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Antiphospholipid Syndrome (antiphospholipid + syndrome)
Kinds of Antiphospholipid Syndrome Selected AbstractsDeep Hypothermic Circulatory Arrest and Bivalirudin Use in a Patient With Heparin-Induced Thrombocytopenia and Antiphospholipid SyndromeJOURNAL OF CARDIAC SURGERY, Issue 1 2007Kay B. Leissner M.D. Methods: Bivalirudin was used during CPB and deep hypothermic circulatory arrest (DHCA) for resection of multiple right atrial masses in a patient with HIT II and antiphospholipid antibodies syndrome (APS). Anticoagulation was monitored with the activated clotting time (ACT) and a target ACT of 450 seconds or greater was maintained. Results: Surgical removal of multiple right atrial masses was successful and there was no evidence of thromboembolic events. Clot was noticed in the cardiotomy and venous reservoir after CPB was discontinued and the system flushed. The postoperative course was uneventful. Conclusions: Anticoagulation was successfully managed with bivalirudin, a new short-acting, and direct thrombin inhibitor. Further studies are necessary to evaluate the safety of bivalirudin during DHCA. [source] ORIGINAL ARTICLE: Thrombin Activatable Fibrinolysis Inhibitor and Clot Lysis Time in Pregnant Patients with Antiphospholipid Syndrome: Relationship with Pregnancy Outcome and ThrombosisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009Maria Angeles Martinez-Zamora Problem, Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis. Method of study, Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined. Results, Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences. Conclusion, Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS. [source] Antiphospholipid syndrome and endocrine damage: why bilateral adrenal thrombosis?EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003Kaspar Berneis Abstract: We describe a rare case of bilateral hemorrhagic infarction of the adrenal glands diagnosed in the context of positive antiphospholipid antibodies (aPL). The patient presented atypical clinical symptoms of adrenal insufficiency. Laboratory investigation showed complete adrenal failure and increased aPL, both manifestations persisted 1 yr after the initial event. MR imaging at baseline was compatible with bilateral hemorrhagic infarction and showed almost complete loss of viable adrenal tissue 1 yr later. Although no direct causal effect can be proved, the sequence of events and the exclusion of other common causes of bilateral adrenal hemorrhage (e.g. tuberculosis, severe coagulation disorder) support an association between aPL and adrenal hemorrhagic infarction. A unique link between particular anatomical characteristics of the adrenal fascicular zone and a novel, previously described, explanation model of aPL-thrombosis is hypothesized. It is based on the properties of late endosomes, which are important organelles participating in cholesterol trafficking and protein sorting within cells and express epitopes recognized by aPL. It would be interesting to investigate adrenal tissue for presence of late endosomes and their aPL relevant epitopes for proof of this tempting hypothesis. Focal accumulation of aPL and isolated, simultaneous, bilateral adrenal infarctions could thus be explained. [source] Antiphospholipid syndrome: a systemic and multidisciplinary diseaseINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 2 2008L. PAGALAVAN Abstract Antiphospholipid syndrome (APS) was first described by Hughes and colleagues in 1983. Since the first few initial descriptions of the syndrome, almost every organ in the body has been reported to be involved in APS. The ,Sapporo' criteria which has been used as the diagnostic criteria since 1999 was recently revised in Sydney before the 11th International Congress on antiphospholipid antibodies in 2006. Over the last 24 years it has evolved into a systemic and multidisciplinary disease. This article looks into the extensive multidisciplinary involvement and presentation of APS including neurology, nephrology, cardiology, respiratory medicine, obstetrics and gynecology, endocrinology, hematology, ophthalmology, dermatology, otorhinolaryngology, gastroenterology, and orthopaedics. [source] Pathophysiology of the antiphospholipid syndromeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2005P. G. DE GROOT Summary., Antiphospholipid syndrome is a distinct disorder with the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Its serological marker is the presence of antiphospholipid antibodies in the blood of these patients. The relation between the presence of antibodies against anionic phospholipids and thromboembolic complications is well established over the last 25 years but the pathophysiology of the syndrome is largely unclear. Even after all these years, there is a