thromboplastin and Autoimmune-Diseases

Preeclampsia is a life-threatening hypertensive disease of pregnancy. The condition is characterized by the presence of autoantibodies that activate the major angiotensin receptor, AT(1). Research conducted during the past decade has shown that these autoantibodies activate AT(1) receptors on a variety of cell types and provoke biological responses that are relevant to the pathophysiology of preeclampsia. The introduction of these autoantibodies into pregnant mice results in hypertension, proteinuria and a variety of other features of preeclampsia including small fetuses and placentas. These findings demonstrate the pathophysiological role of these autoantibodies in preeclampsia. The biological properties of these autoantibodies can be blocked by a 7-amino acid peptide that corresponds to a specific sequence associated with the second extracellular loop of the AT(1) receptor. The fact that autoantibodies from different individuals are directed to a common epitope provides obvious diagnostic and therapeutic opportunities. Research reviewed here raises the intriguing possibility that preeclampsia may be a pregnancy-induced autoimmune condition characterized by the presence of disease-causing angiotensin receptor activating autoantibodies.

Topics: Adoptive Transfer; Angiogenesis Inducing Agents; Animals; Autoantibodies; Autoimmune Diseases; Female; Humans; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Thrombophilia; Thromboplastin

It is widely hypothesized that autoantibodies directly contribute to the prothrombotic state in the antiphospholipid syndrome (APS). The discovery that antiphospholipid autoantibodies are specific for phospholipid-binding plasma proteins (beta2-glycoprotein I, prothrombin, etc.) has allowed a much more precise investigation of the interactions of autoantibodies and antigens, and the effects of these interaction on hemostasis. Recent studies suggest that two types of interactions may be important in the pathophysiology of APS: (1) antibody cross-linking of membrane bound antigens may alter the kinetics of phospholipid-dependent reactions; and (2) antibody cross-linking of antigens bound to cell surface receptors may trigger signal transduction and cellular activation. In light of these findings, previous reports implicating various mechanisms of autoantibody-mediated thrombosis are being re-evaluated.

Topics: Antibodies, Anticardiolipin; Antigen-Antibody Reactions; Antiphospholipid Syndrome; Autoantibodies; Autoantigens; Autoimmune Diseases; beta 2-Glycoprotein I; Cell Adhesion; Epitopes; Glycoproteins; Hemostasis; Humans; Lupus Coagulation Inhibitor; Membrane Lipids; Models, Immunological; Monocytes; Phospholipids; Plasminogen Activator Inhibitor 1; Thrombophilia; Thromboplastin; Thrombosis

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which have been defined by varying laboratory test systems. Lupus anticoagulants (LA) and anticardiolipin antibodies (ACA) are the two most prominent members of this family of antibodies. LA are detected utilizing various phospholipid (PL) dependent tests of coagulation (e.g., activated partial thromboplastin time [APTT], Kaolin Clotting Time [KCT], dilute Russell Viper Venom Time [dRVVT]). Originally, LA were thought to be a laboratory nuisance since the vast majority of individuals with LA did not bleed. Paradoxically, patients with LA were found to have an increased incidence of thromboembolic events and also recurrent spontaneous abortions (RSA). Thus, the laboratory detection of LA has become part of the work up of patients with thromboembolic disorders and RSA. ACA are detected using solid phase assay systems (radioimmunoassay or ELISA). The presence of ACA has the same clinical implications as that of LA. Although originally it was suggested ACA and LA were the same antibody, it is now well accepted that they, in many instances, are different antibodies. Therefore, it is critical for laboratories to evaluate patient samples for both LA and ACA. In approximately 60% of circumstances, both antibodies will be found. In the remaining cases, there will be discordance between the two test systems. The question of whether APA are causative, coincidental, or a consequence of the clinical complications of RSA and thrombosis remains controversial. Recent evidence based on prospective clinical studies and analysis of markers of in vivo coagulation suggests APA are causative.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abortion, Habitual; Adult; Animals; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Autoimmune Diseases; beta 2-Glycoprotein I; Cattle; Eicosanoids; Endothelium, Vascular; Female; Glycoproteins; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Pregnancy; Thromboplastin; Thrombosis

