Biomedical subjects

H R Büller

Publications and source records attributed to H R Büller.

At least 91 records · Page 5Linked to original sources

PubMed2000

Changes in perfusion scintigraphy in the first days of heparin therapy in patients with acute pulmonary embolism.

Patients with suspected pulmonary embolism often receive heparin therapy for hours to days before ventilation/perfusion scintigraphy is completed. We assessed to what extent the lung scan classification and pulmonary vascular perfusion changed over a period of 2-4 days of full anticoagulant therapy. In 312 consecutive patients with at least one segmental perfusion defect on the initial perfusion scan, classification of both the initial and the final lung scan allowed us to study alteration in scan classification. Changes in pulmonary perfusion were assessed scintigraphically in a subgroup of 64 patients with proven pulmonary embolism. Among 79 patients with an initial high-probability lung scan, the final scan remained high probability in 77 whereas it became non-diagnostic and normal in one patient each. The lung scan classification did not change in any of the 233 patients who initially had a non-diagnostic scan. Thus, a different lung scan category was observed in only 2 out of 312 patients (0.6%; 95% CI 0.1%-2.3%). The mean pulmonary perfusion at baseline in the subgroup of 64 patients with pulmonary embolism was 62% (SD +/-17%; range 26%-89%). A mean absolute improvement in pulmonary perfusion of only 4%+/-11% (NS) was observed in the 2-4 days of observation. It is concluded that intravenous heparin therapy for a period of 2-4 days has only a minimal influence on the diagnostic lung scan classification and induces only minor changes in pulmonary vascular obstruction in the majority of patients.

Acute Disease↗

PubMed2000

Survey of the management of deep vein thrombosis in general practice in the Netherlands.

BACKGROUND: To investigate the management of (suspected) deep vein thrombosis in general practice. METHODS: Self completing postal questionnaire among a random sample of 692 general practitioners in the Netherlands. RESULTS: The overall response rate was 58%. Eighty-nine percent of the respondents initiated objective evaluation. Less than 3% usually make the diagnosis on clinical grounds only. Ninety-two percent initiated adequate treatment for the last patient with deep vein thrombosis. No more than 4% usually treat patients with acenocoumarol alone. Respondents frequently referred a patient to a specialist, 41% to confirm the diagnosis and 85% for treatment. Already 44% feel that management of deep vein thrombosis is a mandate of the general practitioner. For those who do not, the availability of diagnostic and therapeutic facilities are the main obstacles. CONCLUSION: In general practice objective diagnostic methods to evaluate suspected deep vein thrombosis are routinely used and patients receive adequate treatment. Although patients are frequently referred to the hospital many general practitioners feel that they should be able to take care of these patients themselves. (See Editorial p. 133)

Acenocoumarol↗

PubMed2000

Monitoring therapy with vitamin K antagonists in patients with lupus anticoagulant: effect on different tests for INR determination.

BACKGROUND: Lupus anticoagulant (antiphospholipid antibodies) is associated with venous and arterial thrombosis in patients with and without autoimmune disorders. Vitamin K antagonists are the treatment of choice in patients with thrombosis, of which the dose is titrated by INR monitoring. Several recent reports suggest that the presence of the lupus anticoagulant disturbs the INR test and may lead to unreliable results with a large variation in INR values, dependent on the reagents used. METHODS: We studied 11 lupus anticoagulant positive patients and 11 lupus anticoagulant negative patients, all using vitamin K antagonists. The INR value was determined using seven different tests and the variation in INR values was compared between the two groups. The amidolytic Factor X levels were used as an phospholipid independent measure for intensity of warfarin therapy. Factor VII and X activity were measured to assess the stability of warfarin therapy. RESULTS: The variation of the results with different INR tests within one patient was minimal and comparable in the two groups for INR's in the therapeutic range. The coefficient of variation for the cases and control group was 10.43 and 9.35, respectively. Variation in both groups increased at supratherapeutic levels of anticoagulation and when the anticoagulation was unstable (measured with Factor X/Factor VII ratio). The relationship between INR values and Factor X analysis revealed no influence of the lupus anticoagulant. CONCLUSIONS: In this study, lupus anticoagulant antibodies do not disturb INR laboratory tests. Differences in INR measurements are seen in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved. Abbreviated Abstract. This study investigates the influence of lupus anticoagulant on INR determination tests in patients treated with warfarin. Eleven cases and eleven lupus anticoagulant negative control patients, also on warfarin therapy, were included. Seven INR results per patient were obtained using different laboratory tests. A factor X assay was performed to obtain an independent measure for the intensity of warfarin therapy. The variation of INR results between the cases and controls revealed no difference in these groups. In addition, the relationship between INR values and Factor X analysis indicated no influence of the lupus anticoagulant. What was observed was an increased difference in INR values in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved

