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Biomedical subjects

J Conard

Publications and source records attributed to J Conard.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Association of dysfibrinogenemia and thrombosis. Apropos of a family (Fibrinogen Melun) and review of the literature].

We report a family with history of deep and superficial venous thrombosis. A large number of siblings had numerous episodes of deep venous thrombosis and less frequently arterial thrombosis. The most frequent site was lower limb. Dysfibrinogenaemia seems to play an essential role in predisposition to thromboembolism in this family, other known aetiologies having been excluded. Genetic studies of fibrinogen gene show a point mutation in the gamma chain (364 Asp-Val), the site close to gamma 363 one of the sites involved in fibrin monomers polymerisation, although fibrinogen polymerisation is normal. Review of the 250 families with dysfibrinogenaemia published up to now shows that the prevalence of dysfibrinogenaemia in patients with a history of thromboembolism is about 0.7%, and that thrombosis is observed in about 10% of cases of dysfibrinogenaemia. Abortion risk seems to be increased in women with dysfibrinogenaemia. In contrast thromboembolism risk does not seem to be higher during pregnancy, but may be increased after delivery. The main mechanisms which have been proposed to explain thromboembolism observed in dysfibrinogenaemia are: resistance of the clot to thrombolysis; defective thrombin binding; enhanced platelet aggregation; increased blood viscosity, alteration of clot architecture. This family study together with the previously reported cases supports the hypothesis that there is a link between thrombosis and dysfibrinogenaemia in a small number of patients.

Female↗
PubMed1994

Red blood cell aggregability in patients with a history of leg vein thrombosis: influence of post-thrombotic treatment.

Reversible aggregation of red blood cells (RBC) plays an important role in determining blood flow properties, and it is this aggregation which increases blood viscosity at low shear rates. The structure and sites of venous thrombi, as well as the fact that stasis is a major predisposing factor in venous thrombosis, suggest a strong association between vein thrombosis, slow blood flow and increased blood viscosity. RBC aggregation and disaggregation were measured (SEFAM erythroaggregameter, France) in 54 patients with a history of unexplained leg vein thrombosis. Results were compared to those of controls classified according to age. Increased RBC aggregability was observed in 41% of the patients, and the mean values indicated a significant elevation of RBC aggregability in patients when compared with controls (P < 0.05). Subgroups were compared to study the influence of thrombus recurrence and thrombosis type (deep versus superficial vein thrombosis) on the aggregation parameters. No significant difference was found between these subgroups. The use of compression stockings and veinotropic drugs tended to reduce the abnormalities in RBC aggregability (P < 0.05). An increase in RBC aggregability and in the shear resistance of RBC aggregates, by predisposing to circulatory stasis, is likely to contribute to the evolution and complications of leg vein thrombosis.

Adult↗
PubMed1994

[Ovarian hyperstimulation syndrome and thrombosis. Apropos of a case of thrombosis of the internal jugular vein. Review of the literature].

Thrombosis of the internal jugular vein was associated with a severe syndrome of ovarian hyperstimulation. After in vitro fertilization, a twin pregnancy was obtained in a 31-year-old patient with severe endometriosis. On the day of follicle collection, plasma oestradiol was 3050 mg/ml. Ten ovocytes were collected and 3 embryos were implanted. A syndrome of severe ovarian hyperstimulation (ascites, pleural effusion) developed 3 weeks later and symptomatic treatment was given. Phlebitis of the upper left limb was diagnosed at 9 weeks amenorrhoea and echo-Doppler confirmed the diagnosis of subclavian and internal jugular venous thrombosis. Search for a cause was negative excepting a frank drop in protein S activity to 35%. Post-partum assay and assay in family members confirmed that the deficiency was acquired during pregnancy. The clinical course was favourable with anticoagulant therapy (heparin, then low-molecular weight heparin). Intra-uterine death of one of the fetuses occurred at 21 weeks amenorrhoea and a 2,550 g girl was born by vaginal delivery at 36 weeks. The Apgar score at birth was 10/10. In a review of the literature on vascular events in fertilization, programmes showed that severe syndromes of ovarian hyperstimulation, endogenous hyperestrogenism, multiple pregnancy and predominance of upper limb are the most frequently observed criteria. We emphasize the importance of preventing these thromboembolic events with subcutaneous heparin during the first trimester of pregnancy followed by low-molecular weight heparin, particularly in patients with a history of thromboembolism and/or patients with severe ovarian hyperstimulation.

