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)

The coagulation system can be considered as a balance in which clotting and fibrinolysis have to be in a state of equilibrium. Increased fibrin formation or decreased fibrinolysis can predispose to thromboembolic diseases. Derailments in the clotting system leading to thrombosis center around the regulatory mechanisms, antithrombin III, protein C, protein S and possibly heparin cofactor II. Many cases of congenital or acquired deficiencies or abnormalities or antithrombin III, protein C and S have been described, all predisposing to thrombotic events. Alterations of the fibrinolytic system can also be associated with thromboembolisms. In particular, abnormalities of plasminogen, tissue plasminogen activator release and elevated tissue plasminogen activator inhibitor levels seem to be associated with thromboses. Conceivably also factor XIIa (Hageman factor) and prekallikrein deficiencies, when associated with thrombosis, exert their mechanism through the fibrinolytic system. Finally, about 50% of patients with lupus anticoagulant seem to suffer from thromboembolic disorders. The pathophysiology of this particular association is not known with certainty. Undoubtedly, there will be more disturbances discovered in the hemostasis system that are associated with increased intravascular fibrin formation. The understanding of these derailments is at this time only in its earliest stages of development.
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PMID:Pathophysiology of thrombophilic states. 246 10

In a family of four the whole spectrum of antiphospholipid and associated antibodies was present but without evidence of connective tissue disease. All four members had anticardiolipin antibodies; two had a confirmed lupus anticoagulant. Thrombocytopenia was severe in one and associated with a high titre of antiplatelet antibody, while another member was found to have a positive antiglobulin test. One member also had a low protein C concentration while two had decreased concentration of protein S. Factors that predispose to these antibodies may be environmental as well as genetic. In view of the well known association of spontaneous thrombotic events with some of these antibodies the prognosis for the family members must be guarded.
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PMID:Familial occurrence of the antiphospholipid syndrome. 211 Jan 95

Lupus anticoagulant (LA), an antibody against anionic phospholipid with anticoagulant laboratory manifestations, is paradoxically associated with a high incidence of thrombosis. In the present study we analyzed the phospholipid- and platelet-dependent degradation of factor Va following clotting in plasma from 15 consecutive patients with LA to provide evidence for a distinct procoagulant effect of the antibody. After clotting with 25 micrograms phospholipid/mL, all samples containing LA showed markedly decreased rates of factor Va degradation (k = 0.01 to 0.14 min-1 v 0.27 to 0.35 min-1 in controls). Also with higher phospholipid concentrations (up to 100 micrograms/mL), as well as in the presence of platelets (5 to 33 x 10(7)/mL), significantly less of the procoagulant activity disappeared per unit of time in samples with LA than in controls. Plasma with LA was to a variable extent capable of decreasing or abolishing factor Va inhibition in normal plasma. Most importantly, exogenous activated protein C failed to correct the ineffective factor Va destruction despite adequate protein S levels. These data suggest that LA prevents the formation of the complex essential for rapid proteolysis of factor Va both on phospholipid and on the platelet membrane, thereby compromising the catalytic function of activated protein C. Our findings offer a new opportunity for a more comprehensive evaluation of patients with antiphospholipid antibody in defining the pathogenesis of thrombosis in this clinical condition.
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PMID:Impaired catalytic function of activated protein C: a new in vitro manifestation of lupus anticoagulant. 250 95

Lupus-like anticoagulants (LLA), lupus anticoagulant and/or anticardiolipin antibody, are increasingly recognized in association with venous and arterial thrombotic events. We recently reviewed our experience with patients undergoing revascularization for lower-limb ischemia who were found to have LLA. Nine patients had LLA based on a prolongation of the partial thromboplastin time or by anticardiolipin assay by an enzyme-linked immunosorbent assay system. The ages of the patients ranged from 23 to 57 years. There were seven (78%) men, six (67%) blacks, two (22%) diabetic patients, and three (33%) hypertensive patients. One patient had systemic lupus erythematosus. All patients except one were cigarette smokers. Four patients had concurrent regulatory protein abnormalities: three protein C deficiencies, one protein S deficiency, and one plasminogen deficiency. The nine patients had 10 lower-extremity arterial reconstructions with two postoperative failures within 30 days. Patients were anticoagulated with heparin or aspirin after all but one operation. Patients at risk were identified on the basis of age (less than 51 years), unexplained early graft thrombosis, or history of venous or arterial thrombotic events. This group of patients is believed to be at risk for early postoperative thrombosis. Postoperative anticoagulation after revascularization for patients with LLA may be beneficial.
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PMID:Lupus-like anticoagulants and lower extremity arterial occlusive disease. 250 7

