Increased Fibrinogen Concentration Research Articles

Effects of different blood components on clot retraction analysed by measuring elasticity with a free oscillating rheometer

Free oscillation rheometry (FOR) using the ReoRox® 4 instrument makes it possible, at bedside, to study the coagulation process in blood over time and gives information on clotting time and coagulum elastic properties. In order to find out how various factors influence the FOR analysis we studied the coagulation process and change of elasticity over time in non-anticoagulated and citrated blood samples, plasma samples with various platelet concentrations (0–200 × 109/l) and blood samples with various haematocrit (0–40%). Blood samples supplemented with fibrinogen were analysed to elucidate the importance of fibrinogen on elasticity. The importance of the GPIIb/IIIa receptor on platelets was investigated by comparing the elasticity development in blood samples in presence and absence of a GPIIb/IIIa receptor inhibitor, abciximab. Anticoagulation with citrate did not have major influence on the viscoelastic properties of the coagulum. Increasing number of platelets and increasing fibrinogen concentration resulted in higher elasticity while increasing haematocrit gave lower elasticity. Blood samples with GPIIb/IIIa receptor inhibitor had very low elasticity indicating the importance of functional GPIIb/IIIa receptors. In conclusion we consider FOR to be a useful method to study the elastic properties of the coagulum. Various factors such as the number of red blood cells and platelets as well as the fibrinogen concentration should be taken into consideration when evaluating the results. The ReoRox® 4 instrument had excellent measuring range and unusually small artefactual effects on clot elasticity induced by the instrument in comparison with published results on other instruments.

The Effects of Experimental Hyperthyroidism on Hemorheology and Plasma Fibrinogen Concentration

The present study in female rats determined the effects of experimental hyperthyroidsm on hemorheological parameters and fibrinogen concentration. To induce experimental hyperthyroidism L-thyroxine (0.4 mg/100 g fodder) was added to the fodder of the experimental group rats for 20 d. After experimental duration, T3, T4, and TSH levels, plasma and blood viscosity, hematocrit, erythrocyte rigidity index, and plasma fibrinogen concentration values of both the control and the experimental group animals were determined and evaluated. In the experimental group, T3 and T4 levels were higher and TSH levels lower than that of the control rats (respectively, p < 0.01, p < 0.001, p < 0.001). Plasma viscosity and fibrinogen concentration of hyperthyroid group were found significantly higher than controls (p < 0.01). However there was no significant difference found in blood viscosity, hematocrit, and erythrocyte rigidity index between control and experimental groups. Thus, hyperthyroidism induced increased fibrinogen concentration can alter the rheological structure of blood by inducing increase in plasma viscosity.

Inhalation Of Concentrated Particulate Matter Produces Pulmonary Inflammation and Systemic Biological Effects in Compromised Rats

Although significant progress has been made over the past few years, there is still debate on the causal fractions that are responsible for particulate matter (PM)-associated adverse health effects. A series of 1-d inhalation exposures to concentrated ambient particles (CAPs) were performed in compromised rats, focusing on pulmonary inflammation and changes in blood factors as biological outcomes. Studies were carried out in the Netherlands at an urban background location in Bilthoven, an industrialized location in the city of Utrecht, as well as at a location that is heavily dominated by freeway emissions. It was hypothesized that exposure to CAPs resulted in oxidative stress in the lung, producing a release of inflammatory mediators, which in turn can result in cardiovascular effects. Both spontaneously hypertensive rats and rats preexposed to ozone were studied. The effects were studied at 2d postexposure, focusing on pathology and cell proliferation, bronchoalveolar lavage fluid (BALF) analysis (including cytokines, biochemistry, cell differentials, cell viability and proliferation, and Clara-cell 16 protein), and blood analyses (fibrinogen, Clara-cell 16 protein, Von Willebrand factor, and cell differentials). Using CAPs exposures as a binary term, mild inflammation (increased numbers of neutrophils) and increased lung permeability (protein and albumin leakage in BALF) were evident. In addition, CAPs also produced increased fibrinogen concentrations in blood of spontaneously hypertensive rats. In conclusion, inhalation up to 3700 μg /m3 CAPs in the size range of 0.15–2.5 μm did induce statistically significant effects in the lung and blood, but the effects observed may not potentially be very biologically relevant. PM mass concentrations and lung permeability were weakly associated. This suggests that other PM metrics might be more appropriate.

