fibrin and Thrombocytopenia

Baboons are susceptible to natural Ebola virus (EBOV) infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV) infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited.

Topics: Animals; Base Sequence; Blood Coagulation Factors; Disease Models, Animal; Ebolavirus; Fibrin; Hemorrhagic Fever, Ebola; Humans; Lymphatic Diseases; Marburg Virus Disease; Marburgvirus; Necrosis; Papio; Sequence Homology, Nucleic Acid; Species Specificity; Thrombocytopenia

Topics: Afibrinogenemia; Disseminated Intravascular Coagulation; Fibrin; Humans; Kallikreins; Liver; Liver Cirrhosis; Spleen; Thrombocytopenia

The authors describe the pathophysiology of disseminated intravascular coagulation and the coagulopathy of utilization. The clinical and laboratory data on different types of shock are described. The efficacy of different antithrombotic agents in shock with disseminated intravascular coagulation is shown.

Topics: Blood Coagulation Disorders; Blood Platelets; Cyclic AMP; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysis; Hemostasis; Humans; Microcirculation; Respiratory Distress Syndrome; Shock; Thrombocytopenia; Thrombosis

1. The lack of a general agreement on the definition of PE makes the interpretation of laboratory findings in different series of these patients difficult. 2. Thrombocytopenia is the most common hemostatic abnormality in patients with PE and is caused by platelet consumption. 3. There is little concrete evidence that thrombin mediates the thrombocytopenia in most of these patients. 4. Immune mechanisms or severe vasospasm with resultant endothelial damage may contribute to the thrombocytopenia in some patients.

Topics: Anemia, Hemolytic; Disseminated Intravascular Coagulation; Eclampsia; Epoprostenol; Factor VIII; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Hypertension; Platelet Count; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thrombocytopenia; Thromboxane A2

Disturbances of haemostasis caused immunologically and non-immunologically were observed after transfusion of blood and blood derivatives. Transfusion of heparin blood increased the bleeding susceptibility only in case of pre-existing high-degree defects of haemostasis or if they were performed as massive or exchange transfusions. Massive transfusions with blood stored for a long time will induce complex defects. Under intensive substitution therapy of haemophilia A the so-called paradoxical bleeding will occur in spite of a high factor VIII level. These bleedings are supposed to be disturbances of the thrombocyte function and are caused by fibrin(ogen) derivatives. Post-transfusional thrombocytopenias may be brought to remission by repeated plasmapheresis. Factor specific inhibitory bodies will appear after substitution in a small percentage of haemophilic patients. 5 to 7 days after the onset of therapy an anamnestic reaction can be observed as a titre increase by leaps. Usually, the inhibitory titre will decrease to a mostly low basal value in the course of three to five months. The therapy with cyclophosphamide simultaneously started with the substitution will more frequently prevent the anamnestic reaction or reduce it. Titres with more than 5 units cannot be overcome at the beginning even by higher concentrations of preparations. The substitution therapy should be preceded by exchange transfusions or plasmapheresis of up to 25 units. With still higher titres only procedures of inhibitor-bypassing are possible with factor VIII preparations of animal origin or better with activated prothrombin complex preparations, such as FEIBA. Recent reports give evidence that permanent substitution with factor VIII concentrates at a highest dosage can eliminate the production of inhibitors completely.

Topics: Blood Coagulation Disorders; Blood Transfusion; Cyclophosphamide; Factor IX; Factor IXa; Factor XIII; Fibrin; Fibrinogen; Hemophilia A; Hemostasis; Heparin; Humans; Platelet Aggregation; Thrombocytopenia; von Willebrand Diseases

Topics: Antithrombins; Blood Cell Count; Blood Coagulation Tests; Blood Transfusion; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Terminology as Topic; Thrombocytopenia

Topics: Adenosine Diphosphate; Binding Sites; Blood Platelet Disorders; Blood Platelets; Cell Membrane; Cholesterol; Collagen; Epinephrine; Factor VIII; Fibrin; Glycoproteins; Humans; Membrane Fluidity; Membrane Lipids; Membrane Proteins; Thrombin; Thrombocytopenia

Topics: Animals; Blood Coagulation; Blood Vessels; Endothelium; Fibrin; Hemorrhagic Disorders; Hemostasis; Humans; Platelet Adhesiveness; Platelet Aggregation; Thrombocytopenia

The evidence for intravascular coagulation in liver diseases is critically reviewed. Alternative mechanisms for hypofibrinogenemia and the accelerated disappearance of fibrinogen from blood are proposed, such as loss into extravascular compartments (e.g., ascites, areas of liver necrosis, etc.). Possible mechanisms other than DIC for the elevation of serum FDP are also considered, such as extravascular fibrinogen proteolysis with subsequent transfer of FDP to blood. Therapy is discussed with reference to the current knowledge on pathophysiology of the coagulation defect in liver diseases.

Topics: Afibrinogenemia; Blood Cell Count; Blood Platelets; Disseminated Intravascular Coagulation; Factor V Deficiency; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Half-Life; Hemophilia A; Heparin; Humans; Liver Diseases; Peptide Hydrolases; Thrombocytopenia; Thrombosis

Topics: Afibrinogenemia; Anti-Infective Agents; Antigens; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemagglutination Inhibition Tests; Heparin; Humans; Prothrombin Time; Radioimmunoassay; Thrombin; Thrombocytopenia; Thromboplastin

Topics: Adenine Nucleotides; Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Clot Retraction; Collagen; Fibrin; Fibrinogen; Hemostasis; Kidney Diseases; Liver Diseases; Platelet Adhesiveness; Thrombocytopenia; Thrombocytosis

Heparin-induced thrombocytopenia (HIT) is a major concern for all individuals that undergo cardiac bypass surgeries or require prolonged heparin exposure. HIT is a life- and limb-threatening adverse drug reaction with an immune response following the formation of ultra-large immune complexes that drive platelet activation through the receptor FcγRIIA. Thrombotic events remain high following the standard of care treatment with anticoagulants, while increasing risk of bleeding complications. This study sought to investigate a novel approach to treatment of HIT. Recent reports demonstrate increased procoagulant activity in HIT; however, these reports required analysis ex vivo, and relevance in vivo remains unclear.. Using human and mouse model systems, we investigated the cooperativity of PARs (protease-activated receptors) and FcγRIIA in HIT. We challenged humanized FcγRIIA transgenic mice with or without endogenous mouse Par4 (denoted as IIA-Par4. IIA-Par4. These data demonstrate for the first time the need for dual platelet receptor (PAR and FcγRIIA) stimulation for fibrin formation in HIT in vivo. These results extend our understanding of HIT pathophysiology and provide a scientific rationale for targeting the procoagulant phenotype as a possible therapeutic strategy in HIT.

Topics: Animals; Anticoagulants; Blood Platelets; Fibrin; Heparin; Humans; Mice; Mice, Transgenic; Phenotype; Platelet Factor 4; Thrombocytopenia

In order to improve the safety of COVID-19 vaccines, there is an urgent need to unravel the pathogenesis of vaccineinduced immune thrombotic thrombocytopenia (VITT), a severe complication of recombinant adenoviral vector vaccines used to prevent COVID-19, and likely due to anti-platelet factor 4 (PF4) IgG antibodies. In this study, we demonstrated that 1E12, a chimeric anti-PF4 antibody with a human Fc fragment, fully mimics the effects of human VITT antibodies, as it activates platelets to a similar level in the presence of platelet factor 4 (PF4). Incubated with neutrophils, platelets and PF4, 1E12 also strongly induces NETosis, and in a microfluidic model of whole blood thrombosis, it triggers the formation of large platelet/leukocyte thrombi containing fibrin(ogen). In addition, a deglycosylated form of 1E12 (DG-1E12), which still binds PF4 but no longer interacts with Fcγ receptors, inhibits platelet, granulocyte and clotting activation induced by human anti-PF4 VITT antibodies. This strongly supports that 1E12 and VITT antibodies recognize overlapping epitopes on PF4. In conclusion, 1E12 is a potentially important tool to study the pathophysiology of VITT, and for establishing mouse models. On the other hand, DG-1E12 may help the development of a new drug that specifically neutralizes the pathogenic effect of autoimmune anti-PF4 antibodies, such as those associated with VITT.

Topics: Animals; COVID-19; COVID-19 Vaccines; Epitopes; Fibrin; Humans; Immunoglobulin Fc Fragments; Immunoglobulin G; Mice; Platelet Activation; Platelet Factor 4; Purpura, Thrombocytopenic, Idiopathic; Receptors, IgG; Thrombocytopenia; Thrombosis

Thrombosis is a severe and frequent complication of heparin-induced thrombocytopenia (HIT). However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We evaluate the effect of the addition of pathogenic HIT-like antibodies to blood on the resulting microstructure of the formed clot.. Pathogenic HIT-like antibodies (KKO) and control antibodies (RTO) were added to samples of whole blood containing Unfractionated Heparin and Platelet Factor 4. The formed clot microstructure was investigated by rheological measurements (fractal dimension; d. Our results revealed striking effects of KKO on clot microstructure. A significant difference in d

Topics: Fibrin; Heparin; Humans; Platelet Factor 4; Thrombocytopenia; Thrombosis

BACKGROUND Radiofrequency ablation is a minimally invasive treatment for arrhythmias, including frequent ventricular premature. As a complication of radiofrequency ablation, pseudoaneurysm can be treated conservatively or by ultrasound-guided thrombin injection. CASE REPORT We report a case that a possible allergic reaction to thrombin injected into pseudoaneurysm after radiofrequency ablation. CONCLUSIONS We hope that the report of successful management of the allergic reaction in this case may be of help to other doctors; we also emphasize the importance of checking the patient's history of allergies to thrombin when considering treating pseudoaneurysm with thrombin injection.

