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Biomedical subjects

B Boneu

Publications and source records attributed to B Boneu.

At least 55 records · Page 3Linked to original sources
PubMed1997

The activity of unfractionated heparin and low molecular weight heparins in rabbit plasma--the need for using absolute anti-factor Xa and antithrombin activities.

Rabbit being a common animal model to evaluate the antithrombotic effect of heparins, our purpose was to apply the heparin Standard Independent Unit (SIU) approach to rabbit plasma. To take into account the specificities of the enzymes we have measured the decay constants of factor Xa and of thrombin from autologous and heterologous origins, in presence and in absence of heparin. Different heparins or heparin fractions with a mean molecular weight from 1.7 to 10.5 kDa were used. We found that: a) the decay constants varied strongly between species and between enzymes; b) the decay constants of thrombin were always higher than those of factor Xa; c) the specific anti-factor Xa activity of heparins increased with the molecular weight and was 1.33 times higher when determined with bovine factor Xa than with rabbit factor Xa; d) the specific antithrombin activity of heparins also increased with the molecular weight but was similar when determined with rabbit and human thrombin; e) the specific anti-factor Xa activity was always lower than the specific antithrombin activity; f) the calibration of the heparins and heparin fractions against the 4th International Standard of Heparin expressed in International Units (IU) lead to a systematic overestimation of the anti-factor Xa activity and to an under-estimation of the antithrombin activity. These observations indicate that it may be very important to use the SIU approach and to know the accurate activities to better understand the mechanism of the antithrombotic activity of heparins in experimental models.

Animals↗
PubMed1997

Up-regulation of tissue factor expression by platelet-derived growth factor in human vascular smooth muscle cells in culture--role of mitogen-activated protein kinase and effects of intracellular cyclic AMP.

Human vascular smooth muscle cells (SMCs) isolated from normal adult arteries were investigated for the expression of Tissue Factor (TF) procoagulant activity at their membrane surface and TF antigen in lysed cells. In growing conditions, SMCs expressed high levels of TF activity and antigen. When cells were made quiescent by 72 h of subculture in serum-poor medium, these levels fell to about one third of the initial values. Platelet-derived growth factor BB (PDGF) up-regulated in a dose-dependent manner TF expression with a significant increase (1.8 fold) within five hours. PD 98059, a specific inhibitor of mitogen-activated protein kinase (MAPK) pathway involved in cell response to PDGF, also prevented TF up-regulation. Short-term treatment by Pentoxifylline and dibutyryl cAMP also completely prevented induced TF up-regulation, but remained without effect on baseline levels of quiescent, unstimulated cells. At their effective concentrations, pentoxifylline and dibutyryl cAMP also inhibited the activation of MAPK induced by PDGF. The rapid induction of TF upon growth factor stimulation may be important in circumstances where SMCs proliferate, such as vascular events or vessel development.

Adult↗
PubMed1996

Glycosaminoglycans: clinical use.

Heparins, dermatan sulfate (DS), and Orgaran are the only glycosaminoglycans that have been used as antithrombotic agents in man. The largest experience concerns unfractionated heparin (UH) and its low-molecular-weight derivatives (LMWHs). It is firmly established that UH is efficient and safe in the prevention and treatment of deep vein thrombosis (DVT). Unfractionated heparin is also used as adjunctive therapy in the treatment of arterial thrombosis. Meta-analyses have shown that LMWHs are slightly more efficient than UH. Because they are more convenient for the nurses and the patient, and because they probably induce less bleeding and less immunogallergic thrombocytopenia, they will progressively replace UH in these indications. Clinical experience with DS is still scarce. Unfractionated DS has a low bioavailability after s.c. or i.m. administration; thus, LMW-DS are presently developed. These compounds have a low prohemorrhagic potential, and it has been proven that they are efficient in the prevention of postoperative DVT. Orgaran is a complex mixture of several glycosaminoglycans, excluding heparin. This compound has been found efficient in the prevention and treatment of DVT. Interestingly, in patients presenting heparin-induced thrombocytopenia, Orgaran may be an alternative treatment because a cross-reactivity with heparin is observed in less than 10% of the subjects.

Dermatan Sulfate↗
PubMed1996

New antithrombotic agents for the prevention and treatment of deep vein thrombosis.

