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Biomedical subjects

E Briët

Publications and source records attributed to E Briët.

At least 19 recordsLinked to original sources
PubMed2001

Successful treatment with recombinant factor VIIa of therapy-resistant severe bleeding in a patient with acquired von Willebrand disease.

We describe an elderly man who presented with life-threatening hematuria and gastrointestinal bleeding caused by acquired von Willebrand disease associated with monoclonal gammopathy of undetermined significance (MGUS). Standard therapy with desmopressin, von Willebrand factor-containing factor VIII concentrate, tranexamic acid, and immunoglobulin failed to achieve adequate hemostasis. However, treatment with recombinant activated factor VII (rFVIIa) arrested the bleeding completely. Since acquired von Willebrand disease can lead to life-threatening hemorrhage, clinicians should consider rFVIIa as an effective treatment option if standard therapy fails.

Aged↗
PubMed2000

[Blind spots of the diagnostic hemostasis screen].

The most powerful instrument to establish the presence or absence of a coagulation disorder is the history of the patient. In addition, screening laboratory tests (consisting of the platelet count, bleeding time and global clotting assays, such as the prothrombin time and the activated partial thromboplastin time) may be helpful to support the diagnosis. In two patients, a 21-year-old man and a 10-year-old girl, with a marked history of enhanced bleeding normal screening laboratory tests were found. The male patient had a congenital alpha 2-antiplasmin deficiency and the girl had a homozygous deficiency of factor XIII. Some defects in the coagulation system (such as defects in fibrin network formation and fibrinolysis, but also mild Von Willebrand disease) are indeed not detected by screening laboratory tests. In patients with a strong suspicion of a coagulation disorder such defects should be specifically tested for.

Adult↗
PubMed2000

[Physical diagnosis--percussion and palpation of the spleen].

The accuracy of physical examination of the spleen was investigated in the literature. Ultrasonography or scintigraphy was used to test the findings at physical examination. Physical examination has a low sensitivity, but a reasonably good specificity. The interobserver variability is rather high. In general, palpation is more sensitive and specific than percussion. The findings of percussion improve the accuracy of palpation and the combination has a high specificity, of approximately 90%. The two should therefore be used in conjunction. The sensitivity is much lower although it is greatly influenced by the degree of splenic enlargement and the leanness of the patient.

Humans↗
PubMed1999

Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints.

BACKGROUND: Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin). METHODS: Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery. FINDINGS: We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0.55 [95% CI 0.34-0.90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0.37 [0.25-0.55], and 0.44 [0.22-0.90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2.4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results. INTERPRETATION: Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.

Aminocaproates↗
PubMed1999

Gene-gene and gene-environment interactions determine risk of thrombosis in families with inherited antithrombin deficiency.

To analyze inherited antithrombin deficiency as a risk factor for venous thromboembolism in various conditions with regard to the presence or absence of additional genetic or acquired risk factors, we compared 48 antithrombin-deficient individuals with 44 nondeficient individuals of 14 selected families with inherited antithrombin deficiency. The incidence of venous thromboembolism for antithrombin deficient individuals was 20 times higher than among nondeficient individuals (1.1% v 0.05% per year). At the age of 50 years, greater than 50% of antithrombin-deficient individuals had experienced thrombosis compared with 5% of nondeficient individuals. Additional genetic risk factors, Factor V Leiden and PT20210A, were found in more than half of these selected families. The effect of exposure to 2 genetic defects was a 5-fold increased incidence (4.6% per year; 95% confidence interval [CI], 1.9% to 11.1%). Acquired risk factors were often present, determining the onset of thrombosis. The incidence among those with exposure to antithrombin deficiency and an acquired risk factor was increased 20-fold (20.3% per year; 95% CI, 12.0% to 34.3%). In conclusion, in these thrombophilia families, the genetic and environmental factors interact to bring about venous thrombosis. Inherited antithrombin deficiency proves to be a prominent risk factor for venous thromboembolism. The increased risks among those with exposure to acquired risk factors should be considered and adequate prophylactic anticoagulant therapy in high-risk situations seems indicated in selected families with inherited antithrombin deficiency.

