fibrin and Wounds-and-Injuries

Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. After injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure one or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays have revealed that platelet dysfunction is strongly associated with poor clinical outcomes. However, to date, the mechanism(s) causing clinically significant platelet dysfunction remain poorly understood. We review the pros, cons, and evidence for use of many of the popular assays in trauma, discuss limitations of their use in this patient population, and present approaches that can be taken to develop improved functional assays capable of elucidating mechanisms of trauma-induced platelet dysfunction. Platelet dysfunction in trauma has been associated with need for transfusions and mortality; however, most of the current platelet function assays were not designed for evaluating trauma patients, and there are limited data regarding their use in this population. New or improved functional assays will help define the mechanisms by which platelet dysfunction occurs, as well as help optimize future treatment.

Topics: Blood Platelets; Fibrin; Hemostasis; Humans; Platelet Aggregation; Platelet Function Tests; Thrombosis; Wounds and Injuries

Plasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential role in fibrinolysis. To date, therapeutic targeting of the fibrinolytic system has been for 2 purposes: to promote plasmin generation for thromboembolic conditions or to stop plasmin to reduce bleeding. However, plasmin and plasminogen serve other important functions, some of which are unrelated to fibrin removal. Indeed, for >40 years, the antifibrinolytic agent tranexamic acid has been administered for its serendipitously discovered skin-whitening properties. Plasmin also plays an important role in the removal of misfolded/aggregated proteins and can trigger other enzymatic cascades, including complement. In addition, plasminogen, via binding to one of its dozen cell surface receptors, can modulate cell behavior and further influence immune and inflammatory processes. Plasminogen administration itself has been reported to improve thrombolysis and to accelerate wound repair. Although many of these more recent findings have been derived from in vitro or animal studies, the use of antifibrinolytic agents to reduce bleeding in humans has revealed additional clinically relevant consequences, particularly in relation to reducing infection risk that is independent of its hemostatic effects. The finding that many viruses harness the host plasminogen to aid infectivity has suggested that antifibrinolytic agents may have antiviral benefits. Here, we review the broadening role of the plasminogen-activating system in physiology and pathophysiology and how manipulation of this system may be harnessed for benefits unrelated to its conventional application in thrombosis and hemostasis.

Topics: Animals; Antifibrinolytic Agents; Brain; Conjunctivitis; Enzyme Activation; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; Immunity; Infections; Inflammation; Mice; Plasminogen; Radiodermatitis; Receptors, Cell Surface; Skin Diseases, Genetic; Thrombosis; Tranexamic Acid; Wound Healing; Wounds and Injuries

Monitoring chronic wound [CW] healing is a challenging issue for clinicians across the world. Moreover, the health and cost burden of CW are escalating at a disturbing rate due to a global rise in population of elderly and diabetic cases. The conventional approach includes visual contour, sketches, or more rarely tracings. However, such conventional techniques bring forth infection, pain, allergies. Furthermore, these methods are subjective as well as time-consuming. As such, nowadays, non-touching and non-invasive CW monitoring system based on imaging techniques are gaining importance. They not only reduce patients' discomfort but also provide rapid wound diagnosis and prognosis. This review provides a survey of different types of CW characteristics, their healing mechanism and the multimodal non-invasive imaging methods that have been used for their diagnosis and prognosis. Current clinical practices as well as personal health systems [m-health and e-health] for CW monitoring have been discussed.

Topics: Chronic Disease; Diagnostic Imaging; Fibrin; Fibronectins; Humans; Inflammation Mediators; Microscopy, Confocal; Optical Imaging; Prognosis; Severity of Illness Index; Spectrum Analysis; Tomography, X-Ray Computed; Ultrasonography; Wound Healing; Wounds and Injuries

As our knowledge of the structure and functions of fibrinogen and fibrin has increased tremendously, several key findings have given some people a superficial impression that the biological and clinical significance of these clotting proteins may be less than earlier thought. Most strikingly, studies of fibrinogen knockout mice demonstrated that many of these mice survive to weaning and beyond, suggesting that fibrin(ogen) may not be entirely necessary. Humans with afibrinogenemia also survive. Furthermore, in recent years, the major emphasis in the treatment of arterial thrombosis has been on inhibition of platelets, rather than fibrin. In contrast to the initially apparent conclusions from these results, it has become increasingly clear that fibrin is essential for hemostasis; is a key factor in thrombosis; and plays an important biological role in infection, inflammation, immunology, and wound healing. In addition, fibrinogen replacement therapy has become a preferred, major treatment for severe bleeding in trauma and surgery. Finally, fibrin is a unique biomaterial and is used as a sealant or glue, a matrix for cells, a scaffold for tissue engineering, and a carrier and/or a vector for targeted drug delivery.

Topics: Animals; Fibrin; Fibrinogen; Hemorrhage; Hemostasis; Humans; Infections; Inflammation; Mice; Mice, Knockout; Wound Healing; Wounds and Injuries

Coagulation is a complex cascade whose intact functioning is essential in helping control hemorrhage after injury. While traditionally ascribed to the combined effects of acidosis, hypothermia, factor consumption and factor dilution, coagulopathy is also directly related to injury as well as hypofibrinogenemia and hyperfibrinolysis. Low fibrinogen concentration is readily determined with standard laboratory profiling, but direct analysis of hyperfibrinolysis relies on either thromboelastography or rotational thromboelastometry. Both conditions offer opportunities for therapeutic intervention, and inhibition or abrogation of hyperfibrinolysis in particular may significantly improve survival in patients with injury and massive hemorrhage. Herein, we explore the underpinnings of trauma associated coagulopathy, the basic science behind the role of fibrinogen in acute traumatic coagulopathy, and the rationale behind and the data derived from management of hypofibrinogenemia as well as hyperfibrinolysis.

Topics: Afibrinogenemia; Animals; Antifibrinolytic Agents; Blood Component Transfusion; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Hemostasis; Hemostatic Techniques; Humans; Multicenter Studies as Topic; Plasma; Randomized Controlled Trials as Topic; Tranexamic Acid; Wounds and Injuries

Having shown that intra-dermal injection of fibroblasts decreases the effect of radiation on healing of superficial wounds, we now test the effect of fibroblasts and syngeneic marrow stromal cells on irradiated deep and superficial wounds.. Wistar rats received bilateral buttock irradiation followed by partial excision of the gluteus muscle bilaterally. In Protocol 1, one irradiated wound was treated with 1.2 x 10(7) autologous cells injected intra-dermally. In Protocol 2, the experimental side was treated with a fibrin and autologous cell implant (1.2 x 10(7) cells). Twenty-one days later, wound mechanical characteristics were tested. In Protocol 3, the effect of pooled marrow stromal cells on healing of superficial irradiated wounds in Lewis rats was similarly tested.. The fibrin-fibroblast implant (Protocol 2) had no effect on wound mechanics. Superficial injection of fibroblasts (Protocol 1) significantly improved wound breaking strength when compared to the control group (mean +/- SEM, breaking strength: treated 504.6 +/- 37.0 g vs. control 353.4 +/- 35.2 g, P = 0.005). The dermal injection of marrow stromal cells also resulted in marked increases in breaking strength (mean +/- SEM, breaking strength: treated 338.5 +/- 39.9 g vs. control 187.1 +/- 12.0 g, P < 0.01). In both Protocols 1 and 3, ultimate tensile strength and toughness were increased in the side receiving cell transplantation.. Cell implantation holds promise for decreasing the effect of radiation on healing of irradiated wounds.

Topics: Animals; Bone Marrow Cells; Cell Transplantation; Fibrin; Fibroblasts; Injections, Intradermal; Rats; Rats, Inbred Lew; Rats, Wistar; Stromal Cells; Tensile Strength; Wound Healing; Wounds and Injuries

Fibroblast accumulation in a cutaneous wound requires phenotypic modulation of fibroblasts. In response to injury, resident fibroblasts in the surrounding tissue proliferate for the first 3 days and then at day 4 migrate into the wounded site. Once within the wound, they produce type I procollagen as well as other matrix molecules and deposit these extracellular matrix molecules in the local milieu. By day 7, abundant extracellular matrix has accumulated and fibroblasts switch to a myofibroblast phenotype replete with actin bundles along the cytoplasmic face of the plasma membrane. Wound contraction occurs as these myofibroblast gather in the wound extracellular matrix by extending pseudopodia, attaching to extracellular matrix molecules, such as fibronectin and collagen, then retracting the pseudopodia. Once these processes have been accomplished, the fibroblasts appear to undergo apoptosis. Therefore, during cutaneous wound repair, fibroblasts appear to progress through four phenotypes: first proliferating, second migrating, third synthesizing extracellular matrix molecules, and fourth expressing thick actin bundles as myofibroblasts.

Topics: Animals; Cell Division; Extracellular Matrix; Fibrin; Fibroblasts; Humans; Platelet-Derived Growth Factor; Skin; Transforming Growth Factor beta; Wound Healing; Wounds and Injuries

Recent experimental studies using wound chambers (silicone tubes) sutured to the transected rat sciatic nerve or thigh muscle have shown an accumulation of plasma-containing fluid and the formation of a fibrin/fibronectin clot within the chambers during the early phase. The plasma proteins leaked into the wound due to increased vascular permeability caused by the trauma. The fibrin/fibronectin clot in concert with neurotrophic factors play a key role in the promotion of growth and migration of endothelial cells, Schwann cells and axons during the early phase. Cessation of cell growth and migration coincided with removal of fibrin through fibrinolysis and collagen deposition in the extracellular space. The appearance of extracellular matrix was closely related to the morphological event of differentiation and formation of open capillaries and nerve fascicles. These findings suggest that in addition to hemostasis, fibrin polymerization (thrombosis) and fibrinolysis play vital pathophysiological roles in angiogenesis, nerve regeneration and other aspects of wound healing. These studies emphasize the importance of integrating information from many areas of research in order to understand some of the basic principles in Biology and Medicine.