persisting debate about the specificity and sensitivity of the assays for the detection of antiphospholipid antibodies. We now accept that antibodies to ,2-glycoprotein I rather than to anionic phospholipids are the major pathological antibodies, although there is no clear consensus on how the presence of these antibodies correlates with the different clinical manifestations of the syndrome. In this review, we discuss the current methods of detection of the antibodies and our insight into the pathobiology of the syndrome. We propose a mechanism for describing how the presence of anti- ,2-glycoprotein I antibodies relates to the different clinical manifestations observed. [source] ORIGINAL ARTICLE: Thrombin Activatable Fibrinolysis Inhibitor and Clot Lysis Time in Pregnant Patients with Antiphospholipid Syndrome: Relationship with Pregnancy Outcome and ThrombosisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009Maria Angeles Martinez-Zamora Problem, Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis. Method of study, Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined. Results, Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences. Conclusion, Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS. [source] Asymptomatic myocardial ischemic disease in antiphospholipid syndrome: A controlled cardiac magnetic resonance imaging studyARTHRITIS & RHEUMATISM, Issue 7 2010Karim Sacré Objective Antiphospholipid syndrome (APS) may cause coronary thrombosis. This study was undertaken to determine the prevalence of silent myocardial disease in patients with APS, using late gadolinium enhancement (LGE) of cardiac magnetic resonance imaging (CMRI). Methods Twenty-seven consecutive patients with APS and 81 control subjects without known cardiovascular disease underwent CMRI. The prevalence of occult myocardial ischemic disease, as revealed by LGE, was compared between patients with APS and controls, and factors associated with myocardial disease were identified in patients with APS. Results Myocardial ischemic disease, as characterized by LGE on CMRI, was present in 8 (29.6%) of 27 patients with APS, and imaging with LGE showed a typical pattern of myocardial infarction (MI) in 3 patients (11.1%). The myocardial scarring revealed on CMRI was not detected by electrocardiography or echocardiography. Although both patients with APS and control subjects shared a low risk of cardiovascular events, as calculated with the Framingham risk equation (mean ± SD 5.1 ± 8.2% and 6.5 ± 7.6%, respectively, for the absolute risk within the next 10 years; P = 0.932), the prevalence of myocardial ischemia was more than 7 times higher in patients with APS (P = 0.0006 versus controls). No association was found between myocardial disease in patients with APS and classic coronary risk factors. The presence of myocardial scarring tended to be more closely associated with specific features of APS, such as duration of the disease, presence of livedo, and positivity for anti,,2 -glycoprotein I antibodies. Conclusion The finding of a significant and unexpectedly high prevalence of occult myocardial scarring in patients with APS indicates the usefulness of CMRI with LGE for the identification of silent myocardial disease in such patients. [source] Neurological manifestations of antiphospholipid syndromeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2010Carlos E. M. Rodrigues Eur J Clin Invest 2010; 40 (4): 350,359 Abstract Background, Neurologic disorders are among the most common and important clinical manifestations associated with the antiphospholipid syndrome (APS). It is characterized by diverse neurological manifestations. These include stroke, transient ischaemic attack, Sneddon's syndrome, convulsions/epilepsy, dementia, cognitive deficits, headaches/migraine, chorea, multiple sclerosis-like, transverse myelitis, ocular symptoms and Guillain,Barré syndrome. Material and methods, We review the latest data about neurologic disorders and APS. Results, In patients under 45 years of age, 20% of strokes are potentially associated with APS. Our study group recently reported a correlation between primary APS and peripheral neuropathy. Only one study investigated the occurrence of peripheral neuropathy in patients diagnosed with PAPS through electrophysiological study and showed alterations in 35% of patients. The mechanism of nervous system involvement in APS is considered to be primarily thrombotic. However, other mechanisms have been described, such as antiphospholipid antibodies that bind to the neural tissue, deregulating their functions and having an immediate pathogenic effect. Conclusions, This review summarizes the latest data regarding the clinical aspects, radiological and therapeutic of major neurologic manifestations associated with antiphospholipid antibodies. [source] Clinical