3' Untranslated Regions↗
PubMed1999

[Pharmacotherapeutic choices for correction of disorders of primary hemostasis].

A defective primary haemostatic system is a relatively frequent disorder, due to the increasing use of aspirin and other non-steroid anti-inflammatory agents (NSAIDs) by the general population. Impaired primary haemostasis may result in enhanced perioperative bleeding. Administration of desmopressin is an effective pharmacotherapeutic intervention that will improve the process of primary haemostasis in many cases, with or without additional interventions in the clotting system.

Adult↗
PubMed1998

[Recombinant factor VIIa (eptacog alfa): a new therapeutic option for patients with severe bleeding disorder due to inhibitory antibodies against a coagulation factor].

In 2 patients with severe haemorrhage (a 63-year-old man with haemophilia A (the factor VIII level was 29%) and a 44-year-old woman), of an inhibitory antibody against factor VIII was diagnosed. The development of recombinant factor VIIa (eptacog alpha) has made available a new therapeutic option for patients with an inhibitory antibody against a coagulation factor. Both patients were treated successfully with the new factor after other forms of treatment had failed. The new concept of the coagulation cascade on which the treatment with eptacog alpha is based assumes that the lack of an amplifying loop in the coagulation which takes place via factor IX (in combination with factor VIII) can be compensated by extra stimulation of the principal route (tissue factor-factor VIIa --> factor X) by pharmacological amounts of factor VIIa.

Adult↗
PubMed1998

Well-being of haemophilia patients: a model for direct and indirect effects of medical parameters on the physical and psychosocial functioning.

This study outlines the development and evaluation of a structural equation model for establishing the consequences of haemophilia. The hereditary disorder is characterized by a high tendency to haemorrhages, with recurrent bleeding into the joints causing irreversible joint damage. The model is, in general, an attempt to answer the following questions: what is the effect of haemophilia on the well-being (i.e. satisfaction, health, somatic complaints and self-esteem) of patients and what is the additional or mediating role of other individual characteristics in this pathway? Disease severity, joint impairment and disability are defined as antecedents of well-being and the mediating roles of appraisal (i.e. the personal evaluation of the disease), health beliefs (i.e. locus of control), psychological characteristics (i.e. anxiety, anger, depression and optimism) and social support are investigated. Psychological variables turned out to be the strongest determinants of well-being and partly mediated the detrimental effect of disability on well-being. The role of appraisal remained somewhat unclear, as no significant relationship was established between this personal evaluation of haemophilia and well-being. Nevertheless, appraisal very well reflected the level of disability. An internal locus of control and favourable psychological characteristics appeared to reduce the perceived seriousness of haemophilia. No evidence was found for social support to act as a mediator between disability and well-being. The perception of support did show moderately strong associations with psychological characteristics (i.e. anxiety and depression) and satisfaction ratings. The study merits further research on quantifying the relationships between clinical parameters and psychosocial outcomes in patients with a chronic disease.

Adult↗
PubMed1998

Partial reconstitution of factor VIII activity from a mild Crm+ hemophilia A patient by replacement of the defective A2 domain.