Topics: Animals; Blood Proteins; Fibrin; Neovascularization, Pathologic; Nerve Regeneration; Sciatic Nerve; Wound Healing; Wounds and Injuries

Topics: Arthritis, Rheumatoid; Connective Tissue; Fibrin; Humans; Necrosis; Rheumatoid Factor; Rheumatoid Nodule; Synovitis; Wounds and Injuries

Topics: Blood Coagulation; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysis; Hemostasis; Humans; Platelet Adhesiveness; Platelet Aggregation; Stress, Physiological; Wounds and Injuries

Topics: Arthritis, Rheumatoid; Binding Sites; Cell Transformation, Neoplastic; Collagen; Disseminated Intravascular Coagulation; Fibrin; Fibronectins; Humans; Molecular Weight; Opsonin Proteins; Sepsis; Surgical Procedures, Operative; Wounds and Injuries

There are many reports in the literature of blood test abnormalities occurring in patients with venous or arterial thrombosis. Most of these have not used acceptable criteria for establishing an association between thrombosis and blood tests and, therefore, their interpretation is questionable. Recently, sensitive and specific assays have been developed for the detection of products of intravascular thrombin formation, of plasmin digests of fibrin or fibrinogen and of platelet specific proteins that are released into the plasma when platelets react with stimuli. Blood abnormalities have been sought that can either predict or detect venous thrombosis. Many of the predictive tests evaluated are nonspecific acute phase reactant responses to inflammation; of these, only reduced fibrinolytic activity has been consistently reported to be associated with postoperative venous thrombosis. Hereditary antithrombin III deficiency has been consistently shown to predispose patients to venous thrombosis. Abnormalities of the plasminogen and fibrinogen molecule have also been described in patients with familial or recurrent venous thrombosis but these are rare and the association could be coincidental. Two blood tests, the fibrinopeptide A assay and the assay for fibrin/fibrinogen fragment E are highly sensitive to acute venous thromboembolism in symptomatic patients but both are nonspecific. Elevated levels of beta thromboglobulin and platelet factor 4 have been reported in patients with arterial thromboembolism but the sensitivity and specificity of these findings is presently unknown.

Topics: Antithrombin III; Arteries; Blood Coagulation Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Inflammation; Platelet Adhesiveness; Platelet Aggregation; Risk; Thrombin; Thromboembolism; Thrombophlebitis; Thrombosis; Wounds and Injuries

Topics: Animals; Antifibrinolytic Agents; Autopsy; Blood Coagulation Factors; Dogs; Fibrin; Fibrinolysis; Fibrinolytic Agents; Heart Failure; Humans; Hypoxia; Kidney; Lung; Lymph; Plasminogen Activators; Plasminogen Inactivators; Prostaglandins; Pulmonary Embolism; Pulmonary Veins; Respiration; Respiratory Insufficiency; Syndrome; Thrombin; Wounds and Injuries

Topics: Anti-Bacterial Agents; Ascorbic Acid; Collagen; Cross Infection; Debridement; Diet; Fibrin; Granulation Tissue; Humans; Surgical Instruments; Surgical Wound Dehiscence; Surgical Wound Infection; Sutures; Tissue Adhesives; Wound Healing; Wounds and Injuries; Zinc

Topics: Age Factors; Animals; Avitaminosis; Biomechanical Phenomena; Cats; Cicatrix; Collagen; Connective Tissue; Dehydration; Fibrin; Granulation Tissue; Hormones; Humans; Liver Diseases; Oxygen; Protein Deficiency; Radiation Effects; Rats; Tissue Extracts; Wound Healing; Wounds and Injuries

Topics: Alpha-Globulins; Animals; Basal Metabolism; Blood Proteins; Burns; Carbon Isotopes; Dogs; Environmental Exposure; Fibrin; Fibrinogen; Fractures, Bone; gamma-Globulins; Humans; Iodine Isotopes; Nitrogen; Nitrogen Isotopes; Paralysis; Postoperative Complications; Proteins; Rats; Serum Albumin; Serum Albumin, Radio-Iodinated; Temperature; Wounds and Injuries

Topics: Adenine Nucleotides; Animals; Anticoagulants; Blood Circulation; Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Collagen; Diet; Endotoxins; Fibrin; Fibrinolytic Agents; Humans; Leukocytes; Microscopy, Electron; Myocardial Infarction; Oral Hemorrhage; Platelet Adhesiveness; Thromboembolism; Thrombosis; Wounds and Injuries

Topics: Anemia; Animals; Ascorbic Acid; Biomechanical Phenomena; Cicatrix; Collagen; Denervation; Fibrin; Fibroblasts; Glucocorticoids; Glycoproteins; Glycosaminoglycans; Granulation Tissue; Guinea Pigs; Histamine; Humans; Lathyrism; Microbial Collagenase; Oxygen; Rabbits; Rats; Species Specificity; Stress, Physiological; Time Factors; Wound Healing; Wounds and Injuries

Topics: Blood Platelets; Capillaries; Cardiovascular System; Fibrin; Hemostasis; Humans; Physiology; Research; Wounds and Injuries

Volumetric muscle loss (VML) is traumatic or surgical loss of skeletal muscle with resultant functional impairment. Skeletal muscle's innate capacity for regeneration is lost with VML due to a critical loss of stem cells, extracellular matrix, and neuromuscular junctions. Consequences of VML include permanent disability or delayed amputations of the affected limb. Currently, a successful clinical therapy has not been identified. Mesenchymal stem cells (MSCs) possess regenerative and immunomodulatory properties and their three-dimensional aggregation can further enhance therapeutic efficacy. In this study, MSC aggregation into spheroids was optimized in vitro based on cellular viability, spheroid size, and trophic factor secretion. The regenerative potential of the optimized MSC spheroid therapy was then investigated in a murine model of VML injury. Experimental groups included an untreated VML injury control, intramuscular injection of MSC spheroids, and MSC spheroids encapsulated in a fibrin-laminin hydrogel. Compared to the untreated VML group, the spheroid encapsulating hydrogel group enhanced myogenic marker (i.e., MyoD and myogenin) protein expression, improved muscle mass, increased presence of centrally nucleated myofibers as well as small fibers (<500 μm

Topics: Animals; Cells, Immobilized; Fibrin; Hydrogels; Laminin; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Muscle, Skeletal; Regeneration; Spheroids, Cellular; Wounds and Injuries

Both hyperfibrinolysis and fibrinolysis shutdown can occur after severe trauma. The subgroup of trauma patients with fibrinolysis shutdown resistant to tissue plasminogen activator (t-PA)-mediated fibrinolysis have increased mortality. Fibrin polymerization and structure may influence fibrinolysis subgroups in trauma, but fibrin architecture has not been characterized in acutely injured subjects. We hypothesized that fibrin polymerization measured in situ will correlate with fibrinolysis subgroups.. Blood samples were collected from trauma patients and noninjured controls. We selected samples across a range of fibrinolysis phenotypes (shutdown, physiologic, hyperfibrinolysis) and t-PA sensitivities (sensitive, physiologic, resistant) determined by thrombelastography. Plasma clots were created in situ with fluorescent fibrinogen and imaged using confocal microscopy for analysis of clot architecture in three dimensions. For each clot, we quantified the fiber resolvability, a metric of fiber distinctness or clarity, by mapping the variance of fluorescence intensity relative to background fluorescence. We also determined clot porosity by measuring the size and distribution of the gaps between fibrin fibers in three-dimensional space. We compared these measures across fibrinolysis subgroups.. Fiber resolvability was significantly lower in all trauma subgroups compared with controls (n = 35 and 5, respectively; p < 0.05). We observed markedly different patterns of fibrin architecture among trauma patients stratified by fibrinolysis subgroup. Subjects with t-PA-resistant fibrinolysis shutdown exhibited abnormal, densely packed fibrin clots nearly devoid of pores. Individuals with t-PA-hypersensitive fibrinolysis shutdown had highly irregular clots with pores as large as 2500 μm to 20,000 μm, versus 78 μm to 1250 μm in noninjured controls.. Fiber resolvability was significantly lower in trauma patients than controls, and subgroups of fibrinolysis differ in the porosity of the fibrin clot structure. The dense fibrin network in the t-PA-resistant group may prevent access to plasmin, suggesting a mechanism for thrombotic morbidity after injury.

Topics: Adult; Biomarkers; Blood Coagulation Disorders; Female; Fibrin; Fibrinolysis; Humans; Injury Severity Score; Male; Middle Aged; Polymerization; Retrospective Studies; Thrombelastography; Tissue Plasminogen Activator; Wounds and Injuries; Young Adult

Topics: Antifibrinolytic Agents; Blood Coagulation; Fibrin; Fibrinolysin; Fibrinolysis; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Time Factors; Tranexamic Acid; Wounds and Injuries

Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.

Topics: alpha 1-Antitrypsin; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Disorders; Computer Simulation; Fibrin; Fibrin Clot Lysis Time; Fibrinolysin; Fibrinolysis; Hemorrhage; Humans; Membrane Proteins; Mortality; Pregnancy-Associated alpha 2-Macroglobulins; Thrombin; Tranexamic Acid; Urokinase-Type Plasminogen Activator; Wounds and Injuries

Introduction: The article presents data from literary sources and a statistical analysis of one's own research on the nature, mechanism and prescription of spleen injury in the case of mechanical trauma and the absence of alcohol intoxication. The aim: To study the dynamics of changes in the histological parameters of the spleen injured tissues in case of mechanical trauma depending on the prescription of injury.. Materials and methods: The material of the study was the spleen tissue of 56 males and females aged from 20-60 who died at known and unknown time in the presence and absence of alcohol in the blood. We used histological, histochemical methods, and carried out a statistical analysis of the results.. Results: The obtained results showed that during the mechanical injury of spleen there often developed a capsule and a parenchyma with hematoma in the area of injury. Our records showed that during the first 6 hours after injury, there appeared a hematoma in the center of the injury. Hemolysis of the erythrocyte particles was observed in the center of the hematoma. There were isolated leukocytes and fibrin tissues closer to the edge of the hematoma.. Conclusions: The obtained results indicate that there are several histological changes in the damaged spleen tissues area which directly depend on the time which passed from the moment of injury.