Topics: Aged, 80 and over; Alanine Transaminase; Aneurysm, False; Drug Hypersensitivity; Electrocardiography; Female; Femoral Artery; Fever; Fibrin; Fibrin Fibrinogen Degradation Products; Hemoglobins; Hemostatics; Humans; Hypotension; Injections, Intra-Arterial; Leukopenia; Nausea; Radiofrequency Ablation; Thrombin; Thrombocytopenia; Ventricular Premature Complexes

Topics: Animals; Bacterial Proteins; Fibrin; Heparin; Humans; Immunoglobulin G; Mice, Transgenic; Microfluidic Analytical Techniques; Platelet Aggregation; Platelet Factor 4; Receptors, IgG; Streptococcus pyogenes; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies against complexes between human platelet factor 4 (hPF4) and heparin. A better understanding of the events that initiate the prothrombotic state may improve approaches to antithrombotic management. Here, we visualized thrombus formation in an in vivo murine model and an endothelialized microfluidic system that simulate the pathogenesis of HIT. hPF4 released from platelets predominantly bound to peri-injury endothelium and formed HIT antigenic complexes that were dissociated by heparin. In mice expressing both hPF4+ and human platelet IgG Fc receptor IIA (FcγRIIA), infusion of the HIT-like monoclonal antibody KKO increased fibrin and platelet deposition at sites of injury, followed immediately by antigen formation on proximate endothelial cells. After a few minutes, HIT antigen was detected within the thrombus itself at the interface between the platelet core and the surrounding shell. We observed similar results in the humanized, endothelialized microfluidic system. hPF4 and KKO selectively bound to photochemically injured endothelium at sites where surface glycocalyx was reduced. These studies support the concept that the perithrombus endothelium is the predominant site of HIT antigen assembly. This suggests that disrupting antigen formation along the endothelium or protecting the endothelium may provide a therapeutic opportunity to prevent thrombotic complications of HIT, while sparing systemic hemostatic pathways.

Topics: Animals; Blood Platelets; Disease Models, Animal; Female; Fibrin; Glycocalyx; Heparin; Humans; Male; Mice, Knockout; Platelet Factor 4; Receptors, IgG; Thrombocytopenia; Thrombosis

Platelet- and fibrin-dependent thrombus formation is regulated by blood flow and exposure of collagen and tissue factor. However, interactions between these blood-borne and vascular components are not well understood.. Here, we developed a method to assess whole-blood thrombus formation on microspots with defined amounts of collagen and tissue factor, allowing determination of the mechanical properties and intrathrombus composition. Confining the collagen content resulted in diminished platelet deposition and fibrin formation at high shear flow conditions, but this effect was compensated by a larger thrombus size and increased accumulation of fibrin in the luminal regions of the thrombi at the expense of the base regions. These thrombi were more dependent on tissue factor-triggered thrombin generation. Microforce nanoindentation analysis revealed a significantly increased microelasticity of thrombi with luminal-oriented fibrin. At a low shear rate, fibrin fibers tended to luminally cover the thrombi, again resulting in a higher microelasticity. Studies with blood from patients with distinct hemostatic insufficiencies indicated an impairment in the formation of a platelet-fibrin thrombus in the cases of dilutional coagulopathy, thrombocytopenia, Scott syndrome, and hemophilia B.. Taken together, our data indicate that (1) thrombin increases the platelet thrombus volume; (2) tissue factor drives the formation of fibrin outside of the platelet thrombus; (3) limitation of platelet adhesion redirects fibrin from bottom to top of the thrombus; (4) a lower shear rate promotes thrombus coverage with fibrin; (5) the fibrin distribution pattern determines thrombus microelasticity; and (6) the thrombus-forming process is reduced in patients with diverse hemostatic defects.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Flow Velocity; Blood Platelets; Case-Control Studies; Collagen; Elasticity; Fibrin; Hemophilia B; Humans; Regional Blood Flow; Thrombocytopenia; Thromboplastin; Thrombosis; Time Factors

Inflammation and thrombosis coexist in several disorders. Although it is recognized that leukocytes may induce a procoagulant state at sites of inflammation, the critical molecular determinants of this process remain largely unknown.. To examine mechanisms of inflammation-induced thrombosis, we developed a murine model of thrombotic glomerulonephritis (TGN), a known cause of acute renal failure in patients. This model, induced by lipopolysaccharide and antibody to the glomerular basement membrane, led to rapid glomerular neutrophil recruitment, thrombotic glomerular lesions with endothelial cell injury, and renal dysfunction. In mice immunodepleted of neutrophils or lacking the leukocyte-specific integrin Mac-1, neutrophil recruitment, endothelial injury, glomerular thrombosis, and acute renal failure were markedly attenuated despite the robust generation of renal cytokines. Neutrophil elastase is a likely effector of Mac-1 because its activity was reduced in Mac-1-deficient mice and the phenotype in mice deficient in Mac-1 or neutrophil elastase was similar. Platelets accumulated in glomerular capillaries within 4 hours of TGN before evidence of thrombosis. Platelet immunodepletion before TGN markedly exacerbated hematuria (hemorrhage), inflammation, and injury, whereas thrombocytopenic Mac-1-deficient mice remained resistant to disease, indicating that initial glomerular platelet deposition protects the vessel wall from neutrophil-mediated sequelae. The subsequent thrombosis relied on the interaction of Mac-1 on recruited neutrophils with glycoprotein Ibalpha on platelets as antibody-mediated disruption of this interaction attenuated TGN without affecting renal neutrophil accumulation.. These observations establish Mac-1 on neutrophils as a critical molecular link between inflammation and thrombosis and suggest it as an attractive target for antithrombotic therapy.

Topics: Acute Kidney Injury; Animals; Antibodies; Blood Platelets; Cytokines; Disease Models, Animal; Female; Fibrin; Glomerulonephritis; Leukocyte Elastase; Macrophage-1 Antigen; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neutrophils; Platelet Glycoprotein GPIb-IX Complex; Thrombocytopenia; Thrombosis

Macrothrombocytopenia is a rare condition where large, circulating platelets ranging between approximately 5 and 20 microm are found (typically platelets size range from 1.5 to 2.5 microm). The condition is also characterized by the prevalence of decreased numbers of circulating platelets, bleeding, short circulating times in blood, as well as abnormal platelet destruction. The current research investigates the scanning electron microscopy (SEM) and transmission electron microscopy (TEM) of platelet aggregates and fibrin networks of a family diagnosed with macrothrombocytopenia. Although TEM analysis of macrothrombocytopenia is not novel, little is known regarding the SEM analysis of platelet aggregates and fibrin networks. Here the authors show that macrothrombocytopenia have two different variations of giant platelet aggregates: a bulbous, giant aggregate that is very similar to control aggregates, and a giant flattened aggregate, with a compressed outer rim and a centrally placed area that forms a bulbous pseudopodia-like core. TEM micrographs of controls showed that, as previously seen in the literature, an aggregate contains dense bodies and alpha granules that carry, among other compounds, fibrinogen. TEM micrographs of the individuals with macrothrombocytopenia revealed aggregates with large vacuoles and areas mostly devoid of dense bodies and alpha granules. An interesting observation was that, in the presence of added human thrombin (to initially form the clot), fibrin fiber networks, comparable to that of control fibrin networks, were formed. This might be of clinical interest in the treatment regime and should be investigated further.

Topics: Blood Platelets; Cytoplasmic Granules; Fibrin; Fibrinogen; Humans; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Platelet Aggregation; Platelet Count; Thrombin; Thrombocytopenia; Vacuoles

Coagulopathy and thrombocytopenia often occur in critically ill patients, and disseminated intravascular coagulation (DIC) can lead to multiple organ dysfunction and a poor outcome. However, the relation between coagulopathy and systemic inflammatory response has not been thoroughly clarified. Thus, we evaluated coagulative activity, organ dysfunction, and systemic inflammatory response syndrome (SIRS) in critically ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation.. Two hundred seventy-three patients, who were admitted to 13 critical care centers in Japan and fulfilled the criteria of platelet count of less than 150*10(9)/L, were included. Coagulative variables (platelet count, fibrin/fibrinogen degradation products, and DIC scores), organ dysfunction index (Sequential Organ Failure Assessment [SOFA] score), and SIRS score in each patient were evaluated for 4 consecutive days after fulfilling the above entry criteria. The effect of SIRS on coagulopathy and organ dysfunction was evaluated in these patients.. Both the maximum SIRS score and entry SIRS score had significant relation to the maximum SOFA score during the observation period. Coagulation disorders indicated by the minimum platelet count, maximum DIC scores, and positivity for DIC worsened gradually with increases in SIRS scores. Both the minimum platelet count and maximum DIC scores were significantly correlated with the maximum SOFA score, indicating that a relation exists between coagulopathy and organ dysfunction.. In critically ill patients with thrombocytopenia, coagulopathy and organ dysfunction progress with significant mutual correlation, depending on the increase in SIRS scores. The SIRS-associated coagulopathy may play a critical role in inducing organ dysfunction after severe insult.

Topics: Adult; Aged; Analysis of Variance; Blood Coagulation Disorders; Critical Illness; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Multiple Organ Failure; Platelet Count; Sepsis; Systemic Inflammatory Response Syndrome; Thrombocytopenia

The mechanism of action of recombinant factor VIIa (rFVIIa), which is being considered as an alternative treatment for the control of bleeding episodes in patients with thrombocytopenia, has not been fully characterized. This study was undertaken to explore the effects of rFVIIa and platelet microvesicles on hemostasis in an experimental model of thrombocytopenia. Damaged arterial segments were exposed to thrombocytopenic blood (shear rate 600 s(-1)) either with or without the addition of rFVIIa and/or platelet microvesicles. The presence of fibrin and platelets on the subendothelium were morphometrically quantified and immunolocalization techniques and electron microscopy were used for a more detailed analysis. Both rFVIIa and platelet microvesicles consistently improved fibrin formation on the damaged vascular subendothelium, and microvesicles were shown to be localized at different levels of the fibrin lattice. Further, under conditions of moderate thrombocytopenia, addition of platelet microvesicles potentiated the procoagulant action of rFVIIa. This effect may be due to the phospholipid surface provided by the platelet microvesicles. These studies support the concept that, under conditions of thrombocytopenia, both rFVIIa and platelet microvesicles enhance fibrin formation at sites of vascular damage.

Topics: Arteries; Blood Coagulation; Blood Platelets; Cell Membrane; Factor VII; Factor VIIa; Fibrin; Humans; In Vitro Techniques; Recombinant Proteins; Thrombocytopenia

Despite being well established that snake envenomation causes blood coagulation and fibrinolysis disturbances, scant information is available about blood platelet disorders. Herein we show that experimentally Bothrops jararaca-envenomed rabbits presented thrombocytopenia, hypofibrinogenemia, elevation of von Willebrand factor plasma levels, platelet hypoaggregation in platelet rich plasma and whole blood, normoaggregation in washed platelet suspensions, decreased platelet ATP secretion, normal plasma levels of platelet factor 4, and constant intraplatelet serotonin levels. Furthermore, by flow cytometric analyses, platelets displayed a significant decrease in the expression of a GPIIb-IIIa epitope recognized by P2 monoclonal antibody (p< 0.05) and an increased expression of a ligand-induced binding site (LIBS-1) of GPIIIa (p< 0.05), but total GPIIb-IIIa expression, evaluated with specific polyclonal antibodies, was normal. Fibrinogen and fibrin(ogen) degradation product (FfDP) expression on platelet surface showed no significant alteration. Nonetheless, significant elevations of platelet P-selectin were noticed on circulating platelets. The percentage of circulating reticulated platelets and the survival time of biotinylated platelets of envenomed rabbits were not statistically different from control animals. We suggest that thrombin engendered by procoagulating components of B. jararaca venom has an essential role in the pathogenesis of platelet and coagulation disorders in this experimental model. Increased expression of P-selectin in the experimental group demonstrates that platelets of envenomed rabbits are indeed activated in circulation, and that decreased fibrinogen or increased FfDP levels are not the primary cause of platelet dysfunction. These results imply the existence of an inhibitor in plasma that interferes with platelet aggregation in bothropic envenomation.

Topics: Animals; Antibodies, Monoclonal; Blood Platelet Disorders; Blood Platelets; Bothrops; Collagen; Epitopes; Fibrin; Fibrinogen; Flow Cytometry; Immunohistochemistry; Kidney; Lung; P-Selectin; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Rabbits; Snake Bites; Snake Venoms; Thrombocytopenia; Time Factors; von Willebrand Factor

Recombinant FVIIa (rFVIIa) has been shown to improve hemostasis in patients with thrombocytopenia and to prevent or control bleeding episodes in patients with inherited deficiencies of major PLT glycoproteins, but the mechanism of action is not well understood.. Effects of rFVIIa on hemostasis were explored with an in vitro perfusion technique. Blood samples, from healthy donors or from patients with congenital defects of PLT glycoprotein IIb-IIIa (GPIIb-IIIa), were anticoagulated with low-molecular-weight heparin. Experimental thrombocytopenia (<6000 PLTs/microL) was induced by a filtration procedure. rFVIIa was added to blood samples at therapeutic concentrations. A severe GPIIb-IIIa impairment was also induced by exposure of normal blood samples to a specific antibody. Perfusion studies were performed through annular chambers containing damaged vascular segments. The presence of fibrin and PLTs on the perfused subendothelium was morphometrically quantified.. Under conditions of experimental thrombocytopenia, addition of rFVIIa enhanced fibrin formation in a dose-dependent manner (p < 0.05). Improvements in local fibrin generation and partial restoration of PLT interactions were also observed after incubation of blood from patients with Glanzmann's thrombasthenia with rFVIIa at 5 microg per mL (180 microg/kg). Similar improvements were observed in blood samples incubated with antibodies to GPIIb-IIIa. rFVIIa in whole normal blood also enhanced fibrin formation but PLT deposition was unaffected. Evaluation of prothrombin fragments 1 and 2 in the perfusates confirmed that rFVIIa increased thrombin generation in all cases.. Our data indicate that rFVIIa promotes a procoagulant activity at sites of vascular damage. This mechanism could explain the beneficial hemostatic effect of rFVIIa in patients with thrombocytopenia or with Glanzmann's thrombasthenia.

Topics: Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Factor VIIa; Fibrin; Hemostasis; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prothrombin; Recombinant Proteins; Thrombasthenia; Thrombocytopenia; Thromboplastin

We explored the effect on haemostasis of different factor IX (FIX) concentrates under thrombocytopenic conditions using an in vitro perfusion technique.. A moderate experimental thrombocytopenia (25 000-30 000 platelets/microl) was induced by means of a filtration procedure in blood anticoagulated with low-molecular-weight heparin. The effects of three different FIX concentrates - a prothrombin complex concentrate (PCC), an intermediate-purity concentrate (FIX/X), and a high-purity concentrate (HPFIX) - on platelet deposition and fibrin formation on subendothelium were assessed at two different shear rates (600/second and 1200/second). Activation of the coagulation system was monitored through assessment of prothrombin activation fragment 1 + 2 (F1 + 2).. Fibrin deposition increased after addition of FIX concentrates, but only showed a significant increase in experiments performed after incubation of PCC at the lower shear rate (600/second) (64.25 +/- 9.61% vs. control 31.22 +/- 8.02%; P < 0.05). Addition of FIX concentrates caused a small increase in the percentage of platelet deposition and area of those aggregates. These differences reached levels of statistical significance in the presence of FIX/X and HPFIX in experiments performed at a shear rate of 600/second. F1 + 2 baseline values in anticoagulated thrombocytopenic blood were 1.15 +/- 0.13 nm and reached levels of 2.49 +/- 0.24 and 3.60 +/- 0.33 nm at shear rates of 600 and 1200/second, respectively. Increments in F1 + 2 observed after addition of different FIX concentrates always remained in the previous ranges.. Data from the present study provide experimental support favouring the concept that FIX concentrates containing other activated factors could improve haemostasis under conditions of moderate thrombocytopenia.

Topics: Animals; Aorta; Disease Models, Animal; Factor IX; Fibrin; Hemostasis; Humans; Rabbits; Thrombocytopenia

The possibility of developing synthetic platelet substitutes is a subject of current interest. We explored the possible hemostatic effect of synthetic phospholipid incorporated in multilamellar vesicles (MLVs) or intermediate unilamellar vesicles (IUVs) using a well-characterized experimental system with circulating human thrombocytopenic blood (10 min, 250 s(-1)).. The ability of the liposomes containing different combinations of dipalmitoylphosphatidylcholine (DPPC), phosphatidylethanolamine (PE) and dipalmitoylphosphatidylserine (DPPS) to promote fibrin formation (%F) on the damaged subendothelium was morphometrically evaluated. Generation of thrombin in the system was monitored through prothrombin fragment F1+2 determination.. IUV liposomes containing DPPC, 1DPPS:9DPPC, 1DPPS:3DPPC, 1PE:1DPPC increased fibrin deposition on the subendothelium (53.87 +/- 11.0%; 39.76 +/- 6.75%; 40.69 +/- 10.54% and 32.22 +/- 7.35%, respectively vs. thrombocytopenic blood 11.5 +/- 1.2%; p<0.05), while 9PE:1DPPS IUV liposome failed to promote a procoagulant effect. MLV liposomes containing DPPC alone, 1DPPS:3DPPC and 1PE:1DPPC showed a positive effect on fibrin deposition (85.50 +/- 5.95%, 59.86 +/- 11.55% and 43.73 +/- 7.84% respectively; p<0.05). However, no effect was observed in those experiments performed with liposomes containing 3DPPS:1DPPC. After perfusion experiments, the coagulation system became activated, but differences were not statistically significant vs. control experiments, except for MLV liposomes containing DPPC alone (p<0.05).. These results confirm that, at an experimental level, liposomes containing phospholipids could potentially be used to improve hemostasis in patients with quantitative or qualitative platelet disorders.

Topics: Animals; Aorta; Blood Circulation; Blood Platelet Disorders; Endothelium, Vascular; Fibrin; Hemostatics; Humans; Liposomes; Models, Cardiovascular; Phospholipids; Platelet Count; Rabbits; Thrombocytopenia

The relationship between platelet and leukocyte activation, coagulation, and neointima development was investigated in noninjured murine blood vessels subjected to blood stasis. The left common carotid artery of C57BL/6J mice was ligated proximal to the bifurcation. Tissue-factor expression in luminal leukocytes progressively increased over 2 weeks. On day 3 after ligation, in addition to infiltrated granulocytes, platelet microthrombi and platelet-covered leukocytes as well as tissue-factor-positive fibrin deposits lined the endothelium. Maximal neointima formation in carotid artery cross sections of control mice equaled 28+/-3.7% (n=11) and 42+/-5.1% (n=8) of the internal elastic lamina cross-sectional area 1 and 2 weeks after ligation. In FVIII(-/-) mice, stenosis was significantly lower 1 (11+/-3.6%, n=8) and 2 (21+/-4.7%, n=7) weeks after ligation (both P:<0.01 versus background-matched controls). In u-PA(-/-) mice, luminal stenosis was significantly higher 1 (38+/-7.0%, n=7) and 2 (77+/-5.6%, n=6) weeks after ligation (P:<0.05 and P:<0.01, respectively, versus matched controls). In alpha(2)-AP(-/-) mice, stenosis was lower at 1 week (14+/-2.6%, n=7, P:<0.01) but not at 2 weeks. Responses in tissue-type plasminogen activator or plasminogen activator inhibitor-1 gene-deficient mice equaled that in controls. Reducing plasma fibrinogen levels in controls with ancrod or inducing partial thrombocytopenia with busulfan resulted in significantly less neointima, but inflammation was inhibited only in busulfan-treated mice. We conclude that stasis induces platelet activation, leading to microthrombosis and platelet-leukocyte conjugate formation, triggering inflammation and tissue-factor accumulation on the carotid artery endothelium. Delayed coagulation then results in formation of a fibrin matrix, which is used by smooth muscle cells to migrate into the lumen.

Topics: Afibrinogenemia; Animals; Blood Coagulation; Blood Platelets; Carotid Arteries; Cell Division; Disease Models, Animal; Endothelium, Vascular; Fibrin; Hemostatic Disorders; Inflammation; Leukocytes; Ligation; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular; Platelet Activation; Thrombocytopenia; Thromboplastin; Thrombosis; Tunica Intima

The action of recombinant factor VIIa (rFVIIa) in coagulation deficiencies with increased risk of bleeding was investigated using in vitro perfusion. Blood samples were drawn from healthy donors, a patient with hemophilia A and inhibitors, and six patients undergoing oral anticoagulant treatment. Fragmin 10 U/mL was used as anticoagulant. rFVIIa (10 microg/mL in plasma) was added to blood samples, incubated for 1 minute at 37 degrees C, and perfusion studies performed for 10 minutes at 600 x s(-1) through annular chambers containing damaged vascular segments. Subendothelial fibrin and platelets were expressed as a percentage of subendothelial surface screened. Under different conditions, rFVIIa consistently restored or improved fibrin formation on the damaged vascular subendothelium exposed to circulating blood. It restored fibrin deposition in blood from the hemophilia A patient; in patients undergoing acenocoumarol treatment, it reduced the international normalized ratio (INR) from 2.47 to 1.25 with a significant increase in fibrin deposition. Platelet deposition varied slightly between clinical conditions but was less evident in the hemophilia A patient. These data support the concept that rFVIIa facilitates fibrin formation in these clinical situations, promoting procoagulant activity at sites of vascular damage where tissue factor is exposed. This could improve hemostasis in patients with hemophilia A and inhibitors, and in patients treated with oral anticoagulants.

