Search PubMed⌕ Search

Biomedical subjects

P Sie

Publications and source records attributed to P Sie.

At least 19 recordsLinked to original sources
PubMed2007

Detection and incidence of drug-induced agranulocytosis in hospital: a prospective analysis from laboratory signals.

AIMS: Our objectives were to assess the detection and incidence of drug-induced agranulocytosis in two university hospitals using hematology laboratory data. METHODS: A prospective study was undertaken at Toulouse University Hospital (France) and Navarra University Hospital (Spain) for 1 year (from 1 May 2004 to 30 April 2005). Using a computerized process and hematology laboratory data, all neutrophil counts with a value less than 500/mm(3) were registered, allowing identification of inpatients suffering from agranulocytosis during the period of the study. Medical records of all selected patients were then consulted. Cytostatic drugs were excluded from this study. RESULTS: During the period of the study, 225,659 neutrophil counts were performed in both hospitals, of which 2,835 (1.26%) had a neutrophil count less than 500/mm(3), corresponding to 739 patients. Seventeen patients were excluded because of lack of data, and 20 cases of infants younger than 3 months were excluded. Among the remaining patients (n = 702), 23 cases of drug-induced agranulocytosis (excluding cytostatic drugs) were suspected. All cases were classified as "serious" since they led to death in 2 cases, hospitalization or prolongation of hospitalization in 19 cases and threatening of vital prognosis in 2 cases. Withdrawal of suspected drugs was done in all cases with regression of neutropenia in 21 cases. According to hospitalization data, the annual incidence of drug-induced agranulocytosis was 1.62 (1.0-2.6) per 10,000 inpatients in Toulouse University hospital (based on 534 cases) and 3.24 (0.9-8.3) per 10,000 inpatients in Navarra University Hospital (based on 168 cases). The involved drugs were mainly antibacterial (30.4%), immunosuppressive (17.4%), antithyroid (13.0%), antiplatelet (8.7%) and nonsteroidal anti-inflammatory (8.7%) ones. Only seven cases from Toulouse University Hospital were spontaneously reported by physicians during the same period. Thus, the underreporting coefficient (U) was 2.71 (63.2%) in France. CONCLUSION: Our survey allowed us to identify the suspected drug-induced agranulocytosis through a prospective study in a large sample of inpatients using only laboratory data analysis. We also note an important underreporting rate of this serious adverse drug reaction (ADR) to the official French pharmacovigilance system. Laboratory data analysis could be used for identifying serious ADRs.

Adult↗
PubMed2004

Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk?

BACKGROUND AND OBJECTIVES: Inherited factor VII (FVII) deficiency is a rare bleeding disorder characterized by a poor relationship between reported FVII clotting activity (FVII:C) and bleeding tendency. Our study was aimed at defining biological parameters that are possibly predictive for bleeding risk in this condition. DESIGN AND METHODS: Forty-two FVII-deficient patients (FVII:C <30%) were classified into two opposite clinical groups defined as severe and non-or-mild bleeders. For each patient, plasma samples were collected and then investigated for FVII:C (using a sensitive method and human recombinant thromboplastin as the reagent), FVII antigen, activated FVII coagulant activity (FVIIa:C) and the free-form of tissue factor pathway inhibitor. RESULTS: None of these tests could be used as highly accurate predictors of bleeding. Nevertheless, both FVII:C and FVIIa:C differed significantly between the two clinical groups. Using ROC-curve analysis, two critical values of 8% and 3mIU/mL for FVII:C and FVIIa:C, respectively, could be proposed to discriminate between severe bleeders and non-or-mild bleeders. INTERPRETATION AND CONCLUSIONS: A highly accurate diagnostic test for predicting bleeding tendency in inherited FVII deficiency still eludes definition, highlighting the fact that factors other than FVII itself interfere with the expression of bleeding phenotypes in this condition. Nevertheless, potential critical values using sensitive FVII:C and FVIIa:C methods may be useful in clinical laboratories for FVII-deficient patients. Those patients with FVII:C levels higher than 8% FVII:C or FVIIa:C higher than 3 mIU/mL, with no other hemostatic defect, seem to have a minimal risk of severe bleeding. Extended clinical studies are needed to support these findings.

Adolescent↗
PubMed2003

[Treatment of a septic patient with acquired haemophilia].