Topics: Adult; Female; Fibrin; Forensic Medicine; Hematoma; Histological Techniques; Humans; Leukocytes; Male; Middle Aged; Spleen; Wounds and Injuries; Young Adult

Extensive studies have detailed the molecular regulation of individual components of the hemostatic system, including platelets, coagulation factors, and regulatory proteins. Questions remain, however, about how these elements are integrated at the systems level within a rapidly changing physical environment. To answer some of these questions, we developed a puncture injury model in mouse jugular veins that combines high-resolution, multimodal imaging with functional readouts in vivo. The results reveal striking spatial regulation of platelet activation and fibrin formation that could not be inferred from studies performed ex vivo. As in the microcirculation, where previous studies have been performed, gradients of platelet activation are readily apparent, as is an asymmetrical distribution of fibrin deposition and thrombin activity. Both are oriented from the outer to the inner surface of the damaged vessel wall, with a greater extent of platelet activation and fibrin accumulation on the outside than the inside. Further, we show that the importance of P2Y

Topics: Animals; Blood Coagulation; Blood Platelets; Disease Models, Animal; Fibrin; Hemostasis; Male; Mice; Platelet Activation; Platelet Aggregation Inhibitors; Thrombosis; Veins; Wounds and Injuries

Prothrombotic clot phenotype may characterize patients developing deep vein thrombosis (DVT) despite pharmacological thromboprophylaxis. We studied the role of fibrin clot properties and its potential determinants in individuals who experienced DVT after lower limb injury.. In a case-control study, we assessed 50 patients who developed DVT despite prophylactic use of low-molecular-weight heparins (the failed thromboprophylaxis group) after a lower limb injury, and three age- and sex-matched control groups, 50 patients each: (1) patients with trauma-related DVT without prior thromboprophylaxis; (2) individuals with unprovoked DVT; (3) patients without history of DVT (the no-DVT controls). Fibrin clot properties, along with thrombin concentration and α. Patients who experienced DVT despite thromboprophylaxis following lower limb trauma display a strongly prothrombotic fibrin clot phenotype, including increased clot density and hypofibrinolysis associated with higher plasma α

Topics: Adult; alpha-2-Antiplasmin; Anticoagulants; Blood Coagulation; Case-Control Studies; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Genotype; Heparin, Low-Molecular-Weight; Humans; Lower Extremity; Male; Middle Aged; Odds Ratio; Permeability; Phenotype; Poland; Thrombin; Thrombosis; Ultrasonography, Doppler; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries

Therapeutic polymers have the potential to improve the standard of care for hemorrhage, or uncontrolled bleeding, as synthetic hemostats. PolySTAT, a fibrin-crosslinking peptide-polymer conjugate, has the capacity to rescue fibrin clot formation and improve survival in a model of acute traumatic bleeding. PolySTAT consists of a synthetic polymer backbone to which targeting fibrin-binding peptides are linked. For translation of PolySTAT, the optimal valency of peptides must be determined. Grafting of fibrin-binding peptides to the poly(hydroxyethyl methacrylate)-based backbone was controlled to produce peptide valencies ranging from 0 to 10 peptides per polymer. PolySTATs with valencies of ≈4 or greater resulted in increased clot firmness, kinetics, and decreased breakdown as measured by thromboelastometry. A valency of ≈4 increased clot firmness 57% and decreased clot breakdown 69% compared to phosphate-buffered saline. This trend was characterized by neutron scattering, which probed the structure of clots formed in the presence of PolySTAT. Finally, PolySTAT with valencies of 4 (100% survival; p = 0.013) and 8 (80% survival; p = 0.063) improved survival compared to an albumin control in a femoral artery injury model (20% survival). This work demonstrates tunability of hemostatic polymers and the ability of in vitro assays to predict in vivo efficacy.

Topics: Animals; Blood Coagulation; Blood Coagulation Tests; Chitosan; Cross-Linking Reagents; Fibrin; Hemorrhage; Hemostasis; Humans; Peptides; Rats; Rats, Sprague-Dawley; Thrombelastography; Thrombosis; Wounds and Injuries

Combat injuries are associated with a high incidence of infection, and there is a continuing need for improved approaches to control infection and promote wound healing. Due to the possible local and systemic adverse effects of standard 1% cream formulation (Silvadene), we had previously developed a polyethylene glycol (PEGylated) fibrin hydrogel (FPEG)-based wound dressing for the controlled delivery of silver sulfadiazine (SSD) entrapped in chitosan microspheres (CSM). In this study, we have evaluated the antimicrobial and wound healing efficacy of SSD-CSM-FPEG using a full-thickness porcine wound infected with Pseudomonas aeruginosa. Infected wounds treated with a one-time application of the SSD-CSM-FPEG wound dressing demonstrated significantly reduced bacterial bioburden over time (99·99% of reduction by day 11; P < 0·05) compared with all the other treatment groups. The epithelial thickness and granulation of the wound bed was significantly better on day 7 (150·9 ± 13·12 µm), when compared with other treatment groups. Overall, our findings demonstrate that the SSD-CSM-FPEG wound dressing effectively controls P. aeruginosa infection and promotes wound healing by providing a favourable environment that induces neovascularisation. Collectively, sustained release of SSD using fibrin hydrogel exhibited enhanced benefits when compared with the currently available SSD treatment, and this may have significant implications in the bacterial reduction of infected wounds in military and civilian populations.

Topics: Animals; Anti-Infective Agents, Local; Bandages, Hydrocolloid; Chitosan; Disease Models, Animal; Fibrin; Microspheres; Pseudomonas Infections; Silver Sulfadiazine; Swine; Wound Healing; Wounds and Injuries

Fibrin clot formation, which acts to stabilize a wound following injury, is among the key early aspects of dermal wound healing. This preliminary matrix is eventually degraded via a process known as fibrinolysis and replaced with a collagen-rich matrix that continues to be remodeled to minimize scarring. Disruptions in these carefully coordinated events lead to certain undesirable conditions such as fibrosis and the formation of abnormal scars that are associated with excess amounts of collagen. The hypothesis proposed herein is that the presence of collagen (and potentially other molecules) in an early-phase model of healing alters fibrinolysis and that this effect can be attenuated with mediators of the process.. Laboratory in vitro experiments were conducted using agarose-fibrin gel systems with and without collagen to study fibrinolysis caused by plasmin (a serine protease that degrades fibrin) and the effects of aprotinin (a serine protease inhibitor) and bromelain (an extract from pineapple) on fibrin clot breakdown. The extent of fibrinolysis was monitored at various times (0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours) by measuring the size of rings of fibrinolysis following the diffusion of plasmin. The data obtained at 0.5, 12, and 24-hour time points were considered (because there was no difference found in the data collected for closer intermediates nor for the longer times beyond 24 hours) and were compared using the nonparametric Mann-Whitney U statistical significance test.. The results obtained showed aprotinin significantly inhibited fibrinolysis in systems containing collagen, while bromelain improved fibrinolysis. In general, the presence of increasing amounts of collagen in the system decreased the extent of fibrinolysis.. These findings support the notion that early-phase deposition of collagen contributes to disrupted fibrinolysis, which could lead to impaired healing as well as potentially facilitate control of fibrinolysis.

Topics: Aprotinin; Collagen; Diffusion; Extracellular Matrix; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Models, Biological; Serine Proteinase Inhibitors; Wound Healing; Wounds and Injuries

Although mesenchymal stromal cells (MSCs) can promote wound healing in different clinical settings, the underlying mechanism of MSC-mediated tissue repair has yet to be determined. Because a nonredundant role of pentraxin 3 (PTX3) in tissue repair and remodeling has been recently described, here we sought to determine whether MSC-derived PTX3 might play a role in wound healing. Using a murine model of skin repair, we found that Ptx3-deficient (Ptx3(-/-)) MSCs delayed wound closure and reduced granulation tissue formation compared with wt MSCs. At day 2, confocal microscopy revealed a dramatic reduction in green fluorescent protein (GFP)-expressing Ptx3(-/-) MSCs recruited to the wound, where they appeared to be not only poorly organized in bundles but also scattered in the extracellular matrix. These findings were further confirmed by quantitative biochemical analysis of GFP content in wound extracts. Furthermore, Ptx3(-/-) MSC-treated skins displayed increased levels of fibrin and lower levels of D-dimer, suggesting delayed fibrin-rich matrix remodeling compared with control skins. Consistently, both pericellular fibrinolysis and migration through fibrin were found to be severely affected in Ptx3(-/-) MSCs. Overall, our findings identify an essential role of MSC-derived PTX3 in wound repair underscoring the beneficial potential of MSC-based therapy in the management of intractable wounds.

Topics: Animals; C-Reactive Protein; Cells, Cultured; Disease Models, Animal; Fibrin; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred Strains; Nerve Tissue Proteins; Radiography; Random Allocation; Skin; Wound Healing; Wounds and Injuries

Postinjury fibrinolysis can manifest as three distinguishable phenotypes: 1) hyperfibrinolysis, 2) physiologic, and 3) hypofibrinolysis (shutdown). Hyperfibrinolysis is associated with uncontrolled bleeding due to clot dissolution; whereas, fibrinolysis shutdown is associated with organ dysfunction due to microvascular occlusion. The incidence of fibrinolysis phenotypes at hospital arrival in severely injured patients is: 1) hyperfibrinolysis 18%, physiologic 18%, and shutdown 64%. The mechanisms responsible for dysregulated fibrinolysis following injury remain uncertain. Animal work suggests hypoperfusion promotes fibrinolysis, while tissue injury inhibits fibrinolysis. Clinical experience is consistent with these observations. The predominant mediator of postinjury hyperfibrinolysis appears to be tissue plasminogen activator (tPA) released from ischemic endothelium. The effects of tPA are accentuated by impaired hepatic clearance. Fibrinolysis shutdown, on the other hand, may occur from inhibition of circulating tPA, enhanced clot strength impairing the binding of tPA and plasminogen to fibrin, or the inhibition of plasmin. Plasminogen activator inhibitor -1 (PAI-1) binding of circulating tPA appears to be a major mechanism for postinjury shutdown. The sources of PAI-1 include endothelium, platelets, and organ parenchyma. The laboratory identification of fibrinolysis phenotype, at this moment, is best determined with viscoelastic hemostatic assays (TEG, ROTEM). While D-dimer and plasmin antiplasmin (PAP) levels corroborate fibrinolysis, they do not provide real-time assessment of the circulating blood capacity. Our clinical studies indicate that fibrinolysis is a very dynamic process and our experimental work suggests plasma first resuscitation reverses hyperfibrinolysis. Collectively, we believe recent clinical and experimental work suggest antifibrinolytic therapy should be employed selectively in the acutely injured patient, and optimally guided by TEG or ROTEM.