Topics: Adult; Anticoagulants; Blood Coagulation; Blood Platelets; Coagulants; Dalteparin; Factor VII; Factor VIIa; Fibrin; Hemophilia A; Humans; International Normalized Ratio; Male; Perfusion; Platelet Aggregation; Recombinant Proteins; Stress, Mechanical; Thrombocytopenia

Disseminated intravascular coagulation in humans is frequently associated with Gram-negative bacterial sepsis. Therefore, to examine the role and time frame of the in vivo induction of tissue factor (TF) by bacterial endotoxin, a reverse transcription polymerase chain reaction and a solid-phase ELISA assay were developed to monitor the in vivo production in rabbits, of TF mRNA and TF antigen by peripheral blood leukocytes (PBL).. : Healthy rabbits were injected intravenously with either 1, 10 or 50 microg/kg of Salmonella endotoxin. Blood samples were obtained both before endotoxin administration and at various time points thereafter, up to 24 h. Some experiments were also done to determine whether all-trans retinoic acid would ameliorate the signs of the endotoxin-induced disseminated intravascular coagulation.. PBL counts dropped significantly within 2 h of rabbits receiving the endotoxin, recovering to baseline levels by 24 h. Platelet counts decreased gradually over this same time frame. Fibrin deposition was noted in renal glomerular capillaries at 24 h. An increase (P<0.001) in PBL-associated TF mRNA levels was observed 2 h post-endotoxin (10 microg/kg, n = 8), followed by a gradual decline over the subsequent 24 h. The average increase in TF mRNA at 2 h was approximately 4.6-fold (P<0.001) over that seen at time 0. The amount of mononuclear cell associated TF antigen demonstrated a peak at 2 h post-endotoxin (10 microg/kg, n = 13), with levels approximately 9.6-fold greater than (P<0.001) baseline. Pre-treatment of rabbits with all-trans retinoic acid significantly (P<0.001) ameliorated the PBL-associated increase in TF mRNA and TF antigen levels.. These results suggest that low dose endotoxin (10 microg/kg) faithfully reproduces the non-overt activation of coagulation observed in primates and human volunteers, supporting the hypothesis that TF expression is involved in the in vivo initiation and propagation of disseminated intravascular coagulation. Moreover, all-trans retinoic acid may be effective in modulating in vivo the TF transcription induced by endotoxin.

Topics: Animals; Antithrombin III; Blood Cell Count; Disseminated Intravascular Coagulation; Drug Evaluation, Preclinical; Endotoxemia; Fibrin; Fibrinogen; Gene Expression Regulation; Kidney Glomerulus; Leukocytes; Lipopolysaccharides; Male; Rabbits; RNA, Messenger; Thrombocytopenia; Thromboplastin; Tretinoin

The potential hemostatic effect of infusible platelet membranes (IPM; Cyplex, Cypress Bioscience) prepared from outdated human platelets is investigated.. Increasing concentrations of IPM were added to blood samples anticoagulated with low-molecular-weight heparin, in which platelets and WBC counts had been experimentally reduced by a filtration procedure. Thrombocytopenic blood with IPM was circulated in a perfusion chamber at various shear rates (300, 600, and 1200/sec(-1)), and platelet and fibrin deposition on the surface of a damaged vessel was measured. Prothrombin fragments 1 and 2 (F1+2) levels were also monitored.. Under conditions of severe thrombocytopenia (<6000 platelets/microL) IPM did not increase platelet deposition. However, a dose-dependent increase in fibrin deposition was observed with concentrations of IPM ranging from 0.5 to 2 mg per kg in perfusions at 300 and 600 per sec(-1) (p<0.05 vs. thrombocytopenic blood). Experimental studies performed under conditions of moderate thrombocytopenia and higher shear rates (25, 000-30,000 platelets/microL; at 600 and 1200/sec(-1)) showed that IPM concentrations equivalent to 0.5 or 1 mg per kg improved fibrin deposition (33.5 +/- 9.5% and 37.7 +/- 12.8%, respectively, vs. 22.7 +/- 5.2% in controls) and also promoted a moderate increase in platelet deposition, with a concomitant significant increase in the size of platelet aggregates (p<0.05). Exposure of thrombocytopenic blood to a damaged vessel resulted in an increase of F1+2 levels from 0.8 +/- 0.15 to 1.7 +/- 0.22 nM at 300 per sec(-1) and 1.94 +/- 0.46 nM at 600 per sec(-1). Postperfusion levels of F1+2 after the addition of IPM were always similar to levels in untreated controls.. IPM promotes local procoagulant activity at sites of vascular damage under conditions of severe and moderate thrombocytopenia. IPM also appears to facilitate platelet cohesive functions under conditions of moderate thrombocytopenia.

Topics: Blood Platelets; Cell Membrane; Endothelium, Vascular; Fibrin; Hemostasis; Humans; Platelet Transfusion; Thrombocytopenia

Topics: Antibodies; Anticoagulants; Echocardiography; Female; Fibrin; Heart Valve Prosthesis; Heparin; Humans; Immunoglobulin G; Middle Aged; Mitral Valve; Prosthesis Failure; Reoperation; Thrombocytopenia; Thrombosis

There is considerable evidence for a relationship between hemostasis and malignancy. Since platelet adhesion to tumor cells has been implicated in the metastatic process and plasma levels of fibrinogen (Fg) and soluble fibrin (sFn) monomer are increased in cancer, we hypothesized that these molecules might enhance tumor-platelet interaction. We therefore studied binding of sFn monomer to tumor cells in a static microplate adhesion assay and determined the effect of pre-treating tumor cells with sFn on tumor cell-induced thrombocytopenia and experimental metastasis. Soluble fibrin (produced by adding thrombin to FXIII- and plasminogen-free Fg in the presence of Gly-Pro-Arg-Pro-amide (GPRP-NH2) significantly increased platelet adherence to tumor cells. This effect was primarily mediated by the integrins alphaIIb beta3 on the platelet and CD 54 (ICAM-1) on the tumor cells. Platelets adhered to untreated A375 cells (28 +/- 8 platelets/tumor cell) and this was not significantly affected by pre-treatment of the tumor cells with fibrinogen or GPRP-NH2. Although thrombin treatment increased adherence, pre-incubation of the tumor cells with sFn resulted in a further increase in platelet binding to tumor cells. In contrast to untreated tumor cells, intravenous injection of sFn-treated A 375 cells reduced the platelet count in anticoagulated mice, supporting the in vitro finding that sFn enhanced tumor cell-platelet adherence. In a more aggressive model of experimental metastasis, treating tumor cells with sFn enhanced lung seeding by 65% compared to untreated cells. Extrapolation of our data to the clinical situation suggests that coagulation activation, and subsequent increase in circulating Fn monomer, may enhance platelet adhesion to circulating tumor cells and thereby facilitate metastatic spread.

Topics: Animals; Antigens, CD; Antigens, Human Platelet; Batroxobin; Blood Platelets; Cell Adhesion; Cell Communication; Female; Fibrin; Fibrinolytic Agents; Flow Cytometry; Hemostatics; Humans; Lung Neoplasms; Melanoma, Amelanotic; Mice; Mice, Nude; Platelet Adhesiveness; Receptors, Thrombin; Solubility; Thrombin; Thrombocytopenia; Tumor Cells, Cultured

The therapeutic use of heparin results in thrombocytopenia in 5-30% of patients. In 0.1-1% of patients treated with heparin, the platelet count decreases to between 100 x 10(9)/l and 50 x 10(9)/l and leads to severe synchronous central arterial and venous thrombosis with a mortality of 18-36%. This is known as "white-clot syndrome" or heparin-induced thrombocytopenia II (HIT-II syndrome). Whilst the clinical aspects and the central type of thrombosis in HIT-II syndrome are well documented, the histomorphology and differential diagnosis of thrombosis are not. We report three cases of HIT-II syndrome with thrombosis of the central arteries and veins. The HIT-II thrombi could be differentiated from thrombi of other origins, particularly from mural thrombi. Heparin-induced thrombi were seen on microscopical examination to be like onion skin in structure, and immunohistochemistry showed that they had a markedly reduced content of fibrin and clearly enhanced amounts of IgG and IgM. The layered structure thus implied appositional growth. The thrombi in HIT-II syndrome do not seem to be induced by activation of the coagulation cascade, but by platelet aggregation mediated by anti-platelet antibodies.

Topics: Aged; Autoantibodies; Fatal Outcome; Female; Fibrin; Heparin; Humans; Immunoglobulin G; Immunoglobulin M; Immunohistochemistry; Thrombocytopenia; Thrombosis

Lung fragments from 12 patients were collected immediately after death and studied by light and electron microscopy and by immunohistochemistry to describe the main morphologic and ultrastructural aspects of the lung and platelets in leptospirosis (Weil's syndrome), to search for the possibility of disseminated intravascular coagulation (DIC), and to assess the relationship between endothelial lesions and local platelet aggregation and the leptospiral antigen distribution, as well as its relationship with the intensity of the lesions. The immunohistochemical results for fibrin aggregates were positive in the lumen and/or on the vascular endothelium in nine cases and on the alveolar surface in seven cases, leading to the diagnosis of the adult respiratory distress syndrome in these seven cases. Test results for leptospiral antigen by immunohistochemistry were positive in eight cases with no direct relationship between antigen deposits in the pulmonary vascular endothelium and intensity of the lesions. The ultrastructural findings were uniform and constant. Capillary lesions were characterized by swelling of endothelial cells, an increase in pinocytotic vesicles, and giant dense bodies in the cytoplasm of these cells. No necrosis, rupture, nor exposed subendothelial collagen was observed outside the hemorrhagic areas, and the intercellular junctions were preserved. The lung involvement in severe human leptospirosis presents as hemorrhagic pneumopathy with septal capillary lesions that are the usual cause of death. The thrombocytopenia that was verified in 11 of 12 patients in our study seems to bear no relationship to DIC and seems to be determined by activation, adhesion, and aggregation of platelets to the stimulated vascular endothelium, with an amorphous electron-dense substance between the endothelial cells and the adherent platelets in places where the subendothelial collagen was not exposed.

