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Biomedical subjects

B Boneu

Publications and source records attributed to B Boneu.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Unresectable giant hepatic hemangioma and Kasabach-Merritt syndrome].

The Kasabach-Merritt syndrome was first described in children with cutaneous hemangiomas, but it can exceptionally be associated with visceral hemangiomas, especially in adults. Clotting and fibrinolysis within the hemangioma are thought to cause the coagulopathy observed in the so-called Kasabach-Merritt syndrome. This localised form of intra-vascular coagulation can progress to a secondary increased systemic fibrinolysis with fatal outcome for 20 to 30% of the patients. A transient control of hematologic abnormalities can frequently be obtained with blood product support (platelets, fibrinogen, fresh plasma, cryoprecipitates) and heparinotherapy. But in the adult, the only radical alternative is surgical excision if technically feasible. We reported here the case of a 43 year-old woman with a giant unresectable hepatic hemangioma complicated with a Kasabach-Merritt syndrome.

Adult↗
PubMed1994

Pharmacological properties of CY 216 and of its ACLM and BCLM components in the rabbit.

This study compares some in vivo pharmacological properties of CY 216 and of its ACLM and BCLM components having a molecular weight above and below 5.4 kDa respectively. The anti-factor Xa/antithrombin ratio of these compounds determined in a rabbit plasma system were 2.5 and 1.2 for CY 216 and ACLM respectively while BCLM was devoid of anti-thrombin effect. After bolus intravenous injection, continous infusion and subcutaneous administration, the clearances of anti-factor Xa activity generated by ACLM were, on the average, 2 and 1.5 times higher than those generated by BCLM and CY 216 respectively. The clearances of the anti-thrombin activity were comparable for CY216 and ACLM, and higher than those of the antifactor Xa activity. The duration of the antithrombotic effect was investigated in the Wessler model after a single subcutaneous injection of 1000 anti-factor Xa units of one of the compounds. Using thromboplastin as thrombogenic stimulus, the most efficient agent was ACLM and the antithrombotic activity was essentially correlated to the circulating anti-thrombin activity. Using human serum as thrombogenic stimulus, ACLM and BCLM were more efficient than CY 216 and the antithrombotic activity was mainly correlated to the anti-factor Xa activity. The ability of the 3 compounds to inhibit venous thrombosis growth was compared: they were found equipotent and the antithrombotic effect was independent of the anti-thrombin activity. The prohaemorrhagic properties were compared in the rabbit ear model. The activity of the 3 compounds were comparable and significantly less prohaemorrhagic than unfractionated heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Low molecular weight heparin therapy: is monitoring needed?

Recent meta-analyses indicate that low molecular weight heparins (LMWH) are more effective than unfractionated heparin (UH) in preventing and treating deep vein thrombosis. This article presents the arguments for and against the need for laboratory monitoring. At the present time, the only tests currently available for monitoring LMWH therapy are those which measure the anti Xa activity in the plasma. Due to lower binding to plasma proteins and to cell surfaces, the plasma anti Xa activity generated by a given dose of LMWH is more predictable than for UH. Some clinical trials suggest that LMWH delivered at the recommended dose expose the patient to less bleeding risk than UH. Several meta-analyses indicate comparable risk while any overdose unacceptably increases the haemorrhagic risk. The lowest dose of LMWH still effective in treating established DVT is presently unknown; some reports indicate that inadequate doses of LMWH are associated with a lack of efficacy for prevention. An overview of the published clinical trials indicates that the LMWH dose has never been monitored for prevention of DVT. In the treatment of established DVT, several trials have been performed without any monitoring, while in others the dose was adapted to target a given anti Xa activity. These considerations suggest that in prevention of DVT, monitoring the dose is not required.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Laboratory investigations and prediction of thrombotic risk in polycythemia vera.

Thrombotic accidents remain a major cause of morbidity and of fatal outcome in polycythemia vera (PV). High haematocrit which increases whole blood viscosity is the only identified predictive factor of thrombosis in PV. Neither high platelet count nor any abnormal platelet function have been found significantly linked to the thrombotic risk. There are recent development allowing to better characterize plasma hypercoagulability. The predictive value of these new tests has not yet been evaluated in PV.

Hematocrit↗
PubMed1994

Dermatan sulfate is a more potent inhibitor of clot-bound thrombin than unfractionated and low molecular weight heparins.