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

Since most patients with thrombophilia in Israel are referred for diagnosis to our center, it was possible to estimate the relative frequency of the hereditary disorders leading to thrombophilia. 107 unrelated patients were evaluated over 4 years. Diagnoses were established in 23 patients (21.5%) while in 84 (78.5%) no abnormality was detected. Antithrombin III deficiency was found in 8 patients (7.5%), dominant protein C deficiency in 6 (5.6%), recessive homozygous protein C deficiency in 1, protein S deficiency in 3 (2.8%) and dysfibrinogenemia in 1. Four additional patients (3.7%) had a lupus anticoagulant. The frequency of deep vein thrombosis and pulmonary embolism was similar in patients with and without a definite diagnosis. Thrombosis of visceral or cerebral vessels and a positive family history were more frequent among patients in whom a definite diagnosis was made. In both groups there was a substantial lag between the time of presentation of the first thrombotic episode and the time of evaluation. Since the number of referred patients with thrombophilia has gradually increased over the period of the study, it is at present impossible to establish the prevalence of the various hereditary disorders leading to thrombophilia in the population.
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PMID:The relative frequency of hereditary thrombotic disorders among 107 patients with thrombophilia in Israel. 252 86

Proteins C and S are two vitamin K-dependent plasma proteins that work in concert as a natural anticoagulant system. Activated protein C is the proteolytic component of the complex and protein S serves as an activated protein C binding protein that is essential for assembly of the anticoagulant complex on cell surfaces. The anticoagulant activity is expressed through the selective inactivation of Factors Va and VIIIa. Many patients deficient in proteins C and S have been described and have an associated thrombotic tendency, but not all heterozygous protein C and S deficient individuals experience thrombotic complications. Multiple mechanisms and/or drugs can lead to acquired deficiencies of these proteins: oral anticoagulation, liver disease, DIC and in the case of protein S, lupus erythematosus, nephrotic syndrome, pregnancy and certain hormones. The anticoagulant activity of protein C decreases rapidly after administration of warfarin (i.e., with a time course similar to Factor VII). This rapid decrease may lead to a transient imbalance and contribute to coumarin induced skin necrosis. Protein S antigen levels do not decrease as rapidly, but protein S functional levels are often low in patients with an acute thrombus. The discrepancy between antigen and function results from elevations in C4b-binding protein, which complexes reversibly with protein S. Unlike free protein S, the complex does not function in the anticoagulant pathway. The available information all suggest that deficiency of protein C and protein S should be considered a risk factor contributing to recurrent thrombotic disease and that the function of these proteins is altered by many common clinical conditions which have associated an increased risk of thrombosis.
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PMID:Anticoagulation proteins C and S. 295 34

Protein C (PC), a 62,000-molecular weight vitamin K-dependent serine protease zymogen, is a natural anticoagulant that occurs in plasma at 4 mg/L. Activated PC inactivates clotting factors V and VIII and is also profibrinolytic. Activated PC is enhanced in its anticoagulant activity by protein S (PS), another vitamin K-dependent protein. Protein S is found in platelets and endothelial cells as well as in plasma. Inherited PC deficiency and PS deficiency have been associated with venous thrombosis. Both heterozygous PC and PS deficiency appear to be inherited in an autosomal dominant manner in some families. Homozygous PC deficiency presents as neonatal purpura fulminans and results in massive venous thrombosis of the skin and other organs within the first few days of life. Symptomatic heterozygous PC deficiency and PS deficiency have been treated with oral anticoagulants, successfully minimizing recurrence of thrombosis. Coumarin-induced skin necrosis, a rare complication of oral anticoagulant therapy usually seen within three to five days of initiation of therapy, has also been associated with heterozygous PC deficiency. The short half-life of PC (six to eight hours) compared with most of the vitamin K-dependent clotting factors (greater than 30 hours) is the probable reason for this paradoxical response to oral anticoagulants in some PC-deficient patients, since a transient imbalance of procoagulant and anticoagulant factors may exist during initiation of oral anticoagulant therapy. