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Biomedical subjects

J Vermylen

Publications and source records attributed to J Vermylen.

At least 19 recordsLinked to original sources
PubMed1992

Cell surface heparan sulfate proteoglycans from human vascular endothelial cells. Core protein characterization and antithrombin III binding properties.

Human aortic endothelial cells (HAEC) and human umbilical vein endothelial cells (HUVEC) were labeled with 35SO(4)2- for 48 h. The membrane-associated proteoglycans were solubilized from these monolayers with detergent and purified by ion-exchange chromatography on Mono Q, incorporation in liposomes, and gel filtration. The liposome-intercalated proteoglycans were 125I-iodinated and treated with heparitinase before SDS-polyacrylamide gel electrophoresis. Radio-labeled proteins with apparent molecular masses of 130, 60, 46, 35, and 30 kDa (HAEC) and 180, 130, 62, 43, and 35 kDa (HUVEC) were detected by autoradiography. Further characterization by affinity chromatography on immobilized monoclonal antibodies and by Northern blot analysis provided evidence for the expression of syndecan, glypican, and fibroglycan in human endothelial cells. Most of the heparan sulfate which accumulated in the subendothelial matrix was implanted on a 400-kDa core protein. This protein was immunologically related to perlecan and bound to fibronectin. Binding studies on immobilized antithrombin III suggested that all membrane-associated heparan sulfate proteoglycan forms had the capacity to bind to antithrombin III but that high affinity binding was more typical for glypican. Most of the proteoglycans isolated from the extracellular matrix also bound only with low affinity to antithrombin III. These results imply that glypican may specifically contribute to the antithrombotic properties of the vascular wall.

Antithrombin III↗
PubMed1992

Disturbed platelet aggregation to collagen associated with an antibody against an 85- to 90-Kd platelet glycoprotein in a patient with prolonged bleeding time.

We studied a 5-year-old girl presenting with a markedly prolonged bleeding time. Her platelets were refractory to collagen stimulation, but the response to other agonists was normal. There were no coagulation abnormalities as measured by standard tests. Two-dimensional electrophoresis showed no abnormalities of the patient's platelet membrane glycoproteins. When the patient's plasma or purified plasma IgG was mixed with normal platelets, collagen-induced platelet aggregation was blocked. Western blotting showed the presence of an antibody in the patient's plasma directed against a protein of molecular weight 85 to 90 Kd under both reducing and nonreducing conditions. This protein comigrated with glycoprotein (GP) IV immunoprecipitated by OKM5 from 125I-labeled platelets. Immunoprecipitation of 125I-labeled normal platelet glycoproteins with the patient's IgGs also yielded an 85- to 90-Kd protein that migrated on the diagonal following nonreduced/reduced two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Despite similarities in electrophoretic behavior, the antigen was not demonstrated to be GPIV, since purified GPIV was not recognized by the antibody.

Antibodies↗
PubMed1992

Thromboxane synthase inhibitors and receptor antagonists.

Platelet activation plays a major role in myocardial infarction and in reocclusion following successful thrombolysis, as corroborated by several clinical studies using aspirin. However, the overall reduction of new vascular complications in patients with symptomatic arterial disease by aspirin was only around 25%. Therefore, there is great interest in finding new means to inhibit platelet activation more efficiently. One line of research has focused on ways to interfere with the action of thromboxane A2 in a more selective way than aspirin does. As such, the development of thromboxane synthase inhibitors, followed by thromboxane receptor antagonists, raised hopes for a better treatment. However, both classes of drugs have some drawbacks, which could be overcome by combining them. This aim has led to the development of compounds that intrinsically possess both activities. Ongoing research indicates that such a dual inhibitor may indeed be more powerful than either aspirin or drugs with the single actions.

Aspirin↗
PubMed1992

HIV-related thrombocytopenia.

HIV-related chronic ITP is caused by an accelerated platelet destruction due to adsorption of circulating immune complexes and to specific anti-platelet antibodies, but perhaps also by a defective thrombopoiesis resulting from invasion of the megakaryocytes by the retrovirus. Treatment is needed when platelet numbers drop beneath 20.10(9)/L or when severe bleeding symptoms occur. Steroids, commercially available immunoglobulins for IV use, AZT and anti-Rh immunoglobulins can be administered, although relapses are frequent after withdrawal of the drugs. Recurrences after splenectomy are far less common, but the progression towards AIDS might be accelerated.

Antigen-Antibody Complex↗
PubMed1992

Are antiphospholipid antibodies clinically relevant in dialysis patients?

