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Biomedical subjects

M V Huisman

Publications and source records attributed to M V Huisman.

At least 55 records · Page 3Linked to original sources

[Acquired haemophilia A].

A 74-year-old man developed a severe bleeding disorder on the basis of acquired Factor VIII (F VIII) inhibitor. Coagulation assays showed a prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT);F VIII level was 0.07 IU and F VIII inhibitor level 8.8 Bethesda units (BU). At least half the cases of acquired haemophilia A are associated with pregnancy, the postpartum period or an underlying malignancy or autoimmune disease. Haemorrhagic diathesis can be severe and life-threatening. Treatment of acute haemorrhages consists of human or porcine factor VIII concentrate, activated prothrombin complex concentrate (FEIBA) or recombinant factor VIIa, depending on the antibody titre. Immunosuppressive therapy is successful in at least 60% of the patients in making the inhibitor disappear. In patients with a spontaneous haemorrhagic diathesis, a thorough medical history should be taken, coagulation assays should be performed and a specialist should be consulted.

Aged↗

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↗

Bleeding classification in clinical trials: observer variability and clinical relevance.

To evaluate the bleeding classification in a recent trial on venous thrombosis treatment, a selection of reported bleeding episodes was adjudicated twice by an independent committee and graded by the treating physician and independent clinical experts on the clinical severity and impact on the patient's life. The kappa values for the dichotomy major bleeding versus minor or no bleeding were 0.79 (95% CI, 0.57-1.0) for the agreement between the two members of the adjudication committee and 0.77 (95% CI, 0.52-1.0) for the agreement between both adjudication sessions. The kappa values for the dichotomy major or minor bleeding versus no bleeding were 0.42 and 0.44. The weighted kappa values for the agreement between the treating physician and the independent experts were 0.76 for the clinical severity and 0.79 for the impact on the patient's life (95% CI, 0.63-0.88 and 0.70-0.89). The association between the adjudication result expressed as major bleeding or minor or no bleeding and the clinical grading by the treating physician resulted in an ROC curve with an area under the curve of 0.98 for the clinical severity and 0.99 for the impact on the patient's life. The dichotomy major or minor bleeding versus no bleeding resulted in areas under the curve of 0.70 and 0.66. In conclusion, the applied criteria for major bleeding are reproducible and clinically relevant. The criteria for minor bleeding are not reproducible and are less associated with the observed clinical relevance.

Clinical Trials as Topic↗

Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis.

BACKGROUND: It has been reported that women with an inherited deficiency of antithrombin, protein C, or protein S have an increased risk for developing venous thromboembolic disease during pregnancy and the postpartum period. However, because the available data on risk are flawed, it is difficult to define a rational, efficacious, and safe policy about prophylaxis for venous thromboembolism in these women. OBJECTIVE: To determine the frequency of venous thromboembolism during pregnancy and the postpartum period in women with heritable deficiencies of anticoagulant factors. DESIGN: Retrospective cohort study. SETTING: University outpatient clinics in the Netherlands and Italy. PARTICIPANTS: 129 otherwise asymptomatic female family members of patients with a history of venous thromboembolism and an established deficiency of antithrombin, protein C, or protein S. MEASUREMENTS: Medical history, with specific attention to episodes of venous thromboembolism and obstetric history, was taken. The anticoagulant factor status of the study participants was determined. If a patient had an episode of venous thromboembolism, subsequent pregnancies in that patient were not analyzed. RESULTS: Of the 129 women who participated in the study, 60 had anticoagulant factor deficiency and 69 did not. In the nondeficient group, 198 pregnancies occurred; 1 of these (0.5%) was complicated by an episode of venous thromboembolism during the postpartum period. In the deficient group, 169 pregnancies occurred; 7 of these (4.1%) were complicated by an episode of venous thromboembolism during the third trimester of pregnancy (2 pregnancies [1.2%]) and the postpartum period (5 pregnancies [3.0%]). The risk for venous thromboembolism was increased eightfold in deficient women compared with nondeficient women (hazard ratio, 8.0 [95% CI 1.2 to 184]). CONCLUSIONS: Anticoagulant factor-deficient women have an increased risk for venous thromboembolism during pregnancy and the postpartum period. Although data from an appropriate randomized clinical trial are lacking, the frequency of venous thromboembolism seen in deficient women might justify the use of anticoagulative prophylaxis during the third trimester of pregnancy and the postpartum period.