Factor VII↗

PubMed2000

Antiplatelet therapy and other interventions after revascularisation procedures in patients with peripheral arterial disease: a meta-analysis.

OBJECTIVES: To evaluate the efficacy of conservative adjuvant therapy after revascularisation procedures in patients with peripheral arterial disease. DESIGN: meta-analysis. MATERIALS: English-language studies published from 1976 to 1997. METHODS: Reports on conservative therapies in patients with peripheral arterial disease after percutaneous transluminal angioplasty, endarterectomy, thromboendarterectomy or bypass grafting were eligible. Uncontrolled or retrospective studies, double reports or trials without clinical outcomes were excluded. Included studies were graded as level 1 (randomised and double- or assessor-blind), level 2 (open randomised), or level 3 (non-randomised comparative). (Loss of) patency, amputation, vascular events and mortality were the outcomes considered. When feasible, end-of-treatment results, either continuous or binary, were combined with appropriate statistical methods. RESULTS: Thirty-two studies were included. Compared to non-active control, aspirin with dipyridamole improved (loss of) patency (odds ratio (OR) 0.69, 95% confidence interval (CI), 0.53 to 0.90) and mortality (OR 0.80, 95% CI, 0.57 to 1.14); ticlopidine improved (loss of) patency (OR 0.53, 95% CI, 0.33 to 0.85) and amputation (OR 0.29, 95% CI, 0.08 to 1.01). Data on the effectiveness of vitamin-K inhibitors were not conclusive. CONCLUSIONS: Patients with peripheral arterial disease improve their outcome by receiving aspirin with dipyridamole or ticlopidine after a revascularisation procedure.

Arterial Occlusive Diseases↗

PubMed2000

Hereditary and acquired thrombophilia.

During the past decade knowledge about the etiology of venous thromboembolism has increased tremendously. Inherited and acquired risk factors for venous thromboembolism are common in patients as well as in the general population. Whether the presence of most of these risk factors has consequences for the management of symptomatic and asymptomatic individuals is not fully clear at present. Therefore, while searching for new thrombophilic defects, it is crucial to determine the absolute risk for (recurrent) venous thromboembolism as well as other clinical manifestations in carriers. However, tentative guidelines for managing patients and their families are given in this review.

Journal Article↗

PubMed2000

Active implementation of a consensus strategy improves diagnosis and management in suspected pulmonary embolism.

Our consensus-based strategy in the diagnostic management of patients with pulmonary embolism involves a perfusion lung scan, a ventilation lung scan, compression ultrasonography and pulmonary angiography, in sequence. We compared the diagnostic approach in patients with clinically suspected pulmonary embolism before the active implementation of this strategy (retrospective analysis of 618 patients, April 1992-March 1995) and after (prospective study of 250 patients, April 1995-March 1996), with another assessment 1 year later. The measured outcomes were: (i) final diagnosis of pulmonary embolism either directly by pulmonary angiography, indirectly by compression ultrasonography of the leg veins, or with a high probability from a ventilation/perfusion lung scan; (ii) prescription of anticoagulant therapy. Before strategy implementation, pulmonary embolism was adequately confirmed or excluded in 11% of patients with an abnormal perfusion lung scan; in 55% the diagnosis remained uncertain, but the patient received anticoagulants. After implementation, these figures were 58.5% and 13%, respectively. A modest further improvement was observed 1 year later. Active implementation of a consensus-based strategy in the diagnosis of pulmonary embolism increases definite diagnoses, and reduces the numbers treated with anticoagulants. It induces a rapid change in the diagnostic behaviour of physicians.

