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J N Fiessinger

Publications and source records attributed to J N Fiessinger.

At least 73 records · Page 4Linked to original sources
PubMed1997

Interdonor variability of platelet response to thrombin receptor activation: influence of PlA2 polymorphism.

Considering that platelet response to thrombin receptor activation might be critical for the development of arterial thrombosis, we measured the dense granule release under stimulation by the thrombin receptor activating peptide (TRAP) in a series of 102 healthy volunteers. The threshold TRAP concentration which initiated a secretion ranged from 3 to 20 microM. A good concordance (79%, k=0.677) between two tests performed at a 1 month interval indicated that platelet response to thrombin receptor activation was characteristic of each individual donor. Since the threshold concentration required to initiate secretion corresponded to the threshold concentration which induced a biphasic aggregation, all volunteers were genotyped for the PlA2 polymorphism, the Pro33 variant of GPIIIa. Platelets from subjects with the PlA2 polymorphism required higher TRAP concentrations to aggregate than those from subjects with no PlA2 allele (P=0.0012). However, they also required a higher ADP concentration to aggregate. In order to exclude any influence of GPIIIa polymorphism on TRAP-induced secretion, we studied the variability of platelet response to TRAP among the 77 individuals with no PlA2 allele, and found the same interdonor variability with the same distribution of threshold TRAP concentrations as for the 102 individuals. The results suggest that (i) platelet secretion in response to thrombin receptor activation could be a genetically controlled phenotype independent of the GPIIIa polymorphism; (ii) the PlA2 polymorphism is associated with platelet hypoaggregability.

Blood Platelets↗
PubMed1997

Clinical features in 36 patients homozygous for the ARG 506-->GLN factor V mutation.

We analyzed the clinical features of 36 patients homozygous for the Arg 506 to Gln factor V mutation and found a circumstantial event at risk for thrombosis in 29 of the 31 patients with thrombosis. The most frequent predisposing factors were the post-partum period and the use of oral contraceptives in women, and surgery in both sexes. Venous thrombosis recurred in 48% of the patients. One patient had a myocardial infarction at age 33 years, and also had an antiphospholipid syndrome. Homozygous Gln 506 mutation leads to far less severe thrombotic complications than homozygous protein C and protein S deficiencies and does not seem to predispose patients to arterial thrombosis.

Adult↗
PubMed1997

[Venous thromboembolic disease and occult cancers: what investigations should be done? Apropos of 204 patients].

There is no consensus about the investigations which should be performed to detect occult malignancy after an episode of venous thromboembolism. The authors studied 204 patients (167 in-patients and 37 day hospital patients) with deep venous thrombosis or pulmonary embolism to determine the incidence of cancers detected during or after the thrombosis and the diagnostic value of abdomino-pelvic ultrasonography. Of the 167 in-patients, 18 (10.7%) had a known malignancy. After the initial investigations, 7 tumours were detected (4.6%). In all cases, clinical history and examination or chest X-ray were suggestive of neoplasia. Abdomino-pelvic ultrasonography did not detect any cases of occult malignancy. Of the 37 patients seen in the day hospital, only one had known malignant disease and no other cases were detected. After exclusion of the 26 patients with known malignancies or tumours discovered after the initial investigations, the remaining 178 patients were followed up for an average of 27 months. Four cancers (2.5%) were detected in this period. The authors conclude that the occurrence of deep venous thrombosis should lead to investigation for malignant disease: clinical examination, chest X-ray and laboratory tests are sufficient to orientate this investigation. Systematic abdominopelvic ultrasonography does not seem to be worthwhile in this indication.

Abdomen↗
PubMed1997

[Treatment of venous thrombosis with low molecular weight heparin. Progress and outlook].

Low molecular weight heparins are in European countries the standard of treatment for deep venous thrombosis. Initially the use of low molecular weight heparins was derived of the use of unfractionated heparin: two daily subcutaneous injections with a biological adaptation on anti-Xa activity. However, rapidly, the safety of a fixed dose based on the weight was demonstrated and the biological control is no more recommended. A new low molecular weight heparin, tinzaparin, has proved its efficiency in once a day injection, several published trials have demonstrated similar results with others low molecular weight heparins. Thus the treatment of patients with deep venous thrombosis as out patients is actually a major alternative. In the future long term treatment of venous thrombosis with low molecular weight heparins could be an alternative to the oral anticoagulation. Trials in pregnant women is an emergency, low molecular weight heparins are theoretically the ideal approach for treatment of deep venous thrombosis during pregnancy. Finally low molecular weight heparins are different but the clinical implications of theses differences is still an open question.

Anticoagulants↗
PubMed1996

[Evaluation of an intervention on the prescription and biological surveillance of low-molecular weight heparins in medicine].