Adolescent↗

A single dose of granulocyte-macrophage colony-stimulating factor induces systemic interleukin-8 release and neutrophil activation in healthy volunteers.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are frequently used in the clinical management of neutropenia. These cytokines not only enhance the proliferation of myeloid precursor cells but also influence the function of mature leukocytes. In a previous study, we found that the in vivo effects of G-CSF on neutrophils differed from those in vitro. In the present study, we investigated the effects of a single dose of recombinant GM-CSF (7.5 microg/kg, subcutaneously) on neutrophils, eosinophils, and monocytes in healthy volunteers. We analyzed leukocyte kinetics, phenotypical changes, neutrophil degranulation, and systemic cytokine production. After GM-CSF injection, phenotypical changes included upregulation of CD11b on all three cell types and a decreased expression of L-selectin and Fc(gamma)RIII on neutrophils. Neutrophil degranulation was evident from the increased plasma concentrations of lactoferrin and elastase. GM-CSF induced the release of interleukin-8 (IL-8), but not of IL-6 or tumor necrosis factor alpha. In comparison to the results from our previous study with G-CSF in healthy volunteers, GM-CSF induced a stronger activation of mature neutrophils but had a much less pronounced effect on the production and maturation of neutrophil precursors. These data may help to guide the choice between the two cytokines in different clinical situations.

Adult↗

Reinfection with Legionella pneumophila documented by pulsed-field gel electrophoresis.

A 50-year-old man with chronic lymphocytic leukemia experienced two episodes of community-acquired legionnaires' disease. For determining whether this was the result of relapse or reinfection, Legionella pneumophila strains, cultured from sputum specimens and his home water supply, were characterized by pulsed-field gel electrophoresis. Analysis of the restriction patterns and the clinical data indicated that the second disease period was most likely the result of reinfection. We conclude that after diagnosis of community-acquired legionnaires' disease in an immunocompromised patient, culturing of the domestic water supplies for L. pneumophila should be considered; if such cultures are positive, adequate measures to prevent reexposure have to be taken.

Anti-Bacterial Agents↗

A new computerized impedance plethysmograph: accuracy in the detection of proximal deep-vein thrombosis in symptomatic outpatients.

Because of the lack of specificity of the clinical diagnosis it is appropriate in patients with clinically suspected deep-vein thrombosis to apply an objective test before starting anticoagulant treatment. Impedance plethysmography is a highly accurate technique for the detection of proximal-vein thrombosis with a reported sensitivity and specificity of 93 and 97%, respectively. In all previous reported evaluations of impedance plethysmography an apparatus which was developed in 1971 was used. A new computerized impedance plethysmography, using a novel device to measure impedance, was blindly compared against venography in 443 consecutive outpatients with clinically suspected deep-vein thrombosis. In the first phase of the study the computerized impedance plethysmography test results of 242 symptomatic patients were used to develop a discriminant line. Subsequently, this discriminant line was validated in the second phase of the study in another 201 symptomatic patients. The combined sensitivity and specificity of these two phases for proximal-vein thrombosis was 91% [95% confidence interval (CI), 86 to 94%] and 94% and (95% CI, 90 to 96%), respectively, which compares favourably with impedance plethysmography. It is concluded that computerized impedance plethysmography is a simple, portable, non-invasive technique with a high accuracy for the detection of proximal vein thrombosis. However, before computerized impedance plethysmography can be used as the only test in the diagnosis of deep-vein thrombosis, the safety of withholding anticoagulant treatment to patients with repeated normal computerized test results should be assessed during long-term follow-up studies.

Adolescent↗

Diagnosis of deep-vein thrombosis using an objective Doppler method.

STUDY OBJECTIVE: To determine the diagnostic criteria (phase I) and to assess the accuracy (phase II) of an objective Doppler-Valsalva pressure method as compared with contrast venography for the diagnosis of acute deep-leg-vein thrombosis in symptomatic outpatients. DESIGN: A two-phase prospective study in consecutive patients. Doppler ultrasound strip-chart recordings and venograms were independently analyzed by experienced observers. SETTING: Referral-based medical clinics at university medical centers. PATIENTS: One hundred and ten (phase I) and one hundred and fifty-five (phase II) patients who had clinically suspected venous thrombosis and were referred by their general practitioners were included. METHODS AND MEASUREMENTS: A normal Doppler test result was defined as a cyclic spontaneous signal (S-signal), a continuous S-signal with a Valsalva pressure of less than 6.5 mm Hg, or an absent S-signal with flow after cessation of the Valsalva maneuver. A continuous S-signal with a Valsalva pressure of 6.5 mm Hg or more or an absent S-signal without flow after cessation of the Valsalva maneuver were defined as abnormal test results. The accuracy indices for proximal vein thrombosis in phase II (155 patients; prevalence, 31%) were sensitivity, 91% (95% CI, 79% to 98%), and specificity, 99% (CI, 97% to 100%). All 3 patients with isolated calf-vein thrombosis had normal Doppler test results. CONCLUSIONS: The objective Doppler method is an accurate, reproducible, and simple method for detection of venous thrombosis in symptomatic outpatients.

