fibrin and Leukopenia

Topics: beta-Thromboglobulin; Biocompatible Materials; Blood Coagulation; Blood Platelets; Cell Adhesion; Fibrin; Humans; Infections; Kidney Failure, Chronic; Leukocytes; Leukopenia; Lymphocyte Activation; Membranes, Artificial; Platelet Activation; Platelet Adhesiveness; Platelet Factor 4; Polymethyl Methacrylate; Renal Dialysis; Respiratory Burst; Thrombin; Thromboxane A2

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

Carboxypeptidase B2 (CPB2) is a basic carboxypeptidase with fibrin and complement C3a and C5a as physiological substrates. We hypothesized that in polymicrobial sepsis, CPB2-deficient mice would have sustained C5a activity, leading to disease exacerbation.. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP).. Contrary to our hypothesis, Cpb2(-/-) mice had significantly improved survival, with reduced lung edema, less liver and kidney damage, and less disseminated intravascular coagulation. Hepatic pro-CPB2 was induced by CLP, leading to increased pro-CPB2 levels. Thrombomodulin present on mesothelium supported thrombin activation of pro-CPB2. Both wild-type and Cpb2(-/-) animals treated with a C5a receptor antagonist had improved survival, demonstrating that C5a was detrimental in this model. Treatment with a fibrinolysis inhibitor, tranexamic acid, caused a decrease in survival in both genotypes; however, the Cpb2(-/-) animals retained their survival advantage. Administration of a C3a receptor antagonist exacerbated the disease in both wild-type and Cpb2(-/-) mice and eliminated the survival advantage of Cpb2(-/-) mice. C5a receptor is expressed in both peritoneal macrophages and neutrophils; in contrast, C3a receptor expression is restricted to peritoneal macrophages, and C3a induced signaling in macrophages but not neutrophils.. While C5a exacerbates the peritonitis, resulting in a deleterious generalized inflammatory state, C3a activation of peritoneal macrophages may limit the initial infection following CLP, thereby playing a diametrically opposing protective role in this polymicrobial sepsis model.

Topics: Animals; Antifibrinolytic Agents; Blood Coagulation Disorders; Carboxypeptidase B2; Cecum; Cells, Cultured; Complement C3a; Complement C5a; Disease Models, Animal; Enzyme Activation; Fibrin; Inflammation Mediators; Leukopenia; Ligation; Liver; Macrophage Activation; Macrophages, Peritoneal; Male; Mice, Inbred C57BL; Mice, Knockout; Peritonitis; Protective Factors; Punctures; Risk Factors; Sepsis; Thrombin; Thrombomodulin; Time Factors

Assumptions regarding the elaboration of plasma cross-linked fibrin degradation products (XLFbDPs) in vivo were tested using an experimental model in which particulate human fibrin was infused into rabbits and the products of lysis monitored with an immunoassay utilizing DD-3B6/22, a monoclonal antibody to human cross-linked derivatives. XLFbDPs were generated following the infusion of a suspension of cross-linked fibrin, attaining a peak between 40 and 60 min, then falling at a rate approximating a plasma half-life of 2 h. The major in vivo products of lysis of cross-linked fibrin, identified by SDS-PAGE of immunoextracted plasma, were D-dimer and high-molecular-weight moieties. Peak levels of XLFbDPs achieved correlated with the amount of fibrin administered. Since XLFbDP levels were no higher when fibrin infusion was followed by infusions of streptokinase and human plasminogen, it is concluded that endogenous mechanisms of lysis were already maximally stimulated. Infusions of non-cross-linked (NXL) fibrin or of fibrinogen led to much smaller, but measurable, rises in XLFbDP. In the latter group, XLFbDP levels rose further following fibrinolytic therapy. Treatment with epsilon aminocaproic acid (EACA) caused partial (greater than 50%) inhibition of lysis while pre-treatment with nitrogen mustard, inducing leucopenia, virtually abolished the appearance of XLFbDPs in the circulation. This implies that fibrinolytic responses are substantially dependent upon cellular functions sensitive to nitrogen mustard.

