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)

Systemic lupus erythematosus (SLE) is associated with an increased risk of venous (VTE) and arterial thromboembolism (ATE). Lupus anticoagulant (LA) and anticardiolipin antibodies (ACAs) are established risk factors. We assessed the contribution of deficiencies of antithrombin, protein C, total protein S, factor V Leiden, the prothrombin G20210A mutation and APC resistance, either alone or in various combinations with LA and/or ACAs, to the thrombotic risk in a cohort of 144 consecutive patients with SLE. Median follow-up was 12.7 years. VTE had occurred in 10% and ATE in 11% of patients. LA,ACAs, factor V Leiden, and the prothrombin mutation were identified as risk factors for VTE. Annual incidences of VTE were 2.01 (0.74-4.37) in patients with one of these disorders and 3.05 (0.63-8.93) in patients with 2 disorders. The risk of VTE was 20- and 30-fold higher, respectively, compared with the normal population. In contrast with LA and ACAs, thrombophilic disorders did not influence the risk of ATE. In conclusion, factor V Leiden and the prothrombin mutation contribute to the risk of VTE in patients with SLE, and potentiate this risk when one of these thrombophilic defects are combined with LA and/or ACAs.
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PMID:The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus. 1502 14

Thromboembolism in pregnancy and the puerperium and inherited or acquired thrombophilia are associated. Thrombophilia can be revealed by pregnancy. Thrombotic risk during pregnancy and the puerperium is higher in asymptomatic women with than without thrombophilia. Antithrombin deficiency, combined deficiencies and homozygous or double-heterozygotes factor V Leiden and factor II G 20210 A mutations are associated with a higher thrombotic risk than heterozygote mutations or protein S and C deficiencies, whereas hyperhomocysteinemia does not appear as a risk factor for maternal thromboembolic disease. Antiphospholipid syndrome with lupus anticoagulant is strongly associated with thrombotic risk in pregnancy and the puerperium. Further studies are required to assess the thrombotic risk in women with preeclampsia as well as early or late recurrent pregnancy loss.
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PMID:[Risk factors of thromboembolism associated with pregnancy and the puerperium. Role of inherited and acquired thrombophilia]. 1502 82

Thrombophilia is characterized by clinical tendency to thrombosis or molecular abnomalities of hemostasis that predisposes to thromboembolic disease. Hereditary thrombophilia may be due to antithrombin deficiency, or protein C or protein S deficiency. More recently, other molecular abnormalities have been described: activated protein C resistance due to factor V Leiden, G 20210 A polymorphism on the prothrombin gene, increased factor VIII plasma levels or hyperhomocysteinemia. Acquired thrombophilia is frequently associated with the antiphospholipid syndrome characterized by thrombosis and presence of lupus anticoagulant or phospholipid-binding antibodies. In some cases, no molecular abnormality is found despite recurrent thrombosis observed in patient and his/her family. This situation can be considered as clinical thrombophilia.
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PMID:[Definition of thrombophilia]. 1502 78

The etiology of venous thromboembolic disease has been the subject of several recent discoveries, particularly on genetic predisposing factors. The laboratory investigation that may help to evaluate the risk for individual patients includes the measurements of coagulation inhibitors (antithrombin, protein C, and protein S) in plasma assays, the search for the factor V Leiden mutation by the plasma activated protein C resistance test (always to be confirmed by DNA analysis when abnormal), and the search for the prothrombin gene mutation by DNA analysis. Among acquired abnormalities, the most frequently involved are phospholipid-dependent autoantibodies associated or not with a subset of antibodies having an anticoagulant effect in vitro (lupus anticoagulant). Other coagulation abnormalities such as increased FVIII, FIX, or FXI levels or hyperhomocysteinemia have been suggested to be risk factors for thrombosis, although additional studies are required to definitively assess their role.
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PMID:Venous thromboembolic disease: risk factors and laboratory investigation. 1519 17

The purpose of the present study was to determine whether using an extended panel of laboratory tests increases the detection of a hypercoagulable state in patients with ocular thromboses. Twenty consecutive patients with ocular thromboses (vein, artery, or choriocapillaris occlusions) underwent testing for activated protein C resistance/factor V Leiden, prothrombin G20210A, lupus anticoagulant, anticardiolipin antibodies, hyperhomocysteinemia, and deficiencies of protein C, protein S, and antithrombin. For each patient, we selected two age-matched and gender-matched individuals without ocular thromboses as controls. Sixteen of the 20 patients (80%) had one or more laboratory tests that supported a hypercoagulable condition. Prothrombin G20210A (P < 0.02) and hyperhomocysteinemia (P < 0.0006) were significantly more frequent in ocular thrombosis patients compared with controls. The most common condition was antiphospholipid antibody syndrome, present in 40% of patients (confirmed by repeat testing at least 6 weeks later), but this did not reach statistical significance compared with the controls. No patients with ocular thromboses had hereditary abnormalities of protein S, protein C, or antithrombin. In conclusion, an extended panel of laboratory tests improved the detection of a hypercoagulable state in ocular thromboses. Testing for homocysteine, antiphospholipid antibodies, and the prothrombin G20210A mutation should be considered in patients with ocular thromboses.
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PMID:Prothrombin gene mutation G20210A, homocysteine, antiphospholipid antibodies and other hypercoagulable states in ocular thrombosis. 1520 87

