Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: KEGG:D03244 (Kaolin)
239 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The laboratory assessment of the lupus anticoagulant, a factor frequently associated with venous and arterial thrombosis, recurrent miscarriages and abortions, is not straightforward, as indicated by the variety of tests proposed and the different results obtained. On account of the marked variability and heterogeneity of lupus anticoagulant among patients, no single test or reagent will identify all patients with lupus anticoagulant, and a panel of several tests has to be used. This is time consuming and increases the workload of the laboratory. The aim of this study was to assess the minimum number of tests necessary for the satisfactory identification of the patient with lupus anticoagulant. Our study confirms that lupus anticoagulant may be present in a significant number of patients with normal routine activated partial thromboplastin time, a test which therefore cannot be used as the sole criterion for identifying patients suspected of having lupus anticoagulant. In contrast all patients who had positive results in at least one test could be detected (100% sensitivity) with two combinations of tests: (1) dilute activated partial thromboplastin time and Kaolin clotting time and (2) dilute activated partial thromboplastin time and tissue thromboplastin inhibition test. Since the latter inhibition test has been reported to give a high number of false-positive or negative results, we suggest the combination of dilute activated partial thromboplastin time and Kaolin clotting time as the standard pair of tests for the screening of suspected lupus anticoagulant patients.
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PMID:An evaluation of several laboratory tests and test combinations in the detection of lupus anticoagulant. 150 2

Six lyophilized plasma samples were sent to 20 "expert" laboratories for assessment of lupus anticoagulant (LA). Four samples contained pooled LA of graded potency mixed with aged normal plasma. One contained LA plus cephalin phospholipid and one contained a nonspecific venom anticoagulant. Sixteen methods were used overall with some participants using up to 8 methods. Results were scored in regard to the known potencies of LA in the samples and other known induced defects. Activated partial thromboplastin time (APTT) tests used by most participants for preliminary screening were relatively sensitive, but non-specific. Platelet or phospholipid neutralization procedures (PNP) appeared to be sensitive and specific but showed a non-linear response to increased LA content. Kaolin clotting time (KCT) tests showed the most sensitive response to increased LA content but the weaker LA were not scored as abnormal by most laboratories as the samples may have contained platelet fragments. Other commonly used tests such as the tissue thromboplastin inhibition (TTI) test and the dilute Russell's viper venom test (DRVVT) were carried out somewhat inconsistently. The variability in performance of tests in different laboratories indicates that standardization of methodology is urgently required. Generally it seemed that most clotting tests were "bypassed" by the addition of phospholipid to a known LA-positive sample in apparently direct proportion to their sensitivity. Sample preparation, especially prevention of contamination with activated platelets is a vital preliminary part in the assay of LA.
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PMID:Comparison of test methods for the lupus anticoagulant: international survey on lupus anticoagulants-I (ISLA-1). 212 77

The detection of lupus anticoagulant is important in laboratory evaluation of patients with thrombotic tendencies. The aim of this workshop was to assess the effectiveness of Australian laboratories in detecting these antibodies and assess the tests used. Fourteen laboratories took part in the exercise, held as a Workshop of the National Meeting of Australian Medical Laboratory Scientists in 1990. Seven unknown plasmas were distributed for testing prior to the meeting. While 100% correctly identified 3 strong inhibitors and a moderate strength inhibitor, the detection rate for specific individual tests varied from 38-100%. The detection rate for 2 weak inhibitors varied from 0-50%. Of the most commonly performed tests the least sensitive was the dilute Russell's viper venom time and the most sensitive was the tissue thromboplastin inhibition test, however, the degree of sensitivity seemed dependent on the source of thromboplastin. In some laboratories the Kaolin clotting time, with variations, was more sensitive. All participants correctly identified a factor VIII inhibitor as not of the lupus type. The false positive detection rate was 0%. All but one of the participating laboratories used 2 or more phospholipid dependent tests for the analysis of lupus anticoagulant (LA) which is in keeping with current international guidelines.
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PMID:Detection of lupus anticoagulant--an Australian perspective. 816 99