Algorithms↗

PubMed2000

The effect of the administration of recombinant activated factor VII (NovoSeven) on perioperative blood loss in patients undergoing transabdominal retropubic prostatectomy: the PROSE study.

Transabdominal retropubic prostatectomy is associated with significant perioperative blood loss, often requiring blood transfusion. However, the administration of allogeneic blood and blood products may induce serious immunological or infectious complications. Several studies show that recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) induces short-term local hemostasis. This ongoing study will evaluate the safety and efficacy of rFVIIa on blood loss in patients with normal coagulation undergoing retropubic prostatectomy. Thirty-six patients will be randomized to three different dose levels and receive either rFVIIa as a single intravenous bolus dose or saline. Perioperative blood loss will be assessed from blood-volume suction containers and drains. Blood sample analysis, physical examination and electrocardiography will be performed postoperatively. Eighteen patients have enrolled in the study. Blood loss was 630-4455 ml (mean = 1698 ml), while the number of red cell transfusions varied between 0 and 4 units (mean = 0.9 units). None of the patients developed venous thromboembolism. An independent committee performed an interim analysis after patient 12 and identified a positive trend between treatment groups (not statistically significant). Although a single bolus injection of rFVIIa appears to decrease perioperative blood loss safely and effectively, definite conclusions must await study completion.

Blood Loss, Surgical↗

PubMed2000

Low-molecular-weight heparins: are they interchangeable?

Unfractionated heparin (UFH) has been used as an antithrombotic agent in the treatment of various clinical entities for over 60 years. Low-molecular-weight heparin (LMWH) com- pounds have gradually replaced UFH for these indications as they have several advantages, including subcutaneous administration and the lack of need for laboratory monitoring. Ever since their introduction, there has been discussion about whether LMWH compounds differ in their efficacy and safety. The best answer is given by direct comparison of two or more preparations; however, such trials are very scarce. Comparison using classical meta-analysis is limited as only a small number of trials with the respective low-molecular-weight heparin compounds are available. The objective of the present analysis has been to use a novel way of plotting the odds ratios of the different studies to compare the efficacy and safety of different LMWH compounds in the initial treatment of patients with venous thromboembolism. Classical meta-analysis revealed reductions in safety and efficacy of 30--40% in favour of LMWHs. Contrasting the log odds ratios of efficacy and safety indicated that there is no conclusive evidence that LMWHs have intrinsic different safety and efficacy profiles.

Anticoagulants↗

PubMed2000

Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis.

PURPOSE: Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR. PATIENTS AND METHODS: In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0. RESULTS: In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0. CONCLUSION: Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy.

Aged↗

PubMed2000

High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism.