Adult↗
PubMed1993

Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency.

Homozygous or double heterozygous protein-C deficiency can present at birth with purpura fulminans or later in life with venous thrombosis. Two homozygous patients who had previously sustained thrombotic episodes were investigated at a time when they were asymptomatic and not receiving antithrombotic therapy. The plasma levels of protein-C antigen and activity in both individuals were approximately 20% of normal. We administered a highly purified plasma-derived protein C concentrate to these individuals and monitored levels of several markers of in vivo coagulation activation. Assays for protein-C activation (activated protein C and protein C activation peptide) showed a sustained increase from reduced baseline levels, whereas thrombin generation (as measured by prothrombin fragment F1 + 2) gradually decreased over about 24 hours into the normal range. These investigations provide direct evidence that protein C is converted to activated protein C in vivo, and that the protein-C anticoagulant pathway is a tonically active mechanism in the regulation of hemostatic system activation in humans.

Adult↗
PubMed1993

Problems of oral anticoagulation in an adult with homozygous protein C deficiency and late onset of thrombosis.

We describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.

Acenocoumarol↗
PubMed1993

Hemostatic and metabolic effects of lowering the ethinyl-estradiol dose from 30 mcg to 20 mcg in oral contraceptives containing desogestrel.

The metabolic and hemostatic effects of two oral contraceptives containing 150 mcg desogestrel and 20 mcg ethinyl-estradiol (EE) (MERCILON) or 30 mcg EE (MARVELON) were compared in order to examine the effect of reducing the EE dose in contraceptive pills. Forty-nine women participated in this randomized study during 6 cycles. In both groups, there was a significant increase in triglycerides, HDL-cholesterol and apoprotein A1; the same increase was observed for SBP and CBG. Slight and transient variations of fasting blood glucose levels were seen in the 30 mcg EE group and in the two groups for fasting insulin levels. The increase in renin substrate was significantly higher with the 30 mcg EE than with the 20 mcg EE pill. In both groups, plasminogen increased significantly, but antithrombin III, total and free protein S and fibrinogen decreased significantly only in women taking the 30 mcg EE pill, whereas there was no significant change in the 20 mcg EE group. Reducing the dose of EE in oral contraceptives from 30 mcg to 20 mcg minimizes their impact on renin substrate and hemostatic parameters.

Apolipoprotein A-I↗
PubMed1993

Identification of nine novel mutations in type I antithrombin deficiency by heteroduplex screening.

We have utilized DNA heteroduplex detection as a method for screening sequences of the antithrombin (AT) gene for the presence of mutations. Affected individuals from 41 kindreds with type Ia antithrombin deficiency were investigated. Heteroduplexes were detected in 12 cases; direct sequencing of the appropriate exons revealed nine cases with novel mutations, and two with previously described mutations. In addition, a new polymorphism in the 5' untranslated region was characterized. The defects included minor insertions and deletions which lead to the removal of intact codons or premature termination, and single base substitutions leading to premature termination or amino acid substitution. In all cases, the affected individuals were heterozygous for the defect and variant AT protein was not detected. In keeping with previous reports the defects associated with type Ia AT deficiency are extremely heterogeneous, the vast majority being point mutations. This study also demonstrates the efficiency of hydrolink gel electrophoresis as a method of screening for unknown mutations by heteroduplex detection.