We further characterised the abnormal factor VIII molecule (factor VIII Leiden) of a Crm+, mild hemophilia A patient with a factor VIII activity of 0.18 IU/ml and a factor VIII antigen of 0.95 IU/ml. Mutation analysis of the coding region, promoter and 3' untranslated region of the factor VIII gene revealed the presence of a C to T substitution at codon 527. This nucleotide change predicts the replacement of an arginine to tryptophan in the A2 domain close to a suggested binding site for factor IXa. Since a previous study of this mutant factor VIII protein suggested that this protein had a reduced affinity for factor IXa, position 527 in the protein might be involved in the interaction with factor IXa. In this study we gathered evidence for our hypothesis that the Arg to Trp mutation at position 527 is the cause of the reduced activity of factor VIII Leiden. Replacement of the mutated A2 domain by wild type A2 domain partially corrected the defect. Factor VIII from normal and factor VIII Leiden plasma was concentrated by cryoprecipitation, activated with thrombin and incubated with excess wild type A2 domain. Competition with excess isolated human A2 domain resulted in a partial reconstitution of the factor VIIa activity of thrombin treated factor VIII Leiden. This supports the hypothesis that the mutation in the A2 domain is the cause of the reduced factor VIII activity.

Factor VIII↗
PubMed1997

[Revision consensus hemophilia: treatment and responsibility. Nederlandse Vereniging van Hemophilia Patients].

Haemophilia is an X-linked clotting disease occurring in 1400 men in the Netherlands. As the result of factor VIII or IX deficiency, haemophilia patients suffer from severe bleedings, spontaneous or caused by trauma. Bleedings mostly occur in major joints and muscles. Repeated bleedings can cause disability. Treatment of haemophilia consists of replacement therapy with factor VIII or IX. The first aim of treatment is to prevent bleedings (prophylaxis). The second aim is to limit joint damage in case of bleeding by timely and adequate substitution therapy. In addition, physical therapy and sports are used to keep patients in shape. Until the introduction of recombinant factor VIII in 1992 only plasma derived factor VIII and IX products were available. Substitution therapy has caused various side effects, such as allergic reactions. Since the introduction of ultra-pure concentrates, allergic reactions have grown rare. Viral infections like HIV and hepatitis C, which were transmitted through blood products, have not occurred in Dutch haemophilia patients since the introduction of adequate viral inactivation steps. In case of development of antibodies against factor VIII or IX, therapy with factor VIII or IX products is insufficient. Antibody formation is more often seen in haemophilia A (25%) than in haemophilia B (2%). In most cases antibodies disappear during so-called immune tolerance induction. This therapy consists of regular infusion with factor VIII or IX. Once an inhibitor has disappeared, patients can be treated normally once more. As haemophilia is a rare and complex disease patients should be treated in specialized centres, preferably by a comprehensive care team. This is even more justified because treatment of haemophilia is costly. Over the last 20 years haemophilia treatment has improved much. This has resulted in a decrease of the number and of the duration of hospitalization, and a decrease in days lost at school or work. This has led to great improvement of the social life of haemophilia patients.

Blood-Borne Pathogens↗
PubMed1997

High intensity of oral anticoagulant therapy in patients with cerebral haemorrhage: cause or consequence of the bleeding?

In assessing the optimal intensity of anticoagulant therapy, the International Normalized Ratio (INR) at admission is used as a basis for INR-specific incidence rates. In 47 patients suffering a haemorrhagic stroke we tested the assumption that the INR at admission is an acceptable measure for the INR that preceded the haemorrhage. We found high D-dimer levels in 70% of the patients, which indicated activated coagulation and fibrinolysis. This was not of such an extent that it could also be measured with other routine coagulation tests, with the possible exception of two patients. We found normal INRs in 33 non-anticoagulated patients, and only a mildly prolonged INR of 1.9 in one patient, which was most probably caused by a vitamin K deficiency. We concluded that the INR at admission can be used in studies to assess the optimal level of anticoagulation.

Administration, Oral↗
PubMed1997

The role of compliance as a cause of instability in oral anticoagulant therapy.

