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)

Lupus anticoagulant, concentrations of anticardiolipin antibodies, antithrombin III, plasminogen, (free) protein S, protein C, prothrombin, platelet counts, and bleeding times were determined in 74 lupus patients (58 with systemic lupus erythematosus; 16 with lupus-like disease) to establish the presence of risk factors for thrombosis in these patients. Of the variables evaluated, lupus anticoagulant had the strongest association with a history of thrombosis. Both positive anticardiolipin antibody concentrations and the presence of (mild) thrombocytopenia were significantly associated with a history of thrombosis and the presence of lupus anticoagulant. Reduced concentrations of antithrombin III, plasminogen, (free) protein S, and protein C were found in some patients but were not associated with either thrombosis or lupus anticoagulant. Mean concentrations of total protein S were significantly lower in patients with thrombosis than in those without and in patients with lupus anticoagulant than in those without. The antigenic concentration of prothrombin was reduced in 3/74 (4%) lupus patients. These three patients had lupus anticoagulant but no history of thrombosis, which suggests that a low prothrombin concentration protects patients with lupus anticoagulant from the development of thrombosis. A prolonged bleeding time was associated with the presence of lupus anticoagulant but not with a history of thrombosis. Analysis by stepwise logistic regression did not disclose additional risk factors for thrombosis in lupus patients with lupus anticoagulant. Increased antithrombin III concentrations and decreased free protein S concentrations are often found in lupus patients, unrelated to lupus anticoagulant or thrombosis.
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PMID:Risk factors for thrombosis in lupus patients. 251 63

This study prospectively evaluates hypercoagulable states in patients under 51 years of age undergoing lower extremity revascularization for ischemia and assesses early outcome after operation. Twenty patients whose ages range from 23 to 50 years (mean 40.8 years) were identified prospectively who underwent lower extremity revascularization and evaluation of hypercoagulability. Fifteen patients were male (75%), 10 were black (50%), six had hypertension (30%), and four were diabetic (20%). All but two were cigarette smokers (90%). Seven aortoiliac procedures and 13 infrainguinal procedures were performed. Six patients had one or more abnormalities of regulatory proteins (protein S deficiency, four; protein C deficiency, three; presence of lupus-like anticoagulant, three; plasminogen deficiency, two). Eight of 17 patients in whom platelet aggregation profiles were obtained showed increased reactivity (47%). Only 4 of 17 patients (24%) were normal when tested for all parameters. Arterial or graft thrombosis developed in four of the 20 patients within 30 days after operation. Hypercoagulability was found in all four patients whose revascularizations failed. A high incidence of hypercoagulable states was found in patients under 51 years of age with lower limb ischemia requiring revascularization. Hypercoagulability may have contributed to early postoperative thrombosis of the vascular procedure.
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PMID:Hypercoagulable states and lower limb ischemia in young adults. 252 8

The intraglomerular location of coagulation-fibrinolysis factors (CFF) and a platelet membrane antigen (glycoprotein IIb-IIIa; GPIIb-IIIa) was determined in 101 patients with various glomerular diseases. Renal biopsy specimens were examined by immunofluorescence microscopy, using antisera against fibrinogen/fibrin reactive antigen (FRA), cross-linked fibrin degradation products (XL-FDP), fibronectin (FN), factor XIII-subunit a (F-XIIIa), plasminogen (Plg), alpha 2-plasmin inhibitor (alpha 2-PI) and GPIIb-IIIa. Intraglomerular deposits of the CFF were found at high rates in patients with IgA glomerulonephritis (GN), membranous nephropathy (MN) and lupus GN. The coexistence of deposits of these factors was ascertained by the double-staining method. The deposition rates of XL-FDP and GPIIb-IIIa were very low in patients with minimal-change nephrotic syndrome and focal glomerulosclerosis. Some cases of diabetic glomerulosclerosis (DGS) showed CFF deposition. FRA deposits associated with F-XIIIa and FN may indicate the presence of the cross-linked fibrin. Furthermore, the presence of Plg deposits together with alpha 2-PI and XL-FDP suggests the deposition of fibrin followed by fibrinolysis, but not of fibrinogen, and the coexistence of GPIIb-IIIa suggests the involvement of platelets in the reactions. These studies provide evidence that stabilized fibrin deposition with subsequent fibrinolysis and platelet activation take place in glomeruli in a fairly large proportion of patients with IgA GN, MN and lupus GN and in some cases of DGS.
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PMID:Intraglomerular deposition of coagulation-fibrinolysis factors and a platelet membrane antigen in various glomerular diseases. 256 3