importance of antibodies against platelet activating factor in antiphospholipid syndrome manifestationsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2000Tektonidou Background We assessed whether antibodies against platelet activating factor (PAF) are related to the presence of antiphospholipid syndrome (APS) clinical manifestations, in particular thrombosis, in patients with connective tissue diseases. Materials and methods Anti-PAF, anticardiolipin (aCL), anti,2 glycoprotein I (anti,2GPI) and antiphosphatidylcholine (anti-PC) antibodies were determined in 52 patients with APS, 29 patients with systemic lupus erythematosus (SLE) aCL but without APS, 30 patients with SLE without aCL, and 30 patients with scleroderma. A new enzyme-linked immunosorbent assay (ELISA) was developed for determining anti-PAF antibodies in a bovine serum-free fashion. Results The ELISA showed high specificity. Homologous inhibition experiments showed 60,70% inhibition. Anti-PAF antibodies were found in 18/52 APS patients, 10/29 SLE/aCL+ patients, 9/30 SLE/aCL, patients and 3/30 scleroderma patients. Anti-PAF antibodies were significantly associated with anti-PC antibodies (odds ratio [OR] 12.7, P < 0.01), and there was a modest association with immunoglobulin G (IgG) aCL (OR 3.1, P > 0.10), but not with IgM aCL or anti,2GPI. Three SLE/aCL+ patients and five SLE/aCL, patients had clinical manifestations characteristic of APS. All these patients had anti-PAF antibodies, while none had high titres of aCL or anti,2GPI antibodies and only one had anti-PC antibodies. Among the combined APS and SLE groups, the presence of anti-PAF antibodies was significantly associated with clinical manifestations which are characteristic of APS (OR 2.6, P = 0.02). The effect was independent of IgG aCL and anti,2GPI antibodies. Conclusions Anti-PAF antibodies are common in APS and SLE and comprise an independent factor for the development of thrombosis. Several patients experiencing thromboses have anti-PAF antibodies without other antiphospholipid specificities. [source] ,Cure' of life-threatening antiphospholipid syndrome with rituximabINTERNAL MEDICINE JOURNAL, Issue 7 2006A. Anandacoomarasamy No abstract is available for this article. [source] Thromboembolism in a patient with transient eosinophilia and thrombocytopeniaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2000Y. Sherer Summary A 24-year-old woman with an unremarkable medical history who developed bilateral deep venous thrombosis and pulmonary emboli is presented. Associated findings were severe eosinophilia and moderate thrombocytopenia. Since the major acquired and hereditary thrombogenic disorders were ruled out in this case (including antiphospholipid syndrome and heparin-induced thrombocytopenia), we believe that the severe eosinophilia per se could be the pro-coagulant factor leading to thrombosis and embolism in our patient. The role of eosinophilia in thrombosis is discussed. [source] Reviews: A review of hereditary and acquired coagulation disorders in the aetiology of ischaemic strokeINTERNATIONAL JOURNAL OF STROKE, Issue 5 2010Lonneke M. L. De Lau The diagnostic workup in patients with ischaemic stroke often includes testing for prothrombotic conditions. However, the clinical relevance of coagulation abnormalities in ischaemic stroke is uncertain. Therefore, we reviewed what is presently known about the association between inherited and acquired coagulation disorders and ischaemic stroke, with a special emphasis on the methodological aspects. Good-quality data in this field are scarce, and most studies fall short on epidemiological criteria for causal inference. While inherited coagulation disorders are recognised risk factors for venous thrombosis, there is no substantial evidence for an association with arterial ischaemic stroke. Possible exceptions are the prothrombin G20210A mutation in adults and protein C deficiency in children. There is proof of an association between the antiphospholipid syndrome and ischaemic stroke, but the clinical significance of isolated mildly elevated antiphospholipid antibody titres is unclear. Evidence also suggests significant associations of increased homocysteine and fibrinogen concentrations with ischaemic stroke, but whether these associations are causal is still debated. Data on other acquired coagulation abnormalities are insufficient to allow conclusions regarding causality. For most coagulation disorders, a causal relation with ischaemic stroke has not been definitely established. Hence, at present, there is no valid indication for testing all patients with ischaemic stroke for these conditions. Large prospective population-based studies allowing the evaluation of interactive and subgroup effects are required to appreciate the role of coagulation disorders in the pathophysiology of arterial