INTRODUCTION: Acquired haemophilia is a rare bleeding diathesis caused by auto-immune depletion of factor VIII. It is characterised by spontaneous haemorrhagic syndrome, which can be fatal sometimes. EXEGESIS: A 71 year-old man presents in a dysimmunitary context (rheumatoid arthritis complicates by an acquired haemophilia) a septicemia with a methicillin resistant staphylococcus aureus. At the time of the hospitalization, the patient is febrile (39 degrees C). The activated partial thromboplastin time is very much increased, the level of factor VIII is lowered by 7% and the title of the inhibitor to factor VIII amounts to 140 Bethesda unities. An haematoma of the right root thigh is also noted. In that case, the concomitant presence of septicemia makes difficult the use of immunosuppressive therapy usually recommended to decrease auto-antibody's level. For the management of the septicemia, an adapted antibiotherapy (vancomycin then teicoplanin) is organized to J1. To control haemorrhagic risk, immunoglobulins are prescribed from d12 to d16, without immediate results. Then prednisone is introduced. We observe a very fast decrease of the anticoagulant circulating title with a neat improvement of the clinical state, allowing so to realize a draining puncture of the psoas. This invasive investigation required the use of prothrombinic complex concentrates ((Feiba) in the dose of 80 UI/kg two to three times a day). Biopsy does not show infection source. CONCLUSION: The infection delayed the prescription of immunosuppressive therapy and the surgery. Use of corticoids, following 5 days of intravenous polyvalent immunoglobulin, was the good choice. After 7 weeks of hospitalization the patient has recovered a normal haemostasis results, and a good general state.

Aged↗
PubMed2002

Myeloma and monoclonal gammopathy of uncertain significance associated with acquired von Willebrand's syndrome. Seven new cases with a literature review.

OBJECTIVES: Acquired von Willebrand's syndrome (AvWS) is an uncommon complication of monoclonal gammopathy of uncertain significance (MGUS) or myeloma. We investigated clinical and laboratory test abnormalities, pathophysiological hypotheses, and treatment options in this poorly known condition. PATIENTS: Five patients with MGUS and two with myeloma who met classic criteria for acquired von Willebrand's syndrome were included in this retrospective study. RESULTS: Acquired von Willebrand's syndrome was diagnosed before the gammopathy in five of the seven patients. The severity of the bleeding events was chiefly dependent on the degree of von Willebrand's factor deficiency and on the presence or absence of gastrointestinal tract angiodysplasia. Bleeding event severity was similar in patients with nonmalignant and malignant disease. An antibody that inhibited von Willebrand's factor was detected in all seven patients. Clotting returned to normal after treatment of the malignancy in one of the two patients with myeloma. In patients with MGUS, treatment is warranted only when bleeding occurs or before surgery. Von Willebrand's factor concentrates were of limited efficacy because of their short half-life. Intravenous immunoglobulins had a longer-lasting effect (about 3 weeks); this treatment was used on a regular basis in two patients with recurrent bleeding. CONCLUSIONS: A diagnosis of von Willebrand's syndrome in adulthood should prompt a search for a monoclonal gammopathy. In patients with gammopathies, simple clotting tests ensure the diagnosis of acquired von Willebrand's syndrome.

Aged↗
PubMed2001

Role of 4 platelet membrane glycoprotein polymorphisms on experimental arterial thrombus formation in men.

This study investigates whether the polymorphisms of 3 important platelet receptors affected experimental thrombus formation in men. Forty healthy male volunteers randomly recruited were genotyped for the variable number of tandem repeat (VNTR) of GPIbalpha, the -5T/C polymorphism in the Kozak sequence of GPIbalpha, the 807C/T polymorphism of GPIa, and the PI(A1)/PI(A2) polymorphism of GPIIb/IIIa. Platelet thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel plate perfusion chamber to native blood for 4 minutes. The shear rates at the collagen surface were 650 and 2600 x s(-1). At 2600 x s(-1) platelet thrombus formation was significantly related only to the 807C/T polymorphism. In contrast, at 650 x s(-1) thrombus formation was significantly altered only by the Kozak sequence polymorphism. The VNTR and the PI(A1)/PI(A2) polymorphisms did not influence thrombus formation. Thus, platelet thrombus formation is significantly influenced by genetic variations of the GPIbalpha and GPIa receptors. The effect of these polymorphisms was dependent on the blood flow rate.

Adult↗
PubMed1999

Effects of heparin and related sulfated polysaccharides on tissue factor expression induced by mitogenic and non-mitogenic factors in human vascular smooth muscle cells.