Antiphospholipid antibodies are a diverse group of immunoglobulins initially thought to have specificity to phospholipid epitopes. It is apparent that autoimmune anticardiolipin antibodies require a serum cofactor beta-2-glycoprotein I (beta 2GPI) for their binding to phospholipids. Lupus anticoagulant also may bind to phospholipids by beta 2GPI or by prothrombin. The description of binding to protein-phospholipid epitopes may explain several perplexing features of these antibodies both in vitro and in vivo. Antiphospholipid antibodies have a well-established association with clinical disease--in particular thrombosis, thrombocytopenia and recurrent fetal loss. The mechanism of the predisposition to thrombosis seen with these antibodies is poorly understood. It has been suggested that they may cause endothelial dysfunction by causing increased tissue factor expression, by inhibiting prostacyclin secretion or by inhibiting fibrinolysis. Various platelet-activating activities have also been described. The evidence that antiphospholipid antibodies promote thrombosis by effects on endothelium or platelets is inconclusive. Inhibition of protein C activation, or of activated protein C action, has been demonstrated in vitro. A poor correlation between thrombosis in vivo and these inhibitory effects has been found. Beta-2-glycoprotein I has been identified as a cofactor for binding to phospholipid by thrombogenic anticardiolipin antibodies. That beta 2GPI may be a natural anticoagulant of importance remains to be proved. Inhibition by antiphospholipid antibodies of this anticoagulant function could explain the propensity to thrombosis seen in association with these antibodies.

Topics: Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Antibody Specificity; Antiphospholipid Syndrome; Antithrombin III; Autoimmune Diseases; beta 2-Glycoprotein I; Endothelium, Vascular; Epoprostenol; Fibrinolysis; Glycoproteins; Humans; Lupus Coagulation Inhibitor; Platelet Activation; Protein C; Risk; Thromboplastin; Thrombosis

Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Autoimmune Diseases; Blood Platelets; Eicosanoids; Endothelium, Vascular; Female; Fetal Diseases; Fibrinolysis; Humans; Lupus Coagulation Inhibitor; Male; Pregnancy; Pregnancy Complications; Protein C; Protein S; Thromboplastin

Topics: Autoantibodies; Autoimmune Diseases; Blood Coagulation Factors; Blood Coagulation Tests; Collagen Diseases; Drug Hypersensitivity; False Positive Reactions; Female; Hemorrhage; Humans; Immunoglobulin M; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Neoplasms; Pregnancy; Pregnancy Complications, Hematologic; Thromboplastin; Thrombosis

Topics: Autoimmune Diseases; Blood Platelets; Child; Child, Preschool; Energy Metabolism; Enzyme Activation; Histocytochemistry; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Infant; Lymphocyte Activation; Lymphocytes; Macrophages; Platelet Count; Purpura, Thrombocytopenic; Thromboplastin

In this article we address the effect of bacterial or viral infections as well as autoimmune diseases on FGL2 activity in the blood.. Fibrinogen-like protein 2 (FGL2) is a novel prothrombinase capable of initiating thrombin generation independent of the classical coagulation pathway. FGL2 is involved in immune-coagulation response. Considering the tight relationship between coagulation and cancer, FGL2 had been suggested to be utilized as a potential biomarker for cancer. Recently, we have shown that FGL2 activity is increased in blood of B-cell lymphoma patients and decreased during remission. However, it is unclear whether FGL2 activity is simultaneously affected by the presence of conditions other than cancer.. FGL2 procoagulant activity levels were examined in peripheral blood cell samples of 93 patients with clinical diagnosis of various bacterial or viral infections or autoimmune diseases, and 39 healthy controls. Activity was determined according to clotting time measurements. Clinical and demographic data was collected.. FGL2 activity in peripheral blood samples of healthy individuals and patients was rather similar. Moreover, no significant correlation was detected between measured FGL2 activity and clinical or demographic data of the patients. The range of activities was rather broad, indicating high variance (up to 2.5-fold from average) in the basal activity levels in the population.. The presence of infectious/autoimmune diseases does not significantly alter FGL2 activity in the peripheral blood.. While FGL2 activity in the blood is affected by malignancies such as lymphomas, the presence of inflammatory/infectious diseases does not significantly influence basal FGL2 activity. The broad range of FGL2 activities in tested samples indicates that FGL2 is a better marker for follow up implications than diagnostic screening.

