Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preeclampsia/HELLP syndrome has been associated with a high incidence of defects in the protein C pathway and increased anticardiolipin-antibodies/lupus anticoagulants. It is also apparent that thrombophilia is responsible for other pregnancy complications, such as recurrent spontaneous abortion, fetal growth restriction, intrauterine fetal death, and abruptio placentae. ProC Global is a new global dotting assay designed to evaluate the abnormalities in the protein C anticoagulant pathway. It is based on the ability of endogenous activated protein C, generated by activation of protein C by Protac, to prolong an activated partial thromboplastin time. A total of 61 patients with a history of severe preeclampsia or HELLP syndrome and 61 normal pregnant women (controls) were evaluated, 15 of whom had factor V Leiden mutation, 12 had protein C/S deficiency, 30 had a repeated lupus anticoagulants, and 27 increased anticardiolipin antibodies (ACA). All carriers of factor V Leiden mutation (N=15) as well as all the patients with low activated protein C (APC) resistance ratio (N=15) had a ProC Global normalized ratio (NR) less than 0.80 (sensitivity 100%). Twenty-four patients positive for the lupus anticoagulants (LA) and 19 patients positive for ACA (>5.0 IgG U/mL) had a ProC Global NR less than 0.8, while six and eight, respectively, had a ProC Global NR greater than 0.8 (sensitivity, 70%-80%). The detection of a reduced protein C/protein S activity (<70%) was low (sensitivity, 33%-44%). In 25 cases with pathologic ProC Global results, a thrombophilic defect (protein S/LA/ACA without APC resistance) was diagnosed in 18 women; but in 7 cases, no known thrombophilic defect was present. ProC Global is a new screening test to identify patients with defects of the protein C system and an activated dotting system in preeclampsia but cannot correctly cover each thrombophilic component.
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PMID:ProC Global assay in the evaluation of women with history of severe preeclampsia or HELLP syndrome. 1251 22

The activated protein C resistance (APCR) assay is the test of choice to screen for factor V Leiden. We evaluated the effect of lupus anticoagulant on the baseline clotting time of the second-generation APCR assay with plasma samples from 54 patients to determine whether a falsely low APCR ratio could be predicted. We also assessed whether a modification of the assay could make it more reliable in the presence of strong lupus anticoagulants. Of 54 plasma samples, 5 yielded a false-positive APCR ratio, and all 5 had a prolonged baseline clotting time. Further dilution (1:40) of the plasma samples in factor V-deficient plasma led to correction of the APCR ratio and did not affect the sensitivity of the test for factor V Leiden. Our data support that the baseline clotting time is a good predictor of a false-positive APCR test result and should be checked before calculating the ratio. The modified APCR assay reliably identified the false-positive ratios and could be used to screen for factor V Leiden in samples with strong lupus anticoagulant.
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PMID:The effect of lupus anticoagulant in the second-generation assay for activated protein C resistance. 1252 Jun 99

In order to analyze the incidence of thrombophilia in southern Taiwan, we studied the prevalence of antithrombin (AT), protein C (PC), and protein S (PS) deficiencies, the prevalence of factor V Leiden mutation, and the presence of acquired lupus anticoagulant (LA) and anticardiolipin antibody (ACA) in 56 patients < or =65 years old with deep venous thrombosis (DVT). Of 56 patients, 30 were male, 26 female, and the mean age of the patients was 43 years (18-65 years). None had factor V mutation or activated PC resistance; 21 patients (37.5%) showed abnormal results: 4 (7.1%) had AT deficiencies, 6 (10.7%) PC deficiencies, 6 (10.7%) PS deficiencies, 2 (3.6%) a combined PC and PS deficiency, and 3 (5.4%) LA and ACA. Only PC and PS deficiencies were significantly associated with increased risk for the development of thrombosis with an odds ratio of 4.2 (95% confidence interval: 1.2-15.0, P=0.018) and 8.1 (95% confidence interval: 1.6-40.6, P=0.003), respectively. We concluded that the prevalence of heritable thrombophilia (34.0%) in Taiwan is higher than that in Western countries, but that it is lower than previously reported in Hong Kong and Taiwan. We attribute this to selection bias.
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PMID:Incidence of thrombophilia detected in southern Taiwanese patients with venous thrombosis. 1260 91