Besides low molecular weight heparins (LMWHs) a number of new antithrombotic agents have been evaluated mainly in the prevention of deep vein thrombosis (DVT) and, to a lesser extent, in the treatment of established DVT. They include the Pentasaccharide, a synthetic ultra LMWH, Dermatan Sulphate, a glycosaminoglycan which activates heparin cofactor II, Orgaran, a mixture of Heparan and of Dermatan Sulphate, Hirulog and Hirudin, two direct thrombin inhibitors. The efficacy and safety of these compounds have been studied in comparison with a placebo or with unfractionated heparin but not with LMWH which is considered as a gold standard for these clinical indications. It is thus difficult at present to appreciate the advantages of these new antithrombotic agents over conventional LMWH therapy.

Anticoagulants↗
PubMed1996

The performance of the knowledge-based system VALAB revisited: an evaluation after five years.

In 1988, inundated by the tedious work of validation of laboratory reports in a large hospital biochemistry laboratory, we designed VALAB, a knowledge-based system specially dedicated to this iterative function. Coping at first with a few biochemical tests, the program has been progressively expanded to forty-five common chemical tests. Simultaneously some new rules have been introduced to "weight" the conclusion in different circumstances and rules taking into consideration some clinical data have also been written. Moreover the program moved to other disciplines, pH and blood gases, haematology and coagulation. Accordingly the evaluation protocol has been modified, incorporating a new step, the consensus decision of the pathologists, operating within the initial protocol and based upon the various criteria of epidemiology. These major changes and improvements have led us to check and describe again the performance of this updated VALAB knowledge-based system.

Artificial Intelligence↗
PubMed1996

Heparin reverses the procoagulant properties of stimulated endothelial cells.

We examined the ability of unfractionated heparin to modulate the procoagulant activities of stimulated endothelial cells (EC). Confluent human venous umbilical EC were incubated with heparin before or after stimulation, then rinsed extensively to eliminate any heparin in the solution. EC, stimulated for 4 h with endotoxin and interleukin 1 beta, expressed tissue factor and prothrombinase activities. When EC were treated with heparin (6 and 60 micrograms/ml) during the last 10 min of the stimulation period, EC-related procoagulant activities were inhibited in a dose-dependent manner (80-90% inhibition at 60 micrograms/ml). The inhibition was antithrombin-dependent and it disappeared after heparin removal in less than 15 min at 37 degrees C but persisted at 4 degrees C. When EC were treated with heparin (60 micrograms/ml) for 24 h then extensively washed before stimulation, the anticoagulant effect was more modest (50% inhibition). The effect was antithrombin-dependent. Inhibition was maximum after 18-24 h of pretreatment of EC with heparin and was stable for at least 7 h. The cell surface displayed a "heparin-like" activity: treatment by heparin doubled the rate of thrombin-antithrombin complex formation and this effect was heparinase sensitive and chondroitinase ABC insensitive. Thus, heparin modulates the procoagulant properties of stimulated EC according to two distinct mechanisms. The first one is rapid and transient, probably related to the presence of heparin molecules bound at the membrane surface. The second is delayed and persistent, and our results suggest that it is mediated by an increase in the membrane heparan sulfate molecules.

Blood Coagulation↗
PubMed1996

Predicting daily maintenance dose of fluindione, an oral anticoagulant drug.

Due to large inter-individual variations, the dose of vitamin K antagonist required to target the desired hypocoagulability is hardly predictible for a given patient, and the time needed to reach therapeutic equilibrium may be excessively long. This work reports on a simple method for predicting the daily maintenance dose of fluindione after the third intake. In a first step, 37 patients were delivered 20 mg of fluindione once a day, at 6 p.m. for 3 consecutive days. On the morning of the 4th day an INR was performed. During the following days the dose was adjusted to target an INR between 2 and 3. There was a good correlation (r = 0.83, p < 0.001) between the INR performed on the morning of day 4 and the daily maintenance dose determined later by successive approximations. This allowed us to write a decisional algorithm to predict the effective maintenance dose of fluindione from the INR performed on day 4. The usefulness and the safety of this approach was tested in a second prospective study on 46 patients receiving fluindione according to the same initial scheme. The predicted dose was compared to the effective dose soon after having reached the equilibrium, then 30 and 90 days after. To within 5 mg (one quarter of a tablet), the predicted dose was the effective dose in 98%, 86% and 81% of the patients at the 3 times respectively. The mean time needed to reach the therapeutic equilibrium was reduced from 13 days in the first study to 6 days in the second study. No hemorrhagic complication occurred. Thus the strategy formerly developed to predict the daily maintenance dose of warfarin from the prothrombin time ratio or the thrombotest performed 3 days after starting the treatment may also be applied to fluindione and the INR measurement.

