Molecular Basis for Surface-Initiated Non-Thrombin-Generated Clot Formation Following Viral Infection.

In this paper, we propose a model that connects two standard inflammatory responses to viral infection, namely, elevation of fibrinogen and the lipid drop shower, to the initiation of non-thrombin-generated clot formation. In order to understand the molecular basis for the formation of non-thrombin-generated clots following viral infection, human epithelial and Madin-Darby Canine Kidney (MDCK, epithelial) cells were infected with H1N1, OC43, and adenovirus, and conditioned media was collected, which was later used to treat human umbilical vein endothelial cells and human lung microvascular endothelial cells. After direct infection or after exposure to conditioned media from infected cells, tissue surfaces of both epithelial and endothelial cells, exposed to 8 mg/mL fibrinogen, were observed to initiate fibrillogenesis in the absence of thrombin.

The Acute Effect of Chamomile Intake on Blood Coagulation Tests in Healthy Volunteers: A Randomized Trial.

Background: Chamomile administration may have desirable effects in the perioperative setting. Current practice, however, discourages perioperative chamomile use due to a theoretical increase in bleeding. Therefore, we evaluated if chamomile acutely (within 4 h of ingestion) prolongs coagulation assays.

Effect of chamomile intake on blood coagulation tests in healthy volunteers: a randomized, placebo-controlled, crossover trial.

Background: Chamomile is consumed worldwide for enjoyment and its potentially desirable properties. Widespread patient resource websites, however, discourage preoperative chamomile intake, lest bleeding could worsen. This precaution, though, stems largely from indirect evidence in one case report.

Novel characteristics of soluble fibrin: hypercoagulability and acceleration of blood sedimentation rate mediated by its generation of erythrocyte-linked fibers.

Soluble fibrin (SF) in blood consists of monomers lacking both fibrinopeptides A with a minor population in multimeric clusters. It is a substantial component of isolated fibrinogen (fg), which spontaneously self-assembles into protofibrils progressing to fibers at sub-physiologic temperatures, a process enhanced by adsorption to hydrophobic and some metal surfaces. Comparisons of SF-rich (FR) and SF-depleted (FD) fg isolates disclosed distinct molecular imprints of each via an adsorption/desorption procedure using gold surfaced silica microplates.

Fibers Generated by Plasma Des-AA Fibrin Monomers and Protofibril/Fibrinogen Clusters Bind Platelets: Clinical and Nonclinical Implications.

 Soluble fibrin (SF) is a substantial component of plasma fibrinogen (fg), but its composition, functions, and clinical relevance remain unclear. The study aimed to evaluate the molecular composition and procoagulant function(s) of SF.  Cryoprecipitable, SF-rich (FR) and cryosoluble, SF-depleted (FD) fg isolates were prepared and adsorbed on one hydrophilic and two hydrophobic surfaces and scanned by atomic force microscopy (AFM).

Clinical utilization of four-factor prothrombin complex concentrate: a retrospective single center study.

Objective: Four-factor prothrombin complex concentrate (4F-PCC) was approved by the US Food and Drug Administration in 2013 for management of severely bleeding patients on warfarin therapy. We describe use of 4F-PCC at a large, suburban academic center.

Methods: We retrospectively reviewed all patients receiving 4F-PCC from its introduction through 2016 at a large level 1 trauma center.

Randomized controlled trial of 7, 28, vs 42 day stored red blood cell transfusion on oxygen delivery (VO max) and exercise duration.

Background: Few studies have rigorously assessed the impact of red blood cell (RBC) transfusion on oxygen delivery. Several large trials demonstrated no clinical outcome differences between transfusion of shorter-storage vs prolonged-storage RBCs. These trials did not directly assess functional measures of oxygen delivery.

Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling.

Neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to brain repair during CNS disease. The microenvironment within the SVZ stem cell niche controls NSPC fate. However, extracellular factors within the niche that trigger astrogliogenesis over neurogenesis during CNS disease are unclear.

Morphometric characterization of fibrinogen's αC regions and their role in fibrin self-assembly and molecular organization.

The flexible C-terminal parts of fibrinogen's Aα chains named the αC regions have been shown to play a role in fibrin self-assembly, although many aspects of their structure and functions remain unknown. To examine the involvement of the αC regions in the early stages of fibrin formation, we used high-resolution atomic force microscopy to image fibrinogen and oligomeric fibrin. Plasma-purified full-length human fibrinogen or des-αC fibrinogen lacking most of the αC regions, untreated or treated with thrombin, was imaged.

Conformational Flexibility and Self-Association of Fibrinogen in Concentrated Solutions.

We studied the hydrodynamic behavior of fibrinogen, a blood plasma protein involved in blood clotting, in a broad 0.3-60 mg/mL range of concentration and 5-42 °C temperature using pulsed-field gradient H NMR-diffusometry. Arrhenius plots revealed the activation energy for fibrinogen diffusion E = 21.

The influence of surface chemistry on adsorbed fibrinogen conformation, orientation, fiber formation and platelet adhesion.

Unlabelled: Thrombosis is a clear risk when any foreign material is in contact with the bloodstream. Here we propose an immunohistological stain-based model for non-enzymatic clot formation that enables a facile screen for the thrombogenicity of blood-contacting materials. We exposed polymers with different surface chemistries to protease-free human fibrinogen.

Design of a molecular imprinting biosensor with multi-scale roughness for detection across a broad spectrum of biomolecules.

The molecular imprinting technique has tremendous applications in artificial enzymes, bioseparation, and sensor devices. In this study, a novel molecular imprinting (MI) biosensor platform was developed for the detection of a broad range of biomolecules with different sizes. Previously this method has been applied to 2D molecular imprinting, where the height of the self-assembled monolayer (SAM) of around 2 nm limited the maximum dimensions of the molecule that can be imprinted to create template-shaped cavities.

