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D P Brandjes

Publications and source records attributed to D P Brandjes.

At least 19 recordsLinked to original sources
PubMed2001

Low adjusted-dose acenocoumarol therapy in sickle cell disease: a pilot study.

Vasoocclusion is a continuous process in sickle cell disease (SCD) and accumulates to significant end organ damage, mostly irrespective of the occurrence of manifest acute vasoocclusive events. As there are indications that reversing the hypercoagulable state may be of clinical benefit in sickle cell patients, we performed a randomized, double blind, placebo-controlled, cross-over pilot study to assess the efficacy and safety of low-adjusted dose acenocoumarol therapy (International Normalized Ratio: 1.6-2.0) in SCD. Treatment consisted of either acenocoumarol or placebo for 14 weeks, after which treatment was discontinued for a period of five weeks. Then, patients initially on acenocoumarol received placebo (and vice versa) for 14 weeks. Therapy efficacy was assessed by comparing the frequency of vasoocclusive complications, the occurrence of bleeding, and clotting activation between acenocoumarol and placebo treatment of each individual patient. Twenty-two patients (14 homozygous [HbSS] and 8 double heterozygous sickle-C [HbSC]; aged 20-59 years) completed the entire study. Acenocoumarol treatment did not result in a significant reduction of acute vasoocclusive events (three painful crises during acenocoumarol, five painful crises during placebo). There was a marked reduction of the hypercoagulable state (depicted by a decrease in plasma levels of prothrombin F1.2 fragments [P = 0.002], thrombin-antithrombin complexes [P = 0.003], and D-dimer fragments [P = 0.001]) without the occurrence of major bleeding. Even though no clinical benefit (pertaining to the frequency of painful crises) was detected in this pilot study, the value of low adjusted-dose acenocoumarol for preventing specific events (such as strokes) and as a long-term treatment of sickle cell patients should be subject of further study.

Acenocoumarol↗
PubMed2001

Activation of coagulation factor XI, without detectable contact activation in dengue haemorrhagic fever.

A prospective cohort study was performed in 50 patients with dengue haemorrhagic fever (DHF) to determine the potential role of the contact activation system and factor XI activation (intrinsic pathway) in the coagulation disorders in DHF. To establish whether TAFI (thrombin-activatable fibrinolysis inhibitor) was involved in the severity of the coagulation disorders, the TAFI antigen and activity levels were also determined. Markers of contact activation (kallikrein--C1-inhibitor complexes), the intrinsic pathway of coagulation (factor XIa--C1-inhibitor complexes) and TAFI were measured and correlated to thrombin generation markers (thrombin--anti-thrombin complexes (TAT), prothrombin fragment 1+2 (F1+2)) and a marker for fibrinolysis [plasmin--alpha 2--anti-plasmin complexes (PAP)]. Activation of the intrinsic pathway of coagulation was clearly demonstrated by elevated levels of factor XIa--C1-inhibitor complexes, without evidence of contact activation, reflected by undetectable kallikrein--C1-inhibitor complexes. Both TAFI antigen and activity levels were decreased in all patients, which may contribute to the severity of bleeding complications in DHF because of the impaired capacity of the coagulation system to protect the fibrin clot from fibrinolysis. These findings in a human viral infection model are in accordance with earlier findings in bacterial sepsis.

Autoantigens↗
PubMed2001

Diagnostic accuracy of triage tests to exclude pulmonary embolism.

We performed a study in 403 prospectively included patients with suspected pulmonary embolism to compare the accuracy of a combination of the SimpliRED D-dimer assay and an intuitive clinical probability estimate with either one alone. Based on a conjoint diagnostic refer, ence standard, including ventilation-perfusion lung scintigraphy and pulmonary angiography, the prevalence of pulmonary embolism was 31%. We demonstrated a high sensitivity (98%, 95% CI 95-100) and negative predictive value (94%, 95% CI 79-99) for the combination of the two tests. These figures were more favorable than for either test alone. The specificity of the combination was lower (11%, 95% CI 9-12) and consequently the proportion of patients in whom further diagnostic tests would have been avoided was only 8%. We conclude that the combined use of the SimpliRED test and the clinical probability estimate attains a higher sensitivity than either test alone. However, there remains a risk of false negatives and the exclusion efficiency is limited.

Adult↗
PubMed2000

Thyrotoxicosis as a predisposing factor for cerebral venous thrombosis.

