Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.
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PMID:Increased thrombin generation and activity in patients with systemic lupus erythematosus and anticardiolipin antibodies: evidence for a prothrombotic state. 827 47

Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III-complex (TAT) levels were compared in 31 orally anticoagulated patients with inferior vena caval filters and a control group of 31 orally anticoagulated patients without caval filters and the incidence of markers of thrombophilia (deficiency of antithrombin-III, protein C, protein S and factor XII, presence of lupus anticoagulants) was determined. 8 of 31 patients (26%) from the group of caval filter carriers showed markers of thrombophilia (3 protein S deficiencies, 1 protein C deficiency, 2 factor XII deficiencies and 2 patients with lupus anticoagulants). In all orally anticoagulated patients a significant interdependence (p < 0.05) between F1 + 2- and TAT-levels and intensity (INR) of the oral anticoagulation could be observed. Comparison of F1 + 2- and TAT-levels of caval filter carriers and controls revealed no significant difference which leads to the conclusion that inferior vena caval filters do not induce detectable systemic activation of prothrombin under adequate oral anticoagulation therapy.
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PMID:[Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex(TAT) and thrombophilia parameters in orally anticoagulated patients with inferior vena cava filters]. 851 4

Antiphospholipid (aPL) antibodies are associated with thrombosis, recurrent abortions and thrombocytopenia. Studies to determine the mechanisms of action of these antibodies have been hindered by their heterogeneity and limited availability of techniques to isolate and characterize subgroups of the antibodies. We report a new phospholipid affinity chromatography method which enables separation of antiphospholipid positive sera into more than one antibody subpopulation. Sera from five patients with complications of the antiphospholipid syndrome (APS) were studied. Each serum was applied to chromatography columns prepared by coating polystyrene beads (diameter 100 A) with phosphatidylserine (PS) or cardiolipin (CL). A linear salt gradient (0.03-1.0 M NaCl) was used for elution. Eluates were analyzed for phospholipid binding and for inhibition of the prothrombin-thrombin conversion reaction. Each sample yielded two to three peaks for CL and PS affinity columns. Molarities at which peaks were eluted differed between samples. For individual samples, molarities at which peaks were eluted differed between CL and PS columns. These data suggest that aPL antibodies are heterogenous, with differences existing between patients and even within single serum samples. Subpopulations differed in their avidities for CL and PS but generally all had prothrombinase inhibitory activity.
Lupus 1995 Aug
PMID:Demonstration of antiphospholipid antibody heterogeneity by phospholipid column chromatography and salt gradient elution techniques. 852 22

During April-June 1994, at Borgo Roma Polyclinic in Verona, Italy, clinical researchers compared data on 50 healthy women 18-41 who used low-dose combined oral contraceptives (OCs) with data on 50 healthy women matched for age, smoking, education, social class, and biochemical routinary parameters. Almost all the subjects were medical students or medical staff working in the hospital where the study occurred. The researchers aimed to examine the prevalence of resistance to activated protein C (APC) in both groups. They also evaluated protein C, protein S, antithrombin III, and lupus anticoagulant activity. The APC-sensitivity ratio (APC-SR) was much lower in OC users than nonusers (2.6 vs. 2.81; p 0.01). Seven of the eight women with an APC-SR of no greater than 2 (i.e., demonstration of APC resistance) used OCs (p 0.05). Prevalence of APC resistance was higher among OC users than nonusers (14% vs. 2%; p 0.05). Among the eight women with APC resistance, two were heterozygous for the Leiden factor V mutation. One of these women used OCs and the other did not. Two APC resistant women who did not have the Leiden factor V stopped using OCs and their APC-SR subsequently normalized. OC users had higher fibrinogen and protein C levels, a lower protein S level, and shorter prothrombin and activated partial thromboplastin times than nonusers. These findings suggest that OCs may contribute to plasma APC resistance, which in turn increases the risk of venous thrombosis.
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PMID:Resistance to activated protein C in healthy women taking oral contraceptives. 854 95

Some lupus anticoagulants (LA) have been shown to be directed against phospholipid-bound prothrombin. While developing an ELISA to detect anti-prothrombin autoantibodies in patient serum or plasma, no or very low signal was observed using human prothrombin immobilized on plain polystyrene plates. In contrast, the same LA-positive samples bound specifically to prothrombin coated on gamma-irradiated plates, depending on the radiation dose, in the absence of added calcium and phospholipid. Optimization of the assay required the addition of 0.1% Tween 20 to the buffers. Antibody specificity for immobilized prothrombin was ascertained by competition using liposome-bound prothrombin, since fluid-phase prothrombin competed poorly. Seventy-seven of 139 patients (55.4%) with LA related to a variety of underlying diseases possessed anti-prothrombin antibodies (27 IgG, 35 IgM and 15 both isotypes), either isolated or more often associated with anti-beta 2 glycoprotein I (beta 2GPI) antibodies. These included 67-71% of the patients with systemic lupus erythematosus and related disorders, primary antiphospholipid antibody syndrome or drug-induced LA (autoimmune groups), but only 19-20% of those with infection or malignancy (p < 0.001). As previously shown for anti-beta 2GPI antibodies, IgG2 was the predominant IgG subclass reactive with prothrombin. Thus, autoimmune patients with LA have a high incidence of antibodies to beta 2GPI and prothrombin, the binding of which could similarly require high antigen density and/or exposure of cryptic epitopes resulting from protein interaction with an irradiated (i.e. more anionic) polystyrene surface.
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PMID:Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants. 856 Apr 23

