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)

We report a 71-year-old man who developed deep-vein thrombosis after major surgery. Coumarin skin necrosis developed after starting oral anticoagulant therapy. An inhibitor to factor V (61 Bethesda units) with lupus-like features was found as well as a low protein C level. The occurrence of these very rare findings indicates that despite profound procoagulant inhibition (factor V inhibition and anticoagulant therapy), hypercoagulation can occur.
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PMID:Deep-vein thrombosis and coumarin skin necrosis associated with a factor V inhibitor with lupus-like features. 946 52

It is well known that thalassemic patients exhibit an increased frequency of thrombotic events. Most individuals with resistance to activated protein C (APCR) are the result of a point mutation replacing Arg 506 with Gln in the factor V aminoacidic sequence (factor V Leiden). Recently APCR has been shown to account for up to 50% of cases of thrombophilia. In this report, we describe a 10 year old thalassemic intermedia patient heterozygous for Factor V R506Q who developed a stroke following transfusion. Coagulation laboratory values were all within the normal range and there was no evidence of a lupus anticoagulant. Computerized brain tomography showed an ischemic area in the left temporo-parietal region. At follow-up, plasma from the patient demonstrated APCR and molecular diagnostic testing revealed heterozygosity for factor V R506Q. We suggest that the heterozygosity for factor V Leiden could increase the thrombotic risk in thalassemia intermedia. We believe it may be beneficial to screen all intermedia thalassemic patients for APCR especially before starting a transfusional regimen.
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PMID:Resistance to activated protein C as a risk factor of stroke in a thalassemic patient. 949 70

An activated partial thromboplastin time (APTT) based method was developed to determine the anticoagulant response in patient plasma to added purified activated protein C (APC). On the other hand, Bertina et al. (1994) reported that one point mutation of amino acid 506 in the factor V was observed in such APC resistance patients. APC resistance for blood samples with known abnormal findings on the coagulation test also may be determined. Coagmaster II for the APTT assay system (Sankyo, Tokyo, Japan) was employed. The APC resistance assay system was a useful reagent as a screening test for lupus anticoagulant (LA), in addition to APC resistance.
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PMID:Activated protein C resistance assay as a screening test for thromboembolic disposition. 960 96

The composition of antibodies against phospholipids (PLa) was analysed in 54 PLa-positive thrombophilic women, different in the factor V genotype (Arg506-Gln mutation carriers, n=23; and noncarriers, n=31). The presence of antibodies against prothrombin was also studied. The incidence of cardiolipin antibodies (CLa) and lupus anticoagulant (LA) activity was similar among the carriers and noncarriers, while phosphatidylserine antibodies (PSa) were often the only PLa detected in the carriers of the mutation (7/23 vs. 2/31; chi2=5.47, p<0.05). Antibodies against prothrombin were found in 11 of 54 patients. They segregated with PSa (8/19 vs. 3/35; chi2=8.54, p<0.025), but were equally distributed between carriers and noncarriers. The analysis of nAPC-ratio in patients with different PLa showed that it was consistently lower in the mutation carriers in whom none of the PLa caused further suppression. The noncarrier group positive for LA in several assays was associated with a reduction of nAPC-ratio (0.82+/-0.25 vs. 1.12+/-0.22, p<0.05). Our findings indicate that PLa contributing to the development of APC resistance are restricted to those possessing LA activity.
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PMID:Production of phospholipid antibodies in selected thrombophilic women differing in genotype at the 506 site of factor V. 968 88

We compared the sensitivity and specificity of a tissue factor-based assay (FVR) with the addition of a phospholipid/silica preparation, to the commercially available aPTT-based method, APCR (CoatestTM), and a modified aPTT-based method (APCM) which utilized factor V-depleted plasma, for the detection of the factor V Leiden mutation. A total of 110 patients were included in this study. This included 32 patients on coumadin therapy, 7 patients on heparin therapy, 5 patients on both anticoagulants therapy, and 24 patients who were positive for anticardiolipin antibody (ACL) and/or lupus inhibitor (LI). Our data demonstrate that the FVR is not affected by anticoagulation treatment or ACL/LI antibodies, whereas in the APCR method, 33 patients cannot be determined either due to the anticoagulant therapy or presence of the ACL and/or LI. With the APCM method, the clotting endpoint could not be determined in 1 patient due to the presence of a strong LI. The additional phospholipid/silica material utilized in the FVR enhanced the APC degradation of factor Va and therefore sharpened the demarcation between the factor V Leiden-positive and -negative patients. The sensitivity for the APCR, APCM and FVR was 42, 97 and 100% respectively. The specificity for the APCR, APCM and FVR was 94, 96 and 100% respectively.
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PMID:A highly specific functional test for factor V leiden: A modified tissue factor assay for activated protein C resistance. 973 Nov 10