Clot-bound thrombin proteolyses fibrinogen and amplifies the coagulation cascade at its close vicinity, thereby ensuring the growth of fibrin-rich thrombus. The present study compares the ability of various glycosaminoglycans (GAGs) to inhibit these 2 properties. Unfractionated heparin (UH), 3 low molecular weight heparins (LMWHs) with increasing antifactor Xa/antifactor IIa ratio, the synthetic pentasaccharide (PS), devoid of antifactor IIa activity, and dermatan sulfate (DS), a catalyst of thrombin inhibition by heparin cofactor II, were selected on the basis of their different properties. Proteolysis of fibrinogen by clot-bound thrombin was evaluated by measuring fibrinopeptide A (FPA) generation after an incubation of standardized washed clots in plasma for 120 min in absence or in presence of increasing concentrations of heparins or of DS. The results were compared to those obtained when free alpha-thrombin (0.4 nM) was added to plasma in the same experimental conditions. On the basis of equivalent antithrombin units, UH and LMWHs gave identical results. To inhibit by 70% fibrinogen proteolysis induced by clot-bound thrombin (IC 70), 5- to 9-fold higher concentrations of UH or of LMWHs were required in comparison with those required to inhibit free thrombin. For DS, only a 1.3 times higher concentration was required. PS (final concentration 1 anti Xa U.ml-1) was devoid of any inhibitory effect. The amplification of the coagulation cascade induced by clot-bound thrombin was evaluated by measuring the shortening of whole blood clotting time (WBCT) resulting from the incubation of washed clots in native blood. In absence of GAG, clot-bound thrombin reduced WBCT from 18 +/- 2 min to 9 +/- 1 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatan Sulfate↗
PubMed1994

A new chronometric assay to determine plasma antifactor Xa activity which is insensitive to the antithrombin activity of low molecular weight heparins.

Some commercially available chronometric assays are influenced by the residual antithrombin activity of low molecular weight heparins (LMWH) and they underestimate the ex vivo anti Xa activity. We have evaluated a new kit (Staclot-Heparin) highly specific for the anti Xa activity of LMWH. A comparison with the results given by a reference chromogenic method (Stachrom-Heparin) indicates a very good correlation between the 2 assays (r = 0.95, n = 59). This new assay is not influenced by vitamin K antagonist treatments. Clinical biologists now have the possibility of determining the anti Xa activity generated by LMWH easily and accurately, using a chronometric assay.

Antibodies↗
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↗
PubMed1993

Influence of long term oral anticoagulants upon prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-Dimer levels in patients affected by proximal deep vein thrombosis.

We have investigated the influence of long term oral anticoagulants (OAC) upon the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-Dimer in 20 patients affected by a proximal deep vein thrombosis (DVT) diagnosed by ultrasonic duplex scanning. Patients (63 +/- 17 years, mean +/- SD) were sampled at the beginning of the OAC treatment (day 1), which was started 1 to 6 days after diagnosis confirmation and full heparinization, and then 8, 35 and 92 days after. The results were compared to those obtained in a blood donor population (39 +/- 10 years) and to an age-matched healthy population (63 +/- 19 years). The mean INR determined on days 8, 35 and 92 were almost identical (2.8 +/- 0.7, 2.9 +/- 0.9 and 2.8 +/- 0.6 respectively). In contrast, highly significant variations of the three markers were recorded during the observation period. Eight days after the beginning of OAC, increased levels of TAT complexes were associated with subnormal levels of F1 + 2 suggesting persistence of a hypercoagulable state. On the further sampling times, TAT complexes were in the normal range while F1 + 2 were far below the normal range. Between day 1 and day 92, the levels of D-Dimer continuously decreased reflecting a long-term fibrinolytic process. This study clearly indicates that high INR are not systematically associated with very low F1 + 2 levels, particularly in the acute phase of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A comparison of the antithrombotic effects of heparin and of low molecular weight heparins with increasing antifactor Xa/antifactor IIa ratio in the rabbit.