BACKGROUND: Established risk factors, including deficiencies of protein C, protein S or antithrombin and the factor V Leiden and prothrombin mutation, are present in about one third of unselected patients with venous thromboembolism. In addition to these inherited thrombophilic defects, elevated plasma levels of factor VIIIc have been suggested to be important in the pathogenesis of (recurrent) venous thromboembolism. The objective of this study was to assess the relevance of factor VIIIc plasma concentration in consecutive patients with venous thromboembolism. METHOD: We studied the prevalence of elevated plasma levels of factor VIIIc in 65 patients with a proven single episode and in 60 matched patients with documented recurrent venous thromboembolism. The reference group consisted of 60 age- and sex-matched patients who were referred for suspected venous thromboembolism, which was refuted by objective testing and long-term clinical follow-up. To minimalize the influence of the acute phase, blood was obtained at least 6 months after the thromboembolic event and results were adjusted for fibrinogen and C-reactive protein. Factor VIIIc was re-determined several years after the first measurement in a subset of patients to evaluate the variability over time. To study a possible genetic cause, a family study was done. FINDINGS: In the control, single and recurrent episode group, the prevalences of plasma levels of factor VIIIc above 175 IU/dl (90th percentile of controls) were 10% (95% CI: 4 to 21%), 19% (95% CI: 10 to 30%) and 33% (95% CI: 22 to 47%), respectively. For each 10 IU/dl increment of factor VIIIc, the risk for a single and recurrent episode of venous thrombosis increased by 10% (95% CI: 0.9 to 21%) and 24% (95% CI: 11 to 38%), respectively. Both low and high plasma levels of factor VIIIc were consistent over time (R = 0.80, p = 0.01). A family study indicated a high concordance for elevated factor VIIIc plasma concentrations among first degree family members. Adjustment for fibrinogen, C-reactive protein and known thrombophilic risk factors did not change the observed association of elevated factor VIIIc with thrombosis. INTERPRETATION: Elevated plasma levels of factor VIIIc are a significant, prevalent, independent and dose-dependent risk factor for venous thromboembolism. It also predisposes to recurrent venous thromboembolism.

Adult↗

PubMed2000

Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group.

Recent studies have suggested that both the subjective judgement of a physician and standardized clinical models can be helpful in the estimation of the probability of the disease in patients with suspected pulmonary embolism (PE). We performed a multi-center study in consecutive in- and outpatients with suspected PE to compare the potential diagnostic utility of these methods. Of the 517 study patients, 160 (31%) were classified as having PE. Of these patients, 14% had a low probability as estimated by the treating physician, while 25 to 36% were categorized as having a low clinical probability with the use of two previously described clinical models. The objectively confirmed prevalence of PE in these three low probability categories was 19%, 28% and 28%, respectively. The three methods yielded comparable predictive values for PE in the other probability categories. We conclude that a physician's clinical judgement alone and two standardized clinical models, although comparable, perform disappointingly in categorizing the pre-test probability in patients with suspected PE.

Adult↗

PubMed2000

Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism.

BACKGROUND: The main purpose of ventilation scanning, as adjunct to perfusion lung scintigraphy, in acute pulmonary embolism is to allow for the classification of segmental perfusion defects as mismatched, which is generally accepted as proof for the presence of pulmonary embolism. We examined whether this function of the ventilation scan could be replaced by the chest X-ray. METHODS: In 389 consecutive patients with suspected pulmonary embolism and at least one segmental perfusion defect we classified the ventilation/perfusion (V/Q) scan and chest X-ray/perfusion (X/Q) scan as either mismatched or matched. Furthermore we analyzed whether this comparison was different in subgroups of patients with concomitant congestive heart failure or chronic obstructive pulmonary disease. RESULTS: Overall agreement between the X/Q and V/Q scan diagnostic category was found in 341 of 389 patients (88%; 95% CI 84-92%). The positive predictive value for obtaining a mismatched V/Q scan result in case of a mismatched X/Q scan result was 86% (95% CI 81-90%). If the X/Q scan yielded only matched defects the V/Q scan resulted in the same classification in 90% (95% CI 85-95%). Analysis of the small subgroup of patients with chronic obstructive pulmonary disease showed that a mismatched X/Q scan was confirmed by V/Q scanning in 21 of 34 cases (62%; 95% CI 45-78%). CONCLUSION: This study shows that in the great majority of patients with clinically suspected acute pulmonary embolism combination of chest X-ray with perfusion scintigraphy reliably replaced ventilation/perfusion scintigraphy in defining (mis)-matching of segmental perfusion defects. These results need confirmation before the chest X-ray can fully obviate the use of ventilation scintigraphy.

Adult↗

PubMed2000

Fixed-dose, body weight-independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis. EASTERN Investigators.

BACKGROUND: Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism. METHODS: Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee. RESULTS: The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02). CONCLUSION: Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis.