ischaemic stroke and to guide the management of individual patients. [source] Prevalence of antiphospholipid antibodies in Chilean patients with rheumatoid arthritisJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2006Iván Palomo Abstract Antiphospholipid (aPL) antibodies found in patients with autoimmune diseases are also detected in those with inflammatory diseases. The purpose of this study was to examine the prevalence of these antibodies in patients with rheumatoid arthritis (RA), and to evaluate the association of these antibodies with thrombosis and/or other clinical characteristics of this inflammatory disorder. Eighty-four patients with RA and 82 normal controls were studied. Anticardiolipin (aCL), anti-,2 glycoprotein I (anti-,2GPI), and antiprothrombin (aPT) antibodies and the lupus anticoagulant (LA) activity were determined. Seven out of 84 (8.3%) patients were positive for aCL, six out of 84 (7.2%) for anti-,2GPI, and six out of 84 (7.2%) for aPT, while in controls the overall prevalence of aPL antibodies was 3.6% (3 out of 82). All patients and controls were LA negative. There was no correlation between the presence of aPL with thrombosis and/or other clinical features of the antiphospholipid syndrome. We found aPL antibodies in 19.1% (16 out of 84) of the patients with rheumatoid arthritis and this prevalence was statistically higher than in normal controls (P<0.003). In this study, the presence of aPL antibodies was not associated with the development of thrombosis and/or thrombocytopenia. Whether the presence of aPL antibodies implies an increased risk for thrombosis and atherosclerosis in these patients should be studied further. J. Clin. Lab. Anal. 20:190,194, 2006. © 2006 Wiley-Liss, Inc. [source] Use of a new silica clotting time for diagnosing lupus anticoagulant in patients who meet the clinical criteria for antiphospholipid syndromeJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2006Panagiotis Grypiotis Abstract The silica clotting time (SCT) is a phospholipid-dependent coagulation assay used for the laboratory diagnosis of lupus anticoagulant (LA) antibodies. The sensitivity and specificity of a new commercial SCT for identifying LA in patients who meet the clinical criteria for antiphospholipid syndrome (APS), and its association with thrombotic events were evaluated here. Forty-five patients who met the clinical criteria for APS according to the Sapporo International Consensus Statement were examined. Sixty-nine patients who did not meet the clinical criteria for APS, and 20 blood donors were used as controls. Plasma samples from the patients and controls were tested for LA using a new commercial SCT with low and high synthetic phospholipid concentrations. The results were compared with those obtained by diluted Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT). SCT's sensitivity for identifying LA in patients who met the clinical criteria of APS was higher compared to APTT and dRVVT (53.3% vs. 31.1% and 31.1%), and the specificities of these assays were 96.6%, 100%, and 98.9%, respectively. When dRVVT was combined with SCT, and dRVVT was combined with APTT their sensitivities were 57.7% and 48.8%, and their specificities were 96.6% and 98.9%, respectively. A stepwise logistic regression analysis indicated that the combination of dRVVT with SCT was associated with total thrombotic events (odds ratio (OR)=11.5, 95% confidence interval (CI)=1.25,106.3, P=0.031) as well as with venous thrombosis (OR=4.09, 95% CI=1.16,14.43, P=0.028). According to our results, SCT is the most sensitive assay for identifying LA in patients who meet the clinical criteria for APS. Moreover, the highest sensitivity was reached with a combination of SCT and dRVVT. The method's association with total thrombotic events and venous thrombosis was in fact significant. J. Clin. Lab. Anal. 20:15,18, 2006. © 2006 Wiley-Liss, Inc. [source] Steroid-responsive catastrophic antiphospholipid syndromeJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2004ADAM GORDON No abstract is available for this article. [source] Anti-,2 -glycoprotein I antibodies recognizing platelet factor 4,heparin complex in antiphospholipid syndrome in patient substantiated with mouse ModelJOURNAL OF MOLECULAR RECOGNITION, Issue 3 2003Mustapha Bourhim Abstract The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies associated with arterial and/or venous thrombosis, and recurrent abortion accompanied often by thrombocytopenia. These antibodies are heterogeneous and react against phospholipid-binding proteins such as ,2 -glycoprotein I (,2GPI) and prothrombin. The recognition of anti-,2 -glycoprotein I (anti-,2GPI) by platelet factor 4,heparin complex (PF4,Hc) has been previously evoked and partially confirmed by the present inhibition studies. Further, the anti-,2 -glycoprotein I antibodies