Topics: Adult; Antigens, Bacterial; Blood Platelets; Capillaries; Cell Adhesion; Endothelium, Vascular; Female; Fibrin; Hemorrhage; Humans; Immunohistochemistry; Leptospira interrogans; Lung; Lung Diseases; Male; Microscopy, Electron; Middle Aged; Platelet Aggregation; Thrombocytopenia; Weil Disease

Although the importance of injury with consequent activation of endothelium is well-recognized in diseases affecting the glomerular endothelial cell (GEN), research on GEN injury in vivo has been hampered by the lack of adequate animal models. Here we report the establishment and characterization of a new GEN injury model in rats. This model was induced by selective renal artery perfusion with anti-GEN IgG and resulted in the severe acute renal failure with marked platelet deposition and development of a thrombotic microangiopathy involving glomeruli. Peritubular capillary endothelial cells were also damaged that was associated with severe tubular necrosis. Although the glomerular changes were severe, half of the glomeruli recovered by day 10, while interstitial changes remained throughout our observation time course. Proliferation of GEN was observed during the recovery phase. An increased expression of endothelial nitric oxide synthase in GEN was also observed, and may be an adaptive mechanism to counteract the thrombosis and ischemia. This model should be useful to investigate the pathophysiology of renal microvascular diseases and the mechanisms of GEN injury, activation and recovery in vivo.

Topics: Acute Kidney Injury; Anemia; Animals; Blood Urea Nitrogen; Collagen; Complement System Proteins; Disease Models, Animal; Endothelial Growth Factors; Endothelium, Vascular; Fibrin; Kidney; Kidney Glomerulus; Laminin; Lymphokines; Macrophages; Male; Nitric Oxide Synthase; Proteinuria; Rats; Rats, Wistar; Thrombocytopenia; Time Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Topics: Antigens, CD; Antigens, CD34; Blood Cells; Bone Marrow Transplantation; Breast Neoplasms; Cells, Cultured; Colony-Forming Units Assay; Female; Fibrin; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; In Vitro Techniques; Leukapheresis; Megakaryocytes; Methylcellulose; Thrombocytopenia; Transplantation, Autologous

Topics: Aged; Ancrod; Blood Coagulation; Cardiopulmonary Bypass; Fibrin; Heparin; Humans; Male; Thrombocytopenia; Thrombophlebitis; Time Factors; Whole Blood Coagulation Time

Snake bites in Hong Kong are most commonly due to Tr. albolabris (White-lipped pit viper, bamboo snake). We studied 21 cases of envenoming by Tr. albolabris prospectively in order to document the incidence and severity of associated coagulation abnormalities. Eighteen patients (86%) had increased blood concentrations of fibrin degradation products (FDP) ranging from 10-40 micrograms/l to greater than 200 micrograms/l (normal: less than 10 micrograms/l), the majority of whom also had detectable soluble fibrin monomers. Among these 21 patients, 10 had decreased blood concentrations of fibrinogen ranging from 0.3 kg/l to 1.9 g/l (normal: 2-4 gl/l). In 11 cases (52%), the euglobulin clot lysis time was shortened (less than 150 minutes) in association with elevated blood concentrations of FDP (n = 10) and decreased circulating fibrinogen levels (n = 8). Thrombocytopenia and/or prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and/or thrombin time (TT) were present in 10 patients (28%). Increased blood concentrations of FDP and decreased circulating fibrinogen levels were present in most of these cases. Envenoming by Tr. albolabris is therefore frequently associated with a coagulopathy compatible with increased fibrin/fibrinogenolysis. Measurement of blood concentrations of FDP is the most sensitive test for detecting the coagulopathy. There is, however, little correlation between the patterns of clinical manifestations and coagulation abnormalities although more severe clinical features were usually associated with high circulating FDP levels. Only one patient developed systemic bleeding but no fatality was observed. The coagulation abnormalities are usually correctable by replacement therapy. Further studies are required to study the mechanisms of this coagulopathy and its relationship with venom antigenaemia.

Topics: Adult; Aged; Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Crotalid Venoms; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hong Kong; Humans; Male; Middle Aged; Prospective Studies; Serum Globulins; Snake Bites; Thrombocytopenia; Viperidae

The effect of heparin and the synthetic irreversible antithrombin D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone (FPRCH2Cl) was studied on FeCl3-induced thrombotic occlusion of rat carotid arteries. Thrombocytopenia prevented occlusion in five of 7 rats for the 60 min observation period after FeCl3 injury demonstrating platelet dependence in this model of thrombosis. Intravenous injection of heparin (250 units/kg) followed by continuous infusion (250 units/kg/hr) failed to prevent occlusion in four of 6 rats whereas intravenous FPRCH2Cl infusion prevented occlusion at a dose of 200 nmol/kg/min during infusion in 6/6 rats. These findings indicate that thrombin plays a principle role in the platelet-dependent process of arterial thrombosis in FeCl3-damaged rat carotid arteries. Neutralization of the thrombogenic stimulus in this model by the thrombin inhibitor FPRCH2Cl suggests selective thrombin inhibition may be useful in the treatment of arterial thrombosis.

Topics: Amino Acid Chloromethyl Ketones; Animals; Blood Platelets; Carotid Artery Thrombosis; Disease Models, Animal; Ferrous Compounds; Fibrin; Heparin; Male; Rats; Rats, Inbred Strains; Thrombin; Thrombocytopenia

Topics: Aged; Aged, 80 and over; Blood Platelet Disorders; Female; Fibrin; Heparin; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Count; Retrospective Studies; Syndrome; Thrombocytopenia

Disseminated intravascular coagulation (DIC) was produced by an infusion of a prothrombin activator (Echis carinatus venom; 30 minutes; 0.5 NIH thrombin equivalent U/kg) in mongrel dogs (Echis group, n = 7). Fibrinogen declined to below measurable levels (less than 25 mg/dl), and fibrin-fibrinogen degradation products appeared (53 +/- 8 micrograms/ml) at end venom infusion in the Echis group. These alterations were not seen when an irreversible thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine-L-chloromethyl ketone (PPACK) (57 nmol/kg/min for 120 minutes), was given alone (PPACK group, n = 5) or in association with venom (Echis + PPACK group, n = 5). Factor II activity (1% +/- 1%) in the Echis and Echis + PPACK groups was significantly below the PPACK (55% +/- 9%) and the control (79% +/- 2%) levels at 120 minutes. In contrast, factor VIII coagulant (factor VIII:C) activity in the Echis group (1% +/- 1%) remained significantly below that in the Echis + PPACK (68% +/- 8%), PPACK (78% +/- 10%), and control (91% +/- 9%) groups at this interval. No change in factors X (91% +/- 7% to 81% +/- 7%, P not significant) and VII (64% +/- 10% to 48% +/- 11%, P not significant) activities were observed. Hemolysis was observed only in the Echis group, whereas thrombocytopenia and leukopenia were noted in both the Echis and the Echis + PPACK groups. These data show that large amounts of E. carinatus venom produce rapid DIC in vivo, because of the activation of prothrombin. In contrast, the decline in factor VIII:C activity appeared to be the result of the liberated thrombin. PPACK antagonized all of the venom-released thrombin without any major deleterious clotting abnormalities. This inhibitor appears to prevent thrombin-mediated DIC in vivo. In contrast, heparin was found to be an unreliable antagonist of the venom-released thrombin in vitro. PPACK also inhibited the marked hemolysis usually observed after venom. In addition, we found that the esterolytic (N-benzoyl-L-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide HCL) activity of E. carinatus venom degrades fibrinogen in vitro.

Topics: Amino Acid Chloromethyl Ketones; Animals; Disseminated Intravascular Coagulation; Dogs; Endopeptidases; Factor VIII; Factor XII; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemoglobins; Kinetics; Leukopenia; Partial Thromboplastin Time; Prothrombin; Thrombocytopenia; Viper Venoms

We have previously postulated that surface membrane proteins become specifically associated with the internal platelet cytoskeleton upon platelet activation (Tuszynski, G.P., Walsh, P.N., Piperno, J., and Koshy, A. (1982) J. Biol. Chem. 257, 4557-4563). Four lines of evidence are in support of this general hypothesis since we now show that platelet surface receptors for fibrin become specifically associated with the platelet Triton-insoluble cytoskeleton. 1) Fibrin was detected immunologically in the washed Triton-insoluble cytoskeletons of thrombin-activated platelets under conditions where fibrin polymerization and resultant precipitation was blocked with Gly-Pro-Arg-Pro, a synthetic peptide that inhibits polymerization of fibrin monomer. 2) Radiolabeled fibrin bound to thrombin-activated platelets and became associated with the cytoskeleton. 3) The amount of radiolabeled fibrin bound to thrombin-activated thrombasthenic platelets and their cytoskeletons amounted to about 20% of the fibrin bound to thrombin-activated control platelets and their cytoskeletons. 4) The association of fibrin with cytoskeletons and with the platelet surface was nearly quantitatively blocked by an antibody prepared against cytoskeletons (anti-C), an antibody against isolated membranes of Pronase-treated platelets (anti-M1), and a monoclonal antibody to the platelet surface glycoprotein complex, GPIIb-GPIII (anti-GPIII). These antibodies blocked ADP and thrombin-induced platelet aggregation as well as thrombin-induced clot retraction. Analysis of the immunoprecipitates obtained with anti-C, anti-M1, and anti-GPIII from detergent extracts of 125I-surface labeled platelets revealed that these antibodies recognized GPIIb-GPIII. These data suggest that thrombin activation of platelets results in the specific association of fibrin with the platelet cytoskeleton, that this association may be mediated by the GPIIb-GPIII complex, and that these mechanisms may play an important role in platelet aggregation and clot retraction induced by thrombin.

Topics: Blood Platelets; Cell Membrane; Fibrin; Fibrinogen; Humans; Kinetics; Membrane Proteins; Molecular Weight; Receptors, Cell Surface; Receptors, Peptide; Thrombocytopenia

Resonance Thrombography is a method to follow up the coagulation process ex vivo from its very beginning up to its final consolidation phase resp. fibrinolysis. The mode of measurement is adopting the resonance effect of fibrin elasticity. The connection of a cylindric rod and outer cylinder by elastic fibrin fibres will increase the potential natural frequency (38 Hz) of the elastically suspended rod, to which a constant orbital drive of a very small radius is imported electronically. Change of difference between constant drive frequency and varying resonance frequency over time will result in sensitive registration of the Resonance Thrombogram (RTG). The orbital movement of the rod causes a circular flow of blood as long as it is fluid. The speed of flow is comparable to that in a medium sized vein, resembling a physiological situation. The clinical application of RTGraphy is regarding the fact, that there is practically no disturbance of clotting process which is not represented in any change of clot construction. Diagnosis of DIC, demonstration of SFMC as well as of fibrinolysis, differentiation between the effect of fibrin structure and of platelet activity are among the clinical assignments of RTGraphy.