Acute Disease↗

PubMed2000

Clinical evaluation of a monoclonal antibody-based enzyme immunoassay for fibrin degradation products in patients with clinically suspected pulmonary embolism. ANTELOPE-Study Group.

We prospectively evaluated the diagnostic accuracy of the Fibrinostika FbDP assay in 304 consecutive patients with suspected pulmonary embolism and examined potentially useful cut-off points at which the disease can be excluded. The prevalence of pulmonary embolism was 31%. The assay generated an area under the Receiver Operating Characteristic curve of 0.79 (95% CI 0.73-0.84). A cut-off point of 0.05 microg/ml yielded a sensitivity, specificity, negative predictive value and an exclusion efficiency of 100% (95% CI 96-100), 5% (95% CI 2-9), 100% (95% CI 69-100) and 3% (95% CI 2-6), respectively. A clinically useful cut-off point seems to be 0.11 microg/ml which corresponded with a sensitivity, specificity, negative predictive value and an exclusion efficiency of 96% (95% CI 90-99), 27% (95% CI 24-28), 93% (95% CI 84-98) and 20% (95% CI 16-25), respectively. We conclude that the assay has potential clinical utility for the exclusion of pulmonary embolism, but it cannot be used as a sole test.

Adolescent↗

PubMed2000

Effects on coagulation of levonorgestrel- and desogestrel-containing low dose oral contraceptives: a cross-over study.

Combined oral contraceptives (OC) are known to increase the risk of venous thromboembolism. The aim of this randomized, cycle-controlled, cross-over study in 28 healthy volunteers was to assess potential differences between the effects of an OC containing 150 microg levonorgestrel (as representative of the so-called second generation OC) and an OC containing 150 microg desogestrel (as representative of the third generation OC) in combination with 30 microg ethinylestradiol on several coagulation factors and markers of thrombin formation. All participants used each OC for two cycles, and were switched to the other OC after a washout period of two menstrual cycles. The plasma concentrations of factors II, VII, X, and fibrinogen significantly increased during use of both the levonorgestrel- and desogestrel-containing OC's. The plasma concentrations of factor VIII increased, and of factor V decreased, changes which only reached statistical significance during the use of the desogestrel-containing OC. During exposure to the desogestrel-containing OC, as compared with the levonorgestrel-containing OC, both factor VII and factor II showed a greater increase (FVII: 32% and 12% respectively; p <0.0001; FII: 16% and 12% respectively; p = 0.048), whereas factor V showed a greater decrease (-11% and -3% respectively; p = 0.010). Only one of the markers for ongoing coagulation (prothrombin fragment 1+2) showed a significant increase during OC use, whereas concentrations of thrombin-antithrombin complexes and soluble fibrin remained unchanged. For these markers, there was no difference between the tested OC's. We conclude that there are differences between the effects of levonorgestrel and desogestrel-containing OC's on some coagulation factors. Whether these changes provide a biological explanation for the reported differences in venous thromboembolic risk is as yet unclear. The real challenge now becomes to define a pattern of changes in the various systems which, if affected simultaneously, may tip the hemostatic balance towards a prethrombotic state and may lead to overt clinical venous thromboembolism.

Adolescent↗

PubMed2000

Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives.