It has been suggested that kallikrein inhibition may predispose patients with the lupus inhibitor to thrombosis by interfering with the Factor XII-mediated activation of plasminogen. To further investigate this suggestion, the authors measured kallikrein inhibition in 19 patients with the lupus inhibitor. They found that kallikrein inhibition was greater than 100% of that of a normal plasma pool in all patients and greater than 125% in 11 of 19. Kallikrein inhibition was significantly correlated with C1-esterase inhibitor (C1S-INH) concentration, which they measured by rocket immunoelectrophoresis (r = +0.55, P less than 0.05). In three patients the C1S-INH was more than 30% greater than the kallikrein inhibition. Crossed immunoelectrophoresis for C1S-INH in these patients' plasma revealed an electrophoretic mobility identical with that of the normal plasma pool. The authors suggest that C1S-INH-mediated kallikrein inhibition, in conjunction with other coagulation abnormalities, predisposes patients with the lupus inhibitor to thrombosis.
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PMID:Kallikrein inhibition and C1-esterase inhibitor levels in patients with the lupus inhibitor. 311 30

Some molecular defects of components of the coagulation or fibrinolytic system are associated with thromboembolism. One possibility is that physiologic inhibitors of the coagulation system have an abnormal function e.g. protein C, protein S, antithrombin III and cofactor II of heparin. Also a hindered activation of the fibrinolytic system may predispose to thrombosis; the impaired activation may be due to deficient synthesis and/or release of tissue-plasminogen activator, an increased level of its inhibitor or a functional defect of the plasminogen molecule. A few cases of congenital dysfibrinogenemia have been described in which the functional defects of the molecule are held responsible for recurrent thrombosis. An acquired thrombotic disorder is due to the presence of immunoglobulins which prolongs phospholipid-dependent coagulation by binding to epitopes of some phospholipids. This so-called lupus anticoagulant was originally described in patients with systemic lupus erythematosus but is a misnomer as it is more frequently encountered in patients without lupus.
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PMID:[Molecular defects of coagulation factors and of the fibrinolytic system associated with thromboembolism]. 354 55

Methods are described to measure fibrinolysis in healthy persons and in patients with systemic lupus erythematosus. Using the fibrin plate method, total fibrinolytic activity and vascular plasminogen activator were measured. (Total fibrinolytic activity expresses the fibrinolytic potential and consists of both the intrinsic [factor XII-dependent and independent] activities and the extrinsic activities [vascular or tissue type]. Vascular plasminogen activator, assessed in a separate assay, refers to the endothelium-derived component only.) In addition, the degree of inhibition by plasma of both urokinase-induced and of plasmin-induced fibrinolysis were analyzed. Vascular plasminogen activator levels were low in 63% of plasma samples from 55 patients with systemic lupus erythematosus. The level of an inhibitor of plasminogen activation was significantly elevated in 87% of patients and levels of an inhibitor of plasmin were significantly elevated in 29%. The nonspecific serine protease inhibitors, including alpha 2-macroglobulin, were within the normal range in all patients. The natures of inhibitor of plasminogen activation and plasmin inhibitor were studied further. Using both the fibrin plate and the lysis time methods, the data indicated that the urokinase-inhibiting activity increased with time of incubation of plasma-enzyme mixtures, whereas the plasmin inhibiting activity did not. Elevated levels of plasmin inhibitor measured with the fibrin plate method correlated well with prolonged lysis times. Results using the chromogenic substrate S-2251, commonly used as a simple and specific assay for antiplasmin, agreed reasonably well with those using the fibrin plate method, but elevated plasmin inhibitor levels could be quantitated with greater accuracy and sensitivity by the fibrin plate method. Studies with an antiserum directed against alpha 2-antiplasmin showed that inhibitor of plasminogen activation and plasmin inhibitor were different inhibitors, and that plasmin inhibitor was identical to alpha 2-antiplasmin. The abnormalities are discussed in the light of current knowledge on fibrinolysis and as possible mediators in the pathogenesis and perpetuation of lupus glomerulonephritis.
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PMID:Fibrinolysis in health and disease: severe abnormalities in systemic lupus erythematosus. 623

