Anti-β2-Glycoprotein I and Anti-Prothrombin Antibodies in Antiphospholipid-Negative Patients with Thrombosis

2002 ◽  
Vol 88 (11) ◽  
pp. 729-732 ◽  
Author(s):  
Sara Previtali ◽  
Tiziano Barbui ◽  
Monica Galli
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Lupus Erythematosus ◽  
Normal Subjects ◽  
Anticardiolipin Antibodies ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Significant Relationships ◽  
Antiprothrombin Antibodies ◽  
Independent Risk Factors

SummaryWe performed a case-control study to assess whether anti-β2-glycoprotein I and anti-prothrombin antibodies are independent risk factors of thrombosis. Cases were 79 patients with arterial and/or venous thrombosis without lupus anticoagulants, anticardiolipin antibodies and systemic lupus erythematosus; controls were 85 normal subjects. The prevalences and titers of IgG and IgM anti-β2-glycoprotein I and antiprothrombin antibodies were similar in both groups. Cases were analyzed with respect to the arterial or venous type of thrombosis and to the presence of congenital or acquired risk factors for thrombosis: no statistically significant relationships with the presence of anti-β2glycoprotein I and anti-prothrombin antibodies were found. Our data indicate that anti- β2-glycoprotein I and anti-prothrombin antibodies are not risk factors for thrombosis independent of lupus anticoagulants and anticardiolipin antibodies. Their measurement, therefore, is not warranted in the laboratory screening of patients with arterial and/or venous thrombosis.

Lupus Anticoagulants and Thrombosis: Clinical Association of Different Coagulation and Immunologic Tests

2000 ◽  
Vol 84 (12) ◽  
pp. 1012-1016 ◽  
Author(s):  
Jeffrey Dlott ◽  
Francesca Norbis ◽  
Luisa Ruggeri ◽  
Linda Cler ◽  
Douglas Triplett ◽  
...  
Keyword(s):  
At Risk ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Colloidal Silica ◽  
Anticardiolipin Antibodies ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Patients At Risk ◽  
Kaolin Clotting Time

SummaryThe dilute Russell’s viper venom time (dRVVT) and the kaolin clotting time (KCT) are two among the most commonly used coagulation tests for the detection of lupus anticoagulants. The dRVVT seems superior to the KCT in identifying LA-positive patients at risk of thrombosis. However, this relationship is greatly influenced by both the source of reagents and the instrumentation employed to carry out the assays. Therefore, 4 dRVVTs (“home-made” dRVVT, DVV test, Bioclot LA, LA Screen), and one KCT (Kaoclot) were performed in two centers and compared for their retrospective correlation with the thrombotic complications of 72 patients with a previously established diagnosis of lupus anticoagulants. Two other assays (“home-made” KCT, and Colloidal Silica Clotting Time, CSCT) were performed in one of the two centers, and compared with Kaoclot for their clinical correlations in the same population of patients, 44 of whom (61%) had suffered from arterial and/or venous thrombosis. A rather good degree of inter-laboratory and inter-assay correlations of the different tests was found. However, a statistically significant association with thrombosis was found only with the coagulation profile generated using the “homemade” dRVVT. When the commercially available dRVVTs were used, none of the coagulation profiles remained associated with thrombosis. When the assays were analyzed separately, the association with thrombosis was statistically significant for LA screen (p = 0.0019), DVV test (p = 0.0043), and Bioclot (p = 0.0255), and of borderline significance for the “home-made” dRVVT (p = 0.0503) in one center. This last assay was also significantly associated with thrombosis in the other center (p = 0.0139). When venous and arterial thrombosis were considered separately, DVV test was statistically associated with venous thrombosis in both centers (p = 0.0076 and p = 0.0187, respectively), and LA screen in one center (p = 0.0303). No dRVVT was found to correlate with arterial thrombosis. Kaoclot, Colloidal Silica Clotting Time, and the “home-made” KCT did not correlate with thrombosis. The prevalence of IgG and/or IgM antibodies to cardiolipin, β2-glycoprotein I and prothrombin were 74%, 86% and 85%, respectively. Increased titers of IgG anticardiolipin antibodies were associated with arterial thrombosis (p = 0.0375), whereas IgM anti-β2-glycoprotein I antibodies were associated with venous thrombosis (p = 0.0433). In conclusion, these retrospective data support the notion that the dRVVT, rather than other coagulation or ELISA tests, are able to identify lupus anticoagulant-positive patients at risk of thrombosis. This property appears common to several commercially available dRVVT kits, making this type of assay the ideal target of future efforts of laboratory standardization.