Antithrombins↗
PubMed1992

Multicentric evaluation of a new assay for prothrombin fragment F1+2 determination.

A multicenter study of a recently developed ELISA for the determination of prothrombin fragment F1+2 was performed in order to evaluate analytical and clinical aspects. Mean intra-assay and inter-assay reproducibility were found to be 11.0 and 12.6%, respectively. The measuring range covered by the calibration curve reaches from 0.04 to 10.0 nM/l F1+2. Testing 133 healthy subjects a reference range of 0.37 to 1.11 nM/l F1+2 (2.5-97.5 percentile) with a median of 0.66 nM/l F1+2 was calculated. Minor difficulties with blood sampling (venous occlusion for 2 min) did not affect F1+2 plasma concentrations. Significantly increased F1+2 levels were measured in patients with leukemia (p < 0.0001), severe liver disease (p < 0.005) and after myocardial infarction (p < 0.01). Elevated F1+2 concentration before the beginning of heparin therapy (1.25 nM/l) decreased to 0.77 nM/l (p < 0.0001) after 1 day of therapy. For patients in the stable phase of oral anticoagulant therapy decreasing F1+2 concentrations were measured with increasing INR. F1+2 levels were already significantly reduced in patients with INR < 2.0 (0.56 nM/l; p = 0.0005). Thus F1+2 determination may be helpful in identifying activation processes as well as in monitoring anticoagulant therapy.

Administration, Oral↗
PubMed1992

Multicenter evaluation of three commercial methods for measuring protein S antigen.

This collaborative study was designed to assess the performance of commercial methods for protein S (PS) antigen measurement. Twenty-five different samples were distributed deep-frozen (24 plasmas) or lyophilized (one plasma) to five laboratories. They were analyzed blind in each laboratory by the method used locally and by three commercial methods which included two electroimmunoassays (EIA), Asseraplate-PS (Diagnostica Stago), Rellplate-S (American Diagnostica) and an ELISA system, Asserachrom-PS (Diagnostica Stago). 1. Reproducibility. Average between-laboratory coefficients of variation were 15.4%, 17.6% and 25.3% for Asserachrom-PS, Asseraplate-PS and Rellplate-S. 2. Specificity. Results of all methods showed that PS is underestimated when C4b binding protein is high. This influence was particularly evident for the ELISA Asserachrom-PS and disappeared when the antibody-antigen incubation period was prolonged to overnight. 3. Sensitivity. In all laboratories ELISA detected even the lowest PS concentration (4 U/dl), whereas the two EIAs were less sensitive (lower detection limit 14 U/dl). All methods and laboratories correctly diagnosed a plasma sample from a PS congenitally deficient patient. Conclusions. This study shows that better standardization of PS immunoassays is necessary to improve accuracy and reduce interlaboratory variability before a candidate plasma standard can be successfully calibrated in an international collaborative study.

Anticoagulants↗
PubMed1992

Pleiotropic effects of antithrombin strand 1C substitution mutations.

Six different substitution mutations were identified in four different amino acid residues of antithrombin strand 1C and the polypeptide leading into strand 4B (F402S, F402C, F402L, A404T, N405K, and P407T), and are responsible for functional antithrombin deficiency in seven independently ascertained kindreds (Rosny, Torino, Maisons-Laffitte, Paris 3, La Rochelle, Budapest 5, and Oslo) affected by venous thromboembolic disease. In all seven families, variant antithrombins with heparin-binding abnormalities were detected by crossed immunoelectrophoresis, and in six of the kindreds there was a reduced antigen concentration of plasma antithrombin. Two of the variant antithrombins, Rosny and Torino, were purified by heparin-Sepharose and immunoaffinity chromatography, and shown to have greatly reduced heparin cofactor and progressive inhibitor activities in vitro. The defective interactions of these mutants with thrombin may result from proximity of s1C to the reactive site, while reduced circulating levels may be related to s1C proximity to highly conserved internal beta strands, which contain elements proposed to influence serpin turnover and intracellular degradation. In contrast, s1C is spatially distant to the positively charged surface which forms the heparin binding site of antithrombin; altered heparin binding properties of s1C variants may therefore reflect conformational linkage between the reactive site and heparin binding regions of the molecule. This work demonstrates that point mutations in and immediately adjacent to strand 1C have multiple, or pleiotropic, effects on this serpin, leading ultimately to failure of its regulatory function.