Smooth muscle cells (SMCs) of the intima are generally quiescent and non proliferative. Their proliferation due to different stimulations occurs in myointimal hyperplasia and is regularly present in atherogenesis or after transluminal angioplasty leading to vascular occlusive stenosis. In the course of these pathologies, the Tissue Factor (TF) synthesis was upregulated and rapidly expressed at the membrane of the SMCs. Heparin is known to inhibit SMCs proliferation induced by FCS. We evaluated the inhibitory effect of heparin on the expression of TF induced by various mitogenic (FCS, PDGF-BB and EGF) and non-mitogenic (bacterial LPS) agents. Inhibition by heparin of SMCs proliferation induced by the same agonists was also determined. Quiescent human vascular SMCs from normal adult arteries were treated for 1 h by heparin and related sulfated polysaccharides before stimulation by the agonists. All the agonists up-regulated the expression of TF antigen and activity. TF expression induced by the growth factors was inhibited by heparin (IC 50: 10-30 microg/ml), and other sulfated polysaccharides (IC 50: 1-5 microg/ml). SMCs proliferation, late activation of the extracellular signal-regulated kinases (ERK1/2), and PKC activity were inhibited by heparin (IC 50: 30-50 microg/ml) in SMCs stimulated by FCS but not in SMCs treated by PDGF or EGF. In contrast, heparin had no effect on LPS-induced TF expression nor on LPS-induced PKC activation. These results indicate that, besides its well known effect on SMC proliferation, heparin displays an inhibitory effect on cell mediated blood clotting processes through regulation of the TF expression.

Adult↗
PubMed1997

Acute basophilic leukaemia and translocation t(X;6)(p11;q23).

We report two infants with acute basophilic leukaemia associated with a t(X;6)(p11;q23) as the sole abnormality. Morphologic evidence of basophilic lineage was provided by light and electron microscopy. Both patients also had a similar presentation on diagnosis, characterized by clinical signs consistent with a hyperhistaminaemia syndrome, i.e. urticarian rashes and gastro-intestinal disorders evocative of peptic ulcer. Immunophenotypes differed in the two patients, one expressing CD24, CD13 and CD33, whereas only CD117 was found in the other. Basophilic acute leukaemia, a rare group among acute leukaemias, might be nonrandomly associated with a specific chromosomal abnormality, t(X;6)(p11;q23). This new entity might also be identifiable by an uncommon clinical presentation and occurrence in infancy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Identification of 15 different candidate causal point mutations and three polymorphisms in 19 patients with protein S deficiency using a scanning method for the analysis of the protein S active gene.

To screen for point mutations causing protein S deficiency, we used a sequence of techniques specifically for the study of the protein S active gene, PS alpha. This strategy comprises amplification of exons and intron/exon junctions by means of the polymerase chain reaction (PCR) and electrophoresis of the amplified fragments in polyacrylamide gel containing a gradient of denaturing agents (denaturing gradient gel electrophoresis). Only fragments with altered melting behavior are sequenced after asymmetric PCR. Beside the frequent polymorphism already described on Pro 626, we detected 18 different sequence variations by studying exons II, IV, V, VIII, X, and XV in 19 of 100 consecutive patients with protein S deficiency. Fifteen were candidate causal mutations, 4 of which were associated with a qualitative deficiency (type IIa or IIb). The remaining three sequence variations were probably polymorphisms.

Base Sequence↗
PubMed1995

Relationships of plasminogen activator inhibitor activity and lipoprotein(a) with insulin, testosterone, 17 beta-estradiol, and testosterone binding globulin in myocardial infarction patients and healthy controls.

The relationships between plasminogen activator inhibitor (PAi) activity and lipoprotein(a) [Lp(a)] and insulin, testosterone, 17 beta-estradiol, and testosterone binding globulin (TEBG) were assessed in 42 myocardial infarction male patients and 74 healthy controls. Patients had higher levels of insulin than did controls (87 +/- 30 vs. 75 +/- 28 pmol/L, respectively; P < 0.04), and no differences were found in levels of PAi activity, testosterone, 17 beta-estradiol, and TEBG. Lp(a) levels greater than 0.3 g/L were more frequent in patients than in controls (P < 0.002). In all subjects, PAi activity levels were significantly and positively correlated with body mass index (r = 0.20, P < 0.05), triglycerides (r = 0.38, P < 0.0001), and insulin (r = 0.27, P < 0.005) and were negatively correlated with testosterone (r = -0.28, P < 0.005) and TEBG (r = -0.42, P < 0.001). Stepwise multiple regression analysis showed triglyceride, insulin, and TEBG levels to be significantly related to PAi activity. No significant correlations were found between Lp(a) levels and all hormonal variables studied and between Lp(a) and PAi activity (r = -0.06, P < 0.58). These results suggest that TEBG is significantly and independently related to PAi levels.