Synchronized Inhibition of the Phospholipid Mediated Autoactivation of Factor XII in Plasma by β2-glycoprotein I and Anti-β2-glycoprotein I

1995 ◽  
Vol 73 (05) ◽  
pp. 798-804 ◽  
Author(s):  
Inger Schousboe ◽  
Margit Søe Rasmussen
Keyword(s):  
Lupus Erythematosus ◽  
Lupus Anticoagulant ◽  
Response Curve ◽  
Inhibitory Effect ◽  
Factor Xii ◽  
High Antibody ◽  
Contact Activation ◽  
Maximal Inhibition ◽  
Lupus Anticoagulants ◽  
Glycoprotein I

SummaryLupus anticoagulants are a group of antibodies commonly found in patients with autoimmune diseases such as systemic lupus erythematosus. Lupus anticoagulants inhibit phospholipid dependent coagulation and may bind to negatively charged phospholipids. Recent studies have suggested an association between anti-β2-glycoprotein I and a lupus anticoagulant, whose activity is frequently dependent on the presence of β2-glycoprotein I. Based on these observations, the effect of anti-β2-glycoprotein I on the autoactivation of factor XII in plasma was investigated. Autoactivation initiated by the presence of negatively charged phospholipids, but not by sulfatide, was strongly inhibited by immunoaffinity purified anti-β2-glycoprotein I. The dose-response curve of anti-β2-gly coprotein I was identical with that of a precipitating antibody, showing no inhibition at low and high antibody dilutions and maximal inhibition at an intermediate dilution. At high antibody concentrations, an increased rate of factor Xlla activation was observed. This increase was of the same magnitude as the decreased rate observed in plasma supplemented with the same amount of β2-glycoprotein I as in the plasma itself. This confirms the inhibitory effect of β2-GP-I on the contact activation and shows that inhibition is effective on the autoactivation of factor XII in plasma. The inhibitory action of β2-glycoprotein I was independent of the inhibition caused by the anti- β2-glycoprotein I/β2-glycoprotein I complex suggesting a synchronized inhibition of factor XII autoactivation by β2-glycoprotein I and anti-β2-gly coprotein I. The inhibition caused by the antibody is suggested to be caused by a reduced availability of negatively charged phospholipids due to the binding of the anti-β2- GP-I/β2-GP-I complex. This complex may be a lupus anticoagulant.

scholarly journals Incidence and risk factors for deep venous thrombosis of lower extremity after surgical treatment of isolated patella fractures

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhanchao Tan ◽  
Hongzhi Hu ◽  
Xiangtian Deng ◽  
Jian Zhu ◽  
Yanbin Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lower Extremity ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Medical Data ◽  
Limited Information ◽  
Related Factors ◽  
Patella Fractures ◽  
Independent Risk Factors ◽  
Associated Risk Factors