were purified from a patient with primary antiphospholipid syndrome using Affi-gel®-10-,2GPI immunoaffinity chromatography. The purified anti-,2GPI IgM as well as patient serum equally recognized PF4,Hc in ELISA mode. In order to substantiate this data and to better understand we studied an animal model using mouse active immunization with the purified human anti-,2GPI. The mice showed a significant decrease in their platelet count. In addition the ELISA responses of the immunized mice sera were positive against both ,2GPI and PF4,Hc, substantiating the double recognition. Despite many previous reported animal model studies, this is the first time we have shown the specific recognition of anti-,2GPI antibodies by PF4,Hc, the results in the induced mice correlating the data observed with some patients. Copyright © 2003 John Wiley & Sons, Ltd. [source] Digital gangrene: a rare skin symptom in systemic lupus erythematosusJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2000E Vocks Abstract A case of digital gangrene in a patient with systemic lupus erythematosus without secondary antiphospholipid syndrome is reported. The acute onset of the necrotizing acrovasculitis occurred without a history of Raynaud's phenomenon. Preceding symptoms of the systemic lupus erythematosus were arthritis, photosensitivity, alopecia and anorexia. Despite the seriousness of the acute episode the patient achieved an excellent outcome. [source] In vivo inhibition of antiphospholipid antibody-induced pathogenicity utilizing the antigenic target peptide domain I of ,2 -glycoprotein I: proof of conceptJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2009Y. IOANNOU Summary.,Objectives:,In the antiphospholipid syndrome (APS), the immunodominant epitope for the majority of circulating pathogenic antiphospholipid antibodies (aPLs) is the N-terminal domain I (DI) of ,2 -glycoprotein I. We have previously shown that recombinant DI inhibits the binding of aPLs in fluid phase to immobilized native antigen, and that this inhibition is greater with the DI(D8S/D9G) mutant and absent with the DI(R39S) mutant. Hence, we hypothesized that DI and DI(D8S/D9G) would inhibit aPL-induced pathogenicity in vivo. Methods:,C57BL/6 mice (n = 5, each group) were injected with purified IgG derived from APS patients (IgG-APS, 500 ,g) or IgG from normal healthy serum (IgG-NHS) and either recombinant DI, DI(R39S), DI(D8S/D9G), or an irrelevant control peptide (at 10,40 ,g). Outcome variables measured were femoral vein thrombus dynamics in treated and control groups following standardized vessel injury, expression of vascular cell adhesion molecule-1 (VCAM-1) on the aortic endothelial surface, and tissue factor (TF) activity in murine macrophages. Results:,IgG-APS significantly increased thrombus size as compared with IgG-NHS. The IgG-APS thrombus enhancement effect was abolished in mice pretreated with recombinant DI (P , 0.0001) and DI(D8S/D9G) (P , 0.0001), but not in those treated with DI(R39S) or control peptide. This inhibitory effect by DI was dose-dependent, and at lower doses DI(D8S/D9G) was a more potent inhibitor of thrombosis than wild-type DI (P , 0.01). DI also inhibited IgG-APS induction of VCAM-1 on the aortic endothelial surface and TF production by murine macrophages. Conclusion:,Our findings in this proof-of-concept study support the development of recombinant DI or the novel variant DI(D8S/D9G) as a potential future therapeutic agent for APS. [source] Activated protein C resistance determined with a thrombin generation-based test is associated with thrombotic events in patients with lupus anticoagulantsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2007S. LIESTØL Summary.,Background:,Several studies suggest that antiphospholipid antibodies interfere with the activity of activated protein C (APC). This acquired form of APC resistance has been proposed as a possible pathogenic mechanism underlying hypercoagulability associated with the antiphospholipid syndrome (APS).Objectives:,We wanted to investigate the inhibitory effect of recombinant APC (rAPC) on ex vivo thrombin generation in plasma and the modification of this effect by the presence of lupus anticoagulants (LA).Patients/Methods:,We analyzed plasmas from 81 patients with LA (52 patients fulfilling the criteria for the APS) and 91 controls. Percent inhibition of the endogenous thrombin potential (ETP) as a parameter of APC sensitivity was determined in plasmas using a thrombin generation-based APC resistance test probed with rAPC. All results were normalized using pooled normal plasma (PNP) as a reference.Results:,Normalized percent inhibition of ETP by APC was lower in patients with LA [61.4%, 95% confidence interval (CI) 45.8,74.5%] compared to controls (107.8%, 95% CI: 107.1,109.3%). In patients with LA and APS, median inhibition was lower