Topics: Animals; Antifibrinolytic Agents; Fibrin; Fibrinolysis; Humans; Phenotype; Plasminogen; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator; Tranexamic Acid; Wounds and Injuries

Victims of trauma often develop impaired blood clot formation (coagulopathy) that contributes to bleeding and mortality. Fibrin polymerization is one critical component of clot formation that can be impacted by post-translational oxidative modifications of fibrinogen after exposure to oxidants. In vitro evidence suggests that Aα-C domain methionine sulfoxide formation, in particular, can induce conformational changes that prevent lateral aggregation of fibrin protofibrils during polymerization. We used mass spectrometry of plasma from trauma patients to find that fibrinogen Aα-C domain methionine sulfoxide content was selectively-increased in patients with coagulopathy vs. those without coagulopathy. This evidence supports a novel linkage between oxidative stress, coagulopathy, and bleeding after injury.

Topics: Adult; Blood Coagulation; Female; Fibrin; Fibrinogen; Hemorrhage; Humans; Male; Methionine; Middle Aged; Oxidative Stress; Thrombosis; Wounds and Injuries

The aim of this study was to examine the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) in combination with a collagen-fibrin double-layered membrane on wound healing in mice. A collagen-fibrin double-layered membrane was prepared, and the surface properties of the support material were investigated using a scanning electron microscope. Twenty-four mice were prepared for use as full-thickness skin wound models and randomly divided into 3 groups: group A, a control group in which the wounds were bound using a conventional method; group B, a group treated with hUCMSCs combined with a collagen membrane; and group C, a group treated with hUCMSCs combined with a collagen-fibrin double-layered membrane. The postoperative concrescence of the wounds was observed daily to evaluate the effects of the different treatments. Scanning electron microscope observation showed the collagen-fibrin scaffolds exhibited a highly porous and interconnected structure, and wound healing in the double-layered membrane group was better than in groups A or B. Treatment with hUCMSCs combined with a collagen-fibrin double-layered membrane accelerated wound healing.

Topics: Animals; Cells, Cultured; Collagen; Dermis; Disease Models, Animal; Fibrin; Guided Tissue Regeneration; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Neovascularization, Physiologic; Skin; Tissue Engineering; Tissue Scaffolds; Wound Healing; Wounds and Injuries

This research addresses the development and in vitro evaluation of lipid nanoparticle (NP)-based dressings to optimize the delivery of human recombinant epidermal growth factor (rhEGF) for the topical treatment of chronic wounds. The systems investigated were rhEGF-loaded solid lipid nanoparticles (rhEGF-SLN) and rhEGF-loaded nanostructured lipid carriers (rhEGF-NLC) formulated in wound dressings comprising either semi-solid hydrogels or fibrin-based solid scaffolds. Following detailed characterisation of the NP, in vitro diffusion cell experiments (coupled with dermatopharmacokinetic measurements), together with confocal microscopic imaging, conducted on both intact skin samples, and those from which the barrier (the stratum corneum) had been removed, revealed that (a) the particles remained essentially superficially located for at least up to 48h post-application, (b) rhEGF released on the surface of intact skin was unable to penetrate to the deeper, viable layers, and (c) sustained release of growth factor from the NP "drug reservoirs" into barrier-compromised skin was observed. There were no significant differences between the in vitro performance of rhEGF-SLN and rhEGF-NLC, irrespective of the formulation employed. It is concluded that, because of their potentially longer-term stability, the fibrin-based scaffolds may be the most suitable approach to formulate rhEGF-loaded lipid nanoparticles.

Topics: Administration, Topical; Animals; Bandages; Chemistry, Pharmaceutical; Delayed-Action Preparations; Epidermal Growth Factor; Female; Fibrin; Hydrogels; Lipids; Nanoparticles; Nanostructures; Skin; Skin Absorption; Swine; Wounds and Injuries

In vitro evaluation of antibacterial and antifungal drugs encapsulated fibrin nanoparticles to prove their potential prospect of using these nanocomponent for effective treatment of microbial infested wounds.. Surfactant-free oil-in-water emulsification-diffusion method was adopted to encapsulate 1 mg/ml each of antimicrobial drugs (Ciprofloxacin and Fluconazole) in 4 ml of aqueous fibrinogen suspension and subsequent thrombin mediated cross linking to synthesize drug loaded fibrin nanoparticles.. Ciprofloxacin loaded fibrin nanoparticles (CFNPs) showed size range of 253 ± 6 nm whereas that of Fluconazole loaded fibrin nanoparticles (FFNPs) was 260 ± 10 nm. Physico chemical characterizations revealed the firm integration of antimicrobial drugs within fibrin nanoparticles. Drug release studies performed at physiological pH 7.4 showed a release of 16% ciprofloxacin and 8% of fluconazole while as the release of ciprofloxacin at alkaline pH 8.5, was 48% and that of fluconazole was 37%. The antimicrobial activity evaluations of both drug loaded systems independently showed good antibacterial activity against Escherichia coli (E.coli), Staphylococcus aureus (S. aureus) and antifungal activity against Candida albicans (C. albicans). The in vitro toxicity of the prepared drug loaded nanoparticles were further analyzed using Human dermal fibroblast cells (HDF) and showed adequate cell viability.. The efficacies of both CFNPs and FFNPs for sustained delivery of encapsulated anti microbial drugs were evaluated in vitro suggesting its potential use for treating microbial infested wounds (diabetic foot ulcer).

Topics: Anti-Infective Agents; Candida albicans; Escherichia coli; Fibrin; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; Wounds and Injuries

Split-skin grafting (SSG) is the gold standard treatment for full-thickness skin defects. For certain patients, however, an extensive skin lesion resulted in inadequacies of the donor site. Tissue engineering offers an alternative approach by using a very small portion of an individual's skin to harvest cells for propagation and biomaterials to support the cells for implantation. The objective of this study was to determine the effectiveness of autologous bilayered tissue-engineered skin (BTES) and single-layer tissue-engineered skin composed of only keratinocytes (SLTES-K) or fibroblasts (SLTES-F) as alternatives for full-thickness wound healing in a sheep model. Full-thickness skin biopsies were harvested from adult sheep. Isolated fibroblasts were cultured using medium Ham's F12: Dulbecco modified Eagle medium supplemented with 10% fetal bovine serum, whereas the keratinocytes were cultured using Define Keratinocytes Serum Free Medium. The BTES, SLTES-K, and SLTES-F were constructed using autologous fibrin as a biomaterial. Eight full-thickness wounds were created on the dorsum of the body of the sheep. On 4 wounds, polyvinyl chloride rings were used as chambers to prevent cell migration at the edge. The wounds were observed at days 7, 14, and 21. After 3 weeks of implantation, the sheep were euthanized and the skins were harvested. The excised tissues were fixed in formalin for histological examination via hematoxylin-eosin, Masson trichrome, and elastin van Gieson staining. The results showed that BTES, SLTES-K, and SLTES-F promote wound healing in nonchambered and chambered wounds, and BTES demonstrated the best healing potential. In conclusion, BTES proved to be an effective tissue-engineered construct that can promote the healing of full-thickness skin lesions. With the support of further clinical trials, this procedure could be an alternative to SSG for patients with partial- and full-thickness burns.

Topics: Animals; Cattle; Cell Transplantation; Cells, Cultured; Disease Models, Animal; Fibrin; Fibroblasts; Graft Survival; Keratinocytes; Male; Random Allocation; Risk Assessment; Sheep; Skin Transplantation; Skin, Artificial; Tissue Engineering; Transplantation, Autologous; Wound Healing; Wounds and Injuries

Skin injury is followed by accumulation of a fibrin based provisional matrix which normally drives the process of wound repair. Exogenous fibrin with extra cellular matrix (ECM) components can also favor the wound healing process. In a preliminary study we found that lyophilized fibrin sheet (FS) arrest bleeding from rabbit skin wound but it remained dry during the repair period and did not accelerate the healing process better than untreated control. In the current study, hyaluronic acid (HA) was incorporated into FS and the resultant HA-FS promoted water retention and improved wound healing process. Gross-morphology, histopathology and histomorphometry were employed to compare qualitative and quantitative difference of wound healing in treated group against controls. In experimental sites (HA-FS), re-epithelialization was completed by 14 days with neo-vascularization and deposition of wavy bundles of collagen in the treated sites. Rate of healing process was different in treated and untreated wounds and most striking difference was the appearance of appendages, sebaceous gland and hair follicle at some locations in HA-FS treated sites. Therefore, HA with fibrin can create an effective wound care matrix which promotes water retention and wound healing potential.

Topics: Acute Disease; Animals; Extracellular Matrix; Fibrin; Hyaluronic Acid; Neovascularization, Physiologic; Rabbits; Skin; Skin, Artificial; Tissue Scaffolds; Wound Healing; Wounds and Injuries

This prospective, uncontrolled pilot study evaluated the safety and clinical performance of Leucopatch an additive-free, autologous platelet-rich fibrin in the treatment of recalcitrant chronic wounds. Fifteen patients, with 16 lower extremity chronic wounds of varying etiologies were treated weekly with Leucopatch, prepared at the point of care from a donation of the patients' blood, for 6 weeks, or until healing was complete. The wounds had been present for 2 to 108 months (median 24 months) and ranged in size from 0.4 to 15.7 cm(2) (median 2.3 cm(2)) and had not responded to previous treatments. Of the 13 wounds (12 patients) included in the per-protocol efficacy analysis, 4 healed completely (31%). Mean wound area decreased significantly by 65% (95% confidence interval = 45.6% to 83.8%) resulting in a median wound size of 0.9 cm(2) (range = 0-9.6cm(2)). There were no serious adverse events. Two adverse events, one of noncompliance and one infection, were observed; neither was considered to be related to treatment. The results indicate that Leucopatch is easy to prepare and apply in the clinic, is safe, and may be a clinically effective treatment of recalcitrant chronic wounds.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Platelets; Chronic Disease; Confidence Intervals; Female; Fibrin; Humans; Male; Middle Aged; Pilot Projects; Platelet-Rich Plasma; Prospective Studies; Regression Analysis; Secondary Prevention; Statistics as Topic; Transplantation, Autologous; Treatment Failure; United States; Wound Healing; Wounds and Injuries; Young Adult