Topics: Adult; Blood Coagulation; Disseminated Intravascular Coagulation; Elasticity; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Methods; Rheology; Thrombocytopenia

In various human and experimental renal failures some hemostatic parameters indicate the occurrence of intrarenal blood coagulation (1, 2). However, the fact that the common anticoagulants fail to cure the acute renal failure (3) appears to suggest either that they are ineffective against the intrarenal blood coagulation or no causal relationship exists between the hemostatic disturbances and impaired renal function. Therefore this study was undertaken to investigate the relationship between coagulation and impairment of renal function after a 45-min ischemic period in untreated, heparin-treated and in heparin- plus antiplatelet serum (APS)-treated thrombocytopenic animals.

Topics: Animals; Blood Coagulation; Blood Platelets; Fibrin; Heparin; Immune Sera; Ischemia; Kidney Cortex; Male; Rats; Rats, Inbred Strains; Renal Circulation; Thrombocytopenia

In summary, this series of 48 patients with acute and chronic DIC demonstrates the reliability of laboratory tests in both aiding a diagnosis of DIC and in offering reasonable predictability of efficacy of therapy, as noted by the correction of abnormalities after delivery of antiprocoagulant therapy for this syndrome. It appears that the diagnostic tests most likely to aid in diagnosis and to reliably inform the clinician when the intravascular clotting process has been stopped are those that determine the antithrombin-III level, the presence of soluble fibrin monomer, and the finding of elevated fibrin(ogen) degradation products, thrombocytopenia and a prolonged thrombin time in the face of the appropriate type of bleeding in the appropriate clinical setting. In addition, it would appear that mini-dose heparin therapy is highly effective in controlling the intravascular clotting process in acute DIC, whereas antiplatelet therapy utilizing two agents is effective in chronic DIC. In addition, in this population, patients with acute disease demonstrated a 74 percent survival rate and those with chronic disease had a 100 percent survival rate from the disseminated intravascular clotting process.

Topics: Acute Disease; Afibrinogenemia; Antacids; Antithrombin III; Chronic Disease; Dipyridamole; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Partial Thromboplastin Time; Platelet Count; Prothrombin Time; Thrombin Time; Thrombocytopenia

Rats infected with Trypanosoma brucei rhodesiense developed anemia, thrombocytopenia, and hypocomplementemia. Anemia, thrombocytopenia, and sharp reductions in parasitemia were associated with elevated titers of cold-active hemagglutinin, antibody to fibrinogen/fibrin-related products, and immunoconglutinin. Depletion of lytic complement, prolonged partial thromboplastin times, and presence of fibrin monomers in the blood occurred at the time anemia and significant elevations in precipitable immune complexes were observed. Terminally, consumption of immunologic factors coincided with accelerated partial thromboplastin times. At death, convulsions and hemoptysis with labored breathing suggested that the animals died of respiratory failure and that disseminated intravascular coagulation may have occurred. It is suggested that microthrombiosis might have resulted from the immunologic interaction of complex-coated blood cells with immunoconglutinin and contributed to the terminal disease signs.

Topics: Agglutinins; Anemia; Animals; Antigen-Antibody Complex; Autoantibodies; Blood Coagulation Disorders; Complement System Proteins; Fibrin; Fibrinogen; Rats; Thrombocytopenia; Trypanosomiasis, African

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

Studies of coagulation were performed prospectively in 41 patients with mild to moderately severe acute pancreatitis. Six patients (15%) presented with coagulation data suggestive of defibrination; two of them had clinical signs of bleeding. No other cause than pancreatitis was found in these 6 patients to account for coagulation abnormalities. Comparing the patients who presented defibrination to those who did not, no difference was observed in clinical course and admission values of serum amylase, fibrinogen, urea, calcium, glucose, transaminase levels, white blood cell count and arterial partial pressure of oxygen. Platelets counts and serum creatinine levels were respectively lower and higher in the first group of patients.

Topics: Acute Disease; Adult; Blood Coagulation Tests; Creatinine; Disseminated Intravascular Coagulation; Fibrin; Humans; Male; Middle Aged; Pancreatitis; Prospective Studies; Thrombocytopenia; Trypsin

To determine whether sulphinpyrazone reduces thrombus formation within artificial kidneys, dialyzer 125I-fibrinogen and platelet and fibrinogen levels during dialysis were compared during a non-treatment control period and while patients were receiving sulphinpyrazone. Mean fibrin deposition within the dialyzers, measured as gram X 10(-3) of clottable fibrinogen, was significantly less during sulphinpyrazone treatment (2.5) than during the control period (5.3). Arterial blood platelet counts and plasma fibrinogen levels during dialysis were higher on treatment despite similar predialysis values during control and treatment periods. The results indicate that sulphinpyrazone reduces fibrin formation within artificial kidneys and, since the reduction in deposition of fibrin alone is insufficient to explain the higher plasma fibrinogen levels during treatment with sulphinpyrazone, suggests that this therapy reduces fibrinogen consumption within the patient during hemodialysis.

Topics: Blood Platelets; Fibrin; Fibrinogen; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Sulfinpyrazone; Thrombocytopenia

Topics: Acute Disease; Afibrinogenemia; Chronic Disease; Disseminated Intravascular Coagulation; Fibrin; Hemostatics; Humans; Hypoprothrombinemias; Thrombocytopenia

Topics: Animals; Cell Membrane; Cell Nucleus; Ciliary Body; Cytoplasm; Eye Diseases; Fibrin; Hemorrhage; Microscopy, Electron; Pigment Epithelium of Eye; Rabbits; Thrombocytopenia

Severe thrombozytopenia, and therefore a lack of phospholipids, delays not only the thrombin formation rate but also, because of retarded factor XIII activation the fibrin stabilizing process. The other clotting factors, especially factor XIII, being within the normal range, this effect is only noted when the platelet count drops below 30 000/mm3.

Topics: Factor VIII; Factor XIII; Female; Fibrin; Humans; In Vitro Techniques; Phospholipids; Thrombin; Thrombocytopenia

Rabbits were injected with a platelet antiserum to examine the role of thrombocytopenia of the precipitation of soluble fibrin by endotoxin.dotoxin. Platelet antiserum removed more than 98% of the circulating platelets, and the resulting thrombocytopenia with platelet counts below 10,000 per mul persisted during the entire 10 hr-period of the experiment. Leukocyte counts were not significantly influenced by the platelet antiserum. Since the rabbits were treated with high doses of heparin, activation of intravascular coagulation by the antiserum did not occur. Precipitation of soluble fibrin was achieved by injection of endotoxin into rabbits with ancrod-induced circulating soluble fibrin. Thrombocytopenia did not prevent the occurrence of glomerular microclots after ancrod and endotoxin administration. On the contrary, if endotoxin was injected into antiserum- and heparin-treated rabbits with circulating soluble fibrin, glomerular microclot formation occurred even in a higher percentage than in control rabbits treated with absorbed platelet antiserum. This investigation indicates that platelet antiserum-induced thrombocytopenia does not protect against precipitation of soluble fibrin by en

Topics: Ancrod; Animals; Blood Platelets; Chemical Precipitation; Disseminated Intravascular Coagulation; Endotoxins; Female; Fibrin; Heparin; Immune Sera; Leukocyte Count; Male; Rabbits; Shwartzman Phenomenon; Thrombocytopenia

Topics: Adolescent; Adult; Blood Platelets; Blood Transfusion; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Hematuria; Hemolytic-Uremic Syndrome; Hemorrhagic Disorders; Heparin; Humans; Male; Melena; Middle Aged; Neurologic Manifestations; Prednisolone; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytopenia

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

The maternal coagulation mechanism has been investigated in an effort to identify its role, if any, in the pathogenesis of eclampsia. Thrombocytopenia was identified in 28 of 95 cases (29 per cent), a prolonged thrombin time in 19 of 38 (50 per cent), abnormally elevated serum fibrinogen-fibrin degradation products in two of 65 (3 per cent), and circulating fibrin monomer in one out of 20 (5 per cent). Overt hemolysis was rare (2 per cent). Thus the pattern as well as the degree of change in the maternal coagulation mechanism differed remarkably from that typical of severe abruptio placentae and of prolonged retention of a dead fetus, the classic obstetric models of fast and slow disseminated intravascular coagulation. It is concluded that the coagulation changes when present in eclampsia are effect rather than cause. Moreover, the changes may evolve primarily from platelet adherence at sites of vascular endothelial damage as the consequence of segmental vasospasm and vasodilatation rather than be triggered by the escape of thromboplastin from the placenta into the maternal circulation.

Topics: Abruptio Placentae; Adolescent; Blood Cell Count; Blood Platelets; Disseminated Intravascular Coagulation; Eclampsia; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemolysis; Humans; Pregnancy; Thrombin; Thrombocytopenia; Time Factors

Topics: Animals; Blood Cell Count; Blood Platelets; Disseminated Intravascular Coagulation; Drug Interactions; Endotoxins; Fibrin; Leukocyte Count; Leukopenia; Mechlorethamine; Neuraminidase; Rabbits; Thrombocytopenia

2 days after ip inoculation of cell-free extracts of HIPA tumour, giant platelets and platelets with band-like inclusions were found in blood of BALB/c mice. Band-like inclusions with platelets have morphologic structure of fibrin. Their presence in the thrombocytes is probably an accidental finding. Giant platelets in the circulating blood are probably due to a disturbed meagacaryocytopoiesis.

Topics: Animals; Blood Platelets; Cell-Free System; Fibrin; Inclusion Bodies; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms, Experimental; Plasmacytoma; Platelet Aggregation; Thrombocytopenia

Acute renal failure developed in a 55-year-old man 6 days after he had received a cadaver renal allograft. This was associated with thrombocytopenia. Extensive intraglomerular fibrin deposition was seen in a renal biopsy specimen. He was treated with corticosteroids, azathioprine, cyclophosphamide and hemodialysis with regional heparinization but not with systemic anticoagulation. This was followed by complete recovery of both renal function and histologic damage despite the fact that he did not receive anticoagulant therapy. This suggests that treatment with anticoagulants may not be necessary for all patients with intraglomerular deposits of fibrin.

