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)

Clotting-based activated protein C (APC) assays have limitations when testing patients on oral anticoagulant (OA) therapy or with a lupus anticoagulant (LA). Predilution in factor V (FV)-deficient plasma and testing with phospholipid-rich Russell Viper venom (RVV)-based methods have been shown to be the most suitable methods when testing these patient groups, respectively. We evaluated a modified RVV based clotting test (Gradileiden V test; Gradipore, Sydney, Australia) in a large patient cohort and determined its sensitivity to the FV Leiden mutation. We also examined whether normal plasma can be used to dilute plasma from warfarinized patients without compromising sensitivity to the FV Leiden mutation. A total of 1,956 plasmas were studied including congenital protein C (five plasmas), and protein S deficiency (five plasmas), LA (29 plasmas), FV Leiden heterozygote (102 plasmas), and homozygote (five plasmas), warfarin (54 plasmas), standard heparin therapy (37 plasmas) and normal healthy controls (21 plasmas). Molecular analysis was performed on all samples. The effect of FV Leiden concentration on the APC ratio was examined by determining the APC resistance of a homozygous plasma serially diluted in six sources of normal plasma (NP). The relationship was non-linear and dependent on the initial APC ratio of the chosen source of NP. APC resistance was demonstrated in the varying sources of NP in dilutions of 1/4 (25% FV Leiden) to 1/32 (3% FV Leiden). A 1/2 dilution in pooled NP is recommended for patients on OA therapy because the test remains sensitive at levels of 25% FV Leiden and this is the dilution routinely used for other applications in a coagulation laboratory. The effect of a LA on the APC ratio was similarly studied by determining the APC resistance of a homozygous plasma serially diluted in two sources of LA-positive plasma. This relationship was also non-linear and dependent on the initial APC ratio of the LA-positive plasma. APC resistance was demonstrated in dilutions of 1/16 (6% FV Leiden) to 1/64 (1.5% FV Leiden) demonstrating the sensitivity of the test to APC resistance in the presence of a LA. Our results show the modified RVV-based test clearly predicts the presence of factor V Leiden in a large cohort of patients. The method offers advantages when testing patients with a LA and patients receiving warfarin providing a 1/2 predilution step in pooled NP is performed. Pooled NP does not affect the sensitivity of the test to the mutation, is routinely used in coagulation laboratories, and is considerably less expensive than FV-deficient plasma.
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PMID:Determination of activated protein C resistance in anticoagulated and lupus positive patients. 1093 5

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chronic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a case-control study. We genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the same geographic area. The observed difference in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0.05) was found by considering the recessive hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency; however, it was protective in men regarding the recessive hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele distribution was similar among the 46 thrombophilic patients (antithrombin, protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men.
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PMID:Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene. 1093 9

The aim of the following presentation is to review certain technical issues complicating clotting tests for lupus anticoagulants (LA). This is a field riddled with incorrect and misleading studies which often make progress difficult and which are difficult to retract. Inconsistent test sensitivity comparisons are sometimes due to incorrect methods being used but are more often due to contamination with platelets and instrument effects. Time dependence of LA is often due to pH drift during incubation and probably all LA are immediate acting (at least in our hands). The use of platelets in confirmatory tests is dangerous and can lead to false-positive results in patients with anti-factor V and heparin-like inhibitors.
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PMID:Conceptions and misconceptions in testing for lupus anticoagulants. 1096 6

Although lower extremity deep venous thrombosis (LEDVT) has been associated with a hypercoagulable state, there are scant data available for patients presenting with upper extremity deep venous thrombosis (UEDVT). Therefore, we conducted a prospective study to determine whether such an association exists for UEDVT. Fifty-two patients who presented with UEDVT at our institution from August 1996 to June 1997 underwent a hematological profile consisting of activated protein C (APC) resistance, antithrombin III (ATIII) level and activity, factor V mutation (arginine 506 to glycine), protein C level and activity, protein S level and activity, factors II and X activity, lupus anticoagulant, and cardiolipin antibody. This represented 68% (52/76) of the total number of patients in whom the diagnosis of UEDVT was made by duplex ultrasonography during this time period. The ages ranged from 9 to 97 (mean 63 +/- 23 years). There were 22 males and 30 females. Twenty-five patients (48%) had a central venous line in place, 4 patients (8%) had a pacemaker, 14 patients (27%) had a history of neoplasm, and 7 patients (13%) had concomitant LEDVT. The results of our study showed that a hypercoagulable state may be an underappreciated contributing factor in the development of UEDVT. Contrary to prior belief that three sets of tests are needed to confirm the presence of a hypercoagulable state, these data also suggest that only two tests may be needed.
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PMID:Upper extremity deep venous thrombosis: an underrecognized manifestation of a hypercoagulable state. 1099 May 49