Topics: Autoimmune Diseases; Blood Coagulation; Communicable Diseases; Fibrinogen; Humans; Thromboplastin

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

Topics: Adult; Autoimmune Diseases; Blood Coagulation; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Pemphigoid, Bullous; Peptide Fragments; Prothrombin; Skin; Skin Diseases; Skin Tests; Thromboplastin; Thrombosis; Urticaria; Young Adult

Anti-vimentin antibodies (AVA) are associated with autoimmunity and solid organ transplantation, conditions associated with vascular disease, but their contribution to disease pathogenesis is unknown. Here, we have examined interactions between AVA (mAb and serum from patients) and various leukocyte populations using whole blood and flow cytometry. Normal blood treated with patient sera containing high AVA-IgM titers or with a vimentin-specific monoclonal IgM led to activation of platelets and other leukocytes, as demonstrated by induced expression of P-selectin, fibrinogen, tissue factor, and formation of platelet:leukocyte (P:L) conjugates and a reduction in platelet counts. This activity was antigen (vimentin)-specific and was not mediated by irrelevant IgM antibodies. Flow cytometry demonstrated that AVA do not bind directly to resting platelets in whole blood, but they bind to approximately 10% of leukocytes. Supernatant, derived from AVA-treated leukocytes, induced platelet activation, as measured by the generation of platelet microparticles, when added to platelet-rich plasma. When AVA were added to whole blood in the presence of CV-6209, a platelet-activating factor (PAF) receptor inhibitor, platelet depletion was inhibited. This suggests that PAF is one of the mediators released from AVA-activated leukocytes that leads to P:L conjugation formation and platelet activation. In summary, AVA bind to leukocytes, resulting in release of a PAF and prothrombotic factor that exert a paracrine-activating effect on platelets. Overall, this proposed mechanism may explain the pathogenesis of thrombotic events in autoimmune diseases associated with AVA.

Topics: Apoptosis; Autoantibodies; Autoimmune Diseases; Blood Platelets; Cell Adhesion; Complement C3d; Culture Media, Conditioned; Fibrinogen; Humans; Immunoglobulin M; Immunosorbent Techniques; Leukocytes; P-Selectin; Platelet Activating Factor; Platelet Activation; Pyridinium Compounds; Recombinant Proteins; Thrombophilia; Thromboplastin; Vimentin

The changes in levels of peripheral major lymphocyte subsets were monitored with 10 adult cynomolgus monkeys (5 females and 5 males) during the 9 weeks after immunization with chick type-II collagen in Freund's complete adjuvant. Three females and 3 males developed overt arthritis determined by swelling of small joints and increase of plasma alkaline phosphatase as well as C-reactive protein. An increase of CD16+ NK cells was observed in four non-arthritis-developed monkeys (two females and two males). There was no significant difference in the fluctuation pattern of CD4+ T cell, CD8+ T cell and CD20+ B cell levels between arthritis-developed monkeys and non-developed ones. In addition, the percentages of CD45RA+ CD4+ T cells to total CD4+ T cells, CD28- CD8+ T cells to total CD8+ T cells, and IgD- B cells to total B cells did not significantly differ between them. On the other hand, a significant increase was demonstrated in CD14-positive cells at 3 weeks after immunization in only arthritis-developed monkeys regardless of sex. The expression of CD14 antigen on the surface of increased cells was low in comparison with those appearing in blood obtained before immunization. In addition, increased CD14low cells showed no response to LPS stimulation. However, there was no significant difference in antibody titer to both chick type-II and monkey type-II collagen between arthritis-developed monkeys and non-developed ones. These results suggest that an increase in number of CD14low monocytes with immature function might be a part of the autoimmune response, and that the appearance of these cells is of pathogenic importance in the arthritic process in cynomolgus monkeys regardless of the production of autoantibody.