The role of paradoxical embolism through patent foramen ovale as a mechanism of cryptogenic stroke is controversial. If a venous source of emboli is relevant, prothrombotic states should be associated with patent foramen ovale and cryptogenic stroke. We assessed the occurrence of several prothrombotic states (factor V Leiden, prothrombin G20210A, deficiencies in protein S, protein C and antithrombin, lupus anticoagulant, anticardiolipin antibodies, elevated factor VIII, resistance to activated protein C) and classical risk factors for venous thrombosis in 57 adult patients with cryptogenic stroke and patent foramen ovale and in 104 matched controls. Prothrombotic states [odds ratio (OR) 2.8; 95% confidence interval (CI), 1.2-6.5; P = 0.021], migraine with aura (OR 4.4; 95% CI 1.8-10.8; P = 0.001) and classical risk factors for venous thrombosis (OR 2.5; 95% CI 1.1-5.7; P = 0.037) were independent risk factors for cryptogenic stroke. In particular factor V Leiden or prothrombin G20210A associated with cryptogenic stroke (P = 0.022) whereas other coagulation abnormalities did not (P = 0.140). Among the patients with prothrombotic states, Valsalva manoeuvre was common at onset of stroke. Our results support the possibility of paradoxical embolism behind strokes in patients with patent foramen ovale.
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PMID:Factor V Leiden and prothrombin gene mutation may predispose to paradoxical embolism in subjects with patent foramen ovale. 1269 49

Sneddon syndrome (SNS) is characterized by the association of ischaemic cerebrovascular events and widespread livedo racemosa. Its pathophysiology is still controversial. The aim of this study was to evaluate the prevalence of factor V Leiden mutation in consecutive patients referred for SNS according to antiphospholipid antibodies (aPL) status. Fifty-three Caucasian patients were enrolled from 1996 to 2001. Diagnosis of SNS was based on the presence of a widespread livedo racemosa and at least one clinical neurologic ischaemic event. The following investigations were performed: detection of antithrombin III, protein C and protein S deficiency, lupus anticoagulant, anticardiolipin and anti-beta2 glycoprotein I antibodies, biologic false-positive test for syphilis, and factor V Leiden mutation by direct genomic analysis. Fisher's test and t-test were used for statistics. Detection of aPL on multiple determinations was negative in 31 patients (group 1) and positive in 22 patients (group 2). Factor V Leiden mutation was detected in six patients (11.3%), heterozygous in all. The frequency of this mutation was statistically higher in group 1 (6/31, 19.3%) than in group 2 (0/22; P = 0.035). Within aPL-negative SNS, the comparison of patients with versus without factor V Leiden mutation showed no difference for clinical data or familial history of thrombosis. A high prevalence of heterozygous factor V mutation was found in aPL-negative patients with SNS. This finding adds further arguments to consider SNS as a heterogeneous entity.
Lupus 2003
PMID:Factor V Leiden mutation in Sneddon syndrome. 1276 5

To better understand potentially reversible causes of idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, and an apparent association of IIH with polycystic-ovary syndrome (PCOS), we assessed associations of IIH with coagulation disorders and with PCOS in 38 women with well-documented IIH. Fifteen women were found to have PCOS; 14 of them were obese, with a body-mass index (BMI) greater than 30 kg/m(2), and 10 were extremely obese (BMI > or = 40). Factor VIII concentration was high (>150%) in 9 of 38 (24%) IIH cases, compared with 0 of 40 healthy adults controls (P(f) =.0009). Familial aggregation of high concentrations of factor VIII, associated with thrombophilia, was documented in all 5 of the 9 high-level factor VIII probands' families who were sampled. Activated partial thromboplastin time (APTT) was prolonged (> or =31.5 seconds) in 10 of 38 (26%) IIH cases, compared with 1 of 32 (3%) controls (P(f) =.009) and, in 4 of these cases, was accompanied by the lupus anticoagulant. Plasminogen activator inhibitor activity (PAI-Fx) was high (>21.1 U/mL) in 9 of 38 cases (24%), compared with 1 of 40 controls (3%) (P(f) =.006). Lipoprotein A was high (> or =35 mg/dL) in 13 of 37 cases (35%), compared with 5 of 40 controls (13%) (P(f) =.03). IIH cases did not differ (P >.05) from controls for homocysteine, proteins C and S, free S, antithrombin III, ACLAs IgG and IgM, dilute Russell's viper venom time, Factor XI, factor V Leiden G1691A, G20210A prothrombin, C677T MTHFR, plasminogen activator inhibitor 4G/5G, or platelet glycoprotein PL A1A2 mutations. Exogenous estrogens (n = 23), clomiphene (n = 1), or pregnancy (n = 4) accompanied the first appearance of IIH in 28 women. PCOS and coagulation disorders, often augmented by exogenous estrogens or pregnancy, are associated with IIH.
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PMID:Idiopathic intracranial hypertension: associations with coagulation disorders and polycystic-ovary syndrome. 1287 84