Abdomen↗

A double blind three center clinical trial on the short-term efficacy of 0-(beta-hydroxyethyl)-rutosides in patients with post-thrombotic syndrome.

A multi-centre, double blind randomized clinical trial was designed to assess the efficacy and safety of orally administered 0-(beta-hydroxyethyl)-rutosides (HR) capsules in the treatment of 101 patients with post-thrombotic syndrome. Seventeen patients were excluded from the analysis for violation of the study protocol, 41 received HR capsules (1,200 mg/day) and 43 placebo. Mean follow-up scores at the 4th and 8th week show that the HR patients displayed an improved state of tiredness as compared to the placebo's. The mean circumference of the calf for the HR group decreased from 390 (+/- 33) mm at visit one to 382 (+/- 33) mm at visit three, with a mean circumference reduction of 8.7 (+/- 8) mm, compared to a steady placebo circumference of 387 (+/- 31) mm at all 3 visits with a mean circumference reduction of only 2 mm (+/- 9). The estimated treatment effect at week 8 was -6.7 mm, 95% confidence interval (-10.3, -3.0). The mean circumference of the ankle, decreased from 243 (+/- 20) mm to 238 (+/- 20) mm at the 4th week, contrasted with a constant placebo circumference of 241 (+/- 22) mm at both visits. The estimated treatment effect at week 4 was -5.4 mm, 95% confidence interval (-10.2, -0.6). However, at week 8, the estimated treatment effect was only -3.4 mm, 95% confidence interval (-8.6, +1.8). In conclusion, HR capsules may show an improvement in the clinical symptoms and may show a mean circumference reduction of the calf and ankle at the 8th week, in patients with post-thrombotic syndrome.

Adult↗

Detection of deep-vein thrombosis by real-time B-mode ultrasonography.

In 220 consecutive outpatients with clinically suspected deep-vein thrombosis of the leg, we compared contrast venography with real-time B-mode ultrasonography, using the single criterion of vein compressibility with the ultrasound transducer probe. The common femoral and popliteal veins were evaluated for full compressibility (no thrombosis) and noncompressibility (thrombosis). Both veins were fully compressible in 142 of the 143 patients with normal venograms (specificity, 99 percent; 95 percent confidence interval, 97 to 100). All 66 patients with proximal-vein thrombosis had noncompressible femoral veins, popliteal veins, or both (sensitivity, 100 percent; 95 percent confidence interval, 95 to 100). For all patients (including 11 with calf-vein thrombi), sensitivity and specificity were 91 (95 percent confidence interval, 82 to 96) and 99 percent, respectively. The sensitivity for isolated calf-vein thrombosis was only 36 percent. The compression ultrasound test was repeated in a subset of 45 consecutive patients by a second examiner, unaware of the results of the first test, whose results agreed in all patients with those of the first examiner (kappa = 1). We conclude that ultrasonography with the single criterion of vein compressibility is a highly accurate, simple, objective, and reproducible noninvasive method for detecting proximal-vein thrombosis in outpatients with clinically suspected deep-venous thrombosis.

Femoral Vein↗

Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis.

In patients presenting with clinically suspected deep vein thrombosis, symptomatic pulmonary embolism is rarely apparent. To assess the prevalence of silent pulmonary embolism in outpatients with proven deep vein thrombosis but without symptoms of pulmonary embolism, perfusion ventilation lung scans were performed in 101 consecutive patients at presentation. Fifty-one percent of these patients had a high probability lung scan at the initiation of treatment. In comparison, in patients referred with suspected venous thrombosis, but who on subsequent objective testing did not have venous thrombosis (n = 44), the prevalence of a high probability-scan for pulmonary embolus was only 5 percent. At repeat lung scanning, performed after one week of anticoagulant treatment, complete to partial improvement was observed in 68 percent of the patients with initially abnormal scans. Lung-scan detected asymptomatic pulmonary embolism occurs frequently in patients presenting with symptomatic deep venous thrombosis, and the majority of these emboli showed significant to complete resolution within one week of anticoagulant treatment.

Adult↗

Partial protein S gene deletion in a family with hereditary thrombophilia.

Familial thrombophilia, the hereditary predisposition to venous thromboembolic disease, is associated with a protein S deficiency in approximately 8% of the cases. Laboratory measurements of total protein S antigen in affected families have indicated that heterozygotes, ie, individuals carrying both a normal and a defective protein S gene, are severely at risk of developing venous thrombosis at a young age. The recent isolation of protein S cDNA has enabled us to start a search for genetic defects in the protein S gene of heterozygotes. Using Southern blotting on probands of six unrelated families with hereditary protein S deficiency, one proband was found to have a grossly abnormal gene pattern. The abnormality appears to involve at least the deletion of the middle portion of the protein S coding sequence. Family analysis showed that the defect cosegregates with the protein S deficiency. These data agree with the notion that hereditary thrombophilia associated with protein S deficiency is indeed directly the result of a defect in the protein S gene.

DNA Mutational Analysis↗

Management of clinically suspected acute venous thrombosis in outpatients with serial impedance plethysmography in a community hospital setting.

The reported high sensitivity and specificity of impedance plethysmography (IPG) in the diagnosis of proximal vein thrombosis were evaluated in a prospective cohort follow-up study, in which IPG was performed three times over a period of seven days in 243 consecutive outpatients with clinically suspected deep venous thrombosis (DVT). The test was abnormal in 112 patients (46%). The positive predictive value of an abnormal IPG for venography-proved DVT was 90%. One hundred thirty-one patients (54%) with repeatedly normal tests were considered not to have DVT, and anticoagulants were withheld. During six months of follow-up, completed in all patients with repeatedly normal IPG, no patient died of venous thromboembolism and no patient returned with clinically suspected pulmonary embolism. One patient (0.8%) returned after two months with recurrent leg symptoms, and venous thrombosis was documented (95% confidence limits, 0.02% to 4.21%). Another patient, who was nonsymptomatic, had an abnormal IPG at the three-month follow-up visit, and venography revealed venous thrombosis. Patients sent by general practitioners to a community hospital, with clinically suspected acute DVT, can be effectively managed by serial IPG alone.

Ambulatory Care↗

Utility of impedance plethysmography in the diagnosis of recurrent deep-vein thrombosis.

Serial impedance plethysmography has been shown to be a safe and effective alternative to venography in the management of patients with clinically suspected acute venous thrombosis. The rate of normalization of an initial abnormal impedance plethysmogram and, consequently, the usefulness of impedance plethysmography in the management of patients with recurrent symptoms is, however, unknown. In a prospective cohort follow-up study, 161 consecutive patients with proved venous thrombosis and abnormal impedance plethysmograms were studied for one year. After 3, 6, 9, and 12 months, the impedance plethysmograms had normalized in 67%, 85%, 92%, and 95% of the patients, respectively. Thirty-five patients (22%) returned with clinically suspected recurrent thrombosis, of whom 31 had normal impedance plethysmograms prior to their return. In 18 of these patients, repeated tests were normal; these patients did not undergo anticoagulant therapy, and follow-up disclosed no subsequent adverse consequences. In the other 13 patients, the test again became abnormal; 11 patients were shown by venograms to have recurrent deep-vein thrombosis. Consequently, 29 (83%) of the 35 patients in whom the suspicion of recurrent thrombosis arose could have been managed with impedance plethysmography alone without the necessity for venography or anticoagulant therapy. It is concluded that normalization of impedance plethysmography tests occurs in almost all patients within nine months, and that serial impedance plethysmography is useful for patient management in nearly 90% of patients presenting with recurrent symptoms.

Acute Disease↗

Analytical and clinical evaluation of commercial protein C assays.

Protein C deficiency is an important risk factor for thrombosis. Recently several commercial assays for this protein have become available. We evaluated two antigen and three activity assays in 50 healthy volunteers, 52 patients with deep venous thrombosis (DVT) proven by positive impedance plethysmography (IPG) and flebography, and 48 control patients referred to us for objective diagnosis of DVT but with repeatedly negative IPG. All subjects were less than 50 yr of age. Based upon assay performance, correlation of the assays, influence of heparin, and practical ease, an ELISA antigen assay and a chromogenic activity assay are recommended. The prevalence of protein C deficiency cannot be accurately determined from this study, because 3 DVT negative and 13 DVT positive patients were receiving coumarin therapy. However, based upon protein C:factor II antigen ratios, at least 7 of the DVT positive patients are likely to be protein C-deficient. Protein C determination should, therefore, be considered in all DVT patients less than 50 yr of age.

Chromogenic Compounds↗