In the present study, a new functional test for the detection of increased resistance of coagulation factor V to degradation by activated protein C (factor V Leiden mutation) was evaluated. The STA-STACLOT APC-R Test (Diagnostica Stago, Asnieres, France) is based on the specific activation of factor X by Crotalus viridis helleri snake venom. The results are given as clotting time in seconds of the patient's plasma in the presence of venom and activated protein C. The intra-assay coefficient of variation was 2.17% (n=20) for samples within the normal range, and 1.70% and 1.42% (n=20) for the plasma of a heterozygous or a homozygous carrier of the factor V Leiden mutation, respectively. The inter-assay coefficient of variation (n=10) was 7.75% for the plasma of a healthy donor, 5.05% for the plasma of a heterozygous carrier and 3.38% for the plasma of a homozygous individual. The normal range (5th-95th percentile) of 136.4 s-174.7 s was derived from the clotting time of the plasma of 38 healthy controls. Values below 136 s were found in every sample from patients carrying the factor V Leiden mutation (n=52), whereas no patient with protein C (n=11) or protein S deficiency (n=10) had reduced clotting times. Homozygous carriers of the factor V Leiden mutation had clotting times shorter than 66.0 s and heterozygous carriers had clotting times longer than 80.0 s. Thus, based upon the individual clotting time, patients homozygous for factor V Leiden mutation could easily be distinguished from normals or heterozygous individuals. The influence of coagulation factor X, V, or II deficiency on the STACLOT APC-R Test was evaluated and revealed prolonged clotting times at factor V activities below 50%. In the presence of lupus anticoagulant the specificity of the STA-STACLOT APC-R Test was clearly decreased. In the present study, we clearly show that the STA-STACLOT APC-R Test is able to discriminate carriers of the factor V Leiden mutation from healthy controls or patients with protein C or protein S deficiency.
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PMID:Evaluation of a highly specific functional test for the detection of factor V Leiden. 1119 68

Thrombophilia can result from either inherited or acquired conditions. We describe a teenager who developed extensive thrombosis requiring aggressive and prolonged anticoagulation. Laboratory evaluation revealed an acquired lupus anticoagulant, consistent with the antiphospholipid antibody syndrome (APS). DNA analysis revealed inherited thrombophilic mutations in the factor V and methylene tetrahydrofolate reductase genes. We believe that the combination of inherited and acquired hypercoagulable conditions affected her therapeutic response to anticoagulant therapy. Inherited thrombophilic DNA mutations may contribute to the hypercoagulability observed in patients with acquired thrombophilic conditions such as APS and systemic lupus erythematosus.
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PMID:Effects of inherited thrombophilic mutations in an adolescent with antiphospholipid syndrome and systemic lupus erythematosus. 1124 80

Spontaneous inhibitors to coagulation factors are autoantibodies that usually appear in the elderly, but may also occur in patients with immunological disorders such as lupus, lymphoma, asthma or drug reactions. Most antibodies are directed against factor VIII, but any coagulation protein may be affected. They should be suspected in individuals who previously had normal haemostasis, but who now begin to experience bleeding into the skin and muscles, or suffer haemorrhages after routine procedures such as insertion of vascular catheters, intramuscular injections, or minor surgery. The haemostasis laboratory is critical in identifying the particular inhibitor and quantitating its potency. Factor VIII inhibitors prolong the partial thromboplastin time (PTT) but not the prothrombin time (PT), and incubating mixtures of patient plasma and normal plasma enhances the prolongation of the clotting time. The Bethesda assay provides a rough assessment of inhibitor potency. Inhibitors of von Willebrand factor prolong the bleeding time and impair ristocetin-induced platelet aggregation. Factor V inhibitors are associated with a prolonged PTT and PT, not correctable with normal plasma. Patients will often have a history of exposure to bovine thrombin in fibrin glue. The antibodies most difficult to recognize are those that alter fibrin polymerization or stabilization. Abnormal clot retraction or clot solubility in urea solutions are an important clue. The management of these disorders depends on characterization of the inhibitor, and using appropriate clotting factor concentrates to control acute bleeding. For example, recombinant human factor VIII or desmopressin may be effective for patients with low titre factor VIII inhibitors, whereas porcine factor VIII, recombinant factor Vlla, or prothrombin complex concentrates stem bleeding in those with high titres. Inhibitors of von Willebrand factor may be amenable to desmopressin, cryoprecipitate, or von Willebrand factor concentrates. Some patients with factor V inhibitors have responded to platelet transfusions, as the platelet factor V may be shielded from the autoantibody. Bleeding due to factor XIII inhibitors may be managed with fibrogammin, a factor XIII concentrate. All patients should be treated for underlying disorders and given drugs such as corticosteroids and cytotoxic agents to suppress inhibitor formation. Major advances in new immunosuppressive technologies, such as monoclonal B-cell antibodies, offer hope of more effective therapies for spontaneous inhibitors to coagulation factors.
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PMID:Spontaneous inhibitors to coagulation factors. 1125 55

Several methods are now available for the laboratory assessment of activated protein C resistance (APCR). In this study, we evaluated two activated partial thromboplastin time-based assays [Coatest activated protein C (APC) and Diagen protein C activator (PCA)], with and without predilution of test plasma in factor V-deficient plasma (FVdp) and an amidolytic assay (Immuno Ltd, Vienna, Austria). Testing plasmas from normal volunteers who had received 1-deamino-8-D-arginine vasopressin (DDAVP) also assessed the effect of elevated factor VIII on APCR. In the unmodified clotting tests, the Coatest kit gave overlapping results for normal and heterozygous FV:Q506 samples; some FV:Q506 samples on oral anticoagulant therapy (OAT) were misclassified as normal, and some normal samples with high factor VIII levels would be classified as APC resistant. The unmodified Diagen kit correctly classified these three types of sample, but had the disadvantage that prolonged PCA clotting times gave serious problems with instrument end-point detection. Both kits modified by diluting the samples in FVdp correctly classified all the samples, as well as samples from patients with lupus anticoagulant (LA) and patients receiving heparin. The Immunochrom kit correctly classified the normal and FV:Q506 samples, but would have misclassified most normal persons on OAT as well as some patients with LA or receiving heparin therapy as APC resistant.
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PMID:The impact of oral anticoagulant therapy, factor VIII level and quality of factor V-deficient plasma on three commercial methods for activated protein C resistance. 1141 31

This article reports a case of Anton-Babinski syndrome, due to right middle cerebral artery thrombosis and attributed to a likely primary antiphospholipid syndrome. It is always difficult to diagnose the latter, especially in the case of our patient who had a past history of multiple venous thromboses but also a heterozygosity for the mutation of the factor V of Leyden. We reviewed the literature dedicated to the prothrombotic events linked to the presence of these antiphospholipid antibodies: the lupus anticoagulant and the anticardiolipin antibodies.
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PMID:[Clinical case of the month. Report of a case of antiphospholipid syndrome]. 1152 97

The two most common hereditary risk factors for thrombosis are factor V Leiden mutation and a prothrombin gene mutation. There is indeed a thrombotic tendency in patients with systemic lupus erythematosis (SLE) and it is not always associated with antiphospholipid antibodies. We aimed to determine the relationship between both factor V Leiden and prothrombin gene mutations and SLE. Using polymerase chain reaction (PCR) the factor V Leiden and prothrombin gene mutations were evaluated in 55 patients (20 children and 35 adults) with SLE. Although seven patients were found to have factor V Leiden mutation in the heterozygous state, two had the heterozygous G-->A (20210) prothrombin gene mutation. Although one had these two mutations concurrently, these two patients did not have thrombosis. The factor V Leiden mutation frequency (12.7%) was higher than that of our general population (7.1%). On the other hand, seven of the patients with SLE had a thrombotic event. Although of these seven, four (57%) had factor V Leiden mutation, three (43%) had no mutation. Of 48 patients with no thrombotic history, only three had the factor V mutation (6.25%). The prevalence of the factor V Leiden mutation in SLE patients with and without thrombosis was significantly different by Fisher's exact test (p<0.05). The risk of venous thrombosis in patients with factor V Leiden increased threefold compared to that in those without factor V Leiden mutation (odds ratio 20.1; CI 2.99-133.6). Although factor V Leiden mutation seems to play a role in the development of venous thrombosis in SLE, the development of thrombosis in SLE is multifactorial.
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PMID:Survey of factor V leiden and prothrombin gene mutations in systemic lupus erythematosus. 1152 32


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