Platelet Layer Research Articles

Field-structured, multilayered platelets enable high performance, dielectric thermal composites

Moldable, thermally conductive polymer composites have broad applications as thermal interface materials and encapsulants. These thermal composites are generally comprised of single-phase particles that are randomly oriented and dispersed. Magnetic platelets have been shown to give exceptionally high thermal conductivities when magnetically aligned along the intended direction of heat flow, but produce composites that are electrically conductive. We have designed precision multilayered platelets that enable the development of high performance thermal composites that are electrically insulating. These platelets consist of a thin Ni core that permits field alignment, Al or Cu coatings that facilitate heat transport, and dielectric layers of MgF2 or SiO2 that ensure that the final composite is electrically insulating. These platelets can be made flat or corrugated, square or irregular, and the thickness of the various layers can be varied over a wide range. Thermal conductivity data for a variety of platelet compositions, layer thicknesses, and geometries demonstrate that these platelets are highly effective at producing composites with thermal conductivities much greater than that of the resin. Simulation data are presented that show that multilayer platelets have surprising dependencies of their efficiency for heat transfer on the relative thermal conductivities of the various layers. In fact, analysis shows that if the thermal conductivity of the particle phase is much greater than that of the resin, then the thermal conductivity of the composite, at fixed number density of particles, is insensitive to the platelet thickness. These electrically insulating composites would be especially useful as thermally conductive encapsulants for electronic devices.

Analysis of the surface film formed on Mg by exposure to water using a FIB cross-section and STEM–EDS

The composition and structure of the surface film formed on pure Mg exposed at the corrosion potential in pure water for 48h was investigated using a FIB cross-section and STEM–EDS. The surface film formed is duplex in nature, consisting of a thinner, more-porous, nano-crystalline MgO-rich inner layer, and a thicker, less-porous Mg(OH)2-rich outer platelet layer. The results are consistent with the theory that a chemical breakdown (hydration) of the bulk inner MgO layer (native oxide) is a necessary precursor step to the corrosion process that leads to the significant thickening of the partially protective outer Mg(OH)2 layer.

Sea ice salinity and structure: A winter time series of salinity and its distribution

We present a winter time series of Antarctic sea ice salinity from eastern McMurdo Sound, an area close to an ice shelf where a subice platelet layer forms below the sea ice late in winter. This dramatically changes the sea ice structure as the sea ice grows into the subice platelet layer. Every 2 weeks during the 5 months of sea ice formation, salinity profiles were measured, along with detailed measurements of ice structure and growth rates. Once the influence of growth rate on sea ice bulk salinity is removed, the data from 69 cores and the results of a basic parameterization demonstrate that bulk salinity for platelet ice is higher than that for columnar sea ice. We also present measurements of the salinity profile close to the ice‐water interface and use these to investigate the expected regime of fluid flow within the permeable portions of the sea ice, with particular reference to mushy layer and percolation theory. Finally, we provide a new distribution of sea ice salinity from 740 measurements, which can be interpreted as the sum of two spatial fields that we attribute to sea ice samples with and without brine channels and which should be reproduced by any realistic sea ice models. This distribution suggests that two measurements of quantities linearly linked to sea ice salinity must differ by 29% if they are to be considered different with 90% confidence.

Signatures of supercooling: McMurdo Sound platelet ice

AbstractNear ice shelves around Antarctica the ocean becomes supercooled and has been observed to carry small suspended ice crystals. Our measurements demonstrate that these small crystals are persistently present in the water column beneath the winter fast ice, and when incorporated in sea ice they reduce the mean grain size of the sea-ice cover. By midwinter, larger ice crystals below the ice/water interface are observed to form a porous sub-ice platelet layer with an ice volume fraction of 0.25 ± 0.06. The magnitude and direction of the oceanic heat flux varied between (5 ± 6) Wm-2 (upwards) and (-15 ± 10) Wm-2 (downwards) in May, but by September it settled between (-6 ± 2) and (-11 ± 2) W m-2. The negative values imply that the ocean acts as a heat sink which is responsible for the growth of 12% of the ice thickness between June and September. This oceanic contribution should not be ignored in models of Antarctic sea-ice thickness close to an ice shelf.