Administration, Oral↗
PubMed1996

D-dimer test and diagnosis of deep vein thrombosis: a comparative study of 7 assays.

The current D-Dimer ELISA methods provide high sensitivity and negative predictive value for the diagnosis of deep vein thrombosis but these methods are not suitable for emergency or for individual determination. We have evaluated the performance of 3 newly available fast D-Dimer assays (Vidas D-Di, BioMérieux; Instant IA D-Di, Stago; Nycocard D-Dimer, Nycomed) in comparison with 3 classic ELISA methods (Stago, Organon, Behring) and a Latex agglutination technique (Stago). One-hundred-and-seventy-one patients suspected of presenting a first episode of deep vein thrombosis were investigated. A deep vein thrombosis was detected in 75 patients (43.8%) by ultrasonic duplex scanning of the lower limbs; in 11 of them the thrombi were distal and very limited in size (< 2 cm). We compared the performance of the tests by calculating their sensitivity, specificity, positive and negative predictive value for different cut-off levels and by calculating the area under ROC curves. The concordance of the different methods was evaluated by calculating the kappa coefficient. The performances of the 3 classic ELISA and of the Vidas D-Di were comparable and kappa coefficients indicated a good concordance between the results provided by these assays. Their sensitivity slightly declined for detection of the very small thrombi. Instant IA D-Di had a non-significantly lower sensitivity and negative predictive value than the 4 previous assays; however its performance was excellent for out-patients. As expected, the Latex assay had too low a sensitivity and negative predictive value to be recommended. In our hands, Nycocard D-Dimer also exhibited low sensitivity and negative predictive value, which were significantly improved when the plasma samples were tested by the manufacturer. Thus significant progress has been made, allowing clinical studies to be planned to compare the safety and cost-effectiveness of D-Dimer strategy to those of the conventional methods for the diagnosis of venous thrombosis.

Adolescent↗
PubMed1996

Platelet anti-aggregating activity and tolerance of clopidogrel in atherosclerotic patients.

The anti-aggregating activity of five rising doses of clopidogrel has been compared to that of ticlopidine in atherosclerotic patients. The aim of this study was to determine the dose of clopidogrel which should be tested in a large scale clinical trail of secondary prevention of ischemic events in patients suffering from vascular manifestations of atherosclerosis [CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events) trial]. A multicenter study involving 9 haematological laboratories and 29 clinical centers was set up. One hundred and fifty ambulatory patients were randomized into one of the seven following groups: clopidogrel at doses of 10, 25, 50, 75 or 100 mg OD, ticlopidine 250 mg BID or placebo. ADP and collagen-induced platelet aggregation tests were performed before starting treatment and after 7 and 28 days. Bleeding time was performed on days 0 and 28. Patients were seen on days 0, 7 and 28 to check the clinical and biological tolerability of the treatment. Clopidogrel exerted a dose-related inhibition of ADP-induced platelet aggregation and bleeding time prolongation. In the presence of ADP (5 microM) this inhibition ranged between 29% and 44% in comparison to pretreatment values. The bleeding times were prolonged by 1.5 to 1.7 times. These effects were non significantly different from those produced by ticlopidine. The clinical tolerability was good or fair in 97.5% of the patients. No haematological adverse events were recorded. These results allowed the selection of 75 mg once a day to evaluate and compare the antithrombotic activity of clopidogrel to that of aspirin in the CAPRIE trial.

Adult↗
PubMed1996

[Anti-Xa molecules].

Factor Xa plays a central role in the mechanisms of thrombin generation. Recently, molecules have been developed which either catalyse the inactivation of factor Xa by the antithrombin (pentasaccharide) or directly inhibit factor Xa (synthetic inhibitor or peptides extracted from the saliva of tics or leeches). These new molecules allowed to demonstrate that selective factor Xa inhibition exerts an antithrombotic effect in several models of thrombosis. The molecule at the most advanced stage of development is pentassaccharide (phase II), synthetic ultra low molecular weight heparin, with a well defined mechanism of action.

Animals↗
PubMed1995

Cross-reactivity of human molecular markers for detection of prethrombotic states in various animal species.