The Effects of Experimental Hypothyroidism on Hemorheology and Plasma Fibrinogen Concentration

Effects of hypothyroid on hemorheology of patients had widely attracted the attention of researchers during last decade. The present study has been planned with the purpose to determine the effects of experimental hypothyroidism on hemorheological parameters and fibrinogen concentration. To induce experimental hypothyroid methimazole (75 mg/100 g) was added to the fodder of an experimental group rats for 20 d. After experimental duration, plasma and blood viscosity, hematocrit (Hct), hemoglobin, erythrocyte rigidity index, and plasma fibrinogen concentration values of both the control and the experimental group animals were determined and evaluated. The serum T3 and T4 levels of the experimental group were found lower (p < 0.001) but TSH level higher (p < 0.001) than that of the control group. Plasma viscosity and fibrinogen concentration of hypothyroid group were found significantly higher than controls (p < 0.01). Hematocrit and hemoglobin values were also found lower in the experimental group than the control group animals (p < 0.01). However, there was no significant difference found in blood viscosity at the original Hct value but there was a significant increase at standard Hct value (p < 0.01). There was also no change in erythrocyte rigidity index between control and experimental groups. According to these results it may be said that in hypothyroidism, increased fibrinogen concentration may alter the rheological structure of blood by inducing increase in plasma viscosity.

Plasma fibrinogen

Fibrinogen is the major plasma protein coagulation factor. Low plasma fibrinogen concentrations are therefore associated with an increased risk of bleeding due to impaired primary and secondary haemostasis. Fibrinogen is a classical positive acute-phase reactant protein and is an independent predictor of coronary heart disease events. This review considers available methods for measurement of fibrinogen and makes recommendations as to their appropriate use. Total clottable fibrinogen assays are the definitive and reference method for plasma fibrinogen measurement. However, they are time-consuming and are rarely required in clinical practice. Clotting rate assays remain the routine method of choice for investigation, monitoring and treatment of bleeding disorders associated with low plasma fibrinogen concentrations. They are appropriately sited in haematology or haemostasis laboratories, with facilities for further relevant investigations, and expert advice from consultant haematologists on appropriate management. They have also been used in the majority of studies investigating increasing fibrinogen concentrations as a cardiovascular risk factor. Prothrombin-time derived assays are widely used, because they are less expensive and come at no extra cost with prothrombin time assays. However, their results vary widely with analysers and reagents, show discrepancies with clotting rate assays for both low and normal plasma fibrinogen samples, and at present they are not recommended by routine clinical use. Immunoassays (radial immunodiffusion, enzyme-linked immunosorbent assay or nephelometric) are useful in (a) differentiating hypofibrinogenaemia from dysfibrinogenaemia, and (b) assessing cardiovascular risk and acute-phase reactions. Unlike clottable fibrinogen assays, immunoassays can be performed in dipotassium edetate anticoagulated samples.

Nonketotic Hyperosmolar Coma Associated With Splenic Rupture in Congenital Afibrinogenemia.

Nonketotic hyperosmolar coma is uncommon in children. Splenic rupture in congenital afibrinogenemia is also a rare event. The authors described a 5-year-old girl with congenital afibrinogenemia who presented with nonketotic hyperosmolar coma associated with spontaneous splenic rupture. Management consisted of correction of the nonketotic hyperosmolar condition and increasing fibrinogen concentration by blood products, followed by splenectomy, resulting in the survival of the patient.

옥발에서 항응고물질의 정제와 특성

An anticoagulant was purified from corn silk which has been used in Oriental Medicine. The anticoagulant from corn silk has a molecular mass of 135 kDa, and purified by 24 folds with a recovery of 11%. It was not sensitive to heat and protease treatment. However, periodate oxidation of the anticoagulant resulted in loss of activity significantly, implying that a carbohydrate was responsible for an anticoagulant activity. Galactose, glucose, mannose, fucose, glucosamine, and galactosamine were detected after acid hydrolysis by thin layer chromatography (TLC) and Bio-LC. It was confirmed that anticoagulant had OH and NH bonds by IR, supporting that the anticoagulant is composed of neutrosugar and aminosugar. Its anticoagulating activity was measured by delay in thrombin time (TT) and prothrombin time (PT) without affecting clotting by snake venom and delay in activated partial thromboplastin time (APTT). TT was more sensitive than PT, and was delayed two and three times at the concentration of 60 and 88 nM, respectively. The anticoagulating activity was reduced in the thrombin-induced clotting assay using purified fibrinogen according to the increase of fibrinogen concentration with the apparent Ki value of 23 nM.

Acute haemostatic changes in accidentally traumatised dogs

Alterations of the haemostatic system were studied in 30 dogs within 24 h following natural injury. No other exclusion criteria were considered. Most dogs had bone fractures, thoracic and/or abdominal trauma. Compared to the controls, the platelet count and activities of all individual coagulation factors, inhibitors of the blood coagulation system (antithrombin, protein C) and plasminogen were significantly decreased ( P<0.01). The only exceptions were α 2-plasmin inhibitor activity, which did not differ from the control group ( P>0.05), and an increased fibrinogen concentration ( P=0.0113). Deficiencies in the coagulation system were reflected by frequent abnormal results of the screening tests. In most of the animals, the concentrations of soluble fibrin and/or fibrin(ogen) degradation products were above the reference values ( P<0.0001). The absence of a decrease in fibrinogen and α 2-plasmin inhibitor reflects their role as acute phase reactants. The results of this study indicate the high frequency of decompensated consumption of haemostatic components in acutely traumatised dogs.

Genetic regulation of fibrin structure and function: complex gene-environment interactions may modulate vascular risk

Polymorphisms in the fibrinogen and factor XIII genes are associated with atherothrombotic risk, but clinical studies have produced inconsistent results and laboratory studies have not explained these findings. We aimed to investigate interactions between polymorphisms in the factor XIII and fibrinogen genes, fibrinogen concentrations, and other cardiovascular risk factors in relation to fibrin structure and function. We used permeation analysis and electron microscopy to investigate interactions between fibrin structure, factor XIII Val34Leu, fibrinogen Aalpha Thr312Ala, fibrinogen Bbeta Arg448Lys, and fibrinogen concentrations in plasma and purified systems. Increased fibrinogen concentrations were associated with decreases in permeability, with tighter clot structures in the presence of factor XIII 34Val alleles compared with those in the presence of 34Leu alleles. Findings were confirmed by scanning electron microscopy of fibrin. Similar changes in permeability were noted for Aalpha fibrinogen 312Ala compared with that for 312Thr. Our results show interactions between coding polymorphisms in fibrinogen and factor XIII and fibrinogen concentrations that modify fibrin and explain the apparent paradox between epidemiological studies of factor XIII 34Leu and reported in-vitro effects on fibrin structure and function. We suggest a potential complexity of gene-gene and gene-environment interactions in determining cardiovascular risk.