Impact of altered venous hemodynamic conditions on the formation of platelet layers in thromboemboli

Although it is generally believed that the structure of venous thromboemboli is a homogeneous red blood cell-fibrin clot, their structure may be heterogeneous, with non-uniformly distributed platelet layers, known as the lines of Zahn. We tested (a) whether venous thromboemboli ex vivo contained platelet layers, i.e. the lines of Zahn, and (b) whether, according to mathematical modeling, eddies can arise in the venous system, possibly contributing to platelet aggregation. The structure of venous thromboemboli ex vivo was determined by high-resolution magnetic resonance imaging (MRI) and by immunohistochemistry (IHC). High-resolution ultrasound (US) imaging was employed to determine the popliteal vein geometry and hemodynamics in healthy subjects and in subjects with previous venous thrombosis. The US data were then used as input for numerical simulations of venous hemodynamics. MRI and IHC confirmed that 42 of 49 ex vivo venous thromboemboli were structurally heterogeneous with platelet layers. The peak venous flow velocity was higher in patients with partly recanalized deep vein thrombosis than in healthy subjects in the prone position (46 ± 4 cm/s vs. 16 ± 3 cm/s). Our numerical simulation showed that partial venous obstruction with stenosis or malfunctioning venous valves creates the conditions for eddy blood flow. Our experimental results and computer simulation confirmed that the heterogeneous structure of venous thromboemboli with twisted platelet layers may be associated with eddy flow at the sites of their formation.

Chlorophyll fluorescence imaging analysis of the responses of Antarctic bottom-ice algae to light and salinity during melting

Bottom-ice algae within Antarctic sea ice were examined using chlorophyll fluorescence imaging. The detailed structure of the bottom-ice algal community growing in the platelet and congelation layers of solid pieces of sea ice was evident for the first time in chlorophyll imaging mode. Strands of fluorescence representing algal cells were clearly visible growing upward into brine channels in a fine network. Images of effective quantum yield (Ф PSII) revealed that the Ф PSII of algae embedded in the sea ice was approximately 0.5. Furthermore, Ф PSII decreased slightly with distance from the ice–water interface. The response of Antarctic sea ice algae to changes in irradiance and salinity, and the effects of slowly warming and melting the ice block sample were examined using this system. The Ф PSII of bottom-ice algae decreased as irradiance increased and salinities decreased. Bottom-ice algae appear to be most vulnerable to changes in their environment during the melting process of the ice, and this suggests that algae from this region of the ice may not be able to cope with the stress of melting during summer. Chlorophyll fluorescence imaging provides unprecedented imagery of chlorophyll distribution in sea ice and allows measurement of the responses of sea ice algae to environmental stresses with minimal disruption to their physical habitat. The results obtained with this method are comparable to those obtained with algae that have been melted into liquid culture and this indicates that previous melting protocols reveal meaningful data. In this chlorophyll imaging study, rapid light curves did not saturate and this may prevent further use of this configuration.

Stable isotope (δ13C and δ15N) composition of particulate organic matter, nutrients and dissolved organic matter during spring ice retreat at Terra Nova Bay

AbstractConcentration and isotope composition of particulate organic matter were analysed from five coastal sites on the annual fast ice and in the underlying water column at Terra Nova Bay. The highest increases of POC (< 2767 μM C) and PON (< 420 μM N) were reached in bottom ice and the unconsolidated platelet layer, linked with a large accumulation of nutrients and dissolved organic matter. Isotope POM composition in ice habitats was highly varied (δ13CPOC: -30.7 to -15.0‰, δ15NPON: 1.8–9.9‰). Constant negative δ13CPOC (> -29.3‰) and positive δ15NPON (< 9.4‰) values characterized the upper ice horizons, indicating the prevalence of aged detritus in these assemblages. By contrast, isotope composition (δ13CPOC: -15.0 to -29.7‰, δ15NPON: 1.8–9.6‰) and POC/PON ratios (6.2–12.6) changed markedly in bottom ice and interstitial water, even on short time scales, because of the combined effects of internal growth and mixing among freshly produced biomass. Sea ice breakout caused a large settling of particulates in the water column. It changed δ13CPOC (from 7.9 to 1.8‰) and δ15NPON (7.9–1.8‰) values in suspended particulate matter, indicating that inputs from fast ice strongly affect the isotopic signature of the particulate assemblage Antarctic coastal waters.

Pathogenic Hantaviruses Direct the Adherence of Quiescent Platelets to Infected Endothelial Cells

Hantavirus infections are noted for their ability to infect endothelial cells, cause acute thrombocytopenia, and trigger 2 vascular-permeability-based diseases. However, hantavirus infections are not lytic, and the mechanisms by which hantaviruses cause capillary permeability and thrombocytopenia are only partially understood. The role of beta(3) integrins in hemostasis and the inactivation of beta(3) integrin receptors by pathogenic hantaviruses suggest the involvement of hantaviruses in altered platelet and endothelial cell functions that regulate permeability. Here, we determined that pathogenic hantaviruses bind to quiescent platelets via a beta(3) integrin-dependent mechanism. This suggests that platelets may contribute to hantavirus dissemination within infected patients and provides a means by which hantavirus binding to beta(3) integrin receptors prevents platelet activation. The ability of hantaviruses to bind platelets further suggested that cell-associated hantaviruses might recruit platelets to the endothelial cell surface. Our findings indicate that Andes virus (ANDV)- or Hantaan virus (HTNV)-infected endothelial cells specifically direct the adherence of calcein-labeled platelets. In contrast, cells comparably infected with nonpathogenic Tula virus (TULV) failed to recruit platelets to the endothelial cell surface. Platelet adherence was dependent on endothelial cell beta(3) integrins and neutralized by the addition of the anti-beta(3) Fab fragment, c7E3, or specific ANDV- or HTNV-neutralizing antibodies. These findings indicate that pathogenic hantaviruses displayed on the surface of infected endothelial cells bind platelets and that a platelet layer covers the surface of infected endothelial cells. This fundamentally changes the appearance of endothelial cells and has the potential to alter cellular immune responses, platelet activation, and endothelial cell functions that affect vascular permeability. Hantavirus-directed platelet quiescence and recruitment to vast endothelial cell beds further suggests mechanisms by which hantaviruses may cause thrombocytopenia and induce hypoxia. These findings are fundamental to our understanding of pathogenic-hantavirus regulation of endothelial cell responses that contribute to vascular permeability.

Observation and modeling of platelet ice fabric in McMurdo Sound, Antarctica

During the annual growth of landfast ice in McMurdo Sound, Antarctica, an episodic flux of platelet ice crystals from the ocean contributes to the build up of a porous subice platelet layer, which is steadily incorporated into the sea ice cover as it thickens over winter. In November 2007, we examined the spatial variability of these processes by collecting sea ice cores, with simultaneous oceanographic observations, along an east‐west transect in the sound. Previously identified draped and bladed platelet ice types were observed. In addition, we identify resumed columnar growth which appears to be a result of geometric selection from the subice platelet layer after the arrival of new platelet crystals from the ocean has ceased. A numerical model of mechanical platelet ice processes is developed that predicts crystal texture and c axis distributions, producing virtual incorporated platelet ice with known growth history. This model demonstrates how a disordered subice platelet layer arises from an initially flat interface and suggests that such a layer is more likely to form later in the growth season. The model also suggests how the grain boundary density in incorporated platelet ice responds to changes in the flux of loose platelet crystals from the ocean. Application of this result to our 2007 platelet ice observations indicates that sea ice in western McMurdo Sound is subject to larger and more persistent platelet fluxes than the ice in the east. This is consistent with the pattern of in situ supercooling just beneath the ocean surface.