The aim of the present study was to investigate the reactivity of immunoreagents developed for clinical applications in humans in different animal species (hen, mouse, rat, rabbit, guinea-pig, dog, pig, sheep, baboon). Prothrombin fragment 1 + 2, thrombin-antithrombin III complex and fibrinopeptide A were tested for coagulation, platelet factor 4 and beta-thromboglobulin for platelet activation, glycoprotein IIb-IIIa, glycoprotein Ib and P-selectin for platelet membrane glycoproteins, D-dimers for fibrinolysis, thrombomodulin for activation of endothelial cells and thrombospondin and von Willebrand factor for adhesive proteins. Prothrombin fragment 1 + 2, platelet factor 4, beta-thromboglobulin and D-dimers were revealed only in baboons. Fibrinopeptide A was well detected in baboons but weakly in mice, dogs, pigs and sheep. Whereas glycoprotein IIb-IIIa was revealed on guinea-pig, dog and sheep platelets and glycoprotein Ib on rabbit and dog platelets, P-selectin and thrombomodulin were never detected. Thrombospondin was revealed in hens, mice, rats, guinea-pigs, pigs, sheep and baboons and von Willebrand factor in mice, rats, guinea-pigs, dogs, pigs, sheep and baboons. Interestingly, thrombin-antithrombin III complex (TAT) was detected in all species tested except the hen. A time- and dose-dependent increase in TAT was observed when rats, dogs or pigs were infused with thromboplastin (4.5-450 microliters/kg/h), while administration of hirudin (1 mg/kg) abolished this TAT generation. Thus, the TAT immunoassay could provide a tool for the screening of antithrombotic drugs in a number of animal species. However, the possibility of using a wider panel of human immunoreagents would appear to be restricted to baboons which display good species cross-reactivity.

Animals↗
PubMed1995

Relationship between endothelial tissue factor and thrombogenesis under blood flow conditions.

We have evaluated the relationship between the level of tissue factor (TF) expression by stimulated endothelial cells and thrombus formation under blood flow conditions. Cultures of human umbilical venous endothelial cells (HUVECs) were treated in order to express different levels of TF activity. They were stimulated for 4 h with either I) lipopolysaccharides (LPS, 10 micrograms/ml), II) recombinant interleukin 1 beta (IL1 beta, 50 UI/ml) or III) simultaneously with LPS and IL1 beta (LPS+IL1 beta). TF activity was low on confluent HUVECs or on the corresponding extracellular-matrix (ECM prepared by exposure of HUVECs to 0.1 N NH4OH). In contrast, it was high when HUVECs were stimulated with LPS or IL1 beta, and significantly higher (p < 0.05) with LPS+IL1 beta. The TF activity associated with the stimulated ECM was 2-fold higher (p < 0.05) than that expressed on the luminal surface of the stimulated HUVECs, irrespective of the agonist or combination of agonists used. These surfaces were exposed to non-anticoagulated human blood at a venous (50 s-1) and an arterial (650 s-1) wall shear rate in parallel-plate perfusion chambers for 5 min. Thrombus formation was morphologically quantified by measuring the deposition of platelets and fibrin. Fibrin deposition was also immunologically quantified. Fibrin deposition was related to the level of TF expression. Non-stimulated HUVECs and corresponding ECMs were not thrombogenic. The luminal surface of HUVECs stimulated with LPS or IL1 beta alone expressed low levels of TF activity and was a poor inducer of platelet deposition and fibrin deposition (< 15%) at 50 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1995

A comparative study of the anticoagulant and anti-thrombotic effects of unfractionated heparin and a low molecular weight heparin (Fraxiparine) in an experimental model of human venous thrombosis.