OBJECTIVES: We evaluated the effect of oral recommendations documents distributed to prescribing physicians on the use of low-molecular weight heparin (LMWH) and laboratory test orders. METHODS: Prescription of LMWH over a 6 month period was left to the total discretion of the prescribing physician (observation period). An information session and recommendation documents were then proposed describing prophylactic use of LMWH and appropriate hemostasis monitoring tests for curative treatments. Prescriptions and laboratory test orders were then recorded for the next six months (intervention period). RESULTS: Diffusion of recommendation documents to prescribers led to a 50% decrease in the prescription of low-molecular weight heparin for prophylaxis and a significant drop in orders for anti-Xa and prothrombin. CONCLUSION: These results confirm the efficacity of informing prescribing physicians on the use of low-molecular weight heparins and underlines the need to validate methods used for the prevention of venous thrombosis.

Animals↗
PubMed1996

[Treatment of venous thromboembolic disease].

Except for the indications of thrombolytic treatment in severe pulmonary embolism, anticoagulant drugs are the treatment of venous thromboembolism. Low molecular weight heparins once or twice a day are at present the treatment of choice for deep venous thrombosis, however they do not have the legal indication for pulmonary embolism yet. Oral anticoagulants are started as soon as possible and are continued for at least 12 weeks with an INR maintained between 2 and 3. The use of low molecular weight heparins as long term treatment is at present in evaluation but seems promising. Early mobilization associated with compression stockings is an important part of the treatment.

Ambulatory Care↗
PubMed1996

Resistance to activated protein C: role in venous and arterial thrombosis.

Activated protein C resistance is the most prevalent cause of thrombophilia: it is found in 20 to 30% of patients with a deep venous thrombosis history. Activated protein C resistance is due to an arginine 506 to glutamine mutation in factor V. This mutation prevents normal inactivation of activated factor V by activated protein C. The estimated increase in relative risk of venous thrombosis is 5- to 10-fold in heterozygotes, and 50- to 100-fold in homozygotes. Activated protein C resistance does not seem to play a role in arterial thrombosis and in the occurrence of myocardial infarction.

Adult↗
PubMed1996

[Activated protein C resistance: role in venous and arterial thrombosis].

Activated protein C resistance is the most prevalent cause of thrombophilia: it is found in 20% to 30% of patients with a history of deep venous thrombosis history. Activated protein C resistance is due to an arginine 506 to glutamine mutation in factor V. This mutation prevents normal inactivation of activated factor V by activated protein C. The estimated increase in relative risk of venous thrombosis is 5 to 10 fold in heterozygotes, and 50- to 100- fold in homozygotes. Activated protein C resistance does not seem to play a role in arterial thrombosis or in the occurrence of myocardial infarction.

Blood Coagulation Disorders↗
PubMed1996

Treatment of mixed cryoglobulinemia with recombinant interferon alpha and adjuvant therapies. A prospective study on 20 patients.

In order to evaluate the efficacy of interferon alpha (IFNa) in mixed cryoglobulinemia (MC), a prospective multicenter clinical trial was conduced in April 1992. It consisted of treating 20 clinically symptomatic MC patients with IFNa for 26 weeks. Hepatitis C virus (HCV) infection was detected in 16 patients. A complete or partial clinical remission was obtained in 12 patients (60%). Eleven of these 12 responders (91.6%) experienced a clinical relapse less than 12 months after the end of therapy. Side effects were noted in 10 patients (50%). It was concluded that subcutaneously administered IFNa does not provide long-term remission.

Adrenal Cortex Hormones↗
PubMed1996

Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis.

The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin, a low molecular weight heparin, with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis (DVT). Patients were included if they had deep venous thrombosis distal to inguinal ligament and were randomised either before, if it was considered necessary, or after phlebographic verification of the diagnosis. There was no pre-inclusion treatment with unfractionated heparin. One hundred and twenty patients received dalteparin, administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the first or second day, and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range (2 < INR < 3) on two consecutive days. Control phlebograms were taken within 4 days, thereafter. There were no significant differences between the two initial treatment groups in improvements in Marder score. Two major bleeding events occurred in the UFH group versus none in the dalteparin group. One patient in each group experienced clinically significant pulmonary embolism. During a mean follow-up period of 6.9 +/- 1.5 months, recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group. These results confirm those of a previous study on dalteparin in the initial treatment of DVT, and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament. The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH. Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised, studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted.

Acute Disease↗
PubMed1995

Protein C infusion in a patient with inherited protein C deficiency caused by two missense mutations: Arg 178 to Gln and Arg-1 to His.

This paper reports the case of an adult patient with severe protein C(PC) deficiency. She had the first deep vein thrombosis when she was 14 years old and developed skin necrosis when oral anticoagulant treatment was started. The same sequence of thrombotic complications recurred several times. Analysis of the PC gene coding sequences allowed two mutations (Arg-1 to His and Arg 178 to Gln) to be identified in this compound heterozygote. Oral anticoagulant treatment during PC concentrate infusion and low-molecular-weight heparin administration was successful and uncomplicated.

Arginine↗