Genetic defects of antithrombin (AT) or one of the components of the protein C pathway are associated with hereditary thrombophilia. Laboratory assays are currently available to diagnose and type hereditary thrombophilia due to deficiency or dysfunction of one of the anticoagulant factors antithrombin (AT), protein C (PC) and protein S (PS), and APC resistance without the need of DNA analysis. There are no functional tests for the prothrombin mutant G20210A and thrombomodulin mutations, which can be diagnosed by a PCR-based test or by gene analysis, respectively. Hereditary AT deficiency is classified in a quantitative type I and three functional type II deficiencies affecting the reactive site (RS), heparin binding site (HBS), or pleiomorphic site of the AT protein. All four types of hereditary AT deficiencies can be diagnosed by a heparin cofactor assay and one immune assay in combination with crossed immunoelectrophoresis of the AT protein. The combination of an enzyme-linked immunoadsorbent assay (ELISA) and a functional Protac-APTT-based assay for PC will detect quantitative type I and dysfunctional type II PC deficiencies. There is a significant overlap in PC antigen and functional levels between heterozygotes of PC deficiency and normals leaving a gray zone of uncertainty in differentiating congenital PC deficiency and normal individuals. Accurate diagnosis of hereditary PS deficiency should be a combination of tests aimed to measure free PS activity and antigen and total PS antigen levels. APTT-, Xa-, and RVVT-based APC-resistance tests, when test plasmas are diluted in factor V deficient plasma, have increased in sensitivity and specificity to 100% for the discrimination of normal individuals from heterozygotes and homozygotes for factor V Leiden. The RVVT-based APC-resistance test provides better separation of factor V Leiden and normals in the various clinical settings, lupus anticoagulant in particular. The modified APC-resistance tests also claim a separation between heterozygotes and homozygotes for factor V Leiden in the normal population, asymptomatic subjects, and thrombosis patients. Below a certain cut-off level, a minor overlap of normalized APC ratios between heterozygotes and homozygotes for factor V Leiden of thrombosis patients has been shown in one study, which still points to the need to perform the more time consuming and expensive DNA test to identify heterozygotes from the more clinically significant homozygotes. The prothrombin-based APC-resistance test, which measures thrombin activated factor Va in highly diluted test plasma, appears to be the most sensitive and specific of all APC-resistance tests and separates normal individuals from heterozygotes and heterozygotes from homozygotes for factor V Leiden without the need of confirmation by a DNA test.
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PMID:Laboratory diagnosis of hereditary thrombophilia. 976 48

A new automated method for screening defects in the Protein C Pathway (PCP) was evaluated. The "PCP test" is based on a phospholipid-rich Russells viper venom reagent, insensitive to heparin and lupus anticoagulants. To minimize interference from other clotting variables, ratios of the clotting time with and without the addition of a protein C activator were usually determined. Plasma samples from healthy volunteers, patients untreated or on oral anticoagulants, patients with factor V Leiden with and without treatment, and patients with protein C and/or S deficiencies were tested. Mixing patient plasmas 1:1 with individual plasmas deficient in factor V, protein C or S was evaluated for identifying the nature of defects by shortening the screening test. The PCP test was found to be sensitive to APC resistance due to factor V Leiden and by mixing with factor V deficient plasma was also useful despite the effects of oral anticoagulants. Results in the group of patients with previous low protein C or S levels suggest that the method has a better sensitivity to protein C than to protein S deficiency. The automated test was simple to use and gave a between-run coefficient of variation below 3% on normal plasmas.
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PMID:A protein C pathway (PCP) screening test for the detection of APC resistance and protein C or S deficiencies. 976 52