Increased high molecular weight fibrinogen in pre-eclampsia

Introduction: The major coagulation protein fibrinogen (Fg) is a heterogeneous protein with three main fractions: high molecular weight fibrinogen (HMW-Fg), low molecular weight fibrinogen (LMW-Fg) and low molecular weight′ fibrinogen. The clottability of high molecular weight fibrinogen is highest as compared to the other fractions. Pre-eclampsia is associated with a state of hypercoagulability, and with an increase of fibrinogen concentration. The aim of the present study was to examine if the increased total fibrinogen plasma concentration in patients with pre-eclampsia is associated with a change in distribution of the main fibrinogen fractions. Material and Methods: Plasma was collected from 14 patients with pre-eclampsia and from 14 healthy pregnant matched controls. Total fibrinogen concentrations were determined according to Clauss. The percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. The study groups were compared by the Mann–Whitney U-test. Results: The median (range) total fibrinogen concentration in the pre-eclampsia group was 5.04 (3.25–6.51) g/l and in the control group 4.19 (3.61–5.38) g/l ( p<0.05). The median (range) percentage high molecular weight fibrinogen was 76.5 (69.6–84.0)% and 73.0 (69.0–78.9)% in the pre-eclampsia and control group, respectively ( p<0.05). Conclusions: In pre-eclampsia, the concentration of total fibrinogen is increased and the percentage high molecular weight fibrinogen is also slightly higher than in normal pregnancy. These results may be a reflection of the exaggerated inflammatory response, and subsequent endothelial activation, which are currently believed to be the key pathophysiological mechanisms in pre-eclampsia.

Serum amyloid A (SAA) as an aid in the management of infectious disease in the foal: comparison with total leucocyte count, neutrophil count and fibrinogen

Differentiation between infectious and noninfectious disease and rapid initiation of accurate treatment are essential in managing diseases in the neonatal and young foal. Identification of useful inflammatory markers for these purposes is, therefore, of great importance. The aim of this study was to compare the responses of the acute phase protein serum amyloid A (SAA) with the responses of fibrinogen and total leucocyte and neutrophil counts in infectious diseases encountered in the young foal, and to assess whether SAA measurements give additional information useful in the management of these diseases. In a prospective study, foals (n = 25) showing clinical signs indicative of infectious disease were blood sampled on admission and then daily or every second day during hospitalisation. The main presenting signs were neonatal weakness (n = 9), pneumonia (n = 6) and diarrhoea (n = 10). SAA and fibrinogen concentrations on admission were higher in foals with bacterial infections (n = 8) than in foals with nonbacterial or uncertain diagnoses (n = 17). On admission, weak foals with negative blood cultures (n = 3) had normal SAA and fibrinogen concentrations and varying total leucocyte and neutrophil counts. Foals with positive blood cultures (n = 2) had markedly increased SAA, decreased or increased fibrinogen concentration and leuco- and neutropenia. Those with ambiguous blood cultures (n = 3) had moderate to markedly increased SAA concentrations and normal fibrinogen concentration, leucocyte and neutrophil counts on admission. All foals with negative or ambiguous blood cultures recovered and had normal or decreasing SAA concentration on discharge. Both foals with a positive blood culture were subjected to euthanasia. One foal born with equine herpesvirus-1 infection had moderately increased SAA and normal fibrinogen concentration and leuco- and neutropenia. Foals with Rhodococcus equi pneumonia had increased concentrations of all parameters on admission. On discharge, recovered foals had normal SAA concentrations, whereas fibrinogen and total white blood cell count and neutrophil counts were still increased. There were no consistent inflammatory changes in the parameters measured in diarrhoeic foals and there was no statistical difference between rotavirus-positive (n = 4) and -negative (n = 6) foals in this respect. The results of this investigation suggest that SAA might be an aid in the differential diagnostic procedure of neonatally weak foals and in foals with diarrhoea as the main presenting clinical sign and that SAA measurements could add information in the monitoring of treatment in Rhodococcus equi pneumonia by responding more rapidly than the markers used to date.

Adsorption and surface tension of fibrinogen at the air/water interface

Static and dynamic surface tensiometry, ellipsometry, and infrared reflection absorption spectroscopy (IRRAS) were used to probe adsorption of bovine (I-S) fibrinogen (FB) at the air/water interface. Tensiometry data were obtained at 25, 37, or 60 °C and at concentrations from 7.5 to 750 ppm, in water, saline, or phosphate/saline buffer (PBS). The steady state tension decreased with concentration up to 75 ppm and then remained nearly constant at about 50±2 mN m−1. The dynamic surface tension at pulsating area conditions, at 20 or 80 rpm (cycles per min), showed interesting and complex patterns, but tension at minimum area of 38 mN m−1 or higher. Thus, if FB covers the surface, it can inhibit an essential function of effective lung surfactants, which must produce equilibrium tensions between 20 and 30 mN m−1 and minimum tensions below 10 mN m−1. Ellipsometry at 633 nm revealed that the adsorbed layers had refractive indices from 1.35 to 1.39, indicating a high water content, as expected from the non-compact molecular structure of the protein, which has dimensions 5×5×46 nm. The surface layer thicknesses ranged from 14 to 46 nm, and the surface densities ranged from 3 to 16 mg m−2, indicating that if the surface layer is a monolayer, then its average orientation increases with increasing FB concentration. The thicknesses and surface densities were slightly smaller in a PBS solution than in water, with the difference increasing with increasing concentration of FB. This can be attributed to the higher stability, or weaker intermolecular interactions, of the protein molecules in the PBS solution than in water. Unlike ellipsometry and IRRAS, which probe the whole surface layer, tensiometry provides no reliable measures of adsorption densities, probably because only a small portion of the adsorbed protein molecule affects the surface tension.

Hematologic and serum biochemical changes in Salmonella ser Typhimurium-infected calves.

To evaluate hematologic and serum biochemical changes in Salmonella ser Typhimurium-infected calves. 16 male 3- to 4-week-old dairy calves. 13 calves were experimentally infected with S Typhimurium (strains IR715 and CS401, which are derivatives of ATCC 14028), and 3 calves were uninfected controls. Several hematologic and serum biochemical parameters were measured. Hematologic changes included increases in PCV, RBC count, and hemoglobin concentration, associated with a transitory leukopenia characterized by neutropenia and lymphopenia. Biochemical findings included hypoglycemia, increased BUN, creatinine, and fibrinogen concentrations, and decreased sodium, total CO2, calcium, total protein, and albumin concentrations. Increased total bilirubin concentration associated with decreased conjugated bilirubin concentration was also observed. No significant changes in aspartate aminotransferase, gamma-glutamyltranspeptidase, alkaline phosphatase, and creatinine kinase activities were detected. Experimental salmonellosis of calves results in marked to severe dehydration, accompanied by metabolic acidosis, hypoglycemia, and an acute inflammatory response associated with increased fibrinogen concentrations and severe neutropenia immediately after inoculation.

Involvement of fibrinogen specific binding in erythrocyte aggregation

Increased fibrinogen concentration and erythrocyte aggregation are significant risk factors during various cardiovascular diseases and cerebrovascular disorders. Currently, fibrinogen-induced erythrocyte aggregation is thought to be caused by a non-specific binding mechanism. However, the published data on changes in erythrocyte aggregation during hypertension point to the possible existence of other mechanism(s). Therefore, we tested the hypothesis that specific binding of fibrinogen is involved in erythrocyte aggregation. It was found that Oregon Green 488-labeled human fibrinogen specifically binds rat erythrocyte membranes with a K d of 1.3 μM. Further experiments showed that the peptide Arg-Gly-Asp-Ser blocked both fibrinogen-induced aggregation of intact erythrocytes and specific binding of fibrinogen to the erythrocyte membranes. These results suggest that in addition to non-specific binding, a specific binding mechanism is also involved in fibrinogen-induced erythrocyte aggregation.

Alterações no líquido sinovial do joelho de cães com osteoartrite induzida pelo modelo Pond e Nuki

Avaliaram-se as alterações do líquido sinovial do joelho de 19 cães submetidos à desmotomia unilateral do cruzado cranial, baseado no modelo experimental de Pond &amp; Nuki, colhido e analisado aos 30 dias de pós-operatório. Cinco animais foram analisados novamente aos 90 dias de pós-operatório. As características analisadas foram volume, cor, aspecto, densidade, pH, proteínas, fibrinogênio, coágulo de mucina, contagem de hemácias e contagem total e diferencial de células nucleadas. O líquido sinovial apresentou padrão inflamatório que persistiu durante todo o período de observação, com efusão articular. Houve aumento na contagem de células nucleadas e na concentração de fibrinogênio aos 90 dias. A qualidade da precipitação da mucina apresentou melhora aos 90 dias quando comparada à de 30 dias, porém ainda marcadamente anormal. Foi possível concluir que até 90 dias de pós-operatório no modelo utilizado o fluído sinovial apresenta características inflamatórias e não degenerativas.