Topics: Acute Kidney Injury; Azathioprine; Biopsy, Needle; Cadaver; Cyclophosphamide; Fibrin; Graft Rejection; Humans; Kidney Glomerulus; Kidney Transplantation; Male; Methylprednisolone; Middle Aged; Renal Dialysis; Thrombocytopenia; Transplantation, Homologous

Topics: Afibrinogenemia; Animals; Blood Platelets; Disseminated Intravascular Coagulation; Endotoxins; Escherichia coli; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemoglobins; Iodine Radioisotopes; Kinetics; Plasma; Rabbits; Rats; Saline Solution, Hypertonic; Thrombocytopenia

Administration of a potentially dangerous drug like heparin should not be based on theroretical considerations and innumerable case reports but 1) on a firm diagnosis and 2) on a critical evaluation of the clinical benefit. The validity of criteria for the diagnosis of intravascular coagulation (IC) is discussed. It is emphasized in particular that loss of fibrinogen into extravascular spaces can only be excluded by assays of the level and disappearance rate of serum proteins not subject to the proteolytic action of thrombin or plasmin. Even when the diagnosis can be reasonably established, heparin therapy in a particular condition should only be advocated if its clinical benefit has been demonstrated in controlled clinical trails. Our conviction that heparin has as yet a small if any place in the management of patients with so-called intravascular coagulations is based mainly on two sets of arguments, one stemming from a critique of the diagnosis of IC, the other from a general attitude in the evaluation of therapeutic procedures.

Topics: Afibrinogenemia; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysis; Heparin; Humans; Research; Terminology as Topic; Thrombocytopenia

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

Host-versus-graft (HVG) disease is the fatal result of the allogenic reaction which occurs in parental strain mice perinatally inoculated with F(1) hybrid spleen cells. The principal manifestations of the syndrome in RFM/(T(6) X RFM)F(1) mice are thrombocytopenia, intestinal hemorrhage, hepatic necrosis, lymphoproliferative disorders and renal disease due to immune complexes. The discovery of intravascular fibrin deposits in the present studies establishes disseminated intravascular coagulation (DIC) as an intermediary mechanism of HVG disease. It is suggested that the characteristic declines in blood platelet levels, intestinal hemorrhages and hepatic infarcts are triggered principally by immune complexes. Cellular infiltrates of the liver, granulocytosis and hypergammaglobulinemia are other abnormalities which are regularly found in HVG mice and which are also thought to predispose to DIC.

Topics: Animals; Antigen-Antibody Complex; Blood Vessels; Chimera; Disseminated Intravascular Coagulation; Fibrin; Graft vs Host Disease; Hybridization, Genetic; Immunoglobulin G; Infarction; Injections, Intraperitoneal; Kidney; Leukocyte Count; Liver; Mice; Mice, Inbred Strains; Mosaicism; Proteinuria; Spleen; Thrombocytopenia

This study is intended to clarify whether or not platelets are essential to endotoxin-induced precipitation of soluble fibrin representing the second phase of microclot formation. Renal glomerular microclots could be observed in extremely thrombocytopenic rabbits to the same extent as in normal rabbits after the injection of endotoxin into animals with circulating soluble fibrin. Thrombocytopenia was induced by feeding rabbits busulphan, and soluble fibrin was produced by infusing ancrod. The experiments indicate that platelets are not essential to the endotoxin-induced precipitation of soluble fibrin.

Topics: Animals; Blood Coagulation; Blood Platelets; Busulfan; Chemical Precipitation; Depression, Chemical; Endotoxins; Female; Fibrin; Fibrinogen; Leukocyte Count; Male; Platelet Aggregation; Rabbits; Stimulation, Chemical; Thrombocytopenia

In summary, in contrast to a blood-membrane interphase system (artificial kidney), the use of a blood-gas interphase system (bubble oxygenator), even at a low flow rate of 400 ml/min, leads to severe changes in platelet function and number, to a temporary delay in fibrin formation and to a prolonged bleeding time. A definite bleeding tendency expresses the disturbance in hemostatic balance, as predominantly effected by the changes in platelet function. Hemolysis is apparently a minor symptom, and does not express the gravity of this damaging situation.

Topics: Adenosine Diphosphate; Animals; Blood Cell Count; Blood Coagulation; Blood Platelets; Dogs; Extracorporeal Circulation; Fibrin; Hemoglobins; Hemolysis; Kidneys, Artificial; Oxygenators; Platelet Aggregation; Prothrombin Time; Thrombocytopenia; Time Factors

Topics: Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Clot Retraction; Fibrin; Hemostasis; Humans; Platelet Aggregation; Polymers; Thrombocytopenia; Thrombocytosis

After envenomation by the timber rattlesnake (Crotalus horridus horridus) a young man showed massive swelling and ecchymoses of the involved extremity, generalized petechiae and a large hematoma of the left upper eyelid. Two weeks later he was completely well. The first blood sample was incoagulable and showed high titers of fibrin split products by the MISFI and staphylococcal clumping tests. Immounoelectrophoresis showed both D and E fragments, but only D was present at 18 hours. The profound thrombocytopenia and hypofibrinogenemia gradually improved, and split products disappeared. In vitro the venom had thrombin-like activity, clotting fibrinogen or plasma and aggregating platelets. These activities could be inhibited by antivenom but not by heparin. There was no evidence that thrombin formation was actually involved: hence, the syndrome is called DIC-like.

Topics: Adult; Afibrinogenemia; Animals; Antivenins; Blood Coagulation; Disseminated Intravascular Coagulation; Fibrin; Heparin; Humans; In Vitro Techniques; Male; Platelet Aggregation; Snake Bites; Snake Venoms; Snakes; Thrombin; Thrombocytopenia

Topics: Blood Coagulation Factors; Disseminated Intravascular Coagulation; Fever; Fibrin; Fibrinolysis; Hemorrhage; Heparin; Humans; Liver; Sunstroke; Temperature; Thrombocytopenia

Topics: Blood Coagulation Tests; Craniocerebral Trauma; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Hemorrhage; Humans; Thrombocytopenia

The effect of experimental trypanosomiasis on coagulation was studied because a patient in this hospital with Rhodesian trypanosomiasis developed thrombocytopenia with disseminated intravascular coagulation. Rats injected intraperitoneally with this strain of Trypanosoma rhodesiense consistently developed trypanosomiasis and severe thrombocytopenia without changes in hematocrit or concentration of fibrinogen or fibrin split products. At the time of 50% mortality (4-5 days) mean platelet counts per cubic millimeter of infected rats were 18,000+/-9,000 (+/-2 SEM) compared to 1,091,000+/-128,000 in uninfected controls. In vitro, concentrated trypanosomes and trypanosomefree supernates of disrupted organisms added to normal rat, rabbit, or human blood produced platelet aggregation within 30 min. This platelet aggregation was not blocked by inhibitors of ADP, kinins, or early or late components of complement. In vivo thrombocytopenia also occurred in infected rabbits congenitally deficient in C6 and in infected, splenectomized rats. Although the aggregating substance obtained from disrupted trypanosomes is heat-labile, it is active in the presence of complement inhibitors, suggesting that this trypanosomal product may be a protein enzyme or toxin. Since the phenomenon is independent of immune complexes, complement, ADP, and kinins, it appears to represent a new mechanism of microbial injury of platelets and the induction of thrombocytopenia.

Topics: Adenosine; Adenosine Diphosphate; Animals; Blood Cell Count; Blood Platelets; Chymotrypsin; Complement System Proteins; Disseminated Intravascular Coagulation; Edetic Acid; Fibrin; Fibrinogen; Hematocrit; Humans; In Vitro Techniques; Male; Microscopy, Electron; Platelet Adhesiveness; Rabbits; Rats; Thrombocytopenia; Trypanosomiasis; Trypsin; Trypsin Inhibitors

Topics: Blood Coagulation Tests; Carbon Radioisotopes; Carcinoma; Caseins; Disseminated Intravascular Coagulation; Electrophoresis; Esters; Factor XIII; Fibrin; Fibrinogen; Glycine; Hemagglutination Inhibition Tests; Humans; Leukemia; Sepsis; Serum Globulins; Solubility; Thrombocytopenia

Topics: Adenine Nucleotides; Administration, Oral; Alcoholism; Blood Platelets; Blood Proteins; Ethanol; Fibrin; Fibrinogen; Hemostasis; Humans; Immunoelectrophoresis; In Vitro Techniques; Injections, Intravenous; Microscopy, Phase-Contrast; Nucleotides; Platelet Adhesiveness; Silicon Dioxide; Thrombocytopenia; Time Factors

Previous studies have shown that renal cortical fibrinolytic activity is absent in rabbits given one or two injections of endotoxin. Using a fibrin slide technic, we have studied the effect of endotoxin on cortical fibrinolytic activity in rabbits depleted of terminal complement components (C3-C9) by cobra venom factor. The loss of cortical fibrinolytic activity induced by endotoxin is not prevented by pretreatment with cobra venom factor. Additionally, this complement depletion did not prevent development of glomerular fibrin deposition, cortical necrosis or thrombocytopenia in the generalized Shwartzman reaction.