The sera of 69 Chinese patients with systemic lupus erythematosus were tested for the presence of lupus anticoagulant (LA) by a panel of laboratory tests: Kaolin clotting time (KCT), dilute Russell viper venom time (DRVVT) and platelet neutralization procedure (PNP). The prevalence of LA varied among the 3 tests (10-19%), and was 10% when LA was considered present if either KCT or DRVVT and the PNP were positive. Concordance was fair between KCT and PNP, but was poor for DRVVT with either of the other 2 tests. Only 2 of our lupus patients had a history of thrombo-embolic disease, and neither were serologically positive for LA. The incidence of thrombo-embolic diseases and that of LA were both too low in this group of Chinese lupus patients for their association to be evaluated.
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PMID:Evaluation of laboratory tests for lupus anticoagulant in a group of Chinese lupus patients. 816 23

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which have been defined by varying laboratory test systems. Lupus anticoagulants (LA) and anticardiolipin antibodies (ACA) are the two most prominent members of this family of antibodies. LA are detected utilizing various phospholipid (PL) dependent tests of coagulation (e.g., activated partial thromboplastin time [APTT], Kaolin Clotting Time [KCT], dilute Russell Viper Venom Time [dRVVT]). Originally, LA were thought to be a laboratory nuisance since the vast majority of individuals with LA did not bleed. Paradoxically, patients with LA were found to have an increased incidence of thromboembolic events and also recurrent spontaneous abortions (RSA). Thus, the laboratory detection of LA has become part of the work up of patients with thromboembolic disorders and RSA. ACA are detected using solid phase assay systems (radioimmunoassay or ELISA). The presence of ACA has the same clinical implications as that of LA. Although originally it was suggested ACA and LA were the same antibody, it is now well accepted that they, in many instances, are different antibodies. Therefore, it is critical for laboratories to evaluate patient samples for both LA and ACA. In approximately 60% of circumstances, both antibodies will be found. In the remaining cases, there will be discordance between the two test systems. The question of whether APA are causative, coincidental, or a consequence of the clinical complications of RSA and thrombosis remains controversial. Recent evidence based on prospective clinical studies and analysis of markers of in vivo coagulation suggests APA are causative.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protean clinical presentation of antiphospholipid-protein antibodies (APA). 857 80