Ethanol intoxication is a common contributor to traumatic injury. It is unknown whether ethanol consumption contributes to the coagulation differences seen between men and women after trauma. Our aim was to examine the combined effect of ethanol intoxication and gender on coagulation.. Fifty-eight healthy subjects participated and chose to enter into a control group (CG; n = 20; 10 men and 10 women) or drinking group (DG; n = 38; 20 men and 18 women). Venous blood samples for thrombelastography, plasminogen activator inhibitor, thrombin-antithrombin complex, and tissue plasminogen activator were drawn at the beginning of the study. Subjects then interacted in a social atmosphere for at least 2 hours, eating and consuming alcoholic (DG) or nonalcoholic (CG) beverages. After 2 hours, blood alcohol level was determined and blood was drawn for a second set of coagulation studies.. Demographics were similar between groups except for age (36.7 years CG vs. 29.9 years DG; p = 0.009). All baseline thrombelastography measurements were similar between the CG and DG. Blood alcohol levels in the DG were similar between genders at the end of study. At the end of study, a decreased rate of fibrin formation, decreased clot strength, and a decreased rate of fibrin cross-linking was seen in men but not in women. Fibrinolysis was inhibited in drinkers compared with controls.. Consumption of commonly ingested quantities of alcohol correlated with the development of a hypocoagulable state in men but had no effect on coagulation status in women. This phenomenon may contribute to differences in post-trauma coagulation status previously noted between genders.

Topics: Adult; Alcoholic Intoxication; Antithrombin III; Blood Coagulation Disorders; Case-Control Studies; Ethanol; Female; Fibrin; Fibrinolysis; Humans; Male; Oregon; Peptide Hydrolases; Plasminogen Inactivators; Prospective Studies; Sex Characteristics; Statistics, Nonparametric; Thrombelastography; Tissue Plasminogen Activator; Wounds and Injuries

To develop an in-vitro model to evaluate the efficiency of wound-rinsing solutions in removing adherent, hydrophobic, denatured proteins. We hypothesised that saline solutions would be less effective than surfactant-containing solutions in removing denatured proteins.. Prepared slides containing dried blood plasma or fibrin were incubated for up to one hour in histological troughs filled with one of four test solutions: physiological saline solution, Ringer's solution, a surfactant-containing solution and an antiseptic. The concentration of dissolved proteins was measured using a modified Biuret test. Results were analysed by plotting protein concentration against the incubation time.. During the incubation period, the protein concentration increased in all of the test solutions, with the lowest concentration reported in the two saline-based solutions. These stayed clear, while the surfactant-containing solution become opaque, indicating that the surfactant had encased hydrophic substances, such as denatured proteins.. Ringer's solution and saline are inappropriate solvents for adhering wound coatings. A sterile, surfactant-containing wound rinsing solution contains the essential properties for thorough and gentle cleansing of chronic wounds.. None.

Topics: Anti-Infective Agents, Local; Chronic Disease; Drug Evaluation, Preclinical; Fibrin; Humans; Isotonic Solutions; Plasma; Protein Denaturation; Ringer's Solution; Skin Care; Sodium Chloride; Surface-Active Agents; Therapeutic Irrigation; Wound Healing; Wounds and Injuries

The modulation of collagen fibers during experimental skin wound healing was studied in 112 Wistar rats submitted to laser photobiomodulation treatment. A standardized 8mm-diameter wound was made on the dorsal skin of all animals. In half of them, 0.2ml of a silica suspension was injected along the border of the wound in order to enhance collagen deposition and facilitate observation. The others received saline as vehicle. The treatment was carried out by means of laser rays from an aluminum-gallium arsenide diode semiconductor with 9mW applied every other day (total dose=4J/cm2) on the borders of the wound. Tissue sections obtained from four experimental groups representing sham-irradiated animals, laser, silica and the association of both, were studied after 3, 7, 10, 15, 20, 30 and 60 days from the laser application. The wounded skin area was surgically removed and submitted to histological, immunohistochemical, ultrastructural, and immunofluorescent studies. Besides the degree and arrangement of collagen fibers and of their isotypes, the degree of edema, the presence of several cell types especially pericytes and myofibroblasts, were described and measured. The observation of Sirius-red stained slides under polarized microscopy revealed to be of great help during the morphological analysis of the collagen tissue dynamic changes. It was demonstrated that laser application was responsible for edema regression and a diminution in the number of inflammatory cells (p<0.05). An evident increase in the number of actin-positive cells was observed in the laser-treated wounds. Collagen deposition was less than expected in silica-treated wounds, and laser treatment contributed to its better differentiation and modulation in all irradiated groups. Thus, laser photobiomodulation was able to induce several modifications during the cutaneous healing process, especially in favoring newly-formed collagen fibers to be better organized and compactedly disposed.

Topics: Actins; Animals; Collagen; Connective Tissue; Desmin; Female; Fibrin; Low-Level Light Therapy; Male; Microscopy, Electron; Rats; Rats, Wistar; Wound Healing; Wounds and Injuries

Chicken fat clot (CFC), a fibrin-like substance, is sometimes found in the heart and large blood vessels in some autopsy cases. Reports of detailed histological findings of CFC are scant. We therefore examined CFC histologically in 53 autopsy cases and its correlation with ante-mortem or post-mortem evidence. We found three microscopic patterns of CFC: (1) wavelike fibrin fibers (WFF), (2) short fibrin fibers (SFF), and (3) short fibrin fibers mixed with wavelike fibrin fibers (SFF+WFF). WFF were found in the cases that survived less than 3 h after poisoning, burns, asphyxia, intracerebral hemorrhage, etc. SFF were found in the cases that survived more than 1 day after malignant neoplasms and acute or chronic inflammatory diseases, etc. SFF+WFF were found in the cases that died of inflammatory diseases, chronic heart failure, hemorrhagic shock, drowning, etc. About two-thirds of the SFF+WFF cases survived more than 1 day, with the rest surviving less than that. Our study confirmed three CFC patterns and their relation with survival interval. Therefore, these findings can be used as an index of the survival interval of a few acute and most chronic medico-legal death cases.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Fibrin; Forensic Pathology; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasms; Respiratory Tract Diseases; Retrospective Studies; Survival Analysis; Thrombosis; Time Factors; Wounds and Injuries

Screening of a phage library for peptides that bind to clotted plasma in the presence of liquid plasma yielded two cyclic decapeptides, CGLIIQKNEC (CLT1) and CNAGESSKNC (CLT2). When injected intravenously into mice bearing various types of tumors, fluorescein-conjugated CLT peptides accumulated in a fibrillar meshwork in the extracellular compartment of the tumors, but were not detectable in other tissues of the tumor-bearing mice. The tumor homing of both peptides was strongly reduced after coinjection with unlabeled CLT2, indicating that the two peptides recognize the same binding site. The CLT peptide fluorescence colocalized with staining for fibrin(ogen) present in the extravascular compartment of tumors, but not in other tissues. The CLT peptides did not home to tumors grown in fibrinogen-null mice or in mice that lack plasma fibronectin. The CLT peptides also accumulated at the sites of injury in arteries, skeletal muscle, and skin. We conclude that the CLT peptides recognize fibrin-fibronectin complexes formed by clotting of plasma proteins that have leaked into the extravascular space in tumors and other lesions. These peptides may be useful in targeting diagnostic and therapeutic materials into tumors and injured tissues.

Topics: Animals; Blood Coagulation; Cell Line, Tumor; Fibrin; Fibronectins; Humans; Mice; Mice, Knockout; Neoplasms; Peptide Library; Peptides, Cyclic; Tissue Distribution; Wounds and Injuries

Bone marrow-derived progenitor cells play a role in vascular regeneration. However, their homing to areas of vascular injury is poorly understood. One of the earliest responses to an injury is the activation of coagulation and platelets. In this study we assessed the role of hemostatic components in the recruitment of CD34+ cells to sites of injury.. Using an ex vivo injury model, representing endothelial cell (EC) injury or vessel denudation, we studied homing of CD34+ under flow. Platelet aggregates facilitated initial tethering and rolling of CD34+ cells through interaction of P-selectin expressed by platelets and P-selectin glycoprotein ligand-1 (PSGL-1), expressed by CD34+ cells. Ligation of PSGL-1 activated adhesion molecules on CD34+ cells, ultimately leading to firm adhesion of CD34+ cells to tissue factor-expressing ECs or to fibrin-containing thrombi formed on subendothelium. We also demonstrate that fibrin-containing thrombi can support migration of CD34+ cells to the site of injury and subsequent differentiation toward a mature EC phenotype. Additionally, intravenously injected CD34+ cells homed in vivo to denuded arteries in the presence of endogenous leukocytes.. We provide evidence that hemostatic factors, associated with vascular injury, provide a regulatory microenvironment for re-endothelialization mediated by circulating progenitor cells.

Topics: Animals; Antigens, CD34; Blood Coagulation; Blood Platelets; Blood Vessels; Carotid Artery Injuries; Cell Adhesion; Cell Adhesion Molecules; Cell Differentiation; Cell Movement; Endothelial Cells; Endothelium, Vascular; Fibrin; Hemostasis; Humans; Mice; Mice, Inbred C57BL; P-Selectin; Phenotype; Platelet Activation; Regeneration; Stem Cell Transplantation; Stem Cells; Wounds and Injuries

Surgical treatment of skeletal muscle loss resulting from trauma, tumor ablation, or inborn tissue defects is hampered by the scarcity of functional substitute tissue. By using techniques of tissue engineering, reconstitution of skeletal muscle defects might become a more viable option. However, it is necessary to develop an adequate, practical method for delivering myoblasts within a three-dimensional scaffold in vivo. The aim of this study was to create and evaluate a novel method for the transfer of myoblasts with clinically approved components within a three-dimensional matrix.. The authors injected expanded primary male myoblasts into muscle defects in female syngeneic rats using a two-way syringe (Duploject) within a three-dimensional fibrin matrix. Detection and evaluation were performed using Y chromosome in situ hybridization, antidesmin immunostaining, and hematoxylin and eosin staining. To identify possible differences by means of integration, the injected myoblasts were compared with 7 days of precultivated constructs.. Injected myoblasts showed increasing integration into host muscle fibers in a time-dependent manner, exclusively at the injection site. Antidesmin staining revealed a conserved myogenic phenotype of transplanted cells. The fibrin matrix resolved over a period of 12 weeks, with no indication of an inflammatory reaction. No significant difference in the number of detected Y chromosome-positive nuclei was found between the two transplantation groups.. The presented technique of myoblast-fibrin injection indicates a clinical potential for reconstruction of skeletal muscle defects in vivo using a ready-to-use device in combination with tissue-engineering methods.