Thyroid storm is a rare and life-threatening complication of untreated thyrotoxicosis. A number of neurological complications have been described in association with thyrotoxicosis. We report the case of a 28-year-old woman with a thyroid storm on the basis of Graves' disease and probably triggered by a surgical procedure. She developed cerebral venous thrombosis (CVT) of the left transverse and rectus sinus with a venous infarction of the left thalamus. Except for an increased factor VIII clotting activity there were no thrombophilic abnormalities. Similar cases have been described in the literature and the reported incidence of the combination of CVT and thyrotoxicosis is significantly higher than expected by chance alone (0.1 x 10(-6) per year vs. 0.0032 x 10(-6)/year). This case is consistent with the assumption that thyrotoxicosis, probably through a factor VIII-mediated hypercoagulability, may be a predisposing factor for the development of CVT.

Adult↗
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

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↗
PubMed2000

Compression ultrasonography of the leg veins in patients with clinically suspected pulmonary embolism: is a more extensive assessment of compressibility useful?

We performed a multi-center study in consecutive patients with suspected pulmonary embolism to compare the diagnostic accuracy of a two-point compression ultrasonography (only the common femoral vein and popliteal vein) with an extensive examination of compressibility (from the common femoral vein until the trifurcation of calf veins). A total of 479 patients underwent the two-point compression ultrasonography. The prevalence of pulmonary embolism was 32%. The sensitivity and specificity of this procedure were 23% (95% CI 19-26) and 98% (95% CI 96-99), respectively. Extensive compression ultrasonography was performed in 461 (96%) of these 479 patients and showed comparable accuracy indices (sensitivity 25%, 95% Cl 20-28 and specificity 97%, 95% CI 95-99). We conclude that compression ultrasonography has a limited sensitivity for the detection of thrombosis in patients with acute pulmonary embolism within 24 h of presentation. A more extensive assessment of compressibility of the leg veins in these patients has no additional value as compared to the two-point assessment.

Adult↗
PubMed1999

Review: infectious diseases and coagulation disorders.

Infection, both bacterial and nonbacterial, may be associated with coagulation disorders, resulting in disseminated intravascular coagulation and multiorgan failure. In the last few decades a series of in vivo and in vitro studies has provided more insight into the pathogenetic mechanisms and the role of cytokines in these processes. Because of the growing interest in this field, the complexity of the subject, and the fact that many physicians must deal with a variety of infections, current data are reviewed on the association between infectious diseases and the coagulation system. Novel therapeutic intervention strategies that will probably become available in the near future are mentioned, along with those of special interest for infectious disorders for which only supportive care can be given.

Blood Coagulation↗
PubMed1998

Rational antithrombotic therapy and prophylaxis in elderly, immobile patients.

The aging process is associated with increased coagulation and fibrinolysis parameters, resulting in an overall 'prethrombotic state'. This probably explains the increased baseline susceptibility of elderly patients to the development of thromboembolic disease. Additional factors such as major surgery or malignant disease multiply the risk of thromboembolism in this population. Even when adequate antithrombotic therapy is instituted, the mortality associated with thromboembolic disease remains considerable; this underlines the importance of adequate thromboembolic prophylaxis. At present, the use of low molecular weight heparins (LMWHs) in elderly immobile patients appears to be the most effective approach to prophylaxis. The use of compression stockings seems to be effective in the prevention of venous thrombosis, at least in moderate risk surgical patients. In patients undergoing orthopaedic surgery, additional prophylaxis (e.g. with an LMWH) is necessary. In the management of venous thrombosis, patients can initially be treated with a bodyweight-adjusted dosage of an LMWH. In patients with deep vein leg thrombosis or pulmonary embolism, oral anticoagulant therapy should be started as soon as possible, and should be continued for 6 months. However, before starting prophylaxis or therapy, an individual risk assessment should be performed in which the benefits and disadvantages are balanced. Most of the large trials that have studied the effects of thromboembolic prophylaxis have focused on postsurgical patients. However, it will be of great interest to develop more specific prophylactic and therapeutic regimens for different nonsurgical high risk subgroups of patients, particularly the elderly.

Aged↗
PubMed1997

Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism.

