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A Le Querrec

Publications and source records attributed to A Le Querrec.

16 recordsLinked to original sources
PubMed2001

Quantification of lupus anticoagulants in clinical samples using anti-beta2GP1 and anti-prothrombin monoclonal antibodies.

Quantification of lupus anticoagulant (LA) in clinical samples is hampered by the lack of a suitable standard of activity. We evaluated the use of mAbs displaying LA activity for this purpose. As most patient samples contain both beta2Glycoprotein I (beta2GP1) and prothrombin dependent LA, a combination of two mAbs, one of each specificity, was added to normal plasma in a concentration from 0 to 60 microg/ml. Eight assay systems using different reagents and instruments were used. The calibration curves were linear for all but one, with marked differences between the responsiveness to each mAb. A panel of plasmas from 69 patients with persistent LA diagnosed using the SSC-ISTH criteria was tested. An antiphospholipid syndrome (APS) was present in 40, whereas 29 were asymptomatic. LA activities of individual plasmas varied between assays (p < 10(-4)), but homogeneous subgroups were identified. In a majority of samples, LA activity displayed a prothrombin-dependent profile, with a variable contribution of beta2GP1-dependent activity. The latter was associated to beta2GP1 antibodies detected by solid-phase immunoassay. By using 3 dilute Russell viper venom time assays, higher LA titers were found in APS, compared to asymptomatic patients (p <0.05).

Adult↗
PubMed2000

[Mesenteric vein and inferior vena cava thrombosis: disseminated intravascular coagulation and/or G 20210 A mutation of the prothrombin gene?].

The authors report the case of a 30-year-old man who died from pulmonary embolism and multiorgan failure caused by mesenteric and inferior vena cava thrombosis. The patient was found heterozygous for the prothrombin gene variant (G 20210 A). The family study showed the same asymptomatic anomaly in his brother. This recently described mutation is associated with an increased risk for venous thrombosis. The investigations and treatment of mesenteric venous thrombosis are discussed.

Adult↗
PubMed1999

[Resistance to activated protein C and pregnancy: thromboprophylaxis with low molecular weight heparin].

OBJECTIVE: The utilization, during pregnancy, of low molecular weight heparin (enoxaparine) for obstetric thromboprophylaxis for patients with activated protein C resistance, following Factor V Leiden mutation. STUDY DESIGN: Prospective study enrolling 10 pregnant patients heterozygote or homozygote for Factor V Leiden mutation. They all had familial or personal history of severe thrombotic disease and received 40 mg per day of enoxaparine. RESULTS: No thrombosis or hemorrhage were recorded during pregnancies or deliveries. All the infants were doing well. After birth, low molecular, weight heparin were continued between 6 to 12 weeks accordingly allelic status and history. We reviewed the literature on this subject. CONCLUSION: This series confirmed the efficacy, safety and tolerance of low molecular weight heparins which will probably become the next gold standard for obstetric thromboprophylaxis.

Activated Protein C Resistance↗
PubMed1998

Control of oral anticoagulation in patients with the antiphospholipid syndrome--influence of the lupus anticoagulant on International Normalized Ratio. Groupe Méthodologie en Hémostase du Groupe d'Etudes sur l'Hémostases et la Thrombose.

The recommended therapeutic range of International Normalized Ratio (INR) for oral anticoagulant treatment in patients with the antiphospholipid syndrome remains controversial. As a part of this controversy, it has been suggested that lupus anticoagulants (LA) could interfere with the determination of prothrombin time, thus questioning the validity of monitoring the treatment of these patients using INR. To clarify this point, we compared the values of INR obtained in the plasmas of two groups of patients, one without LA (n = 47), and the other with LA (n = 43). INR were determined using 8 different thromboplastin reagents on the same automated coagulation instrument. Chromogenic factor X, which is supposed to be insensitive to the presence of LA, was also measured. The results are the following: provided INR was calculated using calibrated reference plasmas, there was no significant difference between INR values obtained with the 8 reagents, both in the non-LA and in the LA groups (CV: 5.9 and 6.7%. respectively). Closer examination revealed that INR results obtained with one reagent (the recombinant thromboplastin Innovin) diverged from those of the 7 others, leading to an overestimation of INR, to a very large extent in some instances. However this effect was restricted to a subset of the patient population with LA (6 out of 43). Finally, the relationship between INR (average value obtained using the 8 reagents) and factor X was identical in non-LA and in LA patient groups. We conclude that, provided the reagents which display the LA interference are identified and excluded for this purpose, the INR system is valid for monitoring oral anticoagulant treatment in patients with LA.