Arterial hypercoagulability can lead to cerebrovascular disease. Common causes of venous thromboembolism, including factor V Leiden, the prothrombin 20210 mutation, deficiencies of proteins C and S, and antithrombin deficiency are not likely to be associated with stroke. Rather, polymorphisms in fibrinogen, the factor XIII gene, and platelet glycoproteins are congenital abnormalities that have been associated with stroke. Similarly, the acquired conditions, lupus anticoagulants, and heparin-induced thrombocytopenia have a strong association with cerebrovascular disease. This article reviews arterial hypercoagulability as a cause of stroke in adults and identifies an appropriate hypercoagulability workup for patients with idiopathic stroke.
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PMID:Hypercoagulability as a cause of stroke in adults. 1291 52

Until recently the laboratory diagnosis of thrombophilia consisted on investigation of the plasmatic anticoagulant pathways and the search for dysfibrinogenemia and antiphospholipid antibodies/lupus anticoagulants. More recently, the laboratory investigation has been expanded by including activated protein C (APC) resistance, due or not to the presence of the factor V Leiden mutation; hyperprothrombinemia, due to the presence of the prothrombin mutation G20210A and hyperhomocysteinemia, due to impairment of the relevant metabolic pathway because of enzymatic and/or vitamin deficiency. Testing for thrombophilia may be useful for many reasons. First, the results of testing may provide valuable information to assess the risk of recurrence in the proband. Second, testing family members is useful for prophylactic and diagnostic purposes. Third, the identification of patients bearing combined defect helps to identify those at increased risk for thrombosis. Testing is recommended for patients with a past history of thrombosis and should be extended to their first-degree family members. Since most of the tests are not reliable during anticoagulation, it is preferable to postpone laboratory testing until after discontinuation of the treatment. Whenever possible testing should be performed by means of functional assays. DNA analysis is required for the prothrombin mutation G20210A. Laboratory diagnosis for antiphospholipid antibodies/lupus anticoagulant should be performed by a combination of tests including phospholipid-dependent clotting assays and solid phase anticardiolipin antibodies. Hyperhomocysteinemia may be assessed by high-pressure liquid chromatography methods, or by fluorescence polarization immunoassays.
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PMID:Laboratory diagnosis of thrombophilic states: where do we stand? 1367 50

By using a "slow" fluorogenic thrombin substrate and continuous comparison to a simultaneously run calibrator, thrombin generation can be monitored automatically, on line, in clotting PPP or PRP at a throughput of up to 100 samples per hour. The resulting "Thrombogram" in PPP measures hypocoagulability (haemophilias, oral anticoagulants, heparins (-likes), direct inhibitors) and hypercoagulabilities (AT deficiency, prothrombin hyperexpression, prot. C and S deficiency, factor V Leiden, oral contraceptives). In PRP it is diminished in thrombopathies, in von Willebrand disease, by antibodies blocking GPIIb-IIIa or GPIb, or by antiplatelet drugs like aspirin and clopidogrel. Lupus anticoagulant both retards and increases thrombin generation. The thrombogram thus appears to be a broad function test of the haemostatic-thrombotic mechanism of the blood.
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PMID:The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. 1367 51

Cranial dural arteriovenous fistulae (DAVF) may occur post-traumatic or sporadic. The physiopathologic mechanisms of sporadic DAVF are still unclear. A dural sinus thrombosis followed by an increase in venous pressure and/or an increased procoagulatory activity of the coagulation system are associated at least with some DAVF. The objective of this study was to investigate the coagulation profile in patients with DAVF. Thus the association of thrombophilic abnormalities, sinus thrombosis and DAVF should be analyzed. A total of 15 patients with cranial DAVF were included in this study. Blood samples were analyzed for 20210A mutation of the prothrombin gene, resistance to activated protein C and factor V Leiden mutation. Fibrinogen (Fib), Textarin time (TT), antithrombin (AT), protein C and protein S activity, von Willebrand factor antigen (vWF:Ag), Ristocetin cofactor activity (vWF:RCo), D-Dimer (DD) and coagulation factor VIII-activity (F VIII) were determined in all patients. Blood was screened for the occurrence of lupus antiphospholipid antibodies and cardiolipin antibodies. Thrombophilic risk factors were found in 5 (33%) of the 15 patients with cranial DAVF. Four patients had a heterozygote 20210A mutation of the prothrombin gene and one patient had a heterozygote FV Leiden mutation. Sinus thrombosis was detected in two patients with grade 2b DAVF and was associated with a 20210A mutation of the prothrombin gene in both patients. Additionally, one patient had deficient protein C activity and screening for cardiolipin antibodies was positive in three patients. In the current series the frequency of prothrombin Gene 20210A mutation was higher in patients with DAVF compared to the general population, whereas the incidence of Factor V Leiden mutation was not. Therefore in patients with cranial DAVF thrombophilic abnormalities should be considered in the post-operative/post-interventional management.
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PMID:Increased incidence of thrombophilic abnormalities in patients with cranial dural arteriovenous fistulae. 1457 93


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