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)

Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive
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PMID:Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XIa). 23 89

An acquired inhibitor of blood coagulation, similar to that described in patients with Systemic Lupus Erythematosus (SLE), was detected during routine coagulation screening in 10 patients who did not meet the criteria for a diagnosis of SLE. The lupus-like anticoagulant (LLAC) was diagnosed on the basis of prolonged activated partial thromboplastin time (APTT) and/or prothrombin time (PT) which failed to correct when patient plasma was added to normal plasma; an additional criterion was an abnormal tissue thromboplastin inhibition test. No patient had a specific inhibitor directed against factors VIII and IX. Demonstration of LLAC was highly dependent upon the type of reagents adopted in the APTT and PT: the abnormality was detected consistently by one reagent only. One-stage assays of factors VIII and IX were characteristic of the presence of an inhibitor, showing non-parellel dose-response curves or decreased activity at low dilutions which were partially corrected at higher dilutions. Although 7 patients were free of abnormal bleeding, unequivocal signs of haemorrhagic tendency after a surgery were present in the remaining 3 patients. The findings suggest that LLAC is a non-exceptional cause of prolonged coagulation screening tests, and that it may sometimes be associated with impaired haemostasis.
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PMID:The varied sensitivity of partial thromboplastin and prothrombin time reagents in the demonstration of the lupus-like anticoagulant. 47 62

We studied a patient being treated with procainamide in whom we observed a high antinuclear antibody titer and prolonged activated partial thromboplastin (PTT), prothrombin (PT), and Stypven times (ST). Serum antibody concentrations against single-stranded DNA were elevated while those aginst native DNA were not elevated, suggesting the procainamide-induced lupus syndrome. Dilution of the patient's plasma with normal plasma failed to correct the PTT and PT, indicating the presence of an inhibitor(s) to blood coagulation. The anticoagulant activity was associated with the IgG fraction of the patient's serum. Addition of purified or partially purified human factors IX, X, VIII, VII, XIa, prekallikrein, high molecular weight kininogen, or phospholipids to the patient's plasma failed to correct the PTT, PT, or ST; however, purified human factor XII and prothrombin corrected the PTT and ST, respectively. These results indicate that production of antibodies directed against antigenic determinants on coagulation proteins can be a manifestation of procainamide-induced lupus erythematosus.
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PMID:Circulating inhibitors of blood coagulation associated with procainamide-induced lupus erythematosus. 71 99

This report describes a patient with active systemic lupus erythematosus (SLE) who evidenced severe bleeding consequent to a profound and isolated reduction in plasma factor II (prothrombin) activity. Absence of the factor is documented by immunologic means and its return after corticosteroid therapy is demonstrated. The authors recommend inclusion of this acquired coagulopathy among other more traditional diagnostic manifestations of SLE.
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PMID:Absent factor II in systemic lupus erythematosus. Immunologic studies and response to corticosteroid therapy. 81 6

An inhibitor of blood coagulation was detected in the plasma of four schizophrenic patients receiving long-term chlorpromazine therapy. The partial thromboplastin time (PTT) was prolonged in all four patients and the prothrombin time (tpt) was prolonged in one. The inhibitor which resembled in many respects that seen in patients with systemic lupus erythematosus (SLE), was shown to be associated with the tigM-rich fractions of the serum. None of the patients manifested a clinical bleeding tendency and in two, discontinuation of the chlorpromazine was followed by a decrease in the activity of the anticoagulant. While three of the patients had a positive antinuclear antibody test (ANA) and the fourth a false positive serology for syphilis, no further evidence for SLE was found.
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PMID:A chlorpromazine-induced inhibitor of blood coagulation. 88 26

Eighty-three patients with circulating anticoagulants were studied at The New York Hospital. The lupus-type anticoagulant, an inhibitor of the prothrombin activator complex, was demonstrated in 58 patients. The inhibitor was identified using the blood and tissue thromboplastin inhibition tests. Inhibition by the lupus anticoagulant was augmented in 67% of these patients by a cofactor present in normal plasma. The lupus inhibitor was detected primarily because of an unsuspected abnormal coagulation test. One-half of the patients with the lupus-type anticoagulant did not have systemic lupus erythematosus.
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PMID:A clinical study of the lupus anticoagulant. 96 90