The presence and quantification of splenic ice in the McMurdo Sound Notothenioid fish, Pagothenia borchgrevinki (Boulenger, 1902)

Survival of some polar fishes is associated with high levels of circulating antifreeze glycoproteins (AFGPs). AFGP prevent ice growth giving rise to thermal hysteresis. The inhibiting action of AFGPs implies that polar fish contain ice to which AFGPs adsorb. Cryopelagic Pagothenia borchgrevinki, inhabiting the ice-laden waters of McMurdo Sound, Antarctica, were assayed for ice and ice was found on skin, gills, in the intestine, and in the spleen. Two methods used to assess the number of ice crystals in spleens gave comparable results (12.1 +/− 1.9 and 22 +/− 3.8 per spleen). Attempts were made to measure the rate of uptake of ice by P. borchgrevinki held in cages immediately beneath the sub-ice platelet layer in McMurdo Sound; uptake was sporadic. Introduction of ice into fish by spray freezing a small patch of the integument resulted in detection of splenic ice after 1 h, illustrating that a mechanism exists for ice transport from the periphery to the spleen. Splenic ice did not seem to be eliminated from fish held in ice-free water at − 1.6 °C for approximately two months. The relatively small number of splenic ice crystals and the slow rate of ice uptake suggest efficient ice barriers exist in P. borchgrevinki.

Modified heparins inhibit integrin αIIbβ3 mediated adhesion of melanoma cells to platelets in vitro and in vivo

The adhesion of tumor cells with platelets is important in the process of tumor metastasis. A huge work has indicated that anti-adhesion is an effective strategy for metastasis inhibition. In this article, we assess the role of platelet integrin alpha(IIb)beta(3) in adhesion of melanoma cells to platelets and the effects of heparin and modified heparins on the adhesion in vitro and in vivo. We show that platelet integrin alpha(IIb)beta(3) is involved in the interaction of human melanoma A375 cells with platelets, and the high affinity epitope resides on the alpha(IIb) subunit rather than beta(3) subunit. Heparin sulfate-like proteoglycans on tumor cell surface are implicated in the adhesion of A375 cells to integrin alpha(IIb)beta(3). We also show that RO-heparin, CR-heparin, N-2,3-DS-heparin and 2,3-O-DS-heparin can significantly inhibit A375 cells binding to the CHO cells expressing integrin alpha(IIb)beta(3) under static and flow conditions, and remarkably inhibit the adhesion of A375 cells to the immobilized platelet layers under flow conditions. We find that A375 cells and B16F10 cells are arrested in the pulmonary vessels and adhered to platelets, and the initial interaction of tumor cells with platelets in lung vessel and long-term establishment of metastatic foci can be inhibited by heparin as well as CR-heparin and N-2,3-DS-heparin. These data suggest that modified heparins can inhibit tumor cell-platelet interaction mediated by platelet integrin alpha(IIb)beta(3) and modified heparins may be a potential substitute for heparin in inhibiting tumor metastasis.

Platelet function under high shear conditions

Blood platelets are the first line of defense against bleeding and as such involved in the haemostatic repair of damaged vasculature. Their true prowess seems to be displayed under high shear conditions where platelets interact with a variety of plasma proteins, all of which are tightly regulated to close the leak but at the same time prevent lumen occlusion and thromboembolism. The first task is to arrest fast flowing platelets on exposed collagen of the damaged subendothelial surface. Although platelets are endowed with several collagen receptors, most notably integrin alpha2bbeta1 and the immunoglobulin superfamily member GPVI, they can not arrest platelets at high shear rates. The latter requires binding of the platelet receptor GPIbalpha to the A1-binding domain of von Willebrand factor (VWF), which first has to be immobilized from the flowing blood onto the site of injury. Under high shear conditions further accrual of newly arriving platelets again requires VWF, which has to bridge platelets not only to the exposed collagen but also to each other by being sandwiched between the multiple platelet layers of the haemostatic plug.