Adult↗
PubMed1993

Subcutaneous low-molecular-weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis.

BACKGROUND: A low-molecular-weight heparin, enoxaparin sodium, has been shown to be effective and safe in preventing deep vein thrombosis both in general surgery and in high-risk orthopedic surgery. We conducted a controlled, randomized trial with enoxaparin in the treatment of established deep vein thrombosis. METHODS: In a multicenter trial, we compared fixed-dose subcutaneous enoxaparin, given twice daily, with adjusted-dose intravenous unfractionated heparin (UFH) given by continuous intravenous infusion for the initial 10 days of treatment of patients with proximal vein thrombosis. The primary efficacy outcome was the change of the size of the thrombus assessed by repeated venograms between day 0 and day 10. The primary analysis of safety was based on the incidence of major bleeding during 10 days of treatment. RESULTS: There were 67 patients in each group. Venographic assessment of clot size evolution between day 0 and day 10 showed a statistically significant superiority (P < .002) of enoxaparin over the reference treatment with UFH. Moreover, the incidence of overall recurrent thromboembolic events during 10 days of treatment was significantly higher (P < .002) in the UFH group (seven of 67) than in the enoxaparin group (one of 67). There were no serious bleeding complications in either group. CONCLUSIONS: Enoxaparin is at least as effective and safe as UFH under the conditions of this study. Moreover, it is more comfortable for patients and less time-consuming for nurses and laboratories. Thus, our study confirmed, with the use of enoxaparin, other observations that low-molecular-weight heparin provides a real therapeutic advance in the treatment of deep vein thrombosis.

Acute Disease↗
PubMed1993

Antithrombotic properties of a dermatan sulfate hexadecasaccharide fractionated by affinity for heparin cofactor II.

The relationship between the antithrombotic activity of dermatan sulfate (DS) in vivo and its catalytic effect on the inhibition of thrombin by heparin cofactor II (HC II) in vitro was investigated. DS was depolymerized by Smith degradation and the fragments obtained were separated by gel filtration. The fragment of minimal size with full catalytic activity was a hexadecasaccharide, which was further fractionated by affinity for immobilized HC II. Only a small proportion by weight (6.7%) was recovered in the high-affinity fraction, which had about 10 times more catalytic activity than the unfractionated oligosaccharide; the change in activity was primarily caused by the removal of inert materials, recovered in the low-affinity fraction. 1H-NMR spectra indicated strengthening of the signal given by Ido A (2S04) in the high-affinity fraction compared with that of the low-affinity fraction. The anticoagulant activity of the high-affinity fraction was exclusively HC II-dependent. The antithrombotic potency was evaluated in rabbits using the Wessler-thromboplastin model. Half-maximal prevention of thrombosis was obtained after injection of 250 micrograms/kg DS, of 500 micrograms/kg hexadecasaccharide, or of 60 micrograms/kg of its high-affinity fraction. The low-affinity fraction was ineffective at the highest dose tested (1,200 micrograms/kg) and did not potentiate the effect of the high-affinity fraction. These results show that the antithrombotic effect of DS is essentially dependent on HC II binding and activation and that HC II is therefore a suitable target for antithrombotic drugs.

Animals↗
PubMed1992

Influence of molecular weight upon the anticoagulant and pharmacokinetic properties of dermatan sulfate in the rabbit.

In order to improve the pharmacokinetic properties of unfractionated dermatan sulfate (UDS, mean MW: 25kD), the disposition of 4 low molecular weight dermatan sulfates (LMWDS) with a mean MW ranging from 15 to 4 kD was investigated in the rabbit. In comparison with UDS, it was established that after intravenous administration, the half-life of disappearance, the distribution volume and the clearance of the biological activity increased as the mean molecular weight decreased. After subcutaneous administration, the bioavailability of the 4 LMWDS was improved in comparison with that of UDS, but large inter-animal variations were recorded for LMWDS having a mean MW over 9 kD. Therefore the best compromise between biological activity, clearance, half-life of disappearance, bioavailability and reproducibility after subcutaneous administration should be a compound having a MW ranging from 4 to 9 kD.