A leukocyte and erythrocyte adhesiveness/aggregation test to reveal the presence of smoldering inflammation and risk factors for atherosclerosis

The number of white blood cells in the peripheral blood, the presence of inflammation, increased fibrinogen concentrations and hyperlipidemia are established risk factors for atherosclerosis. It is known that hyperfibrinogenemia and hyperlipidemia cause increased erythrocyte aggregation, that inflammation will confer increased adhesive properties upon white blood cells and that the increased number of white blood cells can be detected in the peripheral blood. Therefore, we adopted a simple slide test and image analysis to determine the number of peripheral blood leukocytes and their state of adhesiveness/aggregation together with an erythrocyte adhesiveness/aggregation test to reveal the presence of these risk factors. The significant correlation between the fibrinogen and cholesterol concentration and the erythrocyte aggregation, between the white blood count and the number of leukocytes on the slides, and between the concentration of C-reactive protein and leukocyte adhesiveness indicate that we have succeeded in designing a simple one-step screening test that will identify patients at risk for atherosclerosis.

Chronic animal health assessment during axial ventricular assistance: importance of hemorheologic parameters.

Chronic testing of the Nimbus/UOP Axial Flow Pump was performed on 22 calves for periods of implantation ranging from 27 to 226 days (average, 74 days). The following parameters were measured: plasma free hemoglobin, blood and plasma viscosity, erythrocyte deformability and mechanical fragility, oxygen delivery index (ODI), blood cell counts, hematocrit, hemoglobin, blood urea nitrogen, creatinine, bilirubin, total protein, fibrinogen, and plasma osmolality. Most of the above parameters were stable during the full course of support. Compared with baseline, statistically significant differences during the entire period of implantation were only found in: hematocrit (p<0.001), hemoglobin (p<0.005), red blood cell (RBC) count (p<0.001), and whole blood viscosity (p<0.01). Plasma viscosity and ODI were mostly stable during the period of implantation. In some animals, an acute increase in fibrinogen concentration, plasma and blood viscosity, and a decrease in ODI were found to be early signs of the onset of infection. A small (10%) decrease in deformability of RBCs was found during the first 2 weeks after implantation. This alteration in RBC deformability was highly correlated (r = 0.793) with changes in total plasma protein concentration that fell more than 15% (p<0.001) during the same period. Mechanical fragility of RBCs was found to be slightly increased after implantation. Plasma free hemoglobin remained close to baseline level (p>0.2). After the first 2 weeks of the postoperative period, pump performing parameters for all animals were consistent and stable. In general, the Nimbus/UOP Axial Flow Pump demonstrated basic reliability and biocompatibility and did not produce significant alterations in the mechanical properties of blood or animal health status. The pump provided adequate hemodynamics and was well tolerated by the experimental animal for periods as long as 7.5 months. Monitoring rheologic parameters of blood is very helpful for evaluation of health during heart-assist device application.

Effects of fibrin micromorphology on neurite growth from dorsal root ganglia cultured in three-dimensional fibrin gels.