Administration, Oral↗
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↗
PubMed1994

[Mesentric venous thrombosis. Risk factors, treatment and outcome. An analysis of 18 cases].

Eighteen patients with an acute thrombosis of the splanchnic veins were reviewed. Most of apparently idiopathic cases of splanchnic vein thrombosis are related to an increased coagulation related to a congenital or acquired defect of haemostasis. The aim of this study was to assess the effects of a new and effective treatment. Nine male and 9 female patients (range of age: 19 to 81 years) experienced a mesenteric venous thrombosis. There were 14 mesenteric vein thromboses with infarction, two transient mesenteric venous ischaemias without bowel infarction and two acute thromboses of the splanchnic veins without bowel ischaemia. A coagulopathy was detected in seven patients: oral contraception, protein C (PC) or antithrombin III (AT III) congenital deficiencies, acquired deficiency of AT III, PC and protein S (PS), polycythaemia in the post-partum period and primary myeloproliferative disorder. No coagulopathy was associated with thrombosis in eight cases: mesenteric haematoma, splenomegaly, cirrhosis, appendicectomy, cholescytectomy, chronic heart failure, treatment with beta-adrenergic receptor antagonist and digitalis, stenosis of the portal anastomosis after liver transplantation. Twelve patients required surgery: eight intestinal bowel resections with immediate anastomosis, four resections without immediate anastomosis. Only one patient underwent a second look for a repeat bowel resection. No death occurred in the early postoperative period and 17 out of 18 patients were alive after 12 years. An oral anticoagulant therapy was undertaken from two months to seven years. However, three patients suffered a recurrent thrombosis. Two of them required a long-term anticoagulation. Six patients experienced a portal hypertension and oral anticoagulants were discontinued in three of them because of bleeding oesophageal varices. Six patients were treated only by unfractionated heparin (UFH) or low molecular weight heparin (LMWH) followed by oral anticoagulants. After laparotomy, two were only treated with UFH without any bowel resection, as mesenteric venous ischaemia was too extensive. These observations suggest that the choice between an appropriate medical or surgical treatment is important and must be discussed. Since 1989, the therapeutic choice has been modified by ultrasonography and contrast enhanced computed tomographic scan which confirms diagnosis, allows to follow up and check the effects of anticoagulation and to choose the time for surgery. When the diagnosis is established and the patient's risk is low, the IU . kg(-1) . d(-1) to obtain an antifactor Xa activity between 0.3 and 0.6 antiXa IU mL(-1). When the diagnosis is uncertain and the patient's risk if high a laparotomy is required.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Tumour angiogenesis.

The progressive emergence of a close relationship between the formation of blood vessels in the vicinity of tumour cells and the development and spreading of tumours, strongly suggests that angiogenesis might be a prerequisite for tumour development. Angiogenesis starts and develops in response to two sets of extracellular signals: soluble angiogenic factors and extracellular matrix. Different experimental models have been used to study angiogenesis in vivo, but they have numerous limitations. Three-dimensional culture systems reconstitute normal interactions between endothelial cells and the surrounding extracellular matrix. Numerous parameters including angiogenic growth factors and cytokines, cell-to-cell interactions and cell-to-extracellular matrix adhesion influence the growth and differentiation of endothelial cells in vitro as well as in vivo. Angiogenesis plays a major role not only in tumour growth but also in metastasis development. Mechanisms of switching to angiogenic phenotype have been recently described and onset of angiogenic activity is now recognized as another discrete step in tumorigenesis. Tumour cells can induce b-FGF expression and exportation, VEGF and VEGF receptor expression and inactivation of the cancer suppressor gene encoding for a fragment of thrombospondin. A controlled net proteolytic balance produced by tumour cells or endothelial cells is required to favour migration and invasion of endothelial cells and angiogenesis. The hypothesis that assessment of tumour angiogenesis might predict tumour aggressiveness in human cancer has recently gained support from several clinical studies. This has been shown for cutaneous melanoma, breast carcinoma, and non-small-cell lung cancer by quantitation of microvessels in human biopsies using von Willebrand factor or CD3 antigen labelling with specific antibodies. However, more specific and sensitive markers are needed to improve this approach for predicting tumour aggressiveness. Folkman proposed twenty years ago that inhibition of angiogenesis might represent a suitable complementary strategy for the treatment of various forms of cancer. Since then numerous angiostatic compounds have been identified but very few of them fit the required criteria of a potential drug. Fumagillin and particularly its synthetic analogue AGM 1470 might be developed for use in humans in the near future.