Abstract Background Limited information exists on the incidence of postoperative deep venous thromboembolism (DVT) in patients with isolated patella fractures. The objective of this study was to investigate the postoperative incidence and locations of deep venous thrombosis (DVT) of the lower extremity in patients who underwent isolated patella fractures and identify the associated risk factors. Methods Medical data of 716 hospitalized patients was collected. The patients had acute isolated patella fractures and were admitted at the 3rd Hospital of Hebei Medical University between January 1, 2016, and February 31, 2019. All patients met the inclusion criteria. Medical data was collected using the inpatient record system, which included the patient demographics, patient’s bad hobbies, comorbidities, past medical history, fracture and surgery-related factors, hematological biomarkers, total hospital stay, and preoperative stay. Doppler examination was conducted for the diagnosis of DVT. Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors. Results Among the 716 patients, DVT was confirmed in 29 cases, indicating an incidence of 4.1%. DVT involved bilateral limbs (injured and uninjured) in one patient (3.4%). DVT involved superficial femoral common vein in 1 case (3.4%), popliteal vein in 6 cases (20.7%), posterior tibial vein in 11 cases (37.9%), and peroneal vein in 11 cases (37.9%). The median of the interval between surgery and diagnosis of DVT was 4.0 days (range, 1.0-8.0 days). Six variables were identified to be independent risk factors for DVT which included age category (> 65 years old), OR, 4.44 (1.34-14.71); arrhythmia, OR, 4.41 (1.20-16.15); intra-operative blood loss, OR, 1.01 (1.00-1.02); preoperative stay (delay of each day), OR, 1.43 (1.15-1.78); surgical duration, OR, 1.04 (1.03-1.06); LDL-C (> 3.37 mmol/L), OR, 2.98 (1.14-7.76). Conclusion Incidence of postoperative DVT in patients with isolated patella fractures is substantial. More attentions should be paid on postoperative DVT prophylaxis in patients with isolated patella fractures. Identification of associated risk factors can help clinicians recognize the risk population, assess the risk of DVT, and develop personalized prophylaxis strategies.

scholarly journals FRI0549 RISK OF INVASIVE FUNGAL INFECTION IN SYSTEMIC LUPUS ERYTHEMATOSUS: A NATIONWIDE POPULATION-BASED STUDY IN TAIWAN

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 876.1-876
Author(s):  
C. F. Su ◽  
C. C. Lai ◽  
T. H. LI ◽  
Y. F. Chang ◽  
Y. T. Lin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Mortality Rate ◽  
Fungal Infection ◽  
Incidence Rate ◽  
Invasive Fungal Infection ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Intravenous Steroid ◽  
Independent Risk Factors

Background:Infectious disease is one of the leading causes of mortality in systemic lupus erythematosus (SLE). Among these infections, invasive fungal infection (IFI) carries high mortality rate (25-70%), but the literature of IFI in SLE is limited.Objectives:To investigate the epidemiology and risk factors of invasive fungal infection and its subtypes, including candidiasis, aspergillosis, and cryptococcosis, in SLE patients.Methods:All patients with newly diagnosed SLE between 1997-2012 were enrolled from Taiwan National Health Insurance Research Database, with an age- and sex-matched non-SLE control group in a ratio of 1:10. IFI was identified by ICD9 codes1from discharge record and validated by use of systemic anti-fungal agents. The incidence rate (IR), incidence rate ratio (IRR), cause mortality rate of IFI and its subtypes were compared. A Cox multivariate model with time-dependent covariates was applied to analyse the independent risk factors of IFI.Results:A total of 269 951 subjects (24 541 SLE and 245 410 control) were included. There were 445 episodes of IFI in SLE group. Candida was the most common pathogen (52.8%), followed by cryptococcus and aspergillus. The IR of IFI in SLE was 20.83 per 10,000 person-years with an IRR of 11.1 (95% CI 9.8-12.6) compared to the control (figure 1). Kaplan-Meier curve also disclosed a lower IFI-free survival in SLE (figure 2). The all-cause mortality rate was similar between SLE and the control (26.7 vs 25.7%). In SLE, treatment with mycophenolate mofetil (HR=2.24, 95% CI 1.48-3.37), cyclosporin (HR=1.65, 95% CI 1.10-1.75), cyclophosphamide (HR=1.37, 95% CI 1.07-1.75), oral daily dose of steroid>5 mg prednisolone (HR=1.26, 95% CI 1.01-1.58), and intravenous steroid therapy (HR=29.11, 95% CI 23.30-36.37) were identified as independent risk factors of IFI. Similar analyses were performed for subtypes of IFI. Distinctive risk factors were found between different subtypes of IFI (table 1).Conclusion:SLE patients have a higher risk of IFI. Intravenous steroid therapy is the most important risk factor of IFI. This study provides crucial information for risk stratification of IFI in SLE.References:[1] Winthrop KL, Novosad SA, Baddley JW, et al. Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015 Dec; 74(12):2107-2116.Disclosure of Interests:None declared