Topics: Aminocaproic Acid; Animals; Antibodies, Monoclonal; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Immunoassay; Leukocytes; Leukopenia; Lung; Male; Mechlorethamine; Models, Biological; Plasminogen; Rabbits; Streptokinase

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

This study was performed on patients (n = 18) suffering from strictly defined hyperdynamic septic shock. Plasma factors (C-reactive protein, acid alpha 1-glycoprotein, fibrinogen, fibrinopeptide A, fibrinogen-fibrin split products, factor XIII, antithrombin III, complement factors C3 and C4, inter-alpha-trypsin-inhibitor and alpha 2-macroglobulin) measured during hyperdynamic septic shock were highly abnormal. The activation and consumption of clotting, fibrinolytic and complement factors due to system-specific proteinases (such as thrombokinase or plasminogen activators) seemed to be intensified by the nonspecific proteolytic activity of granulocytic proteinases probably released by the action of endotoxins. Possible therapeutic measures to maintain the endogeneous defence mechanism against enhanced proteolysis during septic shock are discussed.

Topics: Alpha-Globulins; alpha-Macroglobulins; Antithrombin III; Blood Coagulation Factors; Blood Proteins; Complement System Proteins; Female; Fibrin; Humans; Leukocytes; Leukocytosis; Leukopenia; Male; Prospective Studies; Protease Inhibitors; Shock, Septic; Trypsin Inhibitors

As an extension of our studies on vascular responses to endotoxemia, we evaluated sequential ultrastructural lesions of splenic red pulp and correlated these lesions with coagulation changes observed in rhesus monkeys following infusion with endotoxin either as a single bolus (10 mg. per kg.) or at a continuous rate of 10 mg. per kg. per hour for periods up to 16 hours. Controls included monkeys infused with Ringer's lactate solution. Progressive reactions of the splenic cords included increased phagocytic activity of macrophages in association with aggregation and degranulation of platelets and prominent fibrinous deposits characteristically abutting basement membranes of endothelial and reticular cells. The sinuses demonstrated endothelial damage, platelet-fibrin microthrombi obstructing interendothelial slits, and severe engorgement with entrapment of erythrocytes by tactoids of fibrin. The thrombotic lesions of the red pulp developed earlier than similar lesions in hepatic sinusoids, and they were accompanied by progressive thrombocytopenia and disseminated intravascular coagulation. The findings suggest that the unique microcirculation of the spleen is an early target and trigger of endotoxin-induced microthrombosis. It is proposed that phagocytosis of endotoxin by splenic phagocytic cells and associated inflammatory events result in disruption of reticular cells and endothelium leading to massive microthrombosis with breakdown of the splenic filter. In addition, rapid activation of coagulation mechanisms in the red pulp as well as liver sinusoids may promote the development of thrombocytopenia and disseminated intravascular coagulation in endotoxic shock.

Topics: Animals; Blood Pressure; Disseminated Intravascular Coagulation; Endotoxins; Factor XII Deficiency; Fibrin; Inflammation; Leukopenia; Macaca mulatta; Macrophages; Male; Platelet Aggregation; Spleen; Thrombosis

Intravascular coagulation was induced by two appropriately spaced doses of endotoxin and by infusion of thromboplastin. The resulting fibrin deposition was measured by a previously described quantitative technique. Evidence of thrombin elaboration was obtained indirectly by measurement of fibrin monomer (FM) and by the detection and isolation of a thrombin-induced anticlotting activity. Venous segments were isolated at intervals and examined for thrombus formation following 40 minutes of stasis. Endotoxin triggered thrombin elaboration was not detectable in the circulation for at least one hour and was not accompanied by any thrombosis in isolated venous segments. No thrombin elaboration was found in leukopenic rabbits given endotoxin. In the thromboplastin infused animals, the quantity of fibrin deposited in the organs was comparable to that found after endotoxin. However, thrombin was found in the blood immediately and was associated with thrombosis in the isolatet venous segments. Less thrombin-induced anticoagulant activity was found after thromboplastin than after endotoxin. The findings suggest that endotoxin-induced intravascular coagulation is probably not caused by a mechanism of systemic hypercoagulability due to the release of thromboplastic material into the blood stream. A focal process of thrombin elaboration involving leukocytes is postulated. The study is believed relevant to patients with disseminated intravascular coagulation in whom venous thromboembolism is rarely found despite evidence of extensive microvascular fibrin deposition.

Topics: Animals; Blood Coagulation Disorders; Blood Vessels; Disseminated Intravascular Coagulation; Endotoxins; Fibrin; Fibrinogen; Leukocytes; Leukopenia; Mechlorethamine; Rabbits; Thrombin; Thromboplastin

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

Topics: Aniline Compounds; Arthritis; Arthritis, Rheumatoid; Blood Sedimentation; Diagnosis; Diphenylamine; Fibrin; Leukocytosis; Leukopenia; Rheumatic Diseases; Tonsillitis