during 1967, nor between women who were using oral contraceptives and those who were not. The trend in hospital admissions for venous thromboembolism with time corresponded to the trend in the use of oral contraceptives, and there was no evidence to suggest that the number of admissions was affected by publicity about the risk of using the preparations. Of 19 patients with cerebral thrombosis 11 (58%) had been using oral contraceptives, compared with an expected figure of 3.5 from the experience of the control subjects. All the published data (clinical, angiographic, and post-mortem) show that the thrombosis affects the cerebral arteries rather than the cerebral veins. Of 17 patients with coronary thrombosis 2 (12%) had been using oral contraceptives, compared with an expected figure of 2.1. The patients with coronary thrombosis smoked more than the control patients and were, on average, 8.3 lb. (3,765 g.) heavier than control women of the same age and height.The new evidence strengthens the belief that oral contraceptives are a cause of venous thromboembolism and cerebral thrombosis but does not indicate that they are a cause of coronary thrombosis.

Adolescent↗
PubMed1977

Oral contraceptive use and venous thromboembolism: absence of an effect of smoking.

We conducted a case-control study to test the hypothesis that women smokers who use oral contraceptives have an increased risk of developing venous thrombosis. Patients and controls were drawn from two sets of hospital patients already included in the Boston Collaborative Drug Surveillance Programme. Sixty patients with uncomplicated thromboembolism were matched with 180 controls with other diagnoses; all were premenopausal women taking oral contraceptives. Patients with conditions that might predispose to thromboembolism or be related to smoking were excluded. We found no association between smoking habits and thromboembolism. Similarly, we found no association between thromboembolism, smoking, and duration of oral contraceptive use. Thus we conclude that differences in fibrinolytic activity between smokers and non-smokers are not major factors in the aetiology of uncomplicated thromboembolism in women using oral contraceptives.

Clinical Trials as Topic↗
PubMed2006

Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial.

OBJECTIVE: To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism. DESIGN: Double blind randomised placebo controlled trial. SETTING: 35 centres in eight countries. PARTICIPANTS: 849 medical patients aged 60 or more admitted to hospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days. INTERVENTIONS: 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days. OUTCOME MEASURE: The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month. RESULTS: 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of patients treated with fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patients in the fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died. CONCLUSION: Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both fondaparinux and placebo treated patients.

Acute Disease↗
PubMed2006

Cancer and venous thromboembolism. Clinical implications of strong association.

Venous thromboembolism is a common occurrence inpatients with cancer. Among risk factors for thromboembolism are prolonged immobilization, especially during hospital stay, surgery, and chemotherapy with or without adjuvant hormone therapy. Although prophylaxis and treatment of thromboembolism in cancer patients encompass those agents that are commonly utilised in patients free from malignancy, there are many unique issues in cancer patients that often make their use more problematic. Low-molecular weight heparins are the cornerstone of prophylaxis and treatment of venous thromboembolism in cancer patients. Furthermore, they have the potential to prolong patients survival, at least in those with more favourable prognosis. Approximately 10% of patients with idiopathic venous thromboembolism harbour an underlying malignancy that can be detected by an extensive diagnostic work-up. However, whether screening for occult malignancies ultimately improves prognosis and prolongs survival remains to be demonstrated.

Heparin, Low-Molecular-Weight↗
PubMed1992

Thromboembolic complications in beta thalassemia major.

Thromboembolic complications in beta-thalassemia major have seldom been reported and their association with risk factors such as left ventricular failure and postsplenectomy thrombocytosis has remained speculative. In this report we describe 4 patients with unusual thromboembolic manifestations: recurrent arterial occlusion, recurrent pulmonary thromboembolism, venous thrombosis and a fatal cerebrovascular event. Although in all patients both risk factors were present, the precise causes for their thromboembolic complications were not identified. In 1 patient, however, a marked increase in hematocrit following blood transfusion resulted, in all likelihood, in a fatal cerebrovascular infarction. We suspect that these patients (constituting 4% of our beta-thalassemic group) represent a subset of those with high susceptibility to both arterial and venous thromboembolic complications.

Adolescent↗
PubMed2004

Age- and sex-specific incidence, risk, and latency period of a perioperative acute thromboembolism syndrome (PATS).