The designation of Antiphospholipid Syndrome was first applied by Harris in 1987, to a clinical status characterized by the detection of anticardiolipin and/or lupus anticoagulant with clinical thromboembolic manifestations. Recent advances in its study has shown that the inducing antigen is really a complex of phospholipid and protein. Therefore, it became clear that there is a need for a protein cofactor to the formation and action of antiphospholipid antibodies (APL). The authors present a detailed revision of the nature and specificity of APL, described as its proteic counterpart. Their action is surely conditioned by the specific protein involved with phospholipids, as it may be with Beta 2-Glycoprotein 1, Prothrombin, Protein c and s, Anexin V and the association of plasminogen and t-PA. The isotype of immunoglobulins is also very heterogeneous, since it was detected as IgG as well as IgA and IgM immunoglobulins. Furthermore, they can coexist in the same patient and with no clear relationship with thromboembolic manifestations. These aspects demonstrate well the greater variability that is found in these patients in relation to clinical and laboratory manifestations of the disease. For laboratory diagnosis, micro ELISA systems were developed, allowing the identification of antiphospholipid immunoglobulins with relative specificity and accuracy. Finally, the most frequent clinical expression is described, emphasising the pitfalls of clinical and laboratory diagnosis of the antiphospholipid syndrome.
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PMID:[Antiphospholipid immunization syndrome and thrombosis]. 771 5

This review has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects appear to be antithrombin, protein C, and protein S deficiency, and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore, these are the defects which should first be searched for in an individual with unexplained thrombosis. If these more common defects are not found, the rarer defects, including HC-II, plasminogen, or TPA deficiency, dysfibrinogenemia, elevated PAI-1, or heterozygous homocystinemia should be looked for. The incidence of activated protein C co-factor deficiency (APC resistance) is not yet clear but may also represent a common defect. PAI-1 defects may, with time, be shown to be common. Finding these defects has important implications for therapy for the individual patient and for the institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein(a) or defects of extrinsic (tissue factor) pathway inhibitor (EPI, TFPI), may be associated with enhanced risks for thrombosis.
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PMID:Blood protein defects associated with thrombosis. Laboratory assessment. 778 Dec 75

Resistance to activated protein C (RAPC) has been described recently as a cause of trombophilia; this may justify up to 50% of thromboembolic disease without predisposing cause in patients under 45 years. A 29 years-old male with a previous deep venous thrombosis (DVT) in the lower left limb three years earlier, developed a DVT in the right lower limb after a trauma of the knee that required immobilization, was associated to pulmonary thromboembolism diagnosed by gammagraphic methods. The phlebographic study showed femoro-iliaco-caval venous thrombosis. The proband's father and a younger brother had a previous history of thrombotic episodes. The following tests, were performed in the proband and relatives: prothrombin time, aPTT, thrombin time, fibrinogen, (Von Clauss), antithrombin III (chromogenic), protein C and protein S (coagulometry and ELISA), plasminogen (chromogenic) and lupus anticoagulant (ITT, dRVVT, aCL). RAPC was evaluated in two different samples. The proband study was performed under oral anticoagulation treatment (OAT). Control groups were: 21 blood donors and 12 OAT patients. The results showed a decreased response to APC in the proband (ratio 1.5) and relatives: father (1.4), brothers (1.5 and 1.5), while the mother was within the normal range (> or = 2). In normal controls and OAT patients the ratio was over 2. No other abnormalities were detected in the assays performed. It is concluded that RAPC is the cause of this familial trombophilia. RAPC should be included in the evaluation study of trombophilia.
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PMID:[Familial thrombophilia due to resistance to activated protein C]. 798 58

This review has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects appear to be antithrombin, protein C, and protein S deficiency and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore these are the defects that should first be looked for in an individual with unexplained thrombosis. If these more common defects are not found, then the rarer defects, including heparin cofactor II, plasminogen or tissue plasminogen activator deficiency, dysfibrinogenemia, or elevated PAI-1 should next be sought. The importance of finding these defects has significant implications for therapy of the individual patient and for institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein(a) or defects of extrinsic (tissue factor) pathway inhibitor may be associated with enhanced risks of thrombosis.
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PMID:Syndromes of hypercoagulability and thrombosis: a review. 805 29


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