Adolescent↗
PubMed1992

[Coagulation and bronchopulmonary cancers: from clinical aspects to biology].

Activation of coagulation and of the fibrinolytic system has been identified in small cell and non-small cell cancers respectively. For the clinician this poses the diagnostic problem of a thrombosis, which is most often venous with or without pulmonary emboli, complicating the evolution of an already diagnosed cancer. The inverse is that these features may reveal an underlying neoplasm and amongst the most common of these would be bronchopulmonary cancer. Numerous laboratory studies have shown the existence of a state of hyper-coagulability, with disseminated intra-vascular coagulation, which is more or less compensated and is the more marked, the more advanced the cancer is. One should not fail to recognise that this state of hyper-coagulability may be aggravated by certain cytotoxic drugs. At the level of the tumour itself, there seems to be interactions between the cancer cells and the coagulation and fibrinolytic system: these interactions are very different according to the histological type as to whether they are small cell or non-small cell bronchopulmonary cancers.

Anticoagulants↗
PubMed1991

Lupus anticoagulant associated with primary malignant lymphoplasmacytic lymphoma of the spleen: a report of four patients.

Primary lymphoma of the spleen is characterized by predominant splenomegaly. Lymphoplasmacytic malignant lymphoma of the spleen, of low malignancy in the Kiel classification, low and intermediate grade in the National Cancer Institute Working Formulation (NCIWF), is rare. It is often associated with a monoclonal immunoglobulin M (IgM). Four patients presenting with primary splenic lymphoma of plasmacytic type associated with a high level of monoclonal IgM and a lupus anticoagulant (LA) are described. This association has not previously been reported. In contrast with the usual heterogeneity of LA, this LA is relatively homogeneous with an important prolongation of the prothrombin time (greater than 18 sec for a control of 12), more prolonged partial thromboplastin time (PTT) of the mixture patient + control plasma than PTT of the patient plasma. Despite the important coagulation abnormalities, none of these four patients has presented any hemorrhagic or thrombotic complications, even during major surgery such as splenectomy. The lupus-like anticoagulant effect ran parallel with the monoclonal IgM. Survival, after splenectomy and chemotherapy, appears to be favourable: three patients are alive with survivals of greater than or equal to 7 years. The follow-up is as yet too short for the last patient.

Adult↗
PubMed1991

Effects of nomegestrol acetate (5 mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women.

The effects of nomegestrol acetate on circulating hormone levels, metabolic and hemostatic parameters and blood pressure were studied in 36 premenopausal women. The progestogen was administered from day 7 to 25 of the cycle during six cycles at a dosage (5 mg/d) known to inhibit ovulation. Analysis were performed before and in the third and sixth cycles. Estradiol and progesterone levels decreased significantly (p less than 0.001) during treatment. Body weight, fasting blood glucose and insulin, total HDL and LDL cholesterol, apolipoprotein B, fibrinogen and plasminogen did not change significantly. Triglycerides in the third cycle (p less than 0.05) and apolipoprotein A1 levels (p less than 0.01) in both periods of sampling decreased significantly. There was a significant increase in antithrombin III (p less than 0.01). These results indicate that nomegestrol acetate has no deleterious effect on blood glucose and lipids. The decrease in apolipoprotein A1 and increase in antithrombin III may be related either to the decrease in estradiol levels induced by the treatment or to the effect of the progestogen itself.

Adolescent↗