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)

Most causes of abnormal bleeding can be determined from a complete blood count including platelet count and bleeding, prothrombin, activated partial thromboplastin, and thrombin times. Occasionally, further evaluation is necessary, such as tests of factor XIII function, fibrinolysis, and vascular integrity. Possible diagnoses include disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, vitamin K deficiency, von Willebrand's disease, heparin-induced thrombocytopenia, acquired inhibitors of factor VIII, lupus anticoagulants, and coagulation disorders related to the acquired immunodeficiency syndrome.
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PMID:Laboratory evaluation of a bleeding patient. 266 Apr 7

We have investigated the effect of purified immunoglobulin G (IgG) on endothelial cell functions in 16 patients with lupus anticoagulant, 9 of whom had systemic lupus erythematosus (SLE). Spontaneous or thrombin-stimulated secretion of prostacyclin (PGI2) by cultured human endothelial cells from umbilical cord vein (HUVEC) was not inhibited by the patient's IgG. Nor was spontaneous release of tissue plasminogen activator (t-PA) or of its inhibitor (PAI) modified in the presence of patient's IgG. The rate of activation of purified protein C (PC) by HUVEC in the presence of thrombin was significantly lowered by patient's IgG or Fab' fragment (inhibition of 43%). Neutralization of this effect was obtained by incubation of a greater quantity of phospholipids (phosphatidylcholine, phosphatidylserine) with the patient's IgG. Activation of PC was also performed using purified rabbit thrombomodulin (TM) and a similar inhibition of the patient IgG was observed (inhibition of 48%) but the activation of Gla-domainless PC was not modified.
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PMID:Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells--inhibition of thrombomodulin-dependent protein C activation. 284 52

An anticoagulant activity was isolated from the plasma of a patient with a strong lupus-like anticoagulant using gel filtration by high performance liquid chromatography. IgM were detected in this anticoagulant fraction which exhibited specificity towards 50% phosphatidylcholine - 50% phosphatidylserine vesicles and cardiolipin. These phospholipids were able to produce an apparent 3-fold enhancement of purified human protein C activation by human alpha-thrombin in the presence of purified human placenta thrombomodulin. In the absence of phospholipid, the anticoagulant fraction had no effect on thrombomodulin activity. The anticoagulant fraction could neutralize the enhancement of thrombomodulin activity by phospholipid in a dose-dependent manner. This study suggests that the neutralization of phospholipid might result in a reduced activation of protein C which could be responsible for the occurrence of thrombotic complications in a proportion of patients with lupus anticoagulants.
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PMID:An IgM lupus anticoagulant that neutralizes the enhancing effect of phospholipid on purified endothelial thrombomodulin activity--a mechanism for thrombosis. 301 55

The lupus anticoagulant is a risk factor of thrombosis. The non thrombogenic endothelial surface could be a target for the lupus anticoagulant. We have investigated the effect of purified immunoglobulins G of five patients with LA on the thrombomodulin activity of cultured human endothelial cells from umbilical cord vein. The rate of activation of purified protein C (PC) (30 nM) by the endothelial cells in the presence of thrombin (0.1 U/dish) has been measured by hydrolysis of substrate S 2366. Activated PC has been 7.37 +/- 0.78 pmoles X ml-1 X h-1 in the presence of buffer and 7.2 +/- 0.78 pmoles X ml-1 X h-1 in the presence of control IgG (2 mg/dish). Heat aggregated IgG did not induce any significant change. Patient's IgG lowered significantly the rate of PC activation (4.86 +/- 1.04 pmoles X ml-1 X h-1, p less than 0.001). Fab fragment from two of these patient's IgG displayed the same inhibition. Moreover neutralization of this effect was obtained by addition of phospholipids (70% phosphatidylcholine, 30% phosphatidylserine) in excess to patient's IgG. Activation of PC has been also performed using purified rabbit thrombomodulin and a similar inhibition by patient's IgG was found. These results seem to indicate that antibodies present in the IgG fractions containing LA could be directed against phospholipids associated to thrombomodulin activity. Reduction of PC activation if present in the patients with LA could play a role in the occurrence of thrombosis.
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PMID:[Circulating lupus-type anticoagulant, a risk factor for thrombosis by inhibition of protein C activation]. 301 90

In a prospective study assessing haemostatic functions, the activated partial thromboplastin time was prolonged in 134 out of 10,229 patients studied, without an increase in the prothrombin or thrombin times; this abnormality persisted in only 37 of them on a new blood sample. A retrospective analysis was made of 265 patients who had such an isolated prolongation of the activated partial thromboplastin time on two successive blood samples: the causal abnormality remained unexplained in 135 patients; a well defined coagulation disorder without abnormal bleeding tendency was present in 110 patients (1 severe factor XII deficiency, 58 partial factor XI or XII deficiencies and 51 lupus anticoagulants); a bleeding disorder was diagnosed in 20 patients (8 haemophilias, 8 Von Willebrand's diseases, 4 factor VIII inhibitors). The well-iron efficacy of the activated partial thromboplastin time for detecting coagulation abnormalities is counter-balanced by some disadvantages such as the delay for biologic conclusions. In the preoperative assessment of haemostatic functions, rather than taking a routine approach, it would seem better to determine for each patient the need and the extent of biological testing according to the type of planned surgery, the clinical status of the patient and possible bleeding symptoms.
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PMID:[Successes and failures of the activated partial thromboplastin time in the preoperative evaluation]. 308 57

We describe the coagulopathy of a 65-year-old woman with a thrombotic disorder associated with dysfibrinogenemia and lupus anticoagulant (LA). The patient's prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), and batroxobin time were prolonged and could not be corrected by mixing with equal volumes of normal plasma. Fibrinogen quantitation showed approximately twice as much immunoreactive as thrombin-clottable protein. The batroxobin and thrombin clotting times of the patient's isolated fibrinogen were prolonged and could not be corrected by mixture with normal fibrinogen. Turbidimetrically assessed fibrin monomer aggregation in response to thrombin, ancrod, or batroxobin and fibrin monomer reaggregation experiments disclosed clearly delayed onset and a lower maximum opacity. In other turbidimetric and clotting-time experiments, the patient's fibrinogen displayed a dose-dependent inhibition of the reaggregation of normal fibrin. Fibrinopeptide A and B release rates and sialic acid content were normal. Assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reduced samples, the subunit structure of the patient's fibrinogen and its fully cross-linked fibrin was normal. The presence of LA was established by two techniques, the blood thromboplastin inhibition test and the platelet neutralization procedure (PNP). A positive PNP could not be produced by mixing afibrinogenemic plasma with the patient's purified fibrinogen. The patient's inactivated serum and her isolated IgG prolonged the PT and PTT of normal plasma but showed no inhibitory effect on the clotting of purified normal fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dysfibrinogenemia and lupus anticoagulant in a patient with recurrent thrombosis. 311 49

Decreased endothelial cell production of prostacyclin (PGI2) in response to the lupus anticoagulant has been previously demonstrated and postulated to have a causal relationship to the thrombotic events associated with the lupus anticoagulant. Five patients who exhibited the anticoagulant were studied in an effort to determine if a relationship exists between exposure of endothelial cells to the lupus anticoagulant and decreased production of PGI2. Human endothelial cells derived from human umbilical vein grown in culture were exposed to IgG fractions of patient plasmas containing the lupus anticoagulant. PGI2 released per 10(6) cells was determined by radioimmunoassay for 6-keto-PGF-1-alpha. The overall means for the patient and control groups are given by 47 pM/10(6) cells and 12 pM/10(6) cells respectively. This is a statistically significant difference (F = 10.65, p = 0.017) when the effects of different batches of endothelial cells and thrombin stimulation are adjusted for in the analysis of variance model. These results demonstrate that in this homologous human system exposure of endothelial cells to the lupus anticoagulant leads to stimulation rather than inhibition of PGI2 release.
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PMID:The lupus anticoagulant stimulates the release of prostacyclin from human endothelial cells. 313 89