than in patients with LA without APS (44.6%, 95% CI: 30.1,55.7% vs. 78.8%, 95% CI: 73.9,95.8%). This difference also persisted when patients on warfarin therapy were excluded from the APS subgroup.Conclusions:,APC resistance can be demonstrated with a thrombin generation-based test in a majority of patients with the LA laboratory phenotype. A history of thrombotic events in patients with LA is associated with a stronger resistance to the anticoagulant effect of APC. [source] Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2007M. E. VEGA-OSTERTAG Summary.,Background:,The purpose of this study was to examine whether SB 203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor, is effective in reversing the pathogenic effects of antiphospholipid antibodies. Methods:,The adhesion of THP-1 monocytes to cultured endothelial cells (EC) treated with immunoglobulin G (IgG) from a patient with antiphospholipid syndrome (IgG-APS) or control IgG (IgG-NHS) in the presence and absence of SB 203580 was examined. The size of an induced thrombus in the femoral vein, the adhesion of leukocytes to EC of cremaster muscle, tissue factor (TF) activity in carotid artery and in peritoneal macrophages, the ex vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in aorta preparations and platelet aggregation were studied in mice injected with IgG-APS or control IgG-NHS and with or without SB 203580. Results:,SB 203580 significantly reduced the increased adhesion of THP-1 to EC in vitro, the number of leukocytes adhering to EC, the thrombus size, the TF activity in carotid arteries and in peritoneal mononuclear cells, and the expression of VCAM-1 in aorta of mice, and completely abrogated platelet aggregation induced by IgG-APS. Conclusion:,These data suggest that targeting the p38 MAPK pathway may be valuable in designing new therapy modalities for treating thrombosis in patients with APS. [source] Platelet adhesion to dimeric ,2 -glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein Ib, and apolipoprotein E receptor 2,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2007M. T. T. PENNINGS Summary.,Background: The major antigen implicated in the antiphospholipid syndrome is beta2-glycoprotein I (,2GPI). Dimerized ,2GPI binds to apolipoprotein E receptor 2, (apoER2,) on platelets and increases platelet adhesion to collagen under conditions of flow. Aim: To investigate whether the interaction between dimerized ,2GPI and platelets is sufficiently strong to resist shear stresses. Methods: We studied the interaction of platelets with immobilized dimerized ,2GPI under conditions of flow, and further analyzed the interaction using surface plasmon resonance and solid phase immunoassays. Results: We found that dimerized ,2GPI supports platelet adhesion and aggregate formation under venous flow conditions. Adhesion of platelets to dimerized ,2GPI was completely inhibited by the addition of soluble forms of both apoER2, and GPIb,, and the addition of receptor-associated protein and the removal of GPIb, from the platelet surface. GPIb, co-precipitated with apoER2,, suggesting the presence of complexes between GPIb, and apoER2, on platelet membranes. The interaction between GPIb, and dimeric ,2GPI was of intermediate affinity (Kd = 180 nm) and Zn2+, but not Ca2+ -dependent. Deletion of domain V from dimeric ,2GPI strongly reduced its binding to both GPIb, and apoER2,. Antibodies that inhibit the binding of thrombin to GPIb, inhibited platelet adhesion to dimeric ,2GPI completely, while antibodies blocking the binding of von Willebrand factor to GPIb, had no effect. Dimeric ,2GPI showed reduced binding to low-sulfated GPIb, compared to the fully sulfated form. Conclusion: We show that platelets adhere to dimeric ,2GPI under both arterial and venous shear stresses. Platelets adhere via two receptors: GPIb, and apoER2,. These receptors are present in a complex on the platelet surface. [source] Pathophysiology of the antiphospholipid syndromeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2005P. G. DE GROOT Summary., Antiphospholipid syndrome is a distinct disorder with the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Its serological marker is the presence of antiphospholipid antibodies in the blood of these patients. The relation between the presence of antibodies against anionic phospholipids and thromboembolic complications is well established over the last 25 years but the pathophysiology of the syndrome is largely unclear. Even after all these years, there is a persisting debate about the specificity and sensitivity of the assays for the detection of antiphospholipid antibodies. We now accept that antibodies to ,2-glycoprotein I rather than to anionic phospholipids are the major pathological antibodies, although there is no clear consensus on how the presence of these antibodies correlates with the different clinical manifestations of the syndrome. In this review, we discuss the current methods of detection of the antibodies and our insight into the pathobiology of the syndrome. We propose a mechanism for describing how the presence of anti- ,2-glycoprotein I antibodies relates to the different clinical manifestations observed. [source] Anti- ,2-glycoprotein I antibody testing in the laboratory diagnosis of antiphospholipid syndromeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2005V. PENGO No abstract is available for this article. [source] Moderate dose oral anticoagulant therapy in patients with the antiphospholipid syndrome?