Analysis of modeling results for barrier properties in ordered nanocomposite systems

The mass transport properties of composite systems resulting from the dispersion of impermeable platelets in a permeable matrix have been discussed on the basis of the results of a numerical analysis of the problem. In particular, 2-D ordered structures with platelets oriented normally to the average mass flux in the system have been analyzed by using a CFD algorithm, based on a finite volumes method, and the increase of barrier effect is discussed as function of filler loading, platelet shape and dimensions, and arrangement of platelet layers. The numerical solutions obtained were compared with the models most commonly used for correlations of apparent permeability and a new formulation capable to predict the gas transport properties in this simplified nanocomposite geometries has been proposed, based on revision of earlier theories. This relationship correctly describes the enhancement in barrier effect for the systems analyzed for a wide range of filler loading and platelet dimensions and can be reliably used to obtain relevant information on gas permeability in real nanocomposite systems.

Discrimination between red blood cell and platelet components of blood clots by MR microscopy

Magnetic resonance imaging (MRI) of pulmonary emboli obtained ex vivo, verified by immunohistochemistry, showed that platelet layers display brighter signal intensity than areas containing predominantly red blood cells (RBC) in T1-weighted MRI. These results were surprising since platelets do not contain paramagnetic haemoglobin that would enhance magnetic relaxation. Our assumption was that the fibrin meshwork areas with entrapped RBC retain abundant extracellular space filled with serum, whereas platelets regroup into tight aggregates lacking serum, essentially mimicking solid tissue structure, rich with cellular proteins that enhance T1-relaxation. Our hypothesis was examined by MRI and NMR relaxometry of in vitro RBC suspensions and sedimented platelets, as well as by MRI of model clots and pulmonary emboli obtained ex vivo. Pure sedimented platelets exhibited shorter proton spin lattice relaxation times (T1 = 874 +/- 310 ms) than those of venous blood of a healthy male with 40% haematocrit (T1 = 1277 +/- 66 ms). T1-values of RBC samples containing high haematocrit (> or = 80%) resembled T1 of platelet samples. In T1-weighted spin-echo MRI echo time and repetition time (TE/TR = 10/120 ms) the ratio of signal intensities between a non-retracted whole blood clot (with a haematocrit of 35%) and a pure platelet clot was 3.0, and the ratio between a retracted whole blood clot with an estimated haematocrit of about 58% and a pure platelet clot was 2.6. We conclude that T1-weighted MRI can discriminate between platelet layers of thrombi and RBC-rich areas of thrombi that are not compacted to a haematocrit level of > or = 80%.

Abstract 1033: Simultaneous Clot-targeted Factor Xa Inhibition And Selective Blockade Of Activated GPIIb/IIIa On Platelets Results In Delayed But Potent Antithrombotic Effects Without Bleeding Time Prolongation.

Background: We generated phage-display-derived anti-GPIIb/IIIa single-chain antibodies (e.g. scFv SCE5) that specifically bind to the activated GPIIb/IIIa only and thus specifically block activated platelets only. ScFv SCE5 demonstrates strong antithrombotic potency, comparable to the conformation-unspecific blockers tirofiban and eptifibatide. In contrast bleeding times were not prolonged with scFv SCE5. Here we now use the possibility to add effector molecules using molecular biology methods. The highly potent anticoagulant TAP (tick anticoagulant peptide), which is a direct factor Xa (fXa) inhibitor, was used as an effector molecule. Methods and Results: We genetically fused the activation-specific scFv with TAP, expressed the constructs in E.coli and purified the 39 kDa protein via its Histag binding to Nickel beads. Specific binding of the fusion molecules MA2/SCE5-TAP and strong inhibition of fibrinogen binding was proven in flow cytometry; anti-fXa activity was demonstrated in chromogenic assays. In vivo anticoagulative efficiency was determined by Doppler-flow in a ferric chloride-induced carotid artery thrombosis model in mice. Prolongation in occlusion time with SCE5-TAP was significantly stronger compared to SCE5 alone, recombinant TAP, non-binding mut-scFv-TAP as well as the clinical used drugs enoxaparine and eptifibatide. In contrast to the other anticoagulants tested, bleeding time was not prolonged by SCE5-TAP. Flow experiments studying platelet adhesion on collagen revealed a possible mechanism for the unique finding of a fully normal bleeding time: LIBS exposure on adhering platelets and as such the anticoagulative targeting potency of SCE5-TAP was delayed until considerable layers of platelets were deposited. Conclusions: The combination of activation-specific GPIIb/IIIa blockade and fXa inhibition in one clot-targeted molecule further improves in-vivo antithrombotic efficiency without causing any bleeding time prolongation. The delay of the observed targeting effect may allow a sealing of injuries with platelet layers but may be in time for the prevention of occlusive platelet aggregates. The described blockers represent a new type of highly selective drugs that warrant further clinical development.