Defective plasmatic stimulation of prostacyclin (PGI2) production by vascular cells has been described in patients with lupus anticoagulant (LAC). A young woman with recurrent abortions, LAC and evidence for deficient PGI2 production was studied. Serial measurements of a plasma PGI2 inhibitor, LAC and anticardiolipin antibodies (ACA) have been performed before and throughout her fourth pregnancy. Antenatal care and treatment with prednisone and heparin started at 10 weeks gestation. The plasma of our patient continued to inhibit PGI2 production by vascular cells despite treatment. The presence of inhibitor(s) of PGI2 release was confirmed by mixing the patient's plasma with normal plasma. In addition, an IgM lupus anticoagulant fraction (but not the IgG fraction) interfered with the release of arachidonic acid in human endothelial cells induced by thrombin. Despite prednisone and heparin treatment we did not find a complete correction of the LAC activity and the ACA (IgM type) still remained positive before the detection of a fetal death at 26 weeks. The placenta showed abundant infarcts and areas of ischaemic necrosis. We suggest that the defect in vascular PGI2 release could compromise fetal outcome.
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PMID:Serial measurements of a plasma prostacyclin inhibitor in a patient with recurrent abortions and lupus anticoagulant; a case report. 314 99

The results are reported of a clinical and laboratory evaluation of the use of a random-access centrifugal analyzer linked to a personal computer in the management of the routine workload of a hemostasis laboratory. Over a three-month period, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT), and derived fibrinogen (Fib) were performed on a total of 929 samples. Included in the study were 448 samples from patients receiving anticoagulants (oral anticoagulants, 228; heparin, 166; heparin and warfarin, 130) and 351 samples from patients requiring coagulation screens (PT, APTT, TCT, Fib). Tests were done in parallel with tilt-tube manual techniques and the results correlated. The correlation coefficients were PT, 0.99; TCT, 0.72; APTT, 0.96; Fib, 0.97. Discrepancies were analyzed and were due to hypofibrinogenemia and hyperlipidemia. The poorer correlation coefficient of TCT was attributable both to lower reproducibility of the manual test and the effect of dysfibrinogenemia or FDPs in liver disease. In no case was an abnormality or diagnosis missed using the centrifugal analyzer. In several cases the increased sensitivity of the analyzer improved the detection of the lupus anticoagulant. The use of automation was accompanied by a major reduction in workload and reagent costs. The machine has been used to assay a wide range of coagulation tests by clot based and chromogenic substrate methods. In conclusion, a programmed centrifugal analyzer is a safe, efficient, and flexible way of automating routine coagulation tests. It widens the reportoire of tests performed in the Hemostasis laboratory by using a machine capable of being used in other areas of pathology.
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PMID:Automation of routine coagulation testing using a random access centrifugal analyzer. 334 69

To define clinical and laboratory characteristics of the lupus anticoagulant (LA), we reviewed our experience (219 subjects). Subjects were divided into group A, those with the LA and the diagnosis of lupus erythematosus, group B, those with the LA but nonlupus diagnoses, and group C, those with drug-related lupus syndromes. The typical laboratory findings consisted of a prolonged and inhibited plasma clot time (an average of 1.9 times control time) which was proportionately more prolonged than the partial thromboplastin time or activated partial thromboplastin time (APTT) (average 1.3 times control). Ninety-eight percent had a prolonged plasma clot time and 94% had a prolonged partial thromboplastin time. The prothrombin and thrombin times were prolonged in 33 and 25% of subjects, respectively. Washed platelets shortened the APTT in the 22 subjects so tested. Monoclonal protein peaks were seen in 7% of patients. Seventeen episodes of bleeding were observed, but in all but one instance there was another hemostatic defect present. In the 18 patients who underwent major operations, there were no hemorrhagic complications. Fifty-eight episodes of thrombosis were observed with the same incidence in group A (25%) as in group B (26%). Bleeding is rare with the LA but thrombosis is common even without SLE and lupuslike syndromes. The plasma clot time in platelet-rich plasma is more prolonged, and in our experience, is more sensitive in detecting the lupus anticoagulant than is the partial thromboplastin time.
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PMID:Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. 392 59


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