Topics: Animals; Biopolymers; Cell Survival; Cells, Cultured; Culture Media; Desmin; Equipment Design; Female; Fibrin; Fibrinogen; Graft Survival; In Situ Hybridization; Injections, Intramuscular; Male; Muscle, Skeletal; Myoblasts; Rats; Rats, Inbred WKY; Staining and Labeling; Syringes; Thrombin; Tissue Engineering; Transplantation, Isogeneic; Wounds and Injuries; Y Chromosome

In this study we have reported the efficacy of three biomaterials: (a) physiologically clotted fibrin-gelatin composite (PFG), (b) PFG graft copolymerized with 2-hydroxyethyl methacrylate (PFG-HEMA), and (c) PFG graft copolymerized with 2-hydroxypropyl methacrylate (PFG-HPMA) as temporary wound-dressing materials using the rat as an animal model. Full-thickness excision wounds were made on the back of female rats weighing about 150 +/- 10 g. The dressings were applied on the wounds and changed periodically at an interval of 4 days with the respective materials. The wounds treated with PFG-HEMA healed completely on 15th day after wound creation, whereas those treated with PFG and PFG-HPMA resulted in complete healing on the 17th day. The concentrations of collagen, hexosamine, and uronic acid in the granulation tissue were determined. The PFG and its graft copolymers acted as hydrogels, thereby absorbing excess exudates, while still maintaining a moist environment at the wound site. The enhanced wound healing in the experimental animals was reflected in the increased rate of wound contraction. The results of the histological and mechanical studies of the experimental groups revealed that reepithelialization and remodeling of the skin have been achieved by providing a moist environment at the wound site by the biomaterials and thereby hastening the migration of keratinocytes.

Topics: Animals; Bandages; Collagen; Excipients; Female; Fibrin; Gelatin; Granulation Tissue; Hexosamines; Hydrogels; Methacrylates; Rats; Tensile Strength; Uronic Acids; Wound Healing; Wounds and Injuries

In this study, we investigated the role of the hematopoietic cytokine erythropoietin (EPO) during wound healing, the physiological response to tissue injury. We used an in vivo wound-healing assay (fibrin Z-chambers) consisting of fibrin-filled chambers implanted subcutaneously in rats. The fibrin inside the chambers is replaced by granulation tissue consisting of new blood vessels, macrophages and fibroblasts as part of the wound-healing response. Local, exogenous recombinant EPO administration into the fibrin matrix significantly increased granulation tissue formation in a dose-dependent manner. To investigate the physiological role of endogenous EPO during wound healing, we used soluble EPO receptor or anti-EPO monoclonal antibodies to neutralize EPO and observed dose-dependent inhibition of granulation tissue formation, consistent with an important role for EPO in the wound-healing cascade. The ability of recombinant EPO to promote wound healing was associated with a proangiogenic effect during granulation tissue formation. We also found abundant expression of EPO receptor protein in macrophages, cells that play a pivotal role during wound healing. Modulation of wound healing because of administration of recombinant EPO or inhibition of endogenous EPO-EPO receptor correlated with changes in levels of inducible nitric oxide synthase protein in granulation tissue. These data demonstrate a novel function for EPO by providing in vivo evidence for a physiological role during fibrin-induced wound healing.

Topics: Animals; Antibodies; Erythropoietin; Female; Fibrin; Macrophages; Neovascularization, Physiologic; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; Rats, Inbred F344; Receptors, Erythropoietin; Recombinant Proteins; Skin; Solubility; Wound Healing; Wounds and Injuries

The histological aspects of second-intention healing were studied in 5 horses and 5 ponies. Biopsies were taken weekly from standardised wounds on the metatarsus and femoral biceps muscle of one horse and one pony. Sections were stained to enable cell counting and the detection of DNA synthesis, fibrin, smooth muscle actin (SMA), collagen, and bacteria. In the ponies, the number of polymorphonuclear leucocytes (PMNs) was high during the first 3 weeks and subsequently decreased rapidly. In the horses, the initial number of PMNs was lower, but remained persistently elevated during the evaluation period. PMNs were found mainly in the superficial zones. Significantly more fibrin was present in the wounds of the horses. No significant differences were observed in the number of fibroblasts, the amounts of SMA and collagen. However, myofibroblasts were significantly less regularly organised in the wounds of the horses, particularly in the metatarsal wounds. The mitotic activity of the epithelium was temporally reduced in week 3. The mitotic activity of the granulation tissue was initially high but declined rapidly from week 1 onwards, with the exception of the metatarsal wounds of the horses, in which mitotic activity remained significantly higher. Histology confirmed and explained the macroscopical differences in wound healing between horses and ponies by the strict organisation of the myofibroblasts and the more effective acute inflammation in the ponies. Stimulation of the organisation of myofibroblasts and improvement of the efficacy of the inflammatory response in horses may therefore result in better second-intention wound healing in horses in clinical practice.

Topics: Actins; Animals; Biopsy; Collagen; Colony Count, Microbial; DNA; Fibrin; Fibroblasts; Horses; Leukocyte Count; Male; Metatarsus; Mitosis; Muscle, Skeletal; Neutrophils; Wound Healing; Wounds and Injuries

Kininogens have recently been shown to possess antiadhesive, anticoagulant, and profibrinolytic properties and can inhibit platelet activation at low thrombin concentrations. To test whether kininogens have antithrombotic properties in vivo, we devised a model of limited arterial injury confined to removal of the endothelium. Brown-Norway Katholiek strain rats with an absence of low- and high-molecular-weight kininogen due to a single point mutation, A163T, were compared in the thrombosis model to the wild-type animals, which were otherwise genetically identical. Despite an equivalent vascular injury, the mean time (+/-SEM) for a 90% decrease in flow measured by laser Doppler was 38.4+/-17 minutes in the kininogen-deficient rats compared with 194+/-29 minutes in the wild-type animals (P<0.002). The degree of vascular injury was the same. No evidence for disseminated intravascular coagulation (decrease in factor V, antithrombin, or fibrinogen) or excessive fibrinolysis (elevation of fibrinogen degradation products) was found in either group of animals. The results suggest that kininogens have antithrombotic properties at low concentrations of thrombin and that inhibitory peptides derived from kininogen may constitute a new antithrombotic strategy.

Topics: Animals; Aorta; Cysteine Proteinase Inhibitors; Female; Fibrin; Kininogens; Laser-Doppler Flowmetry; Male; Molecular Weight; Point Mutation; Rats; Rats, Inbred BN; Reference Values; Regional Blood Flow; Thrombosis; Tunica Intima; Wounds and Injuries

Topics: Accidents, Traffic; Body Temperature Regulation; Efficiency, Organizational; Emergency Medical Services; Fibrin; Humans; Infusions, Intravenous; Medical Records Systems, Computerized; Shock; Tissue Adhesives; Wounds and Injuries

22 patients undergoing elective hip arthroplasty were studied. In 12 patients, a closed-loop autotransfusion system, without anticoagulant, was used and 10 had an ordinary wound drainage allowing repeated blood sampling from the wound. Plasma concentrations of antithrombin (AT), fibrin, soluble (SF) and fibrin D-dimer were determined preoperatively, 3, 8, and 24 hours after starting surgery. Wound drainage blood had increased concentrations of SF and fibrin D-dimer and decreased concentrations of AT compared to reference values and systemic concentrations in patients. Plasma concentrations of SF, fibrin D-dimer and AT did not differ between patients receiving retrieved blood and those receiving stored red blood cell concentrates (RBCs). Patients receiving blood transfusions had lower AT concentrations at 8 hours after starting surgery than those not receiving such a transfusion.

Topics: Aged; Aged, 80 and over; Antithrombin III; Blood Coagulation; Blood Loss, Surgical; Blood Transfusion, Autologous; Blood Volume; Drainage; Erythrocyte Transfusion; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Follow-Up Studies; Hip Prosthesis; Humans; Male; Middle Aged; Wounds and Injuries

Microvascular endothelial cell invasion into the fibrin provisional matrix is an integral component of angiogenesis during wound repair. Cell surface receptors which interact with extracellular matrix proteins participate in cell migration and invasion. Malignant cells use CD44-related chondroitin sulfate proteoglycan (CSPG) as a matrix receptor to mediate migration and invasion. In this study, we examine whether cell surface CSPG can mediate similar events in nonmalignant wound microvascular endothelial cells or whether use of CSPG for migration and invasion is a property largely restricted to malignant cells. After inhibiting CSPG synthesis with p-nitrophenyl beta-d xylopyranoside (beta-d xyloside), wound microvascular endothelial cells were capable of attaching and spreading on the surface of a fibrin gel; however, their ability to invade the fibrin matrix was virtually eliminated. To begin to examine the mechanism by which endothelial cells use CSPG to invade fibrin matrices, cell adhesion and migration on fibrinogen was examined. Endothelial cell adhesion and migration on fibrinogen were inhibited by both beta-d xyloside and after cleavage of chondroitin sulfate from the core protein by chondroitinase ABC. We have determined that wound microvascular endothelial cells express the majority of their proteoglycan as CSPG and that the CSPG core protein is immunologically related to CD44. PCR studies show that these cells express both the "standard" (CD44H) isoform and an isoform containing the variably spliced exon V3. In addition, anti-CD44 antibody blocks endothelial cell migration on fibrinogen. Affinity chromatography studies reveal that partially purified microvascular endothelial cell CSPG binds fibrinogen. These findings suggest that CD44-related CSPG, a molecule implicated in the invasive behavior of tumor cells, is capable of binding fibrinogen/fibrin, thereby mediating endothelial cell migration and invasion into the fibrin provisional matrix during wound repair.