The Most Important Risk Factors for Carpal Tunnel Syndrome

2021 ◽  
Author(s):  
Ali Asghar Sharifi
Keyword(s):  
Risk Factors ◽  
Carpal Tunnel Syndrome ◽  
Carpal Tunnel ◽  
Clinical Symptoms ◽  
Normal Subjects ◽  
Shape Index ◽  
Mean Values ◽  
Tunnel Syndrome ◽  
Independent Risk Factors ◽  
Hand Length

Background: The aim of this study was to determine the risk factors for carpal tunnel syndrome and its relationship with the severity of the disease. Methods: A total of 131 patients with clinical symptoms of CTS and 131 normal subjects were enrolled, of whom 121 were female both in the CTS cases and the controls. All cases were electro diagnostically confirmed and assigned to three severity groups. BMI, wrist ratio, shape index, digit index and hand length/height ratio were measured in all participants. Mean values for each item were compared between cases and controls and severity subgroups. A logistic regression analysis was performed to determine independent CTS risk factors. Results: The mean values of BMI, wrist ratio and shape index were significantly higher in all CTS patients and females compared to controls, whereas in males only BMI and wrist ratio were higher. The patients in the mild severity subgroup had a significantly lower age and wrist ratio. BMI, wrist ratio and shape index were found to be independent risk factors of CTS development in all patients and females. Conclusion: Our study showed BMI, wrist ratio and shape index as independent risk factors for CTS. These findings are important anatomically and clinically and these are the risk factors of anatomical malfunction of the wrist in CTS.

Antiphospholipid Syndrome: Diagnostic Aspects of Lupus Anticoagulants

2001 ◽  
Vol 86 (07) ◽  
pp. 83-91 ◽  
Author(s):  
J. Arnout
Keyword(s):  
Monoclonal Antibodies ◽  
Antiphospholipid Syndrome ◽  
Autoimmune Disorder ◽  
Coagulation Factors ◽  
Laboratory Diagnosis ◽  
Anticardiolipin Antibodies ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Antigen Antibody

SummaryAntiphospholipid syndrome (APS) is an autoimmune disorder in which antiphospholipid antibodies (aPL) are thought to be involved in the development of venous and/or arterial thrombosis. APL found in this syndrome are antibodies directed against a variety of phospholipid (PL) binding-proteins of which β2-glycoprotein I (β2GPI) and prothrombin are considered to be the major antigens. Some of these antibodies prolong PL-dependent clotting reactions and are termed lupus anticoagulants (LA). Autoimmune aPL which bind through β2GPI to cardiolipin are called anticardiolipin antibodies (aCL). Clinical studies indicate that LA is a stronger risk factor for thrombosis than aCL. The production of monoclonal antibodies against β2GPI and prothrombin has enabled us to understand the mechanism by which LA prolong coagulation in vitro. LA form bivalent antigen-antibody complexes with increased affinity for PL which compete with coagulation factors for the same catalytic surface. These LA positive monoclonal antibodies may be helpful in further improving the laboratory diagnosis of LA.

The Activated Seven Lupus Anticoagulant Assay Detects Clinically Significant Antibodies

2008 ◽  
Vol 14 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Gary W. Moore ◽  
Savita Rangarajan ◽  
Geoffrey F. Savidge
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
Anticardiolipin Antibodies ◽  
Activated Partial Thromboplastin Time ◽  
Systemic Lupus ◽  
Lupus Anticoagulants ◽  
Russell’S Viper ◽  
Clinically Significant