We have compared the anticoagulant and the antithrombotic effects of unfractionated heparin (Calciparine) and low molecular weight heparin (Fraxiparine) in an experimental human venous thrombosis model. One single subcutaneous injection of Calciparine or Fraxiparine was administered to healthy male volunteers at one month interval in a randomised and cross-over design. Ten subjects received doses used in man for preventing venous thrombosis (5,000 IU and 3,075 IU, respectively), and seven other subjects received curative doses (12,500 IU and 6,150 IU, respectively). Thrombus formation was measured 3 h and 8 h after drug administration. Non-anticoagulated human blood was drawn for 5 min directly from an antecubital vein over confluent cultured endothelial cells positioned in a parallel-plate perfusion chamber. The cells were previously stimulated for 4 h with lipopolysaccharides (10 micrograms/ml) and interleukin 1 beta (50 U/ml), resulting in optimal expression of biological active tissue factor. The wall shear rate at the cell surface was 50 s-1 and mimicked venous blood flow conditions. Immunologically quantified fibrin deposition on the stimulated cells was reduced only by curative doses of Calciparine and Fraxiparine at 3 h (3.4 +/- 0.8 versus 1.0 +/- 0.2 micrograms/cm/ and 2.6 +/- 0.8 versus 1.0 +/- 0.1 micrograms/cm2, respectively, p < or = 0.05). The influence of Calciparine and Fraxiparine on the formation of thrombin and fibrin was determined by measuring the plasma levels of thrombin-antithrombin III complexes and fibrinopeptide A (FPA) in blood samples collected distally to the perfusion chamber. The generation of these markers was significantly inhibited (50-83%) by both prophylactic and curative doses of Calciparine and Fraxiparine (p < or = 0.05). However, Fraxiparine still significantly inhibited the thrombin and fibrin generation at 8 h (p < or = 0.05), whereas Calciparine did not. The antithrombotic effects of both heparins were correlated with their plasma activities as measured by the antifactor Xa or the antithrombin assays. Thus, it appears in this model that Calciparine and Fraxiparine produce comparable antithrombotic effects at clinically comparable doses. However Fraxiparine has a longer-lasting anticoagulant activity than Calciparine. These results are in good agreement with clinical observations in man, and thus in favour of our model of human venous thrombogenesis for further studies of antithrombotic molecules.

Adolescent↗
PubMed1995

Pharmacokinetics and tolerance of the natural pentasaccharide (SR90107/Org31540) with high affinity to antithrombin III in man.

This paper reports the results of the first administration of the synthetic natural pentasaccharide with high affinity to antithrombin III (NP) in man. This study was mainly focused upon the pharmacokinetic properties and general tolerance of the compound. Subcutaneous injections of doses < 1.43 mg (1000 anti Xa IU) did not generate measurable anti-Xa activities. After subcutaneous injection of increasing doses from 1.43 to 22.9 mg (1000 to 16,000 anti-Xa IU) to young healthy volunteers, it was found that the maximal concentration (Cmax) and the area under curve (AUC) were linearly correlated to the dose, that the total plasma clearances (CI) were constant and almost 3 times lower than those of the current low molecular weight heparins. Cmax were reached between 1 h and 3 h after the injection and the half-lives (t 1/2) were remarkably constant (13.1 h to 13.9 h). During the first 24 h following the injection, around 50% of the total administered dose was recovered in the urine in an active form, indicating that kidney plays a major roles in the elimination of NP. Consistent with these results, when NP was administered to healthy elderly volunteers having a lower creatinine clearance, the half-life of the compound was longer and the clearance lower. At doses exceeding 22.9, Cmax, and AUC were slightly lower than expected, the percentage of the dose recovered in the urine and the total apparent plasma clearance increased, suggesting that the excess of NP unbound to antithrombin III was excreted faster. NP was also administered at various dosages once or twice a day for 7 days to 20 elderly volunteers. Due to the long half-life of the compound the "steady state" was obtained 2 to 3 days after the first injection at which the mean Cmax was increased 1.5 to 2 times. The general tolerance of the compound was excellent. No relevant prolongations of the prothrombin time, of the activated partial thromboplastin time or of the bleeding time were observed. A re-bleeding phenomenon of the bleeding time incision, probably related to friability of the haemostatic plug, occurred in 3 subjects treated with the highest dose regimens: single injection of 26.6 mg (20,000 anti-Xa IU) (young volunteers) and repeated injections of 11.4 mg (8,000 anti-Xa IU) once a day for 7 days (elderly volunteers). At these times, plasma NP concentrations were between 2.9 and 3.6 micrograms.ml-1 (2 and 2.5 anti-Xa IU.ml-1).

Adolescent↗
PubMed1994

Pharmacokinetic and antithrombotic properties of two pentasaccharides with high affinity to antithrombin III in the rabbit: comparison with CY216.