A cohort of 60 stable dialysis patients (56 haemodialysis, 4 continuous ambulatory peritoneal dialysis) was followed for 1 year to determine the relationship between anticardiolipin (aCL) antibodies and lupus anticoagulant (LA), and clinical events. The outcome measures were death, arterial, venous, and fistula thromboses, and fistula repairs. At baseline 15% had antibodies (5/60 IgG aCL, 3/60 LA, and 1/60 had both); 15 patients had a history of arterial thrombosis (1 patient was aCL positive), seven venous thrombosis (1 patient LA positive), 10 fistula thromboses (1 aCL positive); and 21 had a history of fistula repairs (4 aCL positive). Renal diagnosis, age (66.78 versus 59.67 years) and duration of dialysis (38.11 versus 45.25 months) were similar in patients with and without aCL antibodies or LA. Only the sex ratio showed a female predominance in the aCL- or LA-positive patients compared to the negative patients (3M:6F versus 36M:15F), but this was not significant (P = 0.07). After 1 year there were 10 deaths (1 LA positive), 12 thrombotic events in eight patients (none aCL or LA positive), and nine fistula repairs in seven patients (1 aCL-positive patient). We are unable to show higher rates of death, thrombotic event, or fistula repair in dialysis patients with aCL antibodies or LA followed up for 1 year in one centre. The clinical importance of antiphospholipid antibodies in dialysis patients is uncertain.

Adult↗
PubMed1992

A new lupus anticoagulant neutralization test based on platelet-derived vesicles.

We here present an easily standardizable and reproducible procedure which clearly separates lupus anticoagulants (LA) from coagulation factor inhibitors. This new LA neutralization test makes use of platelet-derived microvesicles which were prepared as follows: gel-filtered platelets (4 x 10(5)/microliters) were incubated with 60 microM of the calcium ionophore A23187 for 20 min at 37 degrees C. The vesicles were separated from the platelet aggregates by centrifugation at 1000 g for 10 min. The vesicle containing supernatant was then spun down at 15,000 g for 15 min, lyophilized and stored at -20 degrees C until used. The vesicles were resuspended in plasma from normal individuals, from patients with LA activity, from patients with factor VIII inhibitors, from patients with congenital factor deficiencies and from patients receiving oral anticoagulants or intravenous heparin. A kaolin clotting time was performed in the absence (KCT) or presence of these vesicles (KCTves) and the ratios of these times to their respective mean normal times were calculated. Segregation of LA patients from all remaining patients except heparinized ones could be made with a high degree of accuracy. A thrombin time was needed to separate LA from heparinized patients. The method was highly reproducible and only minor (negligible) differences in potencies were observed between different vesicle preparations. Both the intra-batch and the inter-batch coefficients of variations on the KCTves were lower than 6%.

Blood Coagulation Factors↗
PubMed1992

A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of Arg854 by Gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele.

We describe a patient with a lifelong bleeding disorder previously classified as von Willebrand's disease (vWD) type I. The factor VIII (FVIII) level in this patient was disproportionately low and we showed that this was due to a decreased factor VIII binding capacity of her vWF. To characterize the molecular defect in this type of vWD, a cDNA-dependent polymerase chain reaction (PCR) amplification was performed using platelet RNA as a template. Direct sequencing of the amplified fragment, which encodes for the FVIII-binding domain, showed a single nucleotide change in exon 20 at codon 854, resulting in the substitution of CAG glutamine (Gln) for CGG arginine (Arg). At the level of the cDNA only the mutated sequence was found, whereas at genomic DNA level the patient was heterozygous for this mutation. This patient is therefore a compound heterozygote for a point mutation resulting in a FVIII-binding defect and a vWF allele with low transcript levels.

Adult↗
PubMed1992

Influence of anticoagulation on blood loss following dental extractions.

The coagulation activity level at which oral surgery procedures can be performed in anticoagulated patients without triggering bleeding complications and without enhancing the risk of developing thrombo-embolic events remains controversial. The objective of the present study was to evaluate blood loss following dental extractions at different levels of anticoagulation and to determine its effect on wound closure rates. Blood loss was measured following the removal of four front teeth in warfarinized rabbits. Immediate blood loss was evaluated by determining the tooth socket bleeding times and by using a technique based on hemoglobin determinations. Long-term blood loss was assessed by comparison of labeled red-blood-cell disappearance curves. The results showed that blood loss following dental extractions was significantly greater in animals anticoagulated at a therapeutic level than in non-anticoagulated control animals. Determination of blood loss at different levels of anticoagulation clearly demonstrated that complete correction of the coagulation activity was unnecessary. Partial correction (INR values of 1.6-1.8) allowed extractions to be performed without extensive blood loss. With this technique of partial correction, the period of interruption of the anticoagulation could be kept very short, and the risk of postoperative bleeding complications was minimal. Wound closure rates were negatively influenced in anticoagulated animals.

Analysis of Variance↗
PubMed1992

Influence of hydroxyethyl starch on coagulation in patients during the perioperative period.

The perioperative use of hydroxyethyl starch (HES) has been implicated as a possible cause of intracranial bleeding. The purpose of this study was to compare the influence on blood coagulation of the isovolemic replacement of 1-L blood loss with either 6% HES (molecular weight [MW] average: 450,000) or 5% human albumin during neurosurgery or lower abdominal surgery. Twenty patients scheduled for brain tumor surgery and 20 patients undergoing transabdominal hysterectomy were studied. The activated partial thromboplastin time, prothrombin time, fibrinogen concentration, factor VIII coagulant, von Willebrand factor antigen, platelet count, and the activated clotting time were compared after induction of anesthesia, after administration of 500 and 1000 mL of colloid solution, and 24 and 48 h postoperatively. All measured coagulation variables remained within physiologic range. Changes in coagulation indices were identical in neurosurgical and hysterectomy patients, except for a larger increase in fibrinogen concentration 24 and 48 h after hysterectomy. The acute phase reaction of factor VIII coagulant and von Willebrand factor, which plays a role in postoperative hypercoagulability, was attenuated by the use of HES. We conclude that isovolemic replacement of 1-L blood loss with either 6% HES (MW average: 450,000) or 5% human albumin does not interfere with normal hemostasis during and after neurosurgery or lower abdominal surgery.

Adult↗
PubMed1991

Continuous quantitative monitoring of mural, platelet-dependent, thrombus kinetics in the crushed rat femoral vein.

A new in vivo method to study the size and dynamics of a growing mural thrombus was set up in the rat femoral vein. The method uses a standardized crush injury to induce a thrombus, and a newly developed transilluminator combined with digital analysis of video recordings. Thrombi in this model formed rapidly, reaching a maximum size 391 +/- 35 sec following injury, after which they degraded with a half-life of 197 +/- 31 sec. Histological examination indicated that the thrombi consisted mainly of platelets. The quantitative nature of the transillumination technique was demonstrated by simultaneous measurement of the incorporation of 111In labeled platelets into the thrombus. Thrombus formation, studied at 30 min interval in both femoral veins, showed satisfactory reproducibility overall and within a given animal. With this method we were able to induce a thrombus using a clinically relevant injury and to monitor continuously and reproducibly the kinetics of thrombus formation in a vessel of clinically and surgically relevant size.

Animals↗
PubMed1991

Possible platelet contribution to pathogenesis of transient neonatal hyperammonaemia syndrome.

The pathogenesis of the transient neonatal hyperammonaemia syndrome is largely unknown. The role of platelet activation was investigated in three preterm infants with this syndrome by non-invasive methods. In all three infants, urinary concentrations of beta-thromboglobulin and 11-dehydrothromboxane B2 levels were much higher during the hyperammonaemia than those in ten control preterm infants. It is possible that transient platelet activation occurs in the portal system of these infants, thereby causing the hyperammonaemia.

Ammonia↗
PubMed1991

Thromboxane synthase inhibitors, thromboxane receptor antagonists and dual blockers in thrombotic disorders.

Thromboxane A2 (TXA2) plays a pivotal role in platelet activation and is involved in the development of thrombosis. Thromboxane synthase inhibitors suppress TXA2 formation and increase the synthesis of the antiaggregatory prostaglandins PGI2 and PGD2; however, accumulated PGH2 may interact with the platelet and vessel wall TXA2 receptor, thus reducing the antiplatelet effects of this class of drug. TXA2 receptor antagonists block the activity of both TXA2 and PGH2 on platelets and the vessel wall. Very recently, drugs possessing both thromboxane synthase-inhibitory and thromboxane receptor-antagonist properties have been developed. Paolo Gresele and colleagues explain here why these drugs can be more efficacious than traditional antiplatelet agents and review the available experimental studies involving these drugs.

Animals↗
PubMed1991

Bilateral carotid artery occlusion: clinical presentation and outcome.

In a 4-year period, 17 patients were diagnosed as having bilateral carotid artery obstruction on ultrasonic duplex examination. Twelve had been referred because of recent neurological symptoms and the remaining 5 during cardiac or peripheral vascular work-up. Three patients had a completely silent occlusion of their two carotid arteries. Cardiac and/or peripheral vascular symptoms were present in 11 subjects. Mean follow-up was 28 months. No further strokes occurred. The 3-year cumulative stroke-free survival by life-table analysis was 75%. Myocardial infarction was the cause of death in 2 of 4 patients. For some patients with bilateral carotid artery occlusion, the clinical outcome is better than anticipated.

Aged↗
PubMed1991

In vitro and in vivo evaluation of two factor VIII concentrates virally inactivated by solvent-detergent or by pasteurization.

The present study compares two new factor VIII preparations currently used in the treatment of haemophilia. A Factor VIII was partially purified from plasma obtained from unpaid voluntary Belgian donors in the blood transfusion centers of Lille and Amsterdam and virus-inactivated by exposure to solvent-detergent (FVIII-SD) or by pasteurization (FVIII-P) respectively. The factor VIII content and the purity of both preparations were assessed in vitro, whereas in vivo we studied the recovery and the plasma half-life of both concentrates. The higher purity of FVIII-SD was confirmed. Factor VIII-P preparations contained more factor VIII than mentioned on the label. Both preparations gave good in vivo recoveries and half-lives. Patients who did not have antibodies to hepatitis B, hepatitis C or HIV at the initial screening, remained negative after six months treatment with the new concentrates. No patients developed neutralizing factor VIII antibodies. Furthermore patients appreciated the ease of administration of both preparations. In conclusion both FVIII concentrates are suited for the treatment of haemophilia A patients.

Antibodies, Viral↗