Topics: Animals; Antibodies, Monoclonal; Cell Adhesion; Cell Movement; Cells, Cultured; Chondroitin Lyases; Chondroitin Sulfate Proteoglycans; Chromatography, Affinity; Endothelium, Vascular; Fibrin; Fibrinogen; Glycosides; Hyaluronan Receptors; Microcirculation; Neoplasm Invasiveness; Polymerase Chain Reaction; Prostheses and Implants; Rabbits; Transcription, Genetic; Wounds and Injuries

Evidence of activation of coagulation was sought in serial plasma samples from 25 ABMT candidates with malignant lymphoma admitted for bone marrow harvesting: 10 females and 15 males, median age 41 years (range 27-58 years). Nineteen patients had non-Hodgkin's lymphoma (NHL) and six had Hodgkin's disease. Of those with NHL, 14 had high-grade and five low- grade disease. The plasma levels of markers of activation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, fibrinopeptide A and fibrinmonomers) increased significantly (P < 0.001) in association with harvesting. Except for fibrinopeptide A, the indicators of activation were still significantly elevated 24 h after marrow aspiration. Beta-thromboglobulin, a marker of the platelet release reaction, also increased significantly (P < 0.01). Four out of nine patients in whom a long-term central venous catheter was inserted just after marrow aspiration, developed catheter-related deep vein thrombosis, verified venographically, shortly after harvesting. These results suggest that patient with malignant lymphoma undergoing marrow harvesting develop a hypercoagulable state, and that insertion of a central intravenous catheter immediately after marrow harvesting should be avoided to prevent the development of symptomatic deep vein thrombosis.

Topics: Adult; Anticoagulants; Antithrombin III; beta-Thromboglobulin; Biomarkers; Blood Coagulation; Bone Marrow Transplantation; Catheterization, Central Venous; Circadian Rhythm; Female; Fibrin; Fibrinolysis; Fibrinopeptide A; Heparin; Hodgkin Disease; Humans; Ilium; Lymphoma; Lymphoma, Non-Hodgkin; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Platelet Count; Premedication; Prothrombin; Sternum; Subclavian Vein; Thrombophlebitis; Transplantation, Autologous; Wounds and Injuries

Full-thickness, circular, cutaneous wounds (4 cm diameter) were created on metacarpi and metatarsi of 5 horses. On day 6, all 4 wounds on each horse received a stored autogenous split-thickness sheet graft. Grafts were obtained from the horse's ventrolateral thorax with a pneumatic dermatome at the time the cutaneous wounds were created. Grafts were coapted to the granulation bed of 2 wounds of each horse with fibrin glue. Grafts were coapted to the cutaneous margin of all 4 wounds of each horse with cyanoacrylate glue. Bandages were changed daily until the study ended at 14 d. When the bandages were changed, ointment containing neomycin, polymyxin B, and bacitracin was applied to all wounds. The viable area of graft was measured on post-grafting d 14 and calculated with a micro-processor. Split-thickness sheet-grafts attached to granulation beds on the metacarpi and metatarsi with fibrin glue had no greater survival than did grafts attached without fibrin glue (P > 0.05).

Topics: Animals; Cyanoacrylates; Female; Fibrin; Horses; Male; Metacarpus; Metatarsus; Orchiectomy; Skin Transplantation; Wounds and Injuries

The terms fibrinoid degeneration and fibrinoid substance were first introduced by Neumann in 1880 to describe some alterations in the staining characteristics of collagen. Collagen fibres which have undergone this change are eosinophilic, homogeneous and take some of the tinctorial properties of fibrin. Lendrum et al. (1962) developed Martius-Scarlet-Blue (MSB) stain, which is preferentially taken up by fibrin. The principle of the method described by Lendrum and his colleagues is the use of acid dyes of different molecular size (Martius yellow, Brilliant Crystal Scarlet 6R, methyl blue) in accordance with the alteration in structure of fibrin at different stages of development. The newest fibrin likely to be found in sections is presumably the fine network of postmortem fibrin. Much of this takes a yellow stain with the MSB method, as do erythrocytes. Slightly older fibrin (16 hours) takes a bright red stain with the MSB. Complete validity of the method depends on prolonged fixation in formal-sublimate. It gives brilliant staining with acid dyes and enhances metachromasia. In the Department of Forensic Medicine in Leeds it was noticed that an alteration in collagen staining with MSB stain was taking place in samples collected from different kinds of injuries, e.g. ligature marks, electrical injuries and burns. Similar changes were only occasionally seen in abrasions. It was therefore decided to inflict different kinds of injuries on the skins of rats and to fresh pieces of human skin in vitro, to observe any alterations in collagen staining with MSB and to assess the significance of these changes in relation to the timing of injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Collagen; Fibrin; Male; Microscopy, Electron; Postmortem Changes; Rats; Rats, Inbred Strains; Skin; Wounds and Injuries

The authors devised two new methods for determining the vital reaction of injured skin and tentatively termed them Method I and Method II. Method I is based on the determination of "fibrin-forming ability" of slices of injured skin in the presence of added fibrinogen. Method II is based on the measurement of the albumin content in the injured skin by rocket-immunoelectrophoresis. These methods have the following characteristics: Both are able to distinguish ante-mortem from post-mortem wounds, even in fresh vital wounds. The fibrin-forming ability in vital wounds undergoes a post-mortem change, and this can be used to distinguish ante-from post-mortem wounds for 2 days after death. On the other hand, the albumin content of wounds is virtually unchanged post-mortem until one week after death. Method II is therefore applicable even to slightly decomposed materials one week after death. It is not recommended that this method be used for the wound in the post-mortem hypostatic area. Regarding the technique, both methods are relatively easy. Both methods are able to estimate the wound age until about 2 days after injury (during wound healing). A more reliable estimate of wound age is possible by using Method I together with Method II.

Topics: Animals; Fibrin; Forensic Medicine; Male; Postmortem Changes; Rats; Rats, Inbred Strains; Serum Albumin; Skin; Wounds and Injuries

The fibrinolytic response to trauma was investigated in 23 patients. Patients were triaged upon arrival in the emergency center into three groups; group I-patients with significant trauma who maintained normal vital signs, had a good prognosis, and tolerated the trauma well (mean injury severity score 8, range 4 to 12); group II--patients with significant trauma and transient episodes of hypotension, hypoxia, or acidosis who recovered (mean injury severity score 22, range 9 to 38); and group III--patients with profound or continued hypoxia and hypotension who eventually died of the trauma (mean injury severity score 41, range 30 to 50). Serial measurements of prothrombin time, activated partial thromboplastin time, and platelet count; concentrations of fibrinogen, plasminogen, and fibrin degradation products; and assays of euglobulin fraction fibrinolytic activity on plasminogen-free and plasminogen-rich fibrin plates were obtained on all patients. Coagulation studies documented a trauma-related coagulopathy that correlated with the degree of trauma. Plasminogen concentrations were initially depressed in all three groups; however by 24 hours group III patients were noted to have significantly elevated plasminogen concentrations while group I and group II patients had normal plasminogen concentrations. Fibrinolytic activity measured on plasminogen-free and plasminogen-rich fibrin plates was initially increased in all three groups with group III patients demonstrating the greatest increase. Over the succeeding 14 hours fibrinolytic activity returned to baseline values in group I and group II patients while group III patients demonstrated no detectable fibrinolytic activity for the remainder of the study period. This absence of fibrinolytic activity and increase in plasminogen concentrations in group III patients is thought to be caused by depletion of the intravascular plasminogen activator with the subsequent development of a hypofibrinolytic state.

Topics: Blood Coagulation; Fibrin; Fibrinogen; Fibrinolysis; Humans; Partial Thromboplastin Time; Plasminogen; Platelet Count; Prothrombin Time; Wounds and Injuries

Topics: Adolescent; Adult; Aged; Aging; Child; Child, Preschool; Collagen; Diabetes Mellitus; Factor XIII; Fibrin; Humans; Infant; Middle Aged; Wound Healing; Wound Infection; Wounds and Injuries

Scanning electron microscopy was used to diagnose incidents of trauma and the pattern of healing following surgical implantation of microporous blood vessel substitutes. Vascular reconstruction procedures using autogenous or synthetic prosthetic materials inflict damage to the adjacent tissues as well as the prosthesis. This effects the thrombotic behavior and healing pattern of the area. The prognoses for long term success are, as a consequence, directly influenced. Various vessel occluding devices were evaluated on canine models with respect to their ability to damage blood vessels at the clamped site. The impact of suture needles on tissues and prosthetic materials was also considered. Of the various vessel clamping devices which are commercially available, those which have elastomeric shields on the clamping components were found to be the most satisfactory. The development of less traumatic surgical devices and possible modifications in the surgical protocols are discussed with the aim of further reducing surgical trauma.

Topics: Animals; Aorta, Abdominal; Arteries; Bioprosthesis; Blood Coagulation; Dogs; Endothelium; Fibrin; Wounds and Injuries

As shown in earlier studies the formation of metastases after i.v. tumor cell injection in rats is increased in the immediate post-traumatic period and treatment with heparin, thrombocytopenia, and defibrinogenation decreases the formation of metastases. Thrombocytopenia also inhibits the stimulating effect of trauma on metastasis formation. The results of the studies reported in this paper show that the changes of metastasis formation induced by the factors mentioned above with few exceptions are well correlated to the lodgement of the injected tumor cells. Thus, heparin treatment and thrombocytopenia decrease the pulmonary lodgement of i.v. injected tumor cells. Trauma increases the pulmonary lodgement of i.v. injected tumor cells but when trauma is combined with thrombocytopenia, the effect of thrombocytopenia dominates and the pulmonary lodgement of tumor cells decreases when compared to control conditions. Despite this, trauma still gives rise to increased tumor cell lodgement during thrombocytopenia.