This study compares the ability of unfractionated heparin (UH) and of three low molecular weight heparins (LMWHs) to inhibit venous thrombosis growth in the rabbit. Logiparin (LHN-1), Fraxiparin (CY216) and CY222 were selected because they present very different antifactor Xa/antifactor IIa ratios: 1.7, 3.8 and 6.8 respectively. Heparins were delivered under continuous intravenous infusion for 4 h at increasing doses from 10 to 250 antifactor Xa U kg-1 h-1. The minimum dose providing the maximum inhibitory effect was 50 antifactor Xa U kg-1 h-1. On the basis of this system of units the four heparins were equipotent antithrombotic agents. Due to the highest antifactor Xa/antifactor IIa ratio, CY222 became the most potent antithrombotic agent when the doses were expressed in antithrombin units. Because UH is cleared faster than LMWHs at low dose regimen, the antifactor Xa steady state concentrations generated by the continuous infusion of any of the LMWHs were higher than those generated by UH. In addition the ex vivo antifactor Xa/antifactor IIa ratio of each of the LMWH was superior to the in vitro ratio. These results indicate that the antithrombotic activity of LMWH is not directly related to its subfraction catalysing thrombin inhibition.

Animals↗
PubMed1993

Comparison of anti-human and anti-porcine factor VIII inhibitor levels in 63 patients with severe haemophilia A. A French Multicentric Study.

The levels of anti-human and anti-porcine factor VIII inhibitors, measured in 63 severe haemophilia A patients, lay in the ranges of < 0.2-2,600 and < 0.2-1,300 Bethesda units per ml (BU/ml), respectively, with a median cross-reactivity of 33%. In 4 patients, human and porcine inhibitor levels were determined using both plasma, either human or porcine, and factor VIII concentrate, either very high purity human or porcine (Hyate:C). A good correlation between titres was found, whatever the source of factor VIII (plasma or concentrate). The cross-reactivity varies from 0 to over 100%, indicating that the evaluation of both human and porcine inhibitors should be mandatory before any treatment with Hyate:C. Results show that of the 46 patients with human inhibitor of more than 5 BU/ml, 21 (46%) with a low porcine inhibitor (< 5 BU/ml) could benefit from Hyate:C.

Animals↗
PubMed1993

Evaluation of six markers of haemostatic system in normal pregnancy and pregnancy complicated by hypertension or pre-eclampsia.

OBJECTIVE: To establish the plasma evolution of prothrombin fragments 1+2 (F 1+2), thrombin-antithrombin III complexes (TAT), fibrin fragment D-Dimers (DD), von Willebrand factor antigen (vWf), Type 1 plasminogen activator inhibitor antigen (PAI) and blood platelet count during normal pregnancy and to compare these values with those obtained in hypertensive or pre-eclamptic pregnancies. DESIGN: Cross-sectional study. SUBJECTS: Forty-seven healthy pregnant women with gestational age ranging between 5 and 40 weeks, and fourteen women with gestational age ranging between 25 and 38 weeks presenting with either gestational hypertension (n = 4) or pre-eclampsia (n = 10). Numbers of nulliparous women in the control, hypertension and pre-eclampsia groups were 13/47 (28%), 1/4 (25%) and 9/10 (90%), respectively. RESULTS: All six markers increased with gestational age in normal pregnant women (P < 0.01). Using the upper limit of 95% prediction interval obtained from regression curves as normality threshold, TAT showed the best sensitivity (71% vs < 30% for F1+2, DD, vWf, PAI and platelet count). CONCLUSION: TAT appears to be an interesting marker for detecting haemostatic system alterations in pregnancies complicated by hypertension or pre-eclampsia. A large prospective study to determine its clinical usefulness for such complicated pregnancies is currently in progress.

Adult↗
PubMed1993

Human type II hyperlipoproteinemia enhances platelet-collagen adhesion in flowing nonanticoagulated blood.

We investigated the effects of high plasma lipid levels on platelet adhesion and platelet thrombus formation in nonanticoagulated human blood on collagen fibrils at an arterial wall shear rate of 2600 seconds-1. Nonanticoagulated blood was drawn directly at a flow rate of 10 mL/min for 3 minutes from an antecubital vein of patients with type IIa (n = 5) and type IIb (n = 4) hyperlipoproteinemia over purified human type III collagen fibrils that were positioned on a plastic coverslip in a parallel-plate perfusion chamber. Results were compared with those obtained in healthy individuals with normal lipid plasma levels (n = 9). Blood-collagen interactions were quantified by morphometry as platelet-collagen adhesion, thrombus volume, and fibrin deposition. Platelet-collagen adhesion in the two groups of patients was significantly higher than in healthy individuals (70.7 [61.2 to 82.0] and 70.3 [66.4 to 81.0] in types IIa and IIb patients, respectively, versus 51.2 [44.5 to 68.6] in control subjects; P < .05. All values are percent median [range]). In contrast, the thrombus volume was similar in the three groups (11.3 [8.0 to 13.0], 9.6 [6.4 to 15.3], and 10.2 [6.8 to 16.1] microns3/microns2 [range], respectively). Differences in fibrin deposition were not observed. Thus, it appears that platelet-collagen adhesion is augmented in patients with type IIa and IIb hyperlipoproteinemia, indicating that the process of thrombogenesis is hastened in these patients.