Various types of circulating anticoagulant are encountered in coagulation testing laboratories. Those associated with bleeding often cause problems in diagnosis. The most common type of acquired coagulation inhibitor not associated with bleeding is the so-called lupus anticoagulant (LA). Differing from SLE which occurs predominantly in women, primary LA occurs both in females and males. LA are now frequently sought in patients with recurrent foetal losses and acquired thrombotic problems as a causative factor, whereas in the past they were regarded as a laboratory nuisance. Due to the complicating effect of inhibitors on clotting tests, diagnosis of various coagulation inhibitors remains difficult. There may also be significant overlap between different types of inhibitors. With the recent interest shown in LA, almost all non-specific inhibitors tend to be classed as LA. LA are defined as phospholipid-interfering antibodies. Current criteria have recently been confirmed and include screening with phospholipid-responsive tests, abnormal mixing studies and correction with phospholipids. However it is becoming clear that even LA as defined may be heterogeneous. Most LA are not directed at negatively-charged phospholipids alone as originally suggested, but rather at complexes of either beta-2-glycoprotein 1 or prothrombin with such phospholipids. There may also be other lipid-associated antigens involved. Although earlier work suggested that all LA functioned through a similar mechanism, there is now some preliminary evidence suggesting that various subclasses of LA may account for discrepant results sometimes obtained with different clotting tests. A variety of improvements to the basic screening tests for LA (APTT, KCT, DTTI and DRVVT) have recently been suggested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diagnostic methodologies for circulating anticoagulants. 857 81

Acquired inhibitors of coagulation causing bleeding manifestations are rare in children, particularly without an associated underlying disorder such as autoimmune disease. We describe an otherwise healthy 1 1/2-year-old girl who had extensive spontaneous bruising and prolonged bleeding from venipuncture sites. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged, with evidence of an immediate-acting inhibitor. Thrombin clotting time, fibrinogen, and platelets were normal. Biologic assay of factors II, V, VII, and X were all low, with increasing values at higher dilutions. However, by immunoassay and/or chromogenic assays, only factor II was reduced. An antibody which failed to neutralize prothrombin activity in vitro was detected against radiolabeled prothrombin. Coagulation studies normalized in parallel with clinical recovery and disappearance of the antibody. This case demonstrates acute hypoprothrombinemia-lupus anticoagulant syndrome as a rare presentation of bleeding diathesis in a healthy young child.
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PMID:Transient hemorrhagic diathesis associated with an inhibitor of prothrombin with lupus anticoagulant in a 1 1/2-year-old girl: report of a case and review of the literature. 860 32

We conducted this study to determine whether antiprothrombin antibody (aPT) [to prothrombin (PT) alone or PT/phosphatidyl serine (PS) complex] actually existed in patients with lupus anticoagulant (LA) and/or anticardiolipin antibody (aCL). aPT to PT alone was positive in 2/7 LA-positive (29%) and 3/7 LA/aCL-positive (43%) patients. aPT to PT/PS complex was positive in 4/7 LA-positive (57%) and 4/7 LA/aCL-positive (57%) patients in the presence of Ca2+. However, none of the aCL-positive patients without LA or the LA/aCL-negative patients were positive for aPT and aPT/PS. Thus, we confirmed the existence of aPT and aPT/PS specifically among LA-positive patients. However, the clinicopathological significance of aPT and aPT/PS in this clinical setting is yet to be clarified.
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PMID:Phosphatidyl serine-dependent antiprothrombin antibody is exclusive to patients with lupus anticoagulant. 867 May 83

The exploration of coagulation in biological practice implies simple routine tests. A normal bleeding time associated with a normal platelet count allows to exclude any primary haemostasis abnormality. A prolonged bleeding time is most frequently the result of a thrombocytopenia, the etiology of which remains to be determined. A prolonged bleeding time is also observed in von Willebrand disease and in thrombopathia. Such diagnosis requires appropriate investigation. The exploration of the coagulation cascade includes prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen level. A congenital or acquired deficiency in one or more coagulation factors should be distinguished from a lupus anticoagulant or from the occurrence of an antibody against a coagulation factor. Indeed, a prolonged APTT is not always related to a bleeding risk. Only the identification of the coagulation abnormality can predict the bleeding or thrombotic risk during surgery. In each case, an appropriate preventive therapy should be prescribed.
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PMID:[Exploration of hemostasis in current practice]. 870 89

It has been speculated that an impairment in anticoagulant pathways (protein C (PC), protein S (PS), resistance to activated protein C (APC)), may contribute to the thrombotic tendency in lupus anticoagulant (LA) patients. Increased plasma levels of fibrinogen are predictive for arterial thrombosis and increased molecular markers of thrombosis are indicative for activation of the clotting cascade. We investigated 25 patients (20 women) with LA. All patients were stratified according to their thromboembolic history and women according to their history of fetal loss. Eighteen patients had a history of venous or arterial thrombosis, or both. Seven of 16 women with at least one pregnancy had a history of fetal loss. The interrelation among the levels of fibrinogen, PC and PS, and resistance to APC, thrombin-antithrombin III complexes (TAT), prothrombin fragment F1 + 2, D-dimer and the history of thrombotic events and obstetric complications in patients with LA were evaluated. LA patients with a history of venous or arterial thrombosis had a significantly higher fibrinogen level than LA patients without (mean 366 versus 304 mg/dl; P = 0.018). Among 16 women a slightly lower mean TAT level in women with fetal loss was found (2.4 versus 4.3 ng/ml; P = 0.02). No other statistically significant difference in the remaining parameters was yielded in both analyzed subgroups. The results of the study suggest an association between increased fibrinogen levels and the history of venous or arterial thrombosis, or both, in patients with LA. In the other investigated parameters, no relationship to the thrombotic or obstetric history was found.
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PMID:Lupus anticoagulant and thromboembolism: evaluation of fibrinogen, natural inhibitors and molecular markers of thrombosis. 873 39


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