The effect of oral contraceptives (OC) on fibrinolytic parameters was investigated in a cycle-controlled cross-over study in which 28 non-OC using women were randomly prescribed either a representative of the so-called second (30 microg ethinylestradiol, 150 microg levonorgestrel) or third generation OC (30 microg ethinylestradiol, 150 microg desogestrel) and who switched OC after a two month wash out period. During the use of OC, the levels of tissue-type plasminogen activator (tPA) activity, plasminogen, plasmin-alpha2-antiplasmin complexes and D-dimer significantly increased (by 30 to 80%), while the levels of plasminogen activator inhibitor- (PAI-1) antigen, PAI-1 activity and tPA antigen significantly decreased (25 to 50%), suggesting an increase in endogenous fibrinolytic activity. These OC-induced changes were not different between the two contraceptive pills. TAFI (thrombin-activatable fibrinolysis inhibitor) levels increased on levonorgestrel, and even further increased on desogestrel. A clot lysis assay that probes both fibrinolytic activity and the efficacy of the coagulation system to generate thrombin necessary to down regulate fibrinolysis via TAFI showed no change of the clot lysis time during OC use. This finding suggests that the OC-induced increase in endogenous fibrinolytic activity is counteracted by an increased capacity of the coagulation system to down regulate fibrinolysis via TAFI. Indeed we observed that during OC use there was a significant increase of F1+2 generation during clot formation. When these assays were performed in the presence of an antibody against factor XI, we observed that the clot lysis time was significantly increased during OC use and that the increase in F1+2 generation during OC therapy was due to a factor XI-independent process, which was significantly higher on desogestrel than on levonorgestrel. These data indicate that the OC-induced inhibition of endogenous fibrinolysis takes place in a factor XI-independent way and is more pronounced on desogestrel than on levonorgestrel-containing OC.

Adolescent↗

PubMed2000

A randomized cross-over study on the effects of levonorgestrel- and desogestrel-containing oral contraceptives on the anticoagulant pathways.

The use of oral contraceptives (OC) causes disturbances of the procoagulant, anticoagulant and fibrinolytic pathways of blood coagulation which may contribute to the increased risk of venous thrombosis associated with OC therapy. Here we report the results of a cycle-controlled randomized cross-over study, in which we determined the effects of so-called second and third generation OC's on a number of anticoagulant parameters. In this study, 28 non-OC using women were randomly prescribed either a second generation (150 microg levonorgestrel/30 microg ethinylestradiol) or a third generation OC (150 microg desogestrel/30 microg ethinylestradiol) and who switched to the other OC after a two month wash out period. The anticoagulant parameters determined were: antithrombin (AT), alpha2-macroglobulin (alpha2-M), alpha1-antitrypsin, protein C inhibitor (PCI), protein C, total and free protein S and activated protein C sensitivity ratios (APC-sr) measured with two functional APC resistance tests which quantify the effect of APC on either the activated partial thromboplastin time (aPTT) or on the endogenous thrombin potential (ETP). During the use of desogestrel-containing OC the plasma levels of alpha2-M, alpha1-antitrypsin, PCI and protein C significantly increased, whereas AT and protein S significantly decreased. Similar trends were observed with levonorgestrel-containing OC, although on this kind of OC the changes in AT, PCI and protein S (which was even slightly increased) did not reach significance. Compared with levonorgestrel, desogestrel-containing OC caused a significant decrease of total (p <0.005) as well as free protein S (p <0.0001) and more pronounced APC resistance in both the aPTT (p = 0.02) and ETP-based (p <0.0001) APC resistance tests. These observations indicate that the activity of the anticoagulant pathways in plasma from users of desogestrel-containing OC is more extensively impaired than in plasma from users of levonorgestrel-containing OC.

Activated Protein C Resistance↗

PubMed2000

Use of a new monoclonal antibody-based enzyme immunoassay for soluble fibrin to exclude pulmonary embolism. ANTELOPE-Study Group.

We prospectively evaluated the diagnostic performance of a new soluble fibrin assay in 303 consecutive patients with suspected pulmonary embolism and examined potentially useful cut-off levels at which this disease can be safely excluded. In addition, the diagnostic accuracy was calculated in the subgroups of in- and outpatients. The ROC curve of the assay in the total study cohort had an area under the curve of 0.69. The cut-off level associated with a sensitivity and negative predictive value of 100% was 20 ng/ml, but the specificity was only 4%. The cut-off level with a sensitivity of 90% was 30 ng/ml, which corresponded with a specificity and negative predictive value of 27% and 86%. respectively. The diagnostic performance was comparable in the subgroups of in- and outpatients. We conclude that the soluble fibrin assay has a low diagnostic accuracy and seems unsuitable as a screening test for the exclusion of pulmonary embolism.

Adult↗