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2005No abstract is available for this article. [source] A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS),JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2005G. FINAZZI Summary.,Background:,The optimal intensity of oral anticoagulation for the prevention of recurrent thrombosis in patients with antiphospholipid antibody syndrome is uncertain. Retrospective studies show that only high-intensity oral anticoagulation [target international normalized ratio (INR) >3.0] is effective but a recent randomized clinical trial comparing high (INR range 3.0,4.0) vs. moderate (INR 2.0,3.0) intensities of anticoagulation failed to confirm this assumption. Methods:,We conducted a randomized trial in which 109 patients with antiphospholipid syndrome (APS) and previous thrombosis were given either high-intensity warfarin (INR range 3.0,4.5, 54 patients) or standard antithrombotic therapy (warfarin, INR range 2.0,3.0 in 52 patients or aspirin alone, 100 mg day,1 in three patients) to determine whether intensive anticoagulation is superior to standard treatment in preventing symptomatic thromboembolism without increasing the bleeding risk. Results:,The 109 patients enrolled in the trial were followed up for a median time of 3.6 years. Mean INR during follow-up was 3.2 (SD 0.6) in the high-intensity warfarin group and 2.5 (SD 0.3) (P < 0.0001) in the conventional treatment patients given warfarin. Recurrent thrombosis was observed in six of 54 patients (11.1%) assigned to receive high-intensity warfarin and in three of 55 patients (5.5%) assigned to receive conventional treatment [hazard ratio for the high intensity group, 1.97; 95% confidence interval (CI) 0.49,7.89]. Major and minor bleeding occurred in 15 patients (two major) (27.8%) assigned to receive high-intensity warfarin and eight (three major) (14.6%) assigned to receive conventional treatment (hazard ratio 2.18; 95% CI 0.92,5.15). Conclusions:,High-intensity warfarin was not superior to standard treatment in preventing recurrent thrombosis in patients with APS and was associated with an increased rate of minor hemorrhagic complications. [source] The antigenic binding site(s) of antibodies to factor XII associated with the antiphospholipid syndromeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2005S. L. HARRIS Summary., Phospholipid binding proteins, including factor XII (FXII), are known to be targeted by antiphospholipid antibodies (aPA). Factor XII antibodies (FXIIab) have been described in some patients with the antiphospholipid syndrome (APS) and have been shown to lead to reduced levels of FXII. The antigenic binding site(s) and the pathophysiological effects of FXIIab are unknown. In an attempt to elucidate the binding site of these antibodies, immobilized plasma kallikrein was used to cleave FXII into its 52-kDa heavy-chain (HCFXII) and 28-kDa light-chain (LCFXII) components. Plasma samples from 12 female patients with definite APS and FXIIab were investigated for the presence of antibodies to FXII, HCFXII and LCFXII. All but one patient's plasma reacted to FXII, HCFXII and LCFXII in a similar manner. One patient gave markedly reduced positivity to HCFXII and LCFXII, suggesting that the FXIIab in this patient had a higher affinity for the intact FXII molecule. To further investigate the antigenic binding site(s) of FXII, 150 biotinylated peptides of the known FXII sequence were synthesized using a MultipinTM peptide synthesis procedure. The IgG and IgM fractions of the 12 patients' plasma were purified by affinity chromatography. The synthesized peptides were captured on streptavidin plates and individual patients' purified FXIIab assayed against the peptides in a modified enzyme-linked immunosorbent assay (ELISA). Two regions were identified as possible antigenic binding site(s) for FXIIab: one in the growth factor domain and the other in the catalytic domain. [source] Aspirin inhibits endothelial cell activation induced by antiphospholipid antibodiesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2004S. Dunoyer-Geindre Summary., Background : Antiphospholipid antibodies (APLA) have been shown to