Thrombosis-associated antifibrinogen IgG1 κ impairs fibrin polymerization and enhances platelet activation.

The present study extends our previous investigation of circulating antibody/fibrinogen/C1q complexes (FgIgC) associated with thrombosis in a heterophenotypic AαR16C proband, by focusing on the molecular and functional characteristics of the FgIgC, isolated by cryoprecipitation, FgIgC components were demonstrated by SDS-PAGE and by rotary shadowing electron microscopy. Affinity chromatography was used to isolate IgG and fibrinogen from FgIgC. Thrombin-induced clots were examined by scanning electron microscopy and turbidity measurements.

Thromboelastographic phenotypes of fibrinogen and its variants: clinical and non-clinical implications.

Introduction: Thromboelastography (TEG), a widely used clinical point of care coagulation test, is poorly understood. To investigate its fibrin determinants we used normal and variant fibrinogen isolates.

Materials And Methods: We focused mainly on the TEG maximum signal amplitude (MA), a shear modulus and clot stiffness indicator.

Soluble gC1qR is an autocrine signal that induces B1R expression on endothelial cells.

Bradykinin (BK) is one of the most potent vasodilator agonists known and belongs to the kinin family of proinflammatory peptides. BK induces its activity via two G protein-coupled receptors: BK receptor 1 (B1R) and BK receptor 2. Although BK receptor 2 is constitutively expressed on endothelial cells (ECs), B1R is induced by IL-1β.

Control of anti-thrombogenic properties: surface-induced self-assembly of fibrinogen fibers.

Wound healing is a complex process initiated by the formation of fibrin fibers and endothelialization. Normally, this process is triggered in a wound by thrombin cleavage of fibrinopeptides on fibrinogen molecules, which allows them to self spontaneously-assemble into large fibers that provide the support structure of the clot and promote healing. We have found that the fibrous structures can also form without thrombin on most polymer or metal surfaces, including those commonly used for stents.

Thrombotic thrombocytopenic purpura and its look-alikes: a single institution experience.

At presentation, variant or "look-alike" conditions can resemble TTP. We reviewed charts of 26 consecutive patients treated for presumed TTP. Of 15 classic TTP patients, 11 were tested for ADAMTS13; all showed severe deficiency, and inhibitor levels correlated with probability of relapse.

Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGF-beta after vascular damage.

Scar formation in the nervous system begins within hours after traumatic injury and is characterized primarily by reactive astrocytes depositing proteoglycans that inhibit regeneration. A fundamental question in CNS repair has been the identity of the initial molecular mediator that triggers glial scar formation. Here we show that the blood protein fibrinogen, which leaks into the CNS immediately after blood-brain barrier (BBB) disruption or vascular damage, serves as an early signal for the induction of glial scar formation via the TGF-beta/Smad signaling pathway.

Decreased plasmin resistance by clots of a homophenotypic Aalpha R 16H fibrinogen (Kingsport, slower fibrinopeptide A than fibrinopeptide B release).

Reported evidence of a role in fibrinolysis by fibrinopeptide (Fp)B-dependent intermolecular fibrin polymerization contacts and of reversed FpA/FpB release sequence from fibrinogen Kingsport led us to investigate the fibrinolytic properties of Kingsport clots. Clot lysis was induced by either plasmin (pH 7.4) or by a mixture of plasminogen and recombinant tissue plasminogen activator and measured by lysis time and by turbidity (350 nm) time course.

Inherited dysfibrinogenemia: clinical phenotypes associated with five different fibrinogen structure defects.

Hereditary dysfibrinogenemia is a rare clotting disorder, which results from mutations in at least one of the three fibrinogen genes. We examined the frequency of hemostatic clinical and laboratory anomalies at presentation of 37 probands from 12 unrelated families with five different defects (Aalpha R16C, gamma A357T, gamma318-319 del, gamma M310T, and Aalpha R16S), among. The median age was 51 years (11-86 years).

Treatment of patients with dysfibrinogenemia and a history of abortions during pregnancy.

Dysfibrinogenemia is caused by a variety of structural abnormalities in the fibrinogen molecule, which results in a tendency for bleeding and thrombosis as well as obstetric complications. The obstetric complications of dysfibrinogenemia include first-trimester pregnancy loss, hemorrhage, placental abruption, and thrombosis. We conducted a retrospective study of four cases of dysfibrinogenemic patients from one family (fibrinogen Frankfurt III) with a history of recurrent pregnancy loss and who were treated with fibrinogen concentrates.

Homophenotypic Aalpha R16H fibrinogen (Kingsport): uniquely altered polymerization associated with slower fibrinopeptide A than fibrinopeptide B release.

We detail for the first time the uniquely altered fibrin polymerization of homophenotypic Aalpha R16H dysfibrinogen. By polymerase chain reaction amplification and DNA sequencing, our new proposita's genotype consisted of a G>A transition encoding for Aalpha R16H, and an 11 kb Aalpha gene deletion. High-performance liquid chromatography disclosed fibrinopeptide A release approximately six times slower than its fibrinopeptide B.

Polymerization of fibrin: Direct observation and quantification of individual B:b knob-hole interactions.

The polymerization of fibrin occurs primarily through interactions between N-terminal A- and B-knobs, which are exposed by the cleavage of fibrinopeptides A and B, respectively, and between corresponding a- and b-holes in the gamma- and beta-modules. Of the potential knob-hole interactions--A:a, B:b, A:b, and B:a--the first has been shown to be critical for fibrin formation, but the roles of the others have remained elusive. Using laser tweezers-based force spectroscopy, we observed and quantified individual B:b and A:b interactions.