Lupus anticoagulants are a heterogeneous group of autoantibodies detected by their effects on phospholipid-dependent coagulation assays. Persistent lupus anticoagulants are associated with thrombotic disease, but not all are clinically significant. Antibody heterogeneity and reagent and test variability dictate that at least 2 tests, of different types, should be used to screen lupus anticoagulants. The objective of this study was to investigate whether the activated seven lupus anticoagulant assay detects clinically significant antibodies. Eighty-two patients with antiphospholipid syndrome (APS) and 32 with systemic lupus erythematosus + positive for activated seven lupus anticoagulant and who were without thrombosis, who were positive by activated seven lupus anticoagulant assay, were investigated for lupus anticoagulants by dilute Russell's viper venom time, dilute activated partial thromboplastin time, and Taipan snake venom time, and for anticardiolipin antibodies. Fifty-seven of the APS patients were positive for lupus anticoagulants in multiple assays, 25 in activated seven lupus anticoagulant alone. Fourteen of the latter group were previously positive in other antiphospholipid antibodies assays, and 11 had only been positive for lupus anticoagulants by activated seven lupus anticoagulant. Twenty-eight had elevated anticardiolipin antibodies, 6 of whom were from the group that was positive in activated seven lupus anticoagulant only. Eight of the systemic lupus erythematosus + lupus anticoagulants (without thrombosis) patients were positive for lupus anticoagulant by activated seven lupus anticoagulant alone and had only been positive in activated seven lupus anticoagulant previously, and none had elevated anticardiolipin antibodies. The remaining 24 patients were lupus-anticoagulant positive in multiple assays, and 9 had elevated anticardiolipin antibodies. Dilute Russell's viper venom time and Dilute activated partial thromboplastin time are widely used to detect lupus anticoagulants and are considered to detect clinically significant antibodies. Activated seven lupus anticoagulant detected antibodies in APS patients who were positive by these assays and also lupus anticoagulants undetectable by the dilute Russell's viper venom time/dilute activated partial thromboplastin time reagents used, demonstrating its utility as a first-line or second-line assay.

scholarly journals Incidence and locations of deep venous thrombosis of the lower extremity following surgeries of tibial plateau fractures: a prospective cohort study

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Junyong Li ◽  
Yanbin Zhu ◽  
Wei Chen ◽  
Kuo Zhao ◽  
Junzhe Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Tibial Plateau ◽  
Lower Extremities ◽  
Tibial Plateau Fractures ◽  
Targeted Prevention ◽  
Independent Risk Factors ◽  
Laboratory Biomarkers ◽  
Univariate Analyses

Abstract Objective To investigate the incidence of deep venous thrombosis (DVT) of the lower extremities following surgeries of tibial plateau fractures. Methods Retrospective analysis of the prospectively collected data on patients undergoing surgeries of tibial plateau fractures between October 2014 and December 2018 was conducted. Duplex ultrasonography (DUS) was used to screen for postoperative DVT of the bilateral lower extremities. Data on demographics, comorbidities, injury, surgery, and laboratory biomarkers at admission were collected. Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors associated with DVT. Results Among 987 patients included, 46 (4.7%) had postoperative DVT, with incidence rate of 1.0% for proximal and 3.7% for distal DVT. The average interval between operation and DVT was 8.3 days (median, 5.8 days), ranging from 2 to 42 days. DVT involved the injured extremity in 39 (84.8%) patients, both the injured and uninjured extremity in 2 patients (4.3%) and only the uninjured extremity in 5 patients (10.9%). Five risk factors were identified to be associated with postoperative DVT, including age (≥ 41 vs < 41 years) (OR 3.08; 95% CI 1.43–6.61; p = 0.004), anesthesia (general vs regional) (OR 2.08; 95% CI 1.12–3.85; p = 0.021), hyponatremia (OR 2.21; 95% CI 1.21–4.06; p = 0.010), prolonged surgical time (OR 1.04; 95% CI 1.01–1.07; p = 0.017) and elevated D-dimer level (OR 2.79; 95% CI 1.34–4.83; p = 0.004). Conclusion These epidemiologic data may be helpful in individualized assessment, risk stratification, and development of targeted prevention programs.

scholarly journals Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis

2010 ◽  
Vol 128 (5) ◽  
pp. 263-267 ◽  
Author(s):  
Mahendra Narain Mishra ◽  
Varinder Singh Bedi
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Quantitative Estimation ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Factor V ◽  
Cross Sectional ◽  
C Protein ◽  
Lupus Anticoagulants ◽  
Significant Difference

CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56%) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9% each), followed by low protein S (16.6%). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.

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