BACKGROUND: The standard diagnostic approach in patients suspected of having pulmonary embolism starts with perfusion-ventilation lung scanning. If the resulting scan is not diagnostic, pulmonary angiography should be done. The use of tests for deep venous thrombosis has been advocated as an adjunct to establishing the diagnosis of pulmonary embolism, but no prospective studies have provided adequate information about the value of these tests. OBJECTIVE: To determine the accuracy and potential clinical utility of compression ultrasonography in the diagnosis of pulmonary embolism. DESIGN: Prospective cohort study with blinded assessment of ultrasonographic results. SETTING: Teaching hospital. PATIENTS: 397 consecutive inpatients and outpatients in whom pulmonary embolism was clinically suspected. MEASUREMENTS: Sensitivity and specificity of compression ultrasonography. Perfusion-ventilation scanning and angiography were the conjoint gold standard for determining the presence or absence of pulmonary embolism. Also calculated were the number of angiograms and lung scans avoided and the number of patients unnecessarily treated when compression ultrasonography was included in the diagnostic strategy. RESULTS: The overall sensitivity of compression ultrasonography for deep venous thrombosis in patients with pulmonary embolism was 29% (95% CI 22% to 37%); the specificity was 97% (CI, 94% to 99%). Adding ultrasonography to the diagnostic approach before lung scanning would avoid approximately 14% of lung scans and 9% of angiograms but would lead to unnecessary treatment of 13% of patients who have an abnormal ultrasonographic result (2% to 4% of all those receiving anticoagulation). When compression ultrasonography is done only in patients with a nondiagnostic lung scan, 9% of angiographies are prevented at the cost of unnecessarily treating 26% of patients who have an abnormal ultrasonographic result (2% of all patients receiving anticoagulation). CONCLUSION: The diagnostic value of compression ultrasonography for the detection of deep venous thrombosis in patients suspected of having pulmonary embolism is limited; the gain in diagnostic efficiency obtained through the use of ultrasonography may be offset by a loss in diagnostic accuracy.

Adolescent↗
PubMed1997

Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.

BACKGROUND: Post-thrombotic syndrome varies from mild oedema to incapacitating swelling with pain and ulceration. We investigated the rate of post-thrombotic syndrome after a first episode of deep-vein thrombosis and assessed the preventive effect of direct application of a sized-to-fit graded compression stocking. METHODS: Patients with a first episode of venogram-proven proximal deep-vein thrombosis were randomly assigned no stockings (the control group) or made-to-measure graded compression elastic stockings for at least 2 years. Post-thrombotic syndrome was assessed with a standard scoring system that combined clinical characteristics and objective leg measurements. Patients were assessed every 3 months during the first 2 years, and every 6 months thereafter for at least 5 years. The cumulative incidence of mild-to-moderate post-thrombotic syndrome was the primary outcome measure. FINDINGS: Of the 315 consecutive outpatients considered for inclusion, 44 were excluded and 77 did not consent to take part. 194 patients were randomly assigned compression stockings (n = 96) or no stockings (n = 98). The median follow-up was 76 months (range 60-96) in both groups. Mild-to-moderate post-thrombotic syndrome (score > or = 3 plus one clinical sign) occurred in 19 (20%) patients in the stocking group and in 46 (47%) control-group patients (p < 0.001). 11 (11%) patients in the stocking group developed severe post-thrombotic syndrome (score > or = 4), compared with 23 (23%) patients in the control group (p < 0.001). In both groups, most cases of post-thrombotic syndrome occurred within 24 months of the acute thrombotic event. INTERPRETATION: About 60% of patients with a first episode of proximal deep-vein thrombosis develop post-thrombotic syndrome within 2 years. A sized-to-fit compression stocking reduced this rate by about 50%.

Bandages↗
PubMed1997

Hyperhomocysteinaemia and associated disease.

An elevated plasma homocysteine level may result from various environmental and genetic factors. Herediatary causes of severe hyperhomo-cysteinaemia are very rare and usually lead to disease in childhood or adolescence. Common pathology consists of early atherosclerotic vascular changes, arterioocclusive complications and venous thrombosis. Mildly elevated genetically determined plasma homocysteine levels are observed in 5% of the general population. In the last two decades research has shown mild hyperhomocysteinaemia to be linked to an increased risk of premature atherosclerosis, pregnancies complicated by neural tube defects and early pregnancy loss, and venous thrombosis. Homozygosity for thermolabile MTHFR deficiency has been identified as one important genetic factor, which expression is modified by dietary folate intake. Although mild hyperhomocysteinaemia can easily be treated by vitamin supplementation the beneficial effects of such treatment remains to be shown.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1997

Malabsorption syndrome associated with ulceration of the stomach and small bowel caused by chronic intestinal ischemia in a patient with hyperhomocysteinemia.

We describe a 39-year-old woman with an 8-month history of abdominal pain, diarrhea, and weight loss. Clinical and laboratory evaluation indicated the presence of a malabsorption syndrome. Endoscopy revealed multiple gastric ulcerations and an abnormal "picture" of the duodenal mucosa. At duodenal biopsy, necrosis confined to the distal parts of the enteric villi and a polymorphonuclear leukocyte response were found. Further evaluation revealed intestinal ischemia as a result of mesenteric atherosclerosis. After a revascularization procedure was performed, the symptoms disappeared. The macroscopic and microscopic picture of the bowel normalized. In our search for risk factors of atherosclerosis, we found a substantially increased basal plasma homocysteine concentration. This case suggests that hyperhomocysteinemia may have a causal role in the development of symptomatic, premature atherosclerosis of the mesenteric circulation.

Adult↗
PubMed1997

Effects of heparin therapy on fibrinolysis in patients with pulmonary embolism.

Previous investigations suggested that heparin administration to humans enhances the tissue type plasminogen activator (tPA) levels in blood, but it remains uncertain whether this effect induces fibrinolysis. We studied the effect of therapeutic levels of heparinization on plasma markers for fibrinolysis in patients suspected of pulmonary embolism (PE). Blood samples were taken from 49 consecutive patients; 28 had confirmed PE, 21 had PE excluded. On admission, the plasma levels of plasmin-alpha 2antiplasmin complexes and D-dimer were significantly higher in the patient group with PE compared to those in whom PE was excluded. After heparinization the tPA levels increased in both groups, showing that this effect was not dependent on the initial level of activity of fibrinolysis. In spite of this increment in tPA levels, the concentrations of plasmin-alpha 2antiplasmin complexes and D-dimer decreased. In conclusion, although heparinization in patients with or without pulmonary embolism does lead to elevated tPA:Ag levels, this is not accompanied by enhanced fibrinolysis.

Adult↗
PubMed1996

Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group.

BACKGROUND: An intravenous course of standard (unfractionated) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the standard initial in-hospital treatment for patients with deep-vein thrombosis, but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe. Because the latter treatment can be given on an outpatient basis, we compared the two treatments in symptomatic outpatients with proximal-vein thrombosis but no signs of pulmonary embolism. METHODS: We randomly assigned patients to adjusted-dose intravenous standard heparin administered in the hospital (198 patients) or fixed-dose subcutaneous low-molecular-weight heparin administered at home, when feasible (202 patients). We compared the treatments with respect to recurrent venous thromboembolism, major bleeding, quality of life, and costs. RESULTS: Seventeen of the 198 patients who received standard heparin (8.6 percent) and 14 of the 202 patients who received low-molecular-weight heparin (6.9 percent) had recurrent thromboembolism (difference, 1.7 percentage points; 95 percent confidence interval, -3.6 to 6.9). Major bleeding occurred in four patients assigned to standard heparin (2.0 percent) and one patient assigned to low-molecular-weight heparin (0.5 percent; difference, 1.5 percentage points; 95 percent confidence interval, -0.7 to 2.7). Quality of life improved in both groups. Physical activity and social functioning were better in the patients assigned to low-molecular-weight heparin. Among the patients in that group, 35 percent were never admitted to the hospital at all, and 40 percent were discharged early. This treatment was associated with a mean reduction in hospital days of 67 percent, ranging from 29 percent to 86 percent in the various study centers. CONCLUSIONS: In patients with proximal-vein thrombosis, treatment with low-molecular-weight heparin at home is feasible, effective, and safe.

Aged↗
PubMed1996

[Problems in weaning from artificial ventilation: 'motor neuron disease'].

Three patients, two men aged 71 and one aged 73 years, were given artificial respiration because of acute respiratory failure. Subsequently they could not be weaned from artificial respiration, due to causes that were not immediately clear. It was ultimately found that the patients suffered from 'motor neuron disease', in two of them due to progressive spinal muscular atrophy, while the third, apart from loss of anterior horn motor cells, also had thoracic hydromelia. The patients died after termination of the artificial respiration.

Aged↗