Antiprothrombin and anti-beta2-glycoprotein I (beta2-GPI) antibodies belong to the family of antiphospholipid (APL) antibodies and represent the phospholipid-dependent inhibitors of coagulation. They may be distinguished by analyzing the coagulation profiles generated by the comparison of the ratios of two coagulation tests, the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT), commonly adopted for their diagnosis. The KCT profile is caused by antiprothrombin antibodies, whereas anti-beta2-GPI antibodies are responsible for the dRVVT coagulation profile. The presence of aPL antibodies is frequently associated with acquired resistance to activated Protein C (APC-R), but limited information is available regarding the role of the different antibodies in its development. We studied the time-course of activated Factor V (FVa) generation and inactivation in the plasma of 42 patients with well-defined phospholipid-dependent inhibitors of coagulation: 24 displayed the dRVVT coagulation profile, whereas the other 18 cases showed the KCT profile. In normal pooled plasma, the peak values of FVa (mean +/- standard deviation, [SD]: 16.307 +/- 4.372 U/mL) were reached in 4 to 5 minutes and an almost complete inactivation (0.088 +/- 0.123 U/mL) was obtained within 20 minutes. At this time point, values of residual FVa exceeding 2 SD the mean of controls (0.344 U/mL) were considered abnormal. Patients belonging to the KCT coagulation profile group reached the maximal amount of FVa in plasma (22.740 +/- 7.693 U/mL, P = not significant v controls) within 4 to 5 minutes; at 20 minutes, the residual amount of FVa in plasma ranged from 0 to 1.09 U/mL (0.293 +/- 0.298; P = .027), but it was found abnormal in only six of the 18 cases. The time-course of FVa in plasma of patients belonging to the dRVVT coagulation profile group differed from that of normal controls in that the peak values (10.955 +/- 5.092 U/mL) were reached at 10 minutes and the amount of residual FVa at 20 minutes ranged from 0.320 to 14.450 U/ml (2.544 +/- 3.580 U/mL; P = .0191 v normal controls and P = . 0114 v KCT group patients). Twenty of the 24 patients belonging to the dRVVT profile group had an abnormal inactivation of FVa (chi2 = 0.001 v KCT group patients). History of venous thrombosis was experienced by 15 patients: an abnormal rate of FVa inactivation was found in 11 of them (73%) versus 15 of the 27 cases without thrombosis (56%) (x2 = 0.2556). The effect of affinity-purified IgG phospholipid-dependent inhibitors of coagulation on the time-course of FVa generation and inactivation in normal plasma was also investigated. Anti-beta2-GPI, but not antiprothrombin antibodies, hampered the inactivation of FVa by endogenous APC, thus reproducing the behavior of the original plasmas. This effect was strictly beta2-GPI-dependent. In conclusion, our findings confirm that anti-beta2-GPI antibodies identify patients with phospholipid-dependent inhibitors of coagulation at increased risk of thrombosis and suggest acquired APC-R as a possible explanation of the pathogenesis of the thromboembolic events.
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PMID:Differential effects of anti-beta2-glycoprotein I and antiprothrombin antibodies on the anticoagulant activity of activated protein C. 976 96

"Antiphospholipid" (aPL) antibodies comprise two main groups of antibodies, lupus anticoagulant (LA) antibodies and "anticardiolipin" (aCL) antibodies which can be separated by certain chromatographic techniques. In this study we analysed the plasma of 10 patients with aPL antibodies, and were able to demonstrate that in four patients with both clotting test reactivities, the dilute Russell's Viper Venom Time (dRVVT) activity can be separated from the dilute Kaolin Clotting Time (dKCT) reactivity by using a polyacrylamide-immobilised phosphatidylserine column but not with phospholipid liposomes. The differential reactivity of the autoantibodies in this patient population is not due to binding to beta2GPI, prothrombin or protein C in solid-phase immunoassays. Hence LA antibodies detected in different phospholipid-dependent clotting tests detect different populations of antibodies in some APS patients and the routine detection of LA antibodies should be performed with at least two clotting tests looking at different coagulation reactions.
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PMID:Heterogeneity of lupus anticoagulant (LA) antibodies: LA activity in dilute Russell's Viper Venom Time and dilute Kaolin Clotting Time detect different populations of antibodies in patients with the "antiphospholipid" syndrome. 971 48

Prothrombin is a common antigenic target of antiphospholipid antibodies, since anti-prothrombin antibodies are detected in about 50-90% of the patients. To allow proper immune recognition, prothrombin must be adsorbed on suitable anionic surfaces. The epitope(s) have not yet been identified: the majority of anti-prothrombin antibodies appear to be of poly- or oligoclonal nature. Anti-prothrombin antibodies, either alone or in combination with anti-beta2-glycoprotein I antibodies, are responsible for the lupus anticoagulant activity of about 75% of the cases of phospholipid-dependent inhibitors of coagulation. The two antibodies may be discriminated by means of specific coagulation profiles generated by the comparison of the ratio of the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT): the KCT profile, which mainly reflects the presence of anti-prothrombin antibodies and the dRVVT profile, which is mostly associated with anti-beta2-glycoprotein I antibodies. This distinction, although somewhat artificial, may be clinically useful, since the KCT profile identifies patients at low risk to develop thrombosis. Similarly, most of the studies that measured anti-prothrombin antibodies by ELISA failed to find a significant association with thrombosis. In conclusion, the clinical relevance of these antibodies has not yet been established.
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PMID:Prothrombin as cofactor for antiphospholipids. 981 70