Adult↗
PubMed1993

An international multicentre study: Clivarin in the prevention of venous thromboembolism in patients undergoing general surgery. Report of the International Clivarin Assessment Group.

A randomized multicentre double-blind study was organized to evaluate the efficacy and the safety of Clivarin (reviparin-sodium) (anti-Xa/anti-IIa ratio: 3-5 International units) for the prevention of post-operative thromboembolism in patients undergoing general surgery. 1,351 patients were randomly allocated to receive subcutaneously either 5,000 U of unfractionated heparin (UFH) twice a day or 1,750 anti-Xa IU of reviparin-sodium once a day (morning) followed by a placebo injection (evening) for at least 6 days. Deep vein thrombosis (DVT) was detected with the 125I-fibrinogen technique confirmed by phlebography if necessary. After randomization thrombotic risk factors were equally distributed in each group. More than 50% of the patients had a cancer. The incidence of DVT and of pulmonary embolism was 4.8% (CI 95%: 3.3-6.7%) in the reviparin-sodium group and 4.4% (CI 95%: 2.9-6.2%) in the UFH group, a non-significant difference. The number of transfusions required was equivalent in the two groups. However, post-operative bleeding complications, including wound haematomas and internal bleeding, were less frequent in the reviparin-sodium group (P < 0.01). Therefore, for the first time, this study demonstrates that an unusual low dose of a low molecular weight heparin retains its antithrombotic efficacy by comparison with UFH and that the tolerance of this low dose is better.

Adult↗
PubMed1993

[Predisposing factors for thrombosis].

There are a number of predisposing factors to thrombosis. Blood stasis and hypercoagulability are two important factors for the development of venous thrombosis. Several clinical situations are associated with these two factors. Congenital deficiencies in antithrombin III, protein C or protein S, the antiphospholipid antibodies represent well established risk factors. Arterial hypertension, dyslipidemia, tobacco, diabetes and obesity represent risk factors for arterial thrombosis. Hypofibrinolysis high levels fibrinogen and factor VII increases the risk of arterial thrombosis.

Arterial Occlusive Diseases↗
PubMed1992

Effects of heparin, dermatan sulfate and of their association on the inhibition of venous thrombosis growth in the rabbit.

This study compares the ability of unfractionated heparin, of dermatan sulfate, and of their simultaneous administration delivered as continuous intravenous infusion or as a single bolus injection to inhibit the growth of a standardized venous thrombosis in the rabbit. When delivered as continuous intravenous infusion for 4 h, heparin and dermatan sulfate inhibited thrombus growth in a dose dependent manner. The maximum antithrombotic effect of heparin was achieved at the dose of 0.15 mg kg-1 h-1 (25 U kg-1 h-1) which generated a mean plasma concentration of 1.8 micrograms ml-1 (0.31 U ml-1) and a 1.8 fold prolongation of the activated partial thromboplastin time (APTT) in comparison to the pretreatment value. A comparable antithrombotic effect was obtained with dermatan sulfate at the dose of 2 mg kg-1 h-1. This dose generated a mean plasma concentration of 30 micrograms ml-1 and a 1.3 fold APTT prolongation. Increasing these doses up to 10 fold did not improve the antithrombotic effect which did not overpass 60-70% of the controls. When the compounds were delivered simultaneously, the maximum antithrombotic effect (64%) was obtained with the following association: 0.06 mg kg-1 h-1 (10 U kg-1 h-1) for heparin and 1 mg kg-1 h-1 for dermatan sulfate. Increasing these doses up to 4 to 5 fold did not improve the antithrombotic effect. Heparin, dermatan sulfate and the association of both were also delivered as single bolus injections and the resultant antithrombotic effect was determined 4 h after saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