Topics: Adenosine Diphosphate; Animals; Fibrin; Heparin; Lung Neoplasms; Neoplasm Metastasis; Neoplasms, Experimental; Neoplastic Cells, Circulating; Platelet Aggregation; Rats; Thrombocytopenia; Wounds and Injuries

Topics: Animals; Autopsy; Blood Platelets; Clot Retraction; Fibrin; Hemostasis; Histological Techniques; Humans; Microscopy, Electron; Microscopy, Electron, Scanning; Postmortem Changes; Rats; Wounds and Injuries

Topics: Animals; Fibrin; Fibrinogen; Hematocrit; Lung; Male; Nicotinic Acids; Plasminogen Activators; Rats; Thrombin; Time Factors; Turpentine; Wounds and Injuries

In extension of earlier Scanning Electron Microscopical findings on local vital reaction, we initially tried conventional microscopic histology. By standard staining methods--generally used in demonstrating fibrins (Ladew IG, PTAH, PAS etc.) fresh fibrinous mashing was hardly demonstrable. Tryptophan reaction as per Adams brought positive results. By modifying Scanning Electron Microscopic preparation techniques, the surface transverse striation could be shown. For dissolution of the complex morphological structural patterns on the wound surface, Transmission Electron Microscopy was used. Identification of fibrinous filaments was done by their interior transverse striation. Mashing of shaped structure components of the blood in vital and post mortal injuries should be more closely analyzed. Advantages and disadvantages of Scanning and Transmission Electron Microscopic techniques are discussed in view of forensic problems and a tentative judgement passed.

Topics: Animals; Female; Fibrin; Forensic Medicine; Microscopy, Electron, Scanning; Platelet Aggregation; Postmortem Changes; Rats; Staining and Labeling; Time Factors; Wounds and Injuries

Following severe multiple trauma, decreases were observed in a) Free cholesterol, b) Cholesteryl esters, c) Total phospholipids, and d) Lysolecithin. Comparatively slight changes in coagulation parameters did not differ regardless of whether pulmonary complications developed. In contrast, increased fibrin lipid complexing was more closely correlated with clinical data, because: a) Plasmatic lipids, particularly triglycerides complexed with fibrins, were elevated severalfold in patients with adult respiratory distress and fat embolism syndromes when compared with multiple trauma patients without pulmonary complications. This was independent of plasma lipid levels. b) Plasmatic triglycerides complexed with fibrins were significantly higher in patients who died than in those who survived. The considerable changes in the plasma lipid pattern following severe trauma suggest the presence of an abnormal lipoprotein with increased affinity to fibrin, thereby inhibiting fibrinolysis. This might well be one pathogenic mechanism in the development of post-traumatic respiratory distress syndrome.

Topics: Adult; Blood Coagulation Factors; Cholesterol; Cholesterol Esters; Fibrin; Humans; Lipids; Lipoproteins; Lysophosphatidylcholines; Phospholipids; Respiratory Distress Syndrome; Wounds and Injuries

Sufficient clotting factors to ensure coagulation and replacement of lost volume and oxygen-carrying capacity are necessary to obviate many of the complications that may occur when massive transfusions are used in patients with multiple injuries. A regimen that has been successful includes immediate infusion of plasma protein fraction, packed red cells, fresh-frozen plasma, and nonspecific platelets.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Proteins; Blood Transfusion; Disseminated Intravascular Coagulation; Fibrin; Humans; Respiratory Insufficiency; Thrombocytopenia; Transfusion Reaction; Wounds and Injuries

Topics: Blood Cell Count; Blood Circulation; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Blood Transfusion; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysis; Humans; Infusions, Parenteral; Pediatrics; Prothrombin; Shock, Hemorrhagic; Shock, Traumatic; Thrombocytopenia; Wounds and Injuries

Topics: Blood Group Incompatibility; Blood Transfusion; Erythrocytes; Fibrin; Fibrinogen; Humans; Serum Albumin; Transfusion Reaction; Wounds and Injuries

Topics: Animals; Burns; Fibrin; Fractures, Bone; Humans; Hypoxia; Lung; Microcirculation; Pulmonary Edema; Pulmonary Embolism; Wounds and Injuries

Topics: Adult; Arm; Biopsy; Blood Coagulation; Blood Platelets; Blood Transfusion; Blood Vessels; Collagen; Endothelium; Erythrocytes; Female; Fibrin; Granulation Tissue; Hemorrhage; Humans; Male; Microscopy, Electron; Middle Aged; Platelet Adhesiveness; Platelet Aggregation; Time Factors; von Willebrand Diseases; Wounds and Injuries

Topics: Adhesiveness; Animals; Factor XIII; Fibrin; Fibrinolysis; Rats; Skin Transplantation; Tissue Adhesives; Transplantation, Autologous; Wounds and Injuries

The role of the complement system in nonspecific inflammation was investigated by depleting guinea pigs of serum complement with cobra venom factor (CoF). The progress of wound healing was compared in decomplemented and control animals which received buffer and no CoF. When wound tissue sections were assessed at 12 hours after wounding, no morphologic differences were observed between experimental and control wounds. Quantitation of 24-hour wound exudates by a point volumetric method revealed a 50% reduction in infiltrating polymorphonuclear neutrophilic leukocytes (PMN) in the absence of complement. A smaller decrease in mononuclear leukocytes (MNL) was seen. Red cells occupied four times as much space in the experimental wounds at 24 hours. In 48-hour wounds, PMN were still 50% of controls, but were near control levels at 72 hours. Despite the decreased influx of PMN, wound debridement and subsequent fibrogenesis proceeded as in the controls. No differences were seen in fibroblast proliferation, connective tissue formation or capillary regeneration. These results suggest that the complement system is not a primary mediator of inflammation following a nonimmunologic stimulus.

Topics: Animals; Blood Proteins; Capillaries; Cell Nucleolus; Cell Nucleus; Complement System Proteins; Debridement; Endoplasmic Reticulum; Erythrocytes; Exudates and Transudates; Fibrin; Fibroblasts; Granulation Tissue; Guinea Pigs; Leukocyte Count; Macrophages; Male; Microscopy, Electron; Neutrophils; Phagocytosis; Snakes; Venoms; Wound Healing; Wounds and Injuries

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Cell Aggregation; Cell Count; Factor V; Factor VII; Factor X; Fibrin; Fibrinolysin; Humans; Plasminogen; Time Factors; Transfusion Reaction; Wounds and Injuries

Topics: Agglutination; Animals; Biochemical Phenomena; Biochemistry; Collagen; Erythrocytes; Fibrin; Forensic Medicine; Granulation Tissue; Histocytochemistry; Microscopy, Electron, Scanning; Rats; Skin; Time Factors; Wound Healing; Wounds and Injuries

Topics: Animals; Dogs; Electrophoresis, Disc; Enzyme Activation; Fibrin; Fibrinolysin; Hindlimb; Iodine Isotopes; Ligation; Phenols; Plasminogen; Thrombin; Thrombophlebitis; Tourniquets; Vascular Diseases; Veins; Wounds and Injuries

Topics: Arthritis, Rheumatoid; Blood Sedimentation; Exudates and Transudates; Fibrin; Gangrene; Humans; Osteoarthritis; Polyarteritis Nodosa; Synovial Fluid; Vascular Diseases; Wounds and Injuries

Topics: Animals; Aorta, Abdominal; Arteries; Blood Platelets; Cadaver; Endothelium; Fibrin; Forensic Medicine; Humans; Microscopy, Electron, Scanning; Postmortem Changes; Rabbits; Rats; Time Factors; Wounds and Injuries

Topics: Animals; Anti-Bacterial Agents; Bacitracin; Chloramphenicol; Collagen; Fibrin; Hydroxyproline; Penicillins; Rats; Streptomycin; Tetracycline; Time Factors; Wound Healing; Wounds and Injuries

Topics: Animals; Dogs; Enzyme Activation; Epithelium; Fibrin; Fibrinolysis; Formaldehyde; Humans; In Vitro Techniques; Nitrogen Mustard Compounds; Pericardium; Peritoneum; Phenols; Pleura; Wounds and Injuries

Topics: Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysis; Humans; Plasminogen; Wounds and Injuries

Topics: Accidents, Traffic; Aged; Autopsy; Blood Coagulation Disorders; Embolism, Fat; Female; Femoral Fractures; Fibrin; Fracture Fixation, Intramedullary; Fractures, Bone; Humans; Intracranial Embolism and Thrombosis; Lipids; Lung; Male; Middle Aged; Pelvic Bones; Pulmonary Artery; Pulmonary Embolism; Pulmonary Veins; Tibial Fractures; Time Factors; Wounds and Injuries

Topics: Cell Movement; Edema; Fibrin; Fibrinogen; Inflammation; Leukocytes; Lymphocytes; Macrophages; Microcirculation; Phagocytosis; Wounds and Injuries

Topics: Adolescent; Female; Femoral Fractures; Fibrin; Gastrointestinal Diseases; Humans; Lung Diseases; Pregnancy; Pregnancy Complications; Thrombosis; Wounds and Injuries

Topics: Animals; Cytoplasm; Extracellular Space; Fibrin; Microscopy, Electron; Necrosis; Plasma; Rats; Spinal Cord; Wounds and Injuries

Topics: Animals; Blood Coagulation; Brain Neoplasms; Carbon Tetrachloride Poisoning; Carcinoma 256, Walker; Female; Fibrin; Heart Neoplasms; In Vitro Techniques; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Mesentery; Neoplasm Metastasis; Neoplastic Cells, Circulating; Rats; Testicular Neoplasms; Wounds and Injuries

Topics: Arteries; Blood Platelets; Cricetinae; Fibrin; Hemostasis; Hemostatics; Humans; Pathology; Physiology; Research; Thrombosis; Wounds and Injuries

Topics: Embolism; Fibrin; Forensic Medicine; Fractures, Bone; Humans; Pulmonary Embolism; Wounds and Injuries

Topics: Fibrin; Fibrinolysis; Humans; Wounds and Injuries

Topics: Fibrin; Fibrinolysis; Humans; Trypsin; Wound Healing; Wounds and Injuries

Topics: Cornea; Corneal Injuries; Fibrin; Humans; Wounds and Injuries

Topics: Anti-Bacterial Agents; Bacitracin; Fibrin; Humans; Neomycin; Plasma; Psychotherapy; Wounds and Injuries

Topics: Burns; Cornea; Corneal Diseases; Disease; Fibrin; Humans; Wounds and Injuries

Topics: Cervix Uteri; Female; Fibrin; Humans; Inorganic Chemicals; Neoplasms; Wounds and Injuries

Topics: Dura Mater; Fibrin; Fibrin Foam; Frontal Lobe; Humans; Wounds and Injuries