PubMed · 14874369
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1951. [Thrombin cycle].. https://pubmed.ncbi.nlm.nih.gov/14874369/
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The aim of this study was to investigate whole blood coagulation on low blood plasma protein adsorbing surfaces. For this purpose, the polycationic graft copolymer poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), PLL-g-PEG grafted with a cell adhesive peptide containing the amino acid sequence -Arg-Gly-Asp- (RGD), and PLL-g-PEG with a control peptide -Arg-Asp-Gly- (RDG) were adsorbed onto titanium (oxide), forming stable monomolecular adlayers through electrostatic attraction. Free oscillation rheometry and complementary techniques were used to measure the coagulation time (CT) and other interactions of the surfaces with native whole blood, recalcified platelet-rich plasma (PRP), and recalcified citrated platelet-free plasma (PFP). The results show that the uncoated titanium surfaces (reference) activated platelets and quickly triggered the coagulation cascade via the intrinsic pathway, whereas the PLL-g-PEG surfaces displayed a prolonged CT, approximately 2-3 times longer compared to uncoated titanium. We hypothesise that blood coagulates outside the vascular system independent of low protein adsorption to or activation by surfaces, due to the absence of an active down-regulation of procoagulative processes by the vascular endothelium.
Fibrinogen-420 is a minor subclass of human fibrinogen that is so named because of its higher molecular weight compared to fibrinogen-340, the predominant form of circulating fibrinogen. Each of the two Aalpha chains of fibrinogen-340 is replaced in fibrinogen-420 by an Aalpha isoform termed alphaE. Such chains contain a globular C-terminal extension, alphaEC, that is homologous with the C-terminal regions of Bbeta and gamma chains in the fibrin D domain. The alphaEC domain lacks a functional fibrin polymerization pocket like those found in the D domain, but it does contain a binding site for beta2 integrins. Electron microscopy of fibrinogen-340 molecules showed the major core fibrinogen domains, D-E-D, plus globular portions of the C-terminal alphaC domains. Fibrinogen-420 molecules had two additional globular domains that were attributable to alphaEC. Turbidity measurements of thrombin-cleaved fibrinogen-420 revealed a reduced rate of fibrin polymerization and a lower maximum turbidity. Thromboelastographic measurements also showed a reduced rate of fibrin-420 polymerization (amplitude development) compared with fibrin-340. Nevertheless, the final amplitude (MA) and the calculated elastic modulus (G) for fibrin-420 were greater than those for fibrin-340. These results suggested a greater degree of fibrin-420 branching and thinner matrix fibers, and such structures were found in SEM images. In addition, fibrin-420 fibers were irregular and often showed nodular structures protruding from the fiber surface. These nodularities represented alphaEC domains, and possibly alphaC domains as well. TEM images of negatively shadowed fibrin-420 networks showed irregular fiber borders, but the fibers possessed the same 22.5-nm periodicity that characterizes all fibrin fibers. From this result, we conclude that fibrin-420 fiber assembly occurs through the same D-E interactions that drive the assembly of all fibrin fibrils, and therefore that the staggered overlapping molecular packing arrangement is the same in both types of fibrin. The alphaEC domains are arrayed on fiber surfaces, and in this location, they would very likely slow lateral fibril association, causing thinner, more branched fibers to form. However, their location on the fiber surface would facilitate cellular interactions through the integrin receptor binding site.
BACKGROUND AND PURPOSE: Recently, 3 clinical trials revealed encouraging results in recanalization and clinical outcome in acute stroke patients when 2-MHz transcranial Doppler monitoring was applied. This study investigated whether a 1.8-MHz commercial diagnostic ultrasound device has the potential to facilitate thrombolysis using an in vitro stroke model. METHODS: Duplex-Doppler, continuous wave-Doppler, and pulsed wave (PW)-Doppler were compared on their impact on recombinant tissue plasminogen activator (rtPA)-mediated thrombolysis. Blood clots were transtemporally sonicated in a human stroke model. Furthermore, ultrasound attenuation of 5 temporal bones of different thickness was determined. RESULTS: In comparison, only PW-Doppler accelerated rtPA-mediated thrombolysis significantly. Without temporal bone, PW-Doppler plus rtPA showed a significant enhancement in relative clot weight loss of 23.7% when compared with clots treated with rtPA only (33.9+/-5.5% versus 27.4+/-5.2%; P<0.0005). Ultrasound attenuation measurements revealed decreases of the output intensity of 86.8% (8.8 dB) up to 99.2% (21.2 dB), depending on temporal bone thickness (1.91 to 5.01 mm). CONCLUSIONS: Without temporal bone, PW-Doppler significantly enhanced thrombolysis. However, because of a high attenuation of ultrasound by temporal bone, no thrombolytic effect was observed in our in vitro model, although Doppler imaging through the same temporal bone was still possible.