activate endothelial cells (EC) in vitro, as documented by an increased expression of tissue factor as well as leukocyte adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin. Currently, treatment of patients with the antiphospholipid syndrome includes aspirin, particularly for women with recurrent fetal loss. Objective : The present study was undertaken to investigate whether aspirin interferes with EC activation induced by APLA in vitro. Methods : IgG from 14 patients with APLA, and suffering from thrombotic complications and/or pregnancy morbidity, and control IgG were tested for their ability to modify the expression of VCAM-1 in human umbilical vein endothelial cells. VCAM-1 antigen was measured by flow cytometry and its mRNA by quantitative reverse transcriptase-polymerase chain reaction. Results : Incubation of EC with IgG from most of the patients led to a higher VCAM-1 expression compared with incubation with control IgG. The effect of aspirin was studied for the eight IgG samples that induced a more than 50% increase in VCAM-1. Aspirin (10 mm) treatment of the cells significantly reduced the VCAM-1 response to these APLA. Conclusions : Our results indicate that besides its antiplatelet properties, aspirin exerts a protective effect towards APLA at the EC level by decreasing leukocyte adhesion molecule expression at the cell surface. [source] Free flap failure in an anticardiolipin antibody-positive patient with neoplasm,A case reportMICROSURGERY, Issue 3 2010Emiko Asai M.D. We present herein a case of massive arterial thrombosis of a free rectus abdominal musculocutaneous flap used for reconstructive surgery of gingival carcinoma that could not be rescued. A 54-year-old woman underwent the operation. She had experienced two miscarriages in her 20s, but medical history was otherwise uneventful. Intraoperatively, the anastomosed artery often showed massive arterial thrombosis, and the flaps had become necrotic after bilateral flaps were used. Laboratory findings, 7 days postoperatively, showed high levels of immunoglobulin G anticardiolipin antibody. This value normalized by 2 months postoperatively after using chemotherapy. This case does not match the criteria for antiphospholipid syndrome, but some English-language reports have shown rising antiphospholipid antibody levels, particularly anticardiolipin antibodies, in patients with neoplasm. In those cases, levels have normalized after successful therapy. Antiphospholipid antibody levels should be examined before surgery to identify risks of hypercoagulability. © 2010 Wiley-Liss, Inc. Microsurgery, 2010. [source] Haemolytic uraemic syndrome: An overview (Review Article)NEPHROLOGY, Issue 3 2006IRADJ AMIRLAK SUMMARY: Haemolytic uraemic syndrome (HUS) is the most common cause of acute renal failure in children. The syndrome is defined by triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure (ARF). Incomplete HUS is ARF with either haemolytic anaemia or thrombocytopenia. HUS is classified into two subgroups. Typical HUS usually occurs after a prodrome of diarrhoea (D+HUS), and atypical (sporadic) HUS (aHUS), which is not associated with diarrhoea (D,HUS). The majority of D+HUS worldwide is caused by Shiga toxin-producing Esherichia coli (STEC), type O157:H7, transmitted to humans via different vehicles. Currently there are no specific therapies preventing or ameliorating the disease course. Although there are new therapeutic modalities in the horizon for D+HUS, present recommended therapy is merely symptomatic. Parenteral volume expansion may counteract the effect of thrombotic process before development of HUS and attenuate renal injury. Use of antibiotics, antimotility agents, narcotics and non-steroidal anti-inflammatory drugs should be avoided during the acute phase. Prevention is best done by preventing primary STEC infection. Underlying aetiology in many cases of aHUS is unknown. A significant number may result from underlying infectious diseases, namely Streptococcus pneumoniae and human immunedeficiency virus. Variety of genetic forms include HUS due to deficiencies of factor H, membrane cofactor protein, Von Willebrand factor-cleaving protease (ADAMTS 13) and intracellular defect in vitamin B12 metabolism. There are cases of aHUS with autosomal recessive and dominant modes of inheritance. Drug-induced aHUS in post-transplantation is due to calcineurin-inhibitors. Systemic lupus erythematosus and catastrophic antiphospholipid syndrome may also present with aHUS. Therapy is directed mainly towards underlying cause. [source] Acute renal failure in a patient with antiphospholipid syndrome and immune thrombocytopenic purpura treated with eltrombopag,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010C. John Sperati No abstract is available for this article. [source] | ||||||||||||||||||||||||||||||||||