Activated protein C (APC) is a naturally occurring anticoagulant that interacts with factor V and VIII to inhibit the clotting cascade. The prevalence of APC resistance among Korean patients with deep vein thrombosis is ill defined. The aim of the present study was to investigate the prevalence of APC resistance and factor V Leiden mutation in Korean patients with deep vein thrombosis. The presence of factor V Leiden mutation was determined in 49 patients who visited Asan Medical Center. APC ratio was performed in 33 individuals from the above 49 patients. Three patients were excluded from the analysis because their baseline aPTT was prolonged. Resistance to APC was diagnosed when the APC ratio was below 2.55. APC resistance was documented in 8 individuals, representing 27% (8/30) of the patients on whom APC resistance test was performed. The 2 patients, who showed APC resistance, were positive for lupus anticoagulant. None of the 49 patients demonstrated factor V Leiden mutation. These findings indicate that factor V Leiden mutation is rare and APC resistance is less prevalent in Korean patients with deep vein thrombosis than in Caucasians. APC resistance not caused by factor V Leiden mutation may be a risk factor for deep vein thrombosis in this population.
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PMID:Low prevalence of activated protein C resistance and coagulation factor V Arg506 to Gln mutation among Korean patients with deep vein thrombosis. 988 65

When performed with standardized methods and techniques, the bleeding time (BT) depends on variables that physiologically alter primary hemostasis. These variables include number of platelets and platelet function, white and red blood cell counts, vascular factors, hormones, and temperature. Variations within normal limits reflect the in vivo situation and are of no clinical relevance. If the BT is prolonged far above the upper normal limit, however, defects of primary hemostasis have to be anticipated. These include thrombocytopenia or thrombocytopathy, anemia, leukopenia, and deficiencies of plasmatic factors such as von Willebrand factor (vWF), fibrinogen, the lupus anticoagulant, and factor V. The BT can be used as screening test for patients with bleeding symptoms. As a single test, the BT gives the best information in pediatrics, in which defects of primary hemostasis are more common than coagulopathies. In addition, BT can guide the therapy of these patients, because it reflects clinical improvement. When used as a preoperative screening test, BT should be combined with the activated partial thromboplastin time (aPTT) because BT usually does not recognize patients with coagulopathies. With standardized techniques and the knowledge of its merits and limitations, BT is a useful test for diagnosing hemostatic disorders, guiding their therapy, and warning of unexpected bleeding complications during surgery. The BT is especially suited for use in pediatrics for the following reasons: (1) It does not require a venipuncture and is similar to capillary blood sampling if performed with standardized devices adapted for pediatric use; (2) it is an in vivo test informing mostly on defects of primary hemostasis, which are the most common bleeding diatheses in childhood; (3) the results are immediately available; (4) it requires only minimal amounts of blood; and (5) it does not require unphysiological reagents and preparation of the sample. The test requires a highly motivated and experienced operator who knows of the many variables influencing the BT. The interpretation cannot be done without knowledge of the history and physical status of the patient and of the limitations of the BT.
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PMID:The bleeding time in pediatrics. 1006 48

The aim of this study was to evaluate critically the recently modified activated-partial-thromboplastin-time (APTT)-based activated protein C (APC)-resistance tests, which are more specific for the factor V Leiden mutation than the first generation APC-resistance tests. The only modification to these tests is the predilution of the plasma sample in factor-V-deficient plasma. The intended effect of this predilution is to bring the concentrations of all clotting factors, except factor V, to the same normal levels. This, in principle, makes the tests also suitable for assaying the plasma of patients treated with oral anticoagulants and heparin, or of patients with a lupus anticoagulant. However, not every factor-V-deficient plasma is suitable for this application. Because the factor V:factor VIII ratio is important in establishing the APC ratio, the factor-V-deficient plasma should contain a sufficiently high factor VIII concentration. We also found that the optimal dilution to obtain the same APC ratios for patients, whether or not treated with coumarins or heparin, is not the same for each test or factor-V-deficient plasma. We compared two modified APTT-based APC-resistance tests (one developed in our laboratory and one commercial) with respect to their ability to discriminate between carriers and non-carriers of the factor V Leiden mutation. Both modified tests gave complete separation of carriers and non-carriers of the factor V Leiden mutation whether or not they are treated with anticoagulants. This makes these tests very suitable for routine screening.
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PMID:Careful selection of sample dilution and factor-V-deficient plasma makes the modified activated protein C resistance test highly specific for the factor V Leiden mutation. 1007 Aug 30


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