We investigated age- and sex-specific incidence, risk factors, and latency period of a perioperative acute thromboembolism syndrome (PATS) in a large cohort study. We prospectively analyzed data on 21903 consecutive surgery patients to determine the incidence of myocardial infarction, pulmonary embolism, deep venous thrombosis, stroke, and cardiovascular death within 30 postoperative days. Among 255 (1.2 percent) patients with thromboembolism, 105 (0.48 percent) suffered myocardial infarction (mean latency: 5 days), 30 (0.14 percent) suffered pulmonary embolism (6 days), 23 (0.11 percent) suffered deep venous thrombosis (10 days), 97 (0.44 percent) suffered stroke (11 days), and 13 (0.06 percent) died (12 days). The critical period was postoperative week 1 for myocardial infarction and pulmonary embolism, and postoperative week 1 and 2 for deep venous thrombosis, stroke, and death. Risk of all events increased with age (P<0.0001), particularly for over 70 years (odds ratio: 12.5; 95 percent confidence interval, 7.8 to 19.9). Males had an increased risk (P<0.0001) of myocardial infarction (odds ratio; 1.5; 95 percent confidence interval, 1.0 to 2.3). Females had an increased risk (P<0.0001) of pulmonary embolism (odds ratio: 2.7; 95 percent confidence interval, 1.3 to 5.9) and deep venous thrombosis (odds ratio: 9.8; 95 percent confidence interval, 3.3 to 29.3). Risk of thromboembolic event was higher (P<0.0001) in patients with a history of arterial thrombotic events or cancer. Trend analysis indicates that thromboembolic events will increase 3-fold over the next decade. Our findings enable identification of higher risk patients for prophylactic anti-thromboembolic treatment and awareness of the critical postoperative period.

Acute Disease↗
PubMed2005

Venous thromboembolism during pregnancy is not associated with persistent elevated activated protein C (APC) sensitivity ratio based on the endogenous thrombin potential.

Women who are using oral contraceptives can acquire APC resistance, measured by the effect of APC on the endogenous thrombin potential (ETP). The objective of our study was to examine whether persistentAPC resistance determined with an ETP-based normalized APC sensitivity ratio (nAPCsr) is a risk marker for venous thromboembolism in women with pregnancy-associated thromboembolism. We determined the activities of antithrombin, protein C, protein S, and performed a genetic analysis of factor V Leiden G1691A, prothrombin mutation G20210A, and methylenetetrahydrofolate reductase mutation (MTHFR C677T) in 65 women with venous thromboembolism during pregnancy or the puerperium and in 114 normal women. A significantly (p<0.05) higher nAPCsr was present in normal women using hormones, in younger women (<or=45 yrs), and in women with carrier status of factorV Leiden. In normal women without factor V Leiden a significant (p<0.05) negative correlation of nAPCsr with age (r=-0.39), antithrombin activity (r=-0.38), protein S activity (r=-0.26), and a significant positive correlation with hormone intake (r=0.36) was present. nAPCsr is influenced by several coagulation parameters, which are modified by the use of oral contraceptives. Consequently, a multivariate analysis of our data did not show a significant association of nAPCsr to venous thromboembolism, neither as a continuous variable (odds ratio 0.8, 95% CI 0.6-1.1, p=0.10) nor using a cutoff value (nAPCsr cut-off 3.1: odds ratio 1.2, 95% CI 0.3-5.3, p=0.77). Our study demonstrates that nAPCsr is not a risk marker for pregnancy-associated venous thromboembolism.

Activated Protein C Resistance↗
PubMed2005

Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study.

Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.

Adult↗
PubMed2002

Protein C, antithrombin, and venous thromboembolism incidence: a prospective population-based study.

Although deficiencies of protein C and antithrombin, 2 natural plasma anticoagulants, are known risk factors for venous thrombosis, population-based prospective incidence data on these associations are lacking. Venous thromboembolic events have been identified in adults in 2 longitudinal cohort studies, the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). Incidence was examined in relation to prediagnostic plasma levels of protein C (ARIC Study only) and antithrombin. Over a mean of 8.1 years of follow-up, there were 130 incident venous thromboembolic events that were not due to cancer in the ARIC Study. The age-adjusted incidence was elevated 3.36-fold (95% CI 1.24 to 9.11) in the 1.1% of subjects with protein C values <2.0 mg/L compared with subjects with higher values. In contrast, in the ARIC Study and the CHS, there was no association between low plasma antithrombin and venous thromboembolism. In conclusion, in this population-based study, a low protein C, but not antithrombin, level has been determined to be associated with an increased incidence of venous thromboembolism. Attributable risk estimates suggest that low protein C levels account for approximately 2.5% of venous thromboembolic events in the ARIC population.

Adult↗