Topics: Animals; Blood Cell Count; Blood Platelets; Complement System Proteins; Endotoxins; Escherichia coli; Fibrin; Fibrinolysis; Fluorescent Antibody Technique; Goats; Immune Sera; Injections; Kidney Cortex; Kidney Cortex Necrosis; Kidney Glomerulus; Leukocyte Count; Rabbits; Shwartzman Phenomenon; Snakes; Thrombocytopenia; Venoms

Topics: Adenosine Diphosphate; Adult; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Labor, Obstetric; Microscopy, Phase-Contrast; Platelet Adhesiveness; Postpartum Period; Pre-Eclampsia; Pregnancy; Protamines; Prothrombin Time; Thrombocytopenia; Time Factors

Topics: Adenosine Diphosphate; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Atmospheric Pressure; Blood Cell Count; Blood Platelets; Cell Survival; Cholesterol; Diving; Erythrocyte Count; Female; Fibrin; Hematocrit; Hemoglobins; Humans; Male; Physical Exertion; Platelet Adhesiveness; Submarine Medicine; Thrombocytopenia; Time Factors

Topics: Adult; Afibrinogenemia; Blood Cell Count; Blood Platelets; Body Temperature; Chloramphenicol; Digoxin; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Heparin; Humans; Hydrocortisone; Male; Penicillins; Rocky Mountain Spotted Fever; Thrombocytopenia

Topics: Afibrinogenemia; Animals; Basement Membrane; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Capillaries; Capillary Fragility; Capillary Permeability; Clot Retraction; Ecchymosis; Fibrin; Fibrinogen; Hemorrhage; Humans; Methods; Platelet Adhesiveness; Thrombocytopenia; Wound Healing

Topics: Animals; Arteries; Blood Cell Count; Blood Platelets; Dogs; Erythrocytes; Female; Fibrin; Fibrinogen; Immune Sera; Iodine Radioisotopes; Male; Platelet Adhesiveness; Thrombocytopenia; Thrombophlebitis; Thrombosis; Veins

Topics: Adolescent; Adult; Blood Viscosity; Child; Child, Preschool; Cyanosis; Disseminated Intravascular Coagulation; Factor V Deficiency; Fibrin; Fibrinolysis; Heart Defects, Congenital; Heparin; Humans; Infant; Postoperative Complications; Thrombocytopenia; Thrombosis; Veins

Topics: Adult; Aged; Agglutinins; Anticoagulants; Blood Cell Count; Blood Platelets; Chromatography; Citrates; Edetic Acid; Electronics, Medical; Electrophoresis, Starch Gel; Female; Fibrin; Fibrinogen; Glucose; Heparin; Humans; Immunoelectrophoresis; Male; Microscopy, Phase-Contrast; Middle Aged; Oxalates; Thrombocytopenia

Topics: Blood Cell Count; Blood Platelets; Child; Child, Preschool; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Infant; Male; Meningitis; Meningococcal Infections; Neisseria meningitidis; Sepsis; Thrombocytopenia

Topics: Abortion, Induced; Antithrombins; Blood Cell Count; Blood Platelets; Catheterization; Factor V; Female; Fibrin; Fibrinogen; Hemoglobins; Humans; Methods; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytopenia; Time Factors

Topics: Blood Proteins; Complement System Proteins; Dengue; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Hemorrhagic Fevers, Viral; Humans; Shock; Syndrome; Thailand; Thrombocytopenia; Transferrin

Topics: Aged; Anemia, Hemolytic; Disseminated Intravascular Coagulation; Female; Fibrin; Heparin; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Thrombocytopenia

After the intravenous injection of Walker 256 tumour cells into rats the platelet count decreased rapidly and remained low during the following period of observation. The platelet decrease was closely related to the number of cells injected. Intra-arterial tumour cell injections required a considerably higher tumour cell count to produce a comparable thrombocytopenia. Non-viable tumour cells and tumour cell fragments induced a similar decrease of circulating platelets. Neither viable tumour cells nor tumour cell fragments aggregated rat platelets in vitro. The presence of fibrin monomers in tumour cell injected animals suggested intravascular fibrin deposition; the plasma fibrinogen level, however, did not decrease significantly. Isotope studies using (51)Cr labelled platelets revealed a rapid disappearance of the platelets from the circulation and their trapping in the lung-the primary site of tumour cell lodgement. Dipyridamole and ancrod pretreatment did not influence the decrease of platelets and their accumulation in the lung after tumour cell injection. In contrast, heparin completely prevented the thrombocytopenia and the platelet trapping in the lung. From the present experiments it is concluded that embolic tumour cells lead to early endothelial damage, resulting in local thrombin formation with subsequent irreversible platelet aggregation.

Topics: Animals; Blood Cell Count; Blood Platelets; Carcinoma 256, Walker; Chromium; Chromium Isotopes; Dipyridamole; Embolism; Endothelium; Fibrin; Fibrinogen; Heparin; Injections, Intra-Arterial; Injections, Intravenous; Kidney; Liver; Lung; Neoplasm Metastasis; Platelet Adhesiveness; Rats; Spleen; Thrombin; Thrombocytopenia; Time Factors

Topics: Blood Protein Electrophoresis; Collateral Circulation; Fibrin; Fibrinogen; Humans; Immunoelectrophoresis; Immunoglobulin G; Liver Circulation; Liver Cirrhosis; Microcirculation; Thrombocytopenia

Topics: Acute Disease; Adult; Aged; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Chronic Disease; Disseminated Intravascular Coagulation; Ecchymosis; Ethanol; Female; Fibrin; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Mucous Membrane; Protamines; Prothrombin Time; Syndrome; Thrombocytopenia

Topics: Ammonia; Blood Cell Count; Blood Coagulation; Blood Platelets; Blood Proteins; Factor XIII; Factor XIII Deficiency; Fibrin; Fibrinolysin; Fibrinolysis; gamma-Globulins; Humans; Hypergammaglobulinemia; Immune Sera; Methods; Putrescine; Solubility; Streptokinase; Thrombocytopenia; Thrombophlebitis; Time Factors

Topics: Animals; Antigen-Antibody Complex; Blood Cell Count; Blood Platelets; Disseminated Intravascular Coagulation; Factor V; Female; Fibrin; Fibrinogen; Immunization; Immunoglobulin G; Male; Ovalbumin; Rabbits; Thrombocytopenia

Topics: Afibrinogenemia; Animals; Blood Cell Count; Blood Platelets; Cell Survival; Chromium Radioisotopes; Coagulase; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysis; Kidney; Liver; Lung; Rats; Spleen; Splenomegaly; Thrombin; Thrombocytopenia; Time Factors; Venoms

Topics: Anemia, Hemolytic; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Hemangiosarcoma; Humans; Male; Middle Aged; Phagocytosis; Splenectomy; Splenic Neoplasms; Thrombocytopenia

Topics: Blood Coagulation; Blood Platelets; Eclampsia; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Lung; Plasminogen; Pre-Eclampsia; Pregnancy; Radiography; Radionuclide Imaging; Technetium; Thrombocytopenia

Topics: Animals; Antigen-Antibody Reactions; Blood Platelets; Busulfan; Capillaries; Disseminated Intravascular Coagulation; Fibrin; Kidney Glomerulus; Rabbits; Thrombocytopenia

Topics: Animals; Bone Marrow; Chemical and Drug Induced Liver Injury; Feces; Femur; Fibrin; Hemorrhage; Indium; Ions; Kidney; Kidney Tubules; Liver; Lung; Male; Mercury; Mice; Muscles; Necrosis; Oxides; Phagocytosis; Protein Binding; Spleen; Thrombocytopenia; Thrombosis; Water

Topics: Animals; Antigens; Blood Cell Count; Blood Platelets; Blood Pressure; Enzyme Activation; Fibrin; Fibrinogen; Fibrinolysis; Immunoelectrophoresis; Ovalbumin; Plasma; Rabbits; Streptokinase; Thrombocytopenia; Time Factors

Topics: Autopsy; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Hepatitis A; Humans; Thrombocytopenia

Topics: Acute Kidney Injury; Anemia, Hemolytic; Blood Coagulation; Blood Platelets; Blood Transfusion; Blood Urea Nitrogen; Creatinine; Fibrin; Fibrinogen; Heparin; Humans; Infant; Male; Reticulocytes; Thrombocytopenia

Topics: Acute Kidney Injury; Anemia, Hemolytic; Anuria; Blood Cell Count; Blood Coagulation Factors; Blood Transfusion; Central Nervous System Diseases; Disseminated Intravascular Coagulation; Erythrocytes, Abnormal; Fibrin; Hematuria; Hemoglobins; Hemolysis; Heparin; Humans; Hyperkalemia; Infant; Kidney; Kidney Glomerulus; Peritoneal Dialysis; Thrombocytopenia

Topics: Animals; Anticoagulants; Blood Coagulation Tests; Blood Platelets; Endotoxins; Female; Fibrin; Fibrinogen; Heparin; Kidney Cortex Necrosis; Male; Rabbits; Shwartzman Phenomenon; Thrombocytopenia

Topics: Aminocaproates; Antifibrinolytic Agents; Benzoates; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Cyclohexanecarboxylic Acids; Factor V; Factor V Deficiency; Factor VIII; Fibrin; Fibrinolysis; Hemagglutination Tests; Hemorrhage; Heparin; Humans; Immunodiffusion; Immunoelectrophoresis; Plasminogen; Streptokinase; Thrombocytopenia

Topics: Blood Coagulation Factors; Burns; Fibrin; Fibrinolysis; Humans; Thrombocytopenia; Time Factors

Topics: Blood Coagulation Disorders; Fibrin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Thrombocytopenia

Topics: Animals; Blood Coagulation Disorders; Blood Platelets; Busulfan; Fibrin; Fibrinogen; Hemolysis; Injections, Intravenous; Kidney Glomerulus; Models, Biological; Neoplasms; Platelet Adhesiveness; Purpura; Rabbits; Sepsis; Shock; Shwartzman Phenomenon; Sulfonic Acids; Thrombocytopenia

Topics: Biological Assay; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Female; Fibrin; Humans; Immunoelectrophoresis; Male; Neoplasms; Thrombin; Thrombocytopenia; Thromboplastin

Topics: Animals; Blood Coagulation Factors; Fibrin; Rabbits; Thrombocytopenia

Topics: Adaptation, Biological; Afibrinogenemia; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Capillaries; Fibrin; Hemophilia A; Hemorrhage; Humans; Physiology; Thrombocytopenia; Thrombocytosis

Topics: Blood Coagulation; Blood Vessels; Fibrin; Fibrinogen; Humans; Hyalin; Pathology; Purpura; Purpura, Thrombotic Thrombocytopenic; Shwartzman Phenomenon; Thrombocytopenia; Thrombosis

Topics: Aging; Blood Coagulation Tests; Child; Enzymes; Erythroblastosis, Fetal; Fibrin; Humans; Infant; Infant, Newborn; Infant, Premature; Leukemia; Thrombocytopenia

Topics: Coagulants; Fibrin; Fibrinogen; Humans; Purpura; Purpura, Thrombocytopenic; Syndrome; Thrombocytopenia

Topics: Fibrin; Fibrinogen; Humans; Hypnotics and Sedatives; Injections, Intravenous; Purpura; Purpura, Thrombocytopenic; Thrombocytopenia; Urea

Topics: Blood Transfusion; Fibrin; Hemophilia A; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Prothrombin; Syndrome; Thrombocytopenia

Topics: Blood Platelets; Fibrin; Fibrinogen; Humans; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Topics: Fibrin; Microscopy, Electron; Purpura; Purpura, Thrombocytopenic; Thrombocytopenia