Amino Acid Sequence↗
PubMed1992

Two new human hemoglobin variants caused by unusual mutational events: Hb Zaïre contains a five residue repetition within the alpha-chain and Hb Duino has two residues substituted in the beta-chain.

With rare exceptions, the more than 600 human hemoglobin variants described are caused by a single point mutation. Other abnormal features, such as unequal crossing-over, frameshift mutagenesis or double mutations in the same polypeptide chain, have seldom been encountered. We report two new variants caused by such rare mutational events. Hb Zaïre [alpha 116(GH4)-His-Leu-Pro-Ala-Glu-117 (GH5)] is the second example in which a short amino acid sequence is inserted within the alpha-chain. This abnormal hemoglobin results from a tandem repetition of 5 amino-acid residues, from sequence 112 through 116, at the end of the GH corner. Hb Duino is an unstable hemoglobin. It presents within the same beta-chain, the association of two rare point mutations; these substitutions are those found in Hb Newcastle [beta 92(F8)His----Pro] and in Hb Camperdown [beta 104(G6)Arg----Ser]. Family studies demonstrated that the Hb Newcastle abnormality was a de novo mutation of a gene already carrying the Hb Camperdown substitution.

Adult↗
PubMed1990

[Hereditary deficiency of antithrombin III, protein C and protein S. A study of 31 patients from 8 unrelated families].

The families of eight unrelated patients were studied with regard to a hereditary deficiency in antithrombin III (ATIII), protein C, or protein S. These deficiencies were recognized in the course of investigations for deep-vein thrombosis (DVT) in the eight patients. A group of 31 individuals (patients and family members), mostly less than 40-year-old was explored. Two cases of AT III deficiency were discovered, as well as 21 of protein C deficiency, and seven of protein S. Ten of the 30 have had recurrent venous thrombosis at the time of bedrest, trauma, surgery, pregnancy, postpartum or during oral contraceptive treatment. Spontaneous DVT occurred in three cases. Seventeen patients had remained asymptomatic till then. Such patients need antithrombotic treatment during surgery or pregnancy. Prophylactic treatment with enoxaparin in one patient (deficiency in protein C) during her second pregnancy is discussed. It seems that low molecular weight heparin may be a safe alternative to unfractionated heparin. Oral anticoagulants are efficient in preventing reoccurring venous thromboembolism in patients with AT III deficiency. The questions of whether oral anticoagulants should be continued in the long-term in patients with protein C or protein S deficiency who have had a DVT, and whether asymptomatic deficient patients should be given any antithrombotic treatment outside circumstances likely to induce a DVT, remain as yet unanswered.

Adolescent↗
PubMed1987

[Biological criteria for the evaluation of prophylactic treatment with a low molecular weight heparin (Kabi 2165)].

Efficacy of a low molecular weight heparin (Kabi 2165) was compared with that of non-fractionated heparin in the prevention of abdominal surgery postoperative venous thrombosis by means of a double-blind randomized trial in 79 patients. Determination of D. dimers in these patients allowed assessment of specificity of this assay for detection of postoperative venous thrombosis.

Abdomen↗
PubMedDate not supplied

[Treatment of deep venous thrombosis. Comparative study of a low molecular weight heparin fragment (Fragmin) by the subcutaneous route and standard heparin by the continuous intravenous route. A multicenter study].

This open, randomised multicenter trial compares the efficacy and safety of Fragmin administered subcutaneously twice daily with standard heparin administered by continuous infusion in the treatment of deep vein thrombosis (DVT). The initial dose of Fragmin is 100 U anti-Xa/kg/12 h and the further doses are adjusted according to the anti-Xa activity between 0.5 and 0.8 U/ml, 3 hours after the morning injection. The initial dose of standard heparin is 240 UI/kg/12 h. The dose adjustments are based on the daily results of APTT (1.5 - 3 times the control). Treatments efficacy are appreciated when comparing the venography performed before and after 10 days of treatment. The safety is evaluated on clinical parameters and iterative biological tests. Sixty-six patients have been included in this study. Efficacy of the two treatments is equivalent with a phlebographic improvement in respectively 79.3 p. 100 (Heparin Group) and 71.0 p. 100 (Fragmin Group) of the cases and an aggravation in 3.4 p. 100 and 6.4 p. 100 (NS) respectively. The frequency of dosage adjustments is lower and the stability of biological tests is better in the Fragmin group. In conclusion, the administration of Fragmin twice daily by subcutaneous route seems to be equivalent at least to standard heparin continuous infusion in the treatment of recent DVT. The better convenience and safety of Fragmin have to be verified on a larger panel of patients.

Adult↗