Animals↗
PubMed1992

Elevated levels of thrombin-heparin cofactor II complex in plasma from patients with disseminated intravascular coagulation.

An ELISA assay for quantitation of the thrombin-heparin cofactor II complex (T-HC II) in plasma was developed. Plasma was incubated with immobilized, specific antibodies to human thrombin. The second, biotinylated antibody was directed against human HC II. The assay was insensitive to thrombin-antithrombin complex (TAT) and to uncomplexed HC II. In plasma samples from 31 normal individuals (aged 21-68, mean 43.3 years), the T-HC II ranged 0.3-6.1 ng/ml; median 1.5, mean 2.0, and SD 1.6 ng/ml. In plasma samples from 13 patients with disseminated intravascular coagulation (DIC), T-HC II ranged 0.4-30.0 (median 13.5) ng/ml. In plasma samples from 6 patients in which the clinical suspicion of DIC was not verified, T-HC II complex ranged 1.4-14.3 (median 3.6) ng/ml. In plasma samples with elevated T-HC II levels, TAT was usually elevated, and on the average more than was T-HC II. These results indicate that HC II contributes significantly to the inactivation of in vivo generated thrombin.

Adolescent↗
PubMed1992

[Circulating anticoagulants, antiphospholipids and thrombosis].

Antiphospholipids are auto-antibodies which can be detected both by immunological assays and by prolongation of coagulation test times. The latter has lead them to be called "lupus anticoagulant". They act preferentially on anionic phospholipids. Their presence increases the risk of thrombosis, especially in LED. They can appear at all ages, spontaneously, in autoimmune, infectious, or neoplastic pathologies, or after the intake of certain drugs. When these antibodies are associated with thrombosis or repeated fetal loss, the "antiphospholipid syndrome" is evoked. No causal relationship between the presence of these antibodies and thrombosis has yet been demonstrated. Standardization of laboratory diagnosis is not easy, particularly for weak positive samples. Because of their heterogeneity, an association of several tests is required for detection.

Adult↗
PubMed1992

Antithrombotic activity, bleeding effect and pharmacodynamics of a succinyl derivative of dermatan sulphate in rabbits.

This paper compares the pharmacological properties of a new succinyl dermatan sulphate derivative (Suc-DS) to those of the natural dermatan sulphate (DS). Suc-DS was on average 2-3 times more potent than DS in catalysing the inhibition of thrombin by heparin cofactor II and in prolonging the activated partial thromboplastin time and the thrombin clotting time. After bolus injection, Suc-DS was also 2-3 times more potent than DS to prevent experimental venous thrombosis in a Wessler model. Thromboplastin or human serum were used as the thrombogenic stimulus. In contrast, the bleeding effect assessed by rat tail transection technique was comparable. After bolus intravenous injection, the pharmacodynamics of Suc-DS indicated a lower volume of distribution, which was close to the plasma volume, and a slightly lower clearance of elimination. Therefore this chemical alteration of natural DS yields a new compound with an improved antithrombotic benefit/haemorrhagic risk ratio.

Animals↗
PubMed1992

[Circulating lupus coagulants. A paradox in vascular pathology].

Lupus anticoagulants (LA) are acquired inhibitors of coagulation related to the antiphospholipid antibodies. Paradoxically, these anticoagulants do not expose patients to the risk of hemorrhage but, on the contrary, to a thrombotic risk. The association in a patient of an antiphospholipid antibody and a clinical manifestation (thrombosis or equivalent) defines the antiphospholipid syndrome. This syndrome is termed primary or secondary according to whether it appears as an isolated disorder or is associated with an identified disease, frequently autoimmune (systemic lupus erythematous or lupus related syndrome). Clinical complications of LA are arterial or venous thrombosis at various sites. They are frequently recurrent, and deep venous thrombosis of leg, oculo-cerebral ischemic lesions and heart valve complications have all been well documented. Thrombosis of the microcirculation can cause tissue or organ disfunction, the most characteristic effect being repeated abortions. Laboratory demonstration of LA is difficult when the inhibitor is weak, and this should be completed by tests for other antiphospholipid antibodies. Clinical studies are necessary to assess the thrombotic risk of the LA in different clinical conditions and to evaluate the need and type of antithrombotic treatment. The LA are heterogeneous and only a small proportion of patients with LA will develop thrombosis. New tests capable of predicting the thrombotic risk, bases on the physiopathological mechanisms with which LA interfere in vivo, are currently being investigated.

Humans↗