Topics: Alkaline Phosphatase; Animals; Antigens, CD20; Arthritis, Experimental; Autoimmune Diseases; B-Lymphocytes; C-Reactive Protein; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Collagen; Female; Immunization; Killer Cells, Natural; Leukocyte Count; Lipopolysaccharide Receptors; Lipopolysaccharides; Lymphocyte Count; Macaca fascicularis; Male; Monocytes; Receptors, IgG; Thromboplastin

Two human monoclonal antiphospholipid antibodies (APA) of the IgG type, HL-5B and RR-7F have been generated from a patient with primary antiphospholipid syndrome and recurrent cerebral microemboli (H.L.) and from a patient with SLE without evidence of recurrent thrombosis (R.R.). Both monoclonal APA have similar characteristics in ELISA tests. To further analyse the prothrombotic potential, their effect on human monocytes and platelets, and bovine aortic endothelial cells (BAEC) was investigated. Monocytes were isolated from buffy coats by standard techniques. They were incubated either with the respective monoclonal APA in different concentrations, or a control monoclonal IgG of the same subtype, or plasma of the patients, from whom the antibodies were isolated. Incubation with LPS served as positive control. BAEC were grown to confluence, and then incubated with the appropriate agonists. Procoagulant activity (PCA) was determined by a single stage clotting assay. PCA expression after incubation is given as the ratio of the coagulation times observed with media only divided by that observed with the agonist. A PCA ratio >1 indicates the induction of PCA by the agonist. At 1 microg/ml HL-5B yielded a PCA ratio of 1.63 +/- 0.16 while RR-7F induced no significant rise to 1.06 +/- 0.18. Dose response curves showed that RR-7F can induce PCA at higher concentrations. However, its effect is approx. 1/50 of HL-5B based on equimolar antibody concentration. Further analysis indicates that the majority of the PCA induced by monoclonal APA can be inhibited by a specific tissue factor antibody. Neither monoclonal antibody induced PCA in BAEC. Sera from both patients were able to induce PCA in monocytes. However, the PCA ratio of serum from H.L. was higher (1.78) than that of R.R. (1.44). Neither monoclonal APA had an effect on platelets as determined by flow cytometric analysis of CD62P, CD41, CD42b expression and fibrinogen binding with and without previous activation with 5 microM ADP or 15 microM TRAP-6. Similarly, there were no differences in platelet aggregation to different stimuli including submaximal activation. In summary, these data provide further evidence that induction of tissue factor in monocytes is one of the procoagulant effects of APA. Furthermore, the binding specificity of APA is perhaps not suited to predict the biological effects of the antibodies.

Topics: Adenosine Diphosphate; Animals; Antibodies, Antiphospholipid; Antibodies, Monoclonal; Antibody Specificity; Antiphospholipid Syndrome; Autoimmune Diseases; Biomarkers; Blood Coagulation Factors; Blood Platelets; Cattle; Cells, Cultured; Dose-Response Relationship, Immunologic; Endothelium, Vascular; Female; Fibrinogen; Humans; Immunoglobulin G; Intracranial Embolism; Lipopolysaccharides; Lupus Erythematosus, Systemic; Male; Middle Aged; Monocytes; Peptide Fragments; Platelet Activation; Recurrence; Thrombophilia; Thromboplastin

Topics: Adsorption; Annexin A5; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Autoimmune Diseases; Binding, Competitive; Humans; Membrane Lipids; Models, Immunological; Protein Binding; Prothrombin Time; Thrombin; Thromboplastin

Anti-beta2-glycoprotein I (beta2-GPI) antibodies behave as classical Lupus Anticoagulants (LA), as they inhibit phospholipid-dependent coagulation reactions and their activity disappears in the presence of excess exogenous phospholipids (PLs). We have recently shown that a certain amount of PLs in the dilute Russell Viper Venom Time (dRVVT) test system is required to express LA activity of anti beta2-GPI antibodies. We have now extended this observation to two other tests, i.e., Kaolin Clotting Time (KCT) in which PLs are not added, and Tissue Thromboplastin Inhibition test (TTI) in which PLs are extremely diluted. In fact, affinity-purified antibody preparations from 5 patients with antiphospholipid syndrome did not express or only weakly expressed anticoagulant activity in both tests; the mean ratios of coagulation times obtained with purified antibodies and that of control buffer were 1.11 and 1.0 for KCT and TTI, respectively. On the contrary, the mean ratios in dRVVT were 1.31 and 1.49 at a PLs dilution of 1:8 and 1:64, respectively. Therefore, the presence of LA activity due to autoantibodies to beta2-GPI is characterized by a positive dRVVT and negative or only weakly positive KCT and TTI.