To assess the role of non-compliance as a cause of instability in patients on oral anticoagulant therapy, a follow-up study of stably and instably anticoagulated patients and of patients beginning oral anticoagulant therapy was performed. Compliance was assessed by pill counting and with the use of pill bottles in the cap of which a microprocessor registered the exact date and time of opening of the bottle. (In)stability of oral anticoagulant therapy was expressed as the number of INRs and as the time spent within the target range and by squared sigma. Subsequently, as a pilot study, a randomized intervention study in instable, non-compliant patients was performed in which these patients were or were not informed about the real nature of the cap of the pill bottle. Nineteen stable and 19 unstable patients and 30 patients beginning therapy were followed for 3 months or less until therapy stopped. Compliance was better in the previously stably anticoagulated patients, although differences were small. Poor compliance was not a major cause of instability in patients starting therapy. Although the pilot intervention study was too small to assess the role of the special pill bottle, it was shown that compliance can be positively affected.

Administration, Oral↗
PubMed1996

Increased fetal loss in women with heritable thrombophilia.

BACKGROUND: A successful outcome of pregnancy requires an efficient uteroplacental vascular system. Since this system may be compromised by disorders of haemostasis associated with a prothrombotic state, we postulated that maternal thrombophilia might be a risk factor for fetal loss. We studied the relation between heritable thrombophilic defects and fetal loss in a cohort of women with factor V Leiden or deficiency of antithrombin, protein C, or protein S. METHODS: We studied 1384 women enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). Of 843 women with thrombophilia 571 had 1524 pregnancies; of 541 control women 395 had 1019 pregnancies. The controls were partners of male members of the EPCOT cohort or acquaintances of cases. We analysed the frequencies of miscarriage (fetal loss at or before 28 weeks of gestation) and stillbirth (fetal loss after 28 weeks of gestation) jointly and separately. FINDINGS: The risk of fetal loss was increased in women with thrombophilia (168/571 vs 93/395; odds ratio 1.35 [95% Cl 1.01-1.82]). The odds ratio was higher for stillbirth than for miscarriage (3.6 [1.4-9.4] vs 1.27 [0.94-1.71]). The highest odds ratio for stillbirth was in women with combined defects (14.3 [2.4-86.0]) compared with 5.2 (1.5-18.1) in antithrombin deficiency, 2.3 (0.6-8.3) in protein-C deficiency, 3.3 (1.0-11.3) in protein-S deficiency, and 2.0 (0.5-7.7) with factor V Leiden. The corresponding odds ratios for miscarriage in these subgroups were 0.8 (0.2-3.6), 1.7 (1.0-2.8), 1.4 (0.9-2.2), 1.2 (0.7-1.9), and 0.9 (0.5-1.5). Significantly more pregnancy terminations had been done in women with thrombophilia than in controls (odds ratio 2.9 [1.8-4.8]); this discrepancy was apparent in nine of 11 participating centres and for all thrombophilia subgroups. INTERPRETATION: Women with familial thrombophilia, especially those with combined defects or antithrombin deficiency, have an increased risk of fetal loss, particularly stillbirth. Our findings have important implications for therapy and provide a rationale for clinical trials of thromboprophylaxis for affected women with recurrent fetal loss.

Abortion, Spontaneous↗
PubMed1996

Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor.

No defects have been reported in moderately severe type 1 von Willebrand disease (vWD) with a clear autosomal dominant inheritance pattern, and the mechanism underlying this form of vWD remains obscure. We have studied a type 1 vWD family with such a dominant phenotype. The entire coding sequence of the von Willebrand factor (vWF) gene was analyzed by direct sequencing of DNA fragments amplified by polymerase chain reaction. Only one candidate mutation T(3445)-->C in exon 26 was detected that predicts a replacement of cysteine (C) at position 386 of the mature vWF subunit by arginine (R). Both mutant and normal vWF alleles were expressed as shown by analysis of platelet mRNA. This substitution segregates with vWD in the family and was not found in 100 unrelated individuals. The recombinant mutant vWF(C386R) was characterized by expression in 293T cells. The secretion of vWF(C386R) was greatly impaired due to retention in the endoplasmic reticulum. In cotransfections of normal and mutant vWF constructs, the vWF(C386R) subunits caused a dose-dependent decrease in the secretion of vWF. The multimer pattern remained nearly normal and consistent with a dominant vWD type 1 phenotype. The importance of the cysteine residues in the D3 domain of vWF in the pathogenesis of dominant type 1 vWD was further shown by the detection of another cysteine mutation, Cys367-->Phe, in two additional unrelated patients with a similar dominant type 1 vWD phenotype. We conclude that the loss of cysteine pairing in the D3 domain, leaving one free cysteine, can induce a purely quantitative deficiency of vWF by dominantly suppressing the secretion of normal vWF.