This study compares the pharmacokinetic and the antithrombotic properties of two pentasaccharides with high affinity to antithrombin III with those of a conventional low molecular weight heparin, CY216, in the rabbit. On a weight basis, SR 90107A/ORG 31540 (natural pentasaccharide [NPS]) and SR 80027A/ORG 31550 (sulfated pentasaccharide [SPS]) were, respectively, 4.7 and 26 times more potent antifactor Xa inhibitory agents than CY216. They were devoid of antithrombin activity, whereas the antifactor Xa/antithrombin ratio of CY216 was 3.8. After bolus intravenous administration, the clearance (mL/kg/h) of CY216 decreased from 91 +/- 27 for the dose of 12.5 U/kg to 49 +/- 14 for the dose of 50 U/kg and then remained constant up to the highest dose tested (500 U/kg). The clearance of NPS was unrelated to the dose and comparable to that of CY216 over 50 U/kg, whereas that of SPS was 10 times lower. Consistent results were observed after continuous intravenous infusions for 9 hours and subcutaneous administration. The duration of the antithrombotic effect was compared after a single subcutaneous injection of 250 U/kg of either compound in the stasis-Wessler model using human serum as thrombogenic stimulus. Two hours after the injection, the three compounds provided a thrombus prevention of greater than 95% and mean plasma activities of 0.8, 0.9, and 1.9 U/mL for CY216, NPS, and SPS, respectively. Twelve hours after injection, the antithrombotic effects of CY216 and NPS had totally vanished, whereas that of SPS was 68%. At that time, the plasma anti-Xa activities were less than 0.06 U/mL for CY216 and NPS, but 1.1 U/mL for SPS. For the latter compound, significant antithrombotic effects and detectable anti-Xa activities were still recorded 48 hours after the injection. The antithrombotic potency of the three compounds was also compared as their ability to inhibit the growth of a standardized venous thrombosis during 4 hours. The lowest total doses providing the maximum inhibitory effect were 3,125, 1,428, and 62 micrograms/kg for CY216, NPS, and SPS, respectively. These doses generated mean steady state antifactor Xa activities of 1.06, 1.5, and 1.2 anti-Xa U/mL, respectively. These observations indicate that the amplification mechanisms triggered by thrombin bound to fibrin and leading to the generation of new thrombin are essential to ensure venous thrombosis growth and that these mechanisms may be efficiently inhibited by pure antifactor Xa targeting agents.

Animals↗
PubMed1994

Effect of blood flow on thrombin generation is dependent on the nature of the thrombogenic surface.

We have investigated the influence of blood flow on thrombin generation, fibrin formation, and fibrin deposition on procoagulant and nonprocoagulant surfaces. Nonanticoagulated human blood was drawn for 5 minutes directly from an antecubital vein over stimulated endothelial cells expressing tissue factor and over human type III collagen fibrils, positioned in parallel-plate perfusion chambers. The shear rates at these surfaces were 50, 650, and 2,600 s-1. Deposition of platelets and fibrin was measured by morphometry. Thrombin and fibrin formation was determined by measuring prothrombin fragments 1 + 2 (F 1 + 2), thrombin-antithrombin III complexes, (T-AT) and fibrinopeptide A (FPA) in blood effluent from the perfusion chamber at the end of the 5-minute perfusion period. On procoagulant endothelial cells, the thrombi were primarily composed of fibrin. The fibrin deposition (81%, 21%, and 2% at 50, 650, and 2,600 s-1, respectively) and plasma levels of F 1 + 2, T-AT and FPA were shear rate dependent and highest at 50 s-1. There was a positive correlation between F 1 + 2 and T-AT and the fibrin deposition (P < .01). In contrast, the collagen surface triggered primarily thrombi that were composed of platelets. The platelet thrombi and plasma levels of F 1 + 2 and T-AT were also dependent on the shear rate, but highest at 650 and 2,600 s-1. F 1 + 2 and T-AT reached the same level as observed with procoagulant endothelial cells at the higher shear rates. There was a positive correlation between F 1 + 2 and T-AT and the platelet thrombus formation (P < .05), confirming the predominant role of platelets in thrombin generation. Thus, thrombin formation is strongly influenced by the blood flow, and this effect depends on the composition of the thrombogenic surface.

Antithrombins↗
PubMed1994

Increased thrombosis incidence in a family with an inherited protein S deficiency and a high oxygen affinity hemoglobin variant.

Inherited protein S deficiency and the presence of a rare high oxygen affinity hemoglobin variant: Hb Rainier [beta 145 (HC2) Tyr-->Cys] were found in a family. Among 16 studied members, nine were found as carriers of protein S deficiency (type I with decrease of total, free, and activity levels). Six subjects carried the high-affinity hemoglobin variant, which displayed an increase of blood viscosity. Four members combined both abnormalities. Three had thrombotic accidents before the age of 30. We suggest the combination of protein S deficiency and the presence of this hemoglobin variant can lead to a severe primary hypercoagulable state with pathological consequences compared to each genetic defect alone.

Adult↗