Anti-beta2-glycoprotein I (beta2-GPI) antibodies behave as classical Lupus Anticoagulants (LA), as they inhibit phospholipid-dependent coagulation reactions and their activity disappears in the presence of excess exogenous phospholipids (PLs). We have recently shown that a certain amount of PLs in the dilute Russell Viper Venom Time (dRVVT) test system is required to express LA activity of anti beta2-GPI antibodies. We have now extended this observation to two other tests, i.e., Kaolin Clotting Time (KCT) in which PLs are not added, and Tissue Thromboplastin Inhibition test (TTI) in which PLs are extremely diluted. In fact, affinity-purified antibody preparations from 5 patients with antiphospholipid syndrome did not express or only weakly expressed anticoagulant activity in both tests; the mean ratios of coagulation times obtained with purified antibodies and that of control buffer were 1.11 and 1.0 for KCT and TTI, respectively. On the contrary, the mean ratios in dRVVT were 1.31 and 1.49 at a PLs dilution of 1:8 and 1:64, respectively. Therefore, the presence of LA activity due to autoantibodies to beta2-GPI is characterized by a positive dRVVT and negative or only weakly positive KCT and TTI.
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PMID:dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant activity of anti-beta2-glycoprotein I autoantibodies. 1006 2

Lupus anticoagulants belong to the family of antiphospholipid antibodies. They include two phospholipid-dependent inhibitors of coagulation that may be distinguished on the basis of specific coagulation profiles generated from the comparison of the ratios of the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT): when the ratio of the KCT exceeds that of the dRVVT, the plasma is allocated to the "KCT" coagulation profile, when the opposite occurs, the plasma is defined to belong to the "dRVVT" coagulation profile group. We prospectively followed-up a historical cohort of 100 consecutive patients with lupus anticoagulants referred to our Institution between January 1988 and October 1997 to investigate the relationship between their coagulation profile at diagnosis and the development of thrombosis during a median follow-up time of 37.5 months (range 1-115 months). Fifty-six patients were allocated to the "dRVVT" coagulation profile, whereas the other 44 displayed the "KCT" profile. Lupus anticoagulants were transient in 17 patients, without differences between the two groups. None of these patients developed clinical events before disappearance of the phospholipid-dependent inhibitors of coagulation. The 83 cases with persistent lupus anticoagulants consistently displayed the same coagulation profile they had been allocated to at entry. Fourteen patients developed 18 thromboembolic events during the follow-up, with an overall rate of thrombosis of 4.2% patients-year. Twelve of them belonged to the "dRVVT" coagulation profile, whereas the other 2 to the "KCT" profile (p = 0.03). The "dRVVT" coagulation profile gave an odds ratio of thrombosis of 5.25 (95% confidence interval [C.I]: 1.17-23.50). Ten of the 14 patients who developed thrombosis during follow-up had already experienced thrombosis: a previous thrombotic event caused an odds ratio of recurrency of 2.72 (95% C.I.: 0.85-8.73) (p = 0.09). By multivariate analysis, the "dRVVT" coagulation profile was still associated with a trend to a higher risk of thrombosis, but the difference did not reach statistical significance. Increased levels of anticardiolipin antibodies (> 40 GPL and/or MPL units) were found in all the 14 patients (p = 0.0064). The "KCT" coagulation profile was significantly associated (p = 0.005) with moderate thrombocytopenia (platelets 50-150 X 10(9)/l). Neither profile was found to represent a risk factor for the development of recurrent miscarriages, neoplastic diseases and death. In conclusion, the "dRVVT" profile appears to have predictive value with respect to the thrombotic complications suffered by patients with antiphospholipid antibodies.
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PMID:The risk of thrombosis in patients with lupus anticoagulants is predicted by their specific coagulation profile. 1036 39


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