Alleles↗
PubMed1996

Monitoring heparin treatment with the APTT: the effect of methodological changes on the APTT.

OBJECTIVE: To assess the effect on the desired activated partial thromboplastin time (APTT) of altered practice in the laboratory control of heparin treatment. METHODS: Descriptive study of the number of APTTs in the desired range (DR) in 1987 (historical controls) and in 1992/1993. In the latter period, four changes in the implementation of heparin treatment took place: another coagulation analyser was used, laboratory control was intensified with a nomogram as guideline, and the DR was changed form 90-120 to 45-60 s. Furthermore, a standard heparin solution of 417 U/ml was supplied by the hospital pharmacy. RESULTS: The total amount of APTTs in the desired range increased from 19% in 1987 to 46% in 1992/1993, and the DR was reached in 1987 in 1 day by 14%, and in 1992/1993 by 48% of patients. The mean daily heparin dose was higher in 1992/1993 (34.1 * 1000 U, 95% CI 33.4-34.8) than in 1987 (32.3 * 1000 U, 95% CI 31.5-33.0). The starting dose of heparin of 400 U/kg during the first day, following an initial bolus injection of 70 U/kg, was correct in 44% of patients, too low in 46%, and too high in 10%. CONCLUSIONS: The new policy in the laboratory control of heparin treatment resulted in an increased number of APTTs in the DR, and a shorter time to reach this.

Adolescent↗
PubMed1996

Optimal intensity of oral anticoagulant therapy after myocardial infarction.

OBJECTIVES: This study attempted to determine the optimal intensity of anticoagulant therapy in patients after myocardial infarction. BACKGROUND: Treatment with oral anticoagulant therapy entails a delicate balance between over- (risk of bleeding) and under-anticoagulation (risk of thromboemboli). The optimal intensity required to prevent the occurrence of either event (bleeding or thromboembolic) is not known. METHODS: A method was used to determine the optimal intensity of anticoagulant therapy by calculating incidence rates for either event associated with a specific international normalized ratio. The numerator included events occurring at given international normalized ratios, and the denominator comprised the total observation time. RESULTS: The study population included 3,404 myocardial infarction patients enrolled in the ASPECT (Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis) trial. Total treatment was 6,918 patient-years. Major bleeding occurred in 57 patients (0.8/100 patient-years), and thromboembolic complications in 397 (5.7/100 patient-years). The incidence of the combined outcome (bleeding or thromboembolic complications) with international normalized ratio <2 was 8.0/100 patient-years (283 events in 3,559 patient-years), with international normalized ratios between 2 and 3, 3.9/100 patient-years (33 events in 838 patient-years); 3.2/100 patient-years (57 events in 1,775 patient-years) for international normalized ratios between 3 and 4; 6.6/100 patient-years (37 events in 564 patient-years) for international normalized ratios between 4 and 5; and 7.7/100 patient-years (14 events in 182 patient-years) for international normalized ratios >5. After adjustment for achieved international normalized ratio levels, significant predictors were higher levels of systolic blood pressure and age. CONCLUSIONS: If equal weight is given to hemorrhagic and thromboembolic complications, these results suggest that the optimal intensity of long-term anticoagulant therapy for myocardial infarction patients lies between 2.0 and 4.0 international normalized ratio, with a trend to suggest an optimal intensity of 3.0 to 4.0.

Administration, Oral↗