Inhibition of Platelet Glycoprotein Ib and Its Antithrombotic Potential

The platelet receptor glycoprotein (GP)Ib-IX-V complex plays a dominant role in the first steps of platelet adhesion and arterial thrombus formation. Through its interaction with the multimeric plasma protein von Willebrand factor (VWF), which is bound to the damaged subendothelial structures, GPIb-IX-V tethers the platelets from the flowing blood thereby slowing them down. This step is a prerequisite for the collagen receptors to participate in firm adhesion resulting in the formation of a first platelet layer which is the basis for further thrombus formation. Recently, other ligands for GPIb-IX-V besides the extensively studied VWF have been identified, such as: alpha-thrombin, coagulation factor XII (FXII), high molecular weight kininogen (HMWK), factor XI (FXI), integrin Mac-1 and P-selectin. In this review, the interaction of GPIb-IX-V with its different ligands is described and the anticipated or demonstrated in vivo effects are discussed.

Differential Kinetics and Molecular Recognition Mechanisms Involved in Early Versus Late Growth PhaseStaphylococcus aureusCell Binding to Platelet Layers under Physiological Shear Conditions

Staphylococcus aureus adhesion to platelets via microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) is a critical first step in vascular infection. The molecular mechanisms governing adhesion are influenced by the repertoire of MSCRAMMs expressed on the bacterial surface and the fluid mechanical shear rates present in the vasculature. We compared the predominant adhesion mechanisms between early and late growth phase S. aureus under physiological shear conditions. A parallel-plate flow chamber was used to quantify the adhesion of early and late growth phase S. aureus to immobilized platelet layers as a function of wall shear rate. Specifically, we evaluated the influence of clumping factor (Clf) A, ClfB, serine-aspartate repeats, fibronectin-binding proteins (Fnbps), and protein A in supporting S. aureus adhesion to platelets. The ability of the plasma proteins fibrinogen and fibronectin to act as bridging molecules was also investigated. Our results demonstrate a markedly elevated binding efficiency for late growth phase staphylococci to immobilized platelets, compared with that of the early growth phase cells in the high shear regime. During the late growth phase, fibrinogen in concert with von Willebrand factor (vWF) potentiates S. aureus-platelet binding via shear-dependent mechanisms. By contrast, fibrinogen, but not vWF, supports the adhesion of early growth phase S. aureus at the high wall shear rates. During the early growth phase, ClfA is identified as the dominant staphylococcal adhesion receptor, with Fnbps playing a supporting role. The results presented here demonstrate a differential mechanism and binding efficiency for the adhesion of early versus late growth phase S. aureus to immobilized platelets.