Topics: Adolescent; Adult; Antibodies, Anticardiolipin; Antiphospholipid Syndrome; Autoimmune Diseases; beta 2-Glycoprotein I; Blood Coagulation Tests; Female; Glycoproteins; Humans; Immunoglobulin G; Kaolin; Lupus Coagulation Inhibitor; Male; Phospholipids; Prothrombin Time; Sensitivity and Specificity; Thromboplastin

Microparticles (MPs) resulting from vesiculation of platelets and other blood cells have been extensively documented in vitro and have been found in increased numbers in several vascular diseases, but little is known about MPs of endothelial origin. The aim of this study was to analyze morphological, immunological, and functional characteristics of MPs derived from human umbilical vein endothelial cells (HUVECs) stimulated by TNF, and to investigate whether these MPs are detectable in healthy individuals and in patients with a prothrombotic coagulation abnormality. Electron microscopy evidenced bleb formation on the membrane of TNF-stimulated HUVECs, leading to increased numbers of MPs released in the supernatant. These endothelial microparticles (EMPs) expressed the same antigenic determinants as the corresponding cell surface, both in resting and activated conditions. MPs derived from TNF-stimulated cells induced coagulation in vitro, via a tissue factor/factor VII-dependent pathway. The expression of E-selectin, ICAM-1, alphavbeta3, and PECAM-1 suggests that MPs have an adhesion potential in addition to their procoagulant activity. In patients, labeling with alphavbeta3 was selected to discriminate EMPs from those of other origins. We provide evidence that endothelial-derived MPs are detectable in normal human blood and are increased in patients with a coagulation abnormality characterized by the presence of lupus anticoagulant. Thus, MPs can be induced by TNF in vitro, and may participate in vivo in the dissemination of proadhesive and procoagulant activities in thrombotic disorders.

Topics: Antiphospholipid Syndrome; Autoimmune Diseases; Cell Adhesion Molecules; Cells, Cultured; Endothelium, Vascular; Factor VII; Flow Cytometry; Humans; Infections; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Microscopy, Confocal; Neoplasms; Receptors, Vitronectin; Thrombophilia; Thromboplastin; Tumor Necrosis Factor-alpha; Umbilical Veins

Topics: Abortion, Habitual; Adult; Animals; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Drug Monitoring; Female; Humans; International Normalized Ratio; Intracranial Embolism; Intracranial Thrombosis; Male; Middle Aged; Pregnancy; Recombinant Proteins; Recurrence; Risk; Seizures; Thromboembolism; Thrombophilia; Thrombophlebitis; Thromboplastin; Warfarin

Topics: Antiphospholipid Syndrome; Autoimmune Diseases; Female; Humans; Leukocytes, Mononuclear; Male; Models, Biological; Thrombophilia; Thromboplastin

Topics: Autoantibodies; Autoimmune Diseases; Blood Coagulation Factors; Cardiolipins; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Humans; Lupus Coagulation Inhibitor; Phospholipids; Thromboplastin

Topics: Abortion, Habitual; Autoimmune Diseases; Blood Coagulation Factors; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lupus Coagulation Inhibitor; Male; Partial Thromboplastin Time; Phospholipids; Pregnancy; Reagent Kits, Diagnostic; Thromboembolism; Thromboplastin

The relationship between abortive disease and systemic lupus erythematosus is complex as shown by data from the literature and by our 9 patients selected for presenting with abortive disease, circulating anticoagulant and biological signs of autoimmunity. The risk of transformation into a systemic disease is real, although difficult to evaluate in the absence of prospective studies, but the major problem with these patients is the severity of the obstetrical pathology. The sombre foetal prognosis, already reported in the literature, requires close supervision and sustained treatment during pregnancy. For these reasons we suggest calling autoimmune abortive disease the disease which affects women with signs of autoimmunity who have had several, often late foetal deaths associated with the presence of circulatory anticoagulant thought to interfere with placental blood flow.