A new prothrombin-based activated protein C resistance (APC-R) test is described. In this method, the patient sample is prediluted in a plasma depleted of factor V (FV). A reagent containing APC and a specific activator of FV is added. After an incubation period, clotting is initiated by the addition of the FV-dependent prothrombin activator Noscarin. We analyzed 703 samples from patients undergoing thrombophilia screening. By using a predefined cutoff ratio of 2.5, 100% sensitivity and specificity for the detection of a factor V Leiden (FVL) mutation was found. With a cutoff ratio of 1.2, a complete but narrow distinction of FVL heterozygous (n = 192) and FVL homozygous samples (n = 27) was determined. No interference by the international normalized ratio, activated partial thromboplastin time (aPTT), protein S activity, fibrinogen and factor VIII (FVIII) levels, or lupus anticoagulant ratio was detected. The new prothrombin-based APC-R assay provides improved distinction of FV wild-type and FVL carriers compared with the aPTT-based method. By the use of an FV-dependent prothrombin activator, the assay is not influenced by FVIII concentration or lupus anticoagulants.
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PMID:Improved distinction of factor V wild-type and factor V Leiden using a novel prothrombin-based activated protein C resistance assay. 1553 75

Although antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-beta(2)-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.
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PMID:Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis. 1558 39

To study the etiological factors and pathogenisis of venous thrombi and their relations with anticoagulation and fibrinolysis, In 47 patients with venous thrombi anticardiolipin antibody (ACA) was detected by ELISA. lupus anticoagulant (LA) and anti-activative protein C resistance (APCR) were examined by coagulation test; factor V Leiden was determined by PCR; activity of anticoagulation and fibrinolysis of antithrombin (AT), protein C (PC), plasminogen (Plg) were detected by chromophore substrate methods. The results showed that ACA and/or LA were positive in 34% of patients with VT, most of which consisted of ACA IgG and LA; Plg was negative in 9.5% of patients; tPAI elevated in 8.3% of patients (much more than control group, P < 0.005); ATIII, PC, tPA were negative in 4.5%, 4.5%, 2.8% of patients, respectively (no significant difference with control groups, P > 0.05); ATIII, PC and Plg were negative constantly in one patient; factor V Leiden was not detected by PCR. There were no significant differences in anticoagulation and fibrinolysis between antiphospholipoprotein antibody (APA) negative subjects and APA positive subjects, 4 patients of which were positive in APCR, 3 patients were positive in ACA and/or LA, two out of three patients didn't achieved APCR reversion after mixing their blood plasma with normal blood plasma. It is concluded that antiphospholipoprotein antibody and abnormal fibrinolysis were the common pathological factors in venous thrombi. LA and/or ACA disturbs the anticoagulation aspect to develop into acquired APCR which may be a possible cause leading to thrombophilia.
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PMID:[Relationship of antiphospholipoprotein antibodies of venous thrombi with anticoagulation and fibrinolysis]. 1563 50

Thrombophilia can be defined as an increased tendency to thrombosis. There are several defined risk factors for thrombosis, and these are generally separated into acquired and congenital factors. Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, protein C and protein S, and genetic polymorphisms such as prothrombin G20210A and the cleavage-resistant factor mutation, factor V Leiden, which leads to a condition known as activated protein C resistance. Acquired risk factors include antiphospholipid antibodies, detected as lupus anticoagulants, and/or anticardiolipin or anti-beta2-glycoprotein I antibodies. Elevated homocysteine, immobility, increasing age, surgery, cancer, poor nutrition, pregnancy, high levels of clotting factors, and use of oral contraceptives and hormone replacement therapy comprise other risk factors. Each of these constitutes an element of increased risk, which is compounded when concomitant. There is ongoing debate regarding relative and compound risks, the value of laboratory screening, whom to screen for with these markers, and the form and duration of clinical management. This report briefly explores, from a scientist's perspective, some important issues that are sometimes overlooked.
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PMID:Diagnostic issues in thrombophilia: a laboratory scientist's view. 1570 70

We have conducted a series of multilaboratory surveys during the last 6 years to evaluate testing proficiency in the detection of congenital and acquired thrombophilia. For lupus anticoagulant (LA) testing, participant laboratories used a panel of tests, including activated partial thromboplastin time (aPTT; 100% of laboratories), kaolin clotting time (26 to 70%), and Russell's viper venom time (RVVT; 75 to 100%). Coefficients of variation (CVs) for assays ranged from 5 to 40%. RVVT assays appeared to be most sensitive and specific for detection of LA (fewer false-negatives or -positives), although laboratories performed best when they used a panel of tests. For congenital thrombophilia, tests evaluated comprised protein C (PC), protein S (PS), antithrombin (AT), and activated protein C resistance (APCR). Most participant laboratories performed PC using chromogenic (approximately 75%), or clot based (approximately 15%) assays, with few (< 10%) performing antigenic assessments. PS was most often assessed (approximately 60%) by immunological or antigenic assays, usually of free PS, or by functional or clot-based assays (approximately 40%). AT is usually assessed by functional chromogenic assays (approximately 95%). APCR was assessed using aPTT (approximately 50%) or RVVT (approximately 50%) clot-based assays, with the aPTT APCR typically performed using factor V-deficient plasma predilution, but the RVVT APCR typically performed without. Laboratories using the RVVT APCR generally performed better in detection of factor V Leiden-associated APCR, with the aPTT method group yielding higher false-negative and/or false-positive findings (approximately 5% of occasions). Some clot-based PC and PS assays appeared to be influenced by APCR status, and yielded lower apparent PC and PS levels with positive APC resistance. The overall error rate for PC, PS, and AT was approximately 2 to 8% (i.e., false-normal interpretations for deficient plasma or false-abnormal interpretations for normal plasma). The CVs for these assays ranged from 5 to 40%, with highest CVs typically obtained with PS assays.
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PMID:Multilaboratory testing of thrombophilia: current and past practice in Australasia as assessed through the Royal College of Pathologists of Australasia Quality Assurance Program for Hematology. 1570 75


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