The effect of fibrin matrix micromorphology on neurite growth was investigated by measuring the length of neurites growing in three-dimensional fibrin gels with well characterized micromorphologies. Dorsal root ganglia (DRGs) from 7-day chick embryos were entrapped and cultured in gels made from varying concentrations of fibrinogen (5-15 mg/mL) or calcium (2-10 mM). The length of growing neurites was measured with light videomicroscopy, and the number and diameter of fibrin fiber bundles were measured from scanning electron micrographs. An increase in fibrinogen concentration caused a decrease in the average fiber bundle thickness, an increase in the number of fiber bundles, and a marked decrease in neurite length. Gels made with different calcium concentrations had a similar range of variation in fibrin fiber bundle number or diameter, but these variations had little effect on neurite and associated nonneuronal cell outgrowth. These results provide insights into the process of neurite advance within fibrin and may be useful in the design of fibrin-based materials used for peripheral nerve regeneration. Furthermore, this study provides the first detailed experimental data on the micromorphology of fibrin matrices made from more than 5 mg/mL of fibrinogen and indicates that existing kinetic models of fibrin polymerization do not accurately predict fibrin structure at these higher concentrations.

Inhibition of red cell aggregation prevents spontaneous echocardiographic contrast formation in human blood.

Spontaneous echocardiographic contrast (SEC) is a pattern of blood echogenicity that has been attributed to ultrasonic backscatter from blood cell aggregates that form under low shear conditions. Patients with left atrial SEC have an increased thromboembolic risk. This study examined the role of red cell and platelet aggregates in the pathogenesis of SEC in human blood and the effects on SEC of antithrombotic therapy and red cell disaggregatory agents. Blood echogenicity was examined with the use of quantitative videodensitometry over a controlled range of flow velocities in an in vitro model characterized by nonlaminar flow conditions. One hundred ninety study samples were prepared from single fresh blood donations (40 to 120 mL) from 24 healthy volunteers and 11 patients. Whole blood echogenicity was unaltered by depletion of platelets, stimulation of platelet aggregation with adenosine diphosphate, or inhibition of platelet aggregation with aspirin. Low flow-related echogenicity increased with increasing hematocrit (P<.001) but was abolished when red cells were lysed selectively with saponin (P<.001). In the presence of red cells, low flow-related echogenicity increased with increasing fibrinogen concentration (P<.001) and with plasma paraproteins. Low flow-related echogenicity in whole blood was unaltered by heparin and warfarin but was reduced in a dose-dependent manner by dextran 40 (40 mg/mL, 70% reduction, P<.001) and poloxamer 188 (8 mg/mL, 47% reduction, P<.001), which inhibited red cell aggregation. These results support protein-mediated red cell aggregation as the mechanism of SEC in human blood. Inhibition of red cell aggregation, indexed by resolution of SEC, may provide an alternative to anticoagulant and antiplatelet therapy to reduce cardiac thromboembolic risk.

Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral ischemia.

Recent evidence suggests that apolipoprotein E (ApoE) plays a role in neurologic disease. This experiment compared the neurologic and histologic outcome of ApoE-deficient mutant and wild-type mice subjected to a 60- or 90-minute episode of middle cerebral artery filament occlusion and a recovery interval of 24 hours. With 60 minutes of ischemia, there was no mortality. Apolipoprotein E-deficient mice had larger infarcts (cortex: ApoE deficient = 20 mm3 +/- 12, wild-type = 9 +/- 7 mm3, P = 0.03; subcortex: ApoE deficient = 22 +/- 7 mm3, wild-type = 16 +/- 7 mm3, P = 0.07). Hemiparesis was less severe in wild-type animals (P = 0.02). After 90 minutes of ischemia, mortality in ApoE-deficient mice (n = 10) was 40% versus 0% in wild-type mice (n = 10; P = 0.09). Intraparenchymal hemorrhage was found in 3 of the 4 dead mice. No difference in cortical (ApoE deficient = 37 +/- 8 mm3; wild-type = 31 +/- 18 mm3; P = 0.49) or subcortical (ApoE deficient = 30 +/- 11 mm3; wild-type = 32 +/- 18 mm3; P = 0.78) infarct volumes was present among survivors. ApoE-deficient mice had a prolonged activated partial thromboplastin time and increased fibrinogen concentration. This data supports the hypothesis that apolipoprotein E plays a role in the pathophysiology of ischemic brain damage.