Topics: Abortion, Habitual; Adult; Antibodies, Antinuclear; Autoantibodies; Autoimmune Diseases; Blood Coagulation Factors; Female; Fetal Death; Humans; Lupus Coagulation Inhibitor; Pregnancy; Prognosis; Thromboplastin

The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leukocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abortion, Spontaneous; Autoantibodies; Autoimmune Diseases; Blood Coagulation Factors; Blood Coagulation Tests; Brain Diseases; Female; Humans; Immunoglobulins; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Lymphoma; Multiple Myeloma; Paraproteinemias; Pregnancy; Thromboplastin; Thrombosis

The mechanism involved in glomerular fibrin deposition was investigated during mercuric chloride (HgCl2)-induced autoimmune glomerulonephritis in the Brown Norway rat. To ascertain whether the local hemostatic system was activated secondarily to the immunological conflict, the ability of glomerular lysates to induce coagulation in vitro was assessed in treated and control rats. Glomerular procoagulant activity (PCA) of HgCl2-injected rats was measured on day 12 (latent phase of the disease), day 20 (acme), and days 32 and 42 (recovery phase) after the first mercury injection. PCA rose 3-fold (p less than 0.02) at day 20 and then almost returned to control values. Proteinuria, PCA, and the incidence of glomerular fibrin deposits peaked concomitantly at day 20. Glomerular PCA was characterized as thromboplastin. The number of Ia positive cells detected by monoclonal OX-6 antibody was not different from the control number at any phase of the disease; the number of macrophages per glomerular section detected by electron microscopy at day 20 in HgCl2-injected rats was 1.80 +/- 0.60, versus 0.30 +/- 0.11 in the controls. No correlation was found between glomerular PCA and either the number of monocytes/macrophages or of Ia-positive cells present in the glomeruli. Since glomerular PCA was maximal at the onset of fibrin formation in the glomeruli and then decreased toward its basal level, and since the fibrin disappeared, it is concluded that increased production of thromboplastin by glomeruli, with activation of the extrinsic coagulation pathway, may contribute to intraglomerular fibrin deposition in HgCl2-induced glomerulonephritis.

Topics: Animals; Autoimmune Diseases; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Histocompatibility Antigens Class II; Kidney Glomerulus; Macrophages; Male; Mercuric Chloride; Proteinuria; Rats; Rats, Inbred BN; Thromboplastin

Three techniques have been employed for the in vitro detection of circulating platelet antibodies in thrombocytopenic patients affected by 'idiopathic' form or by lupus erythematosus (SLE), the complement fixation test, the platelet factor 3 availability test and the serotonin release test. 29 of the 35 sera tested (82.8%) gave positive results for antiplatelet activity. In particular the serotonin release test allows to distinguish 4 groups of patients: a first group affected by idiopathic form; two groups with autoimmune thrombocytopenia and various degrees of serotonin release, and finally a fourth group which comprises subjects affected by SLE, with circulating immunocomplexes.

Topics: Autoimmune Diseases; Blood Platelets; Chronic Disease; Complement Fixation Tests; Humans; Isoantibodies; Lupus Erythematosus, Systemic; Serotonin; Thrombocytopenia; Thromboplastin

A case of an acquired circulating anticoagulant occurring in a patient suffering from chronic lymphocytic leukaemia with haemolytic anaemia and autoimmune disorders has been reported. The anticoagulant was found to belong to the IgM class. Coagulation studies show that this anticoagulant inhibits the reaction between human prothrombinase andfactor II.

Topics: Anemia, Hemolytic; Autoantibodies; Autoimmune Diseases; Blood Coagulation Tests; Female; Humans; Immunoglobulin M; Leukemia, Lymphoid; Prothrombin; Thromboplastin

Topics: Adult; Autoantibodies; Autoimmune Diseases; Complement Fixation Tests; Cyclophosphamide; Hodgkin Disease; Humans; Isoantibodies; Male; Prednisone; Remission, Spontaneous; Splenectomy; Thrombocytopenia; Thromboplastin

Topics: Autoimmune Diseases; Blood Coagulation; Child; Factor IX; Humans; Immunoglobulin G; Male; Thrombin; Thromboplastin

Topics: Autoimmune Diseases; Female; Hemophilia A; Hemorrhagic Disorders; Humans; Medicine; Pregnancy; Pregnancy Complications, Hematologic; Thromboplastin

Topics: Anticoagulants; Autoimmune Diseases; Blood Coagulation Disorders; Collagen Diseases; Humans; Immunoglobulins; Lupus Erythematosus, Systemic; Thromboplastin