Plasma fibrinopeptide A (FPA) concentrations were measured in clinical blood samples incubated in the collecting syringe for different time periods before addition to heparin and Trasylol, and the rate of in vitro generation of FPA was calculated as the mean increment in FPA concentration per minute over the linear portion of the generation curve. 36 normal individuals had a mean plasma FPA level of 0.64 +/- 0.56 pmol/ml and an FPA generation rate of less than 0.5 pmol/ml per min. Clinical samples with elevated plasma FPA levels manifested slow (less than 1 pmol/ml per min) (28 patients) or rapid FPA generation (greater than 1 pmol/ml per min) (33 patients). Slow FPA generation was found in 10/10 patients with venous thrombosis, in 4/4 with aortic aneurysm, and in several patients with acquired hypofibrinogenemia. In one such patient, addition of fibrinogen resulted in rapid FPA generation whereas thrombin addition was without effect. Rapid FPA generation was generally linear, was usually associated with slower fibrinopeptide B generation and was inhibited by parenteral or in vitro heparin. It is thought to reflect increased thrombin activity and was seen in patients with pulmonary embolism, active systemic lupus erythematosus, renal transplant rejection, and after infusion of prothrombin concentrates. The initial rate of FPA cleavage by thrombin at fibrinogen concentrations from 0.05 to 4 mg/ml showed little change between 2 and 4 mg/ml with a Km of 2.99 muM. At a fibrinogen concentration of 2.5 mg/ml the FPA cleavage rate was 49.2 +/- 1.6 nmol/ml per min per U of thrombin. Exogenous thrombin added to normal blood generated 21.7 nmol/ml per U of thrombin FPA in the first minute with a nonlinear pattern reflecting inactivation of thrombin and the presence of alternative substrates. Hence, the thrombin concentration in the blood cannot be calculated from the FPA generation rate. The FPA generation rates in clinical samples with rapid generation (1-28 pmol/ml per min) could be produced by 2 X 10(-5) to 5.6 X 10(-4) thrombin U/ml acting on purified fibrinogen at physiological conditions of pH, ionic strength, and temperature.
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PMID:The generation of fibrinopeptide A in clinical blood samples: evidence for thrombin activity. 99 37

The clinical and laboratory experience with the lupus anticoagulant was reviewed in 37 patients. The anti-coagulant is thought to act by blocking the activation of prothrombin by the prothrombin activator comlex of factors Xa, V, and phospholipid. Although the anticoagulant has been principally associated with diseases of immune origin, 14 of the present patients had disorders not thought to be immune in nature. Eighteen patients underwent twenty-one operative procedures with only a single episode of excessive bleeding. In the author's experience, the lupus anticoagulant is a rare cause of bleeding.
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PMID:The lupus anticoagulant. 99 35

A wide spectrum of hemostatic abnormalities is found in patients with SLE. Thrombocytopenia and qualitative platelet disorder (impaired aggregation to collagen) are probably both due to antiplatelet antibodies, which can be found in most patients with the disease. About 10% of patients with SLE have a circulating anticoagulant. These circulating anticoagulants are broadly heterogeneous. Although most reported cases act at the level of the prothrombin converting complex, 15 of the 74 cases here reviewed had other points of action. The anticoagulants are probably all antibodies; they differ (with rare exceptions) from other naturally occurring circulating anticoagulants in having an immediate rather than a progressive effect, and in acting, not against pre-existing procoagulants, but against unstable complexes. An anticoagulant of the type found in SLE is only rarely observed in the absence of SLE; its presence in a patient is thus of some diagnostic importance. Hypoprothrombinemia is a common second lesion in patients with circulating anticoagulants. Its pathogenesis is obscure. Two patients with acquired von Willebrand's disease have been observed. All the hemostatic abnormalities found in SLE probably have immunologic bases; all respond to glucocorticoid treatment.
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PMID:Disorders of hemostatic function in patients with systemic lupus erythematosus. 109 75

Of 36 patients with systemic lupus erythematosus, 3 were demonstrated to have an abnormality in their haemostatic mechanism. In 2 this was believed to be on the basis of an auto-antibody to the phospholipid of platelets in the prothrombin activator complex. In the third an inhibitor was directed against factor VIII.
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PMID:Systemic lupus erythematosus and spontaneously arising anticoagulants. 118 58


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