Improved Identification of Endothelial Erosion by Simultaneous Detection of Endothelial Cells (CD31/CD34) and Platelets (CD42b)

Loss of endothelial cells (ECs) with ensuing exposure of thrombogenic subendothelial surface is a common cause of thromboembolic complications in atherosclerotic arteries. Thus, endothelial denudation has emerged as a major contributor to the pathogenesis of atherosclerosis and its complications. Despite ongoing efforts in elucidating the pathogenesis of endothelial erosions in human atherosclerotic arteries, the mechanisms of erosion have remained enigmatic, partly due to lack of well-established methods for its identification. Here the authors point out plausible pitfalls in the current methodology and provide an improved immunohistochemical method for identifying endothelial erosion; i.e., immunofluorescence double staining with antibodies against CD42b and CD31/CD34. This method enables reliable detection of ECs and platelets in the same staining by allowing detection of "pseudoendothelium" caused by CD31 staining of a thin platelet layer covering sites of endothelial erosion. As erosion with a luminal platelet thrombus is likely to represent an in vivo erosion, and erosion without platelets an ex vivo artefact, the method makes it possible to exclude artefactual erosions resulting from sample processing. The novel immunostaining protocol presented here allows more reliable detection of endothelial erosions and so may facilitate studies on the mechanisms involved in the pathogenesis of plaque erosion and acute coronary syndromes.

Staphylococcus aureus Adhesion via Spa, ClfA, and SdrCDE to Immobilized Platelets Demonstrates Shear-Dependent Behavior

The objective of this study is to delineate the molecular mechanisms responsible for Staphylococcus aureus-platelet adhesion as a function of physiologically relevant wall shear stresses. A parallel plate flow chamber was used to quantify adhesion of wild-type, Spa-, ClfA- and SdrCDE- strains to immobilized platelet layers. In the absence of plasma, adhesion increases with increasing wall shear rate from 100 to 5000 seconds(-1). The presence of plasma significantly enhances adhesion at all shear levels. Addition of exogenous fibrinogen yields adhesion levels similar to plasma in the lower shear regimes, but has a diminishing effect on potentiating adhesion at higher shear rates. Alternatively, as shear rate increases von Willebrand factor (VWF) plays an increasingly significant role in mediating binding. Addition of plasma proteins potentiates S aureus-platelet interactions at all shear rates examined. Whereas fibrinogen plays a significant role in all shear regimes, VWF mediation becomes increasingly important as wall shear rate increases. Fibrinogen binding is dependent on bacterial adhesins ClfA and SdrCDE whereas Spa is the dominant receptor for VWF.

Turnover and fate of fibrinogen and platelets at the rabbit aorta wall immediately after a balloon de-endothelializing injury in vivo

A de-endothelializing injury to the artery wall in vivo results in a rapid procoagulant response at the surface of the exposed subendothelium. Activated tissue factor (TF)-bearing cells and hemostasis factors located at the site of injury respond by producing thrombin, and within minutes the principal thrombus-forming, blood-borne components (platelets, fibrinogen) accumulate at the site. To compare their behaviors, the rates of uptake and turnover of rabbit (51)Cr-platelets and rabbit (125)I-fibrinogen were quantified simultaneously during the initial 100-min interval after a balloon catheter injury to the rabbit aorta in vivo. Platelets ( approximately 70,000/mm(2)) and fibrin(ogen) ( approximately 2.8 pmol/cm(2)) saturated the ballooned aorta surface within five minutes after injury. Whereas the adherent platelet and fibrinogen concentrations remained steady at the aorta surface, fibrin(ogen)-related products continued to accumulate slowly in the tunica media (TM) for at least 100 minutes. A relatively small proportion (3.7%/min) of adhered platelets turned over at the ballooned aorta surface at 10 minutes, decreasing to 1.2%/min at 100 minutes. By contrast, a larger proportion of fibrin(ogen) ( approximately 20%/min) was turned over within the platelet layer at 10 minutes, decreasing to 6%/min at 100 minutes. As verified by immunostaining aorta sections and by protein analysis of TM extracts, the uptakes of platelets and fibrinogen at the site of injury contributed to an accumulation of products of platelet releasate and fibrin(ogen) degradation (FDPs) within the TM. These observations improve our understanding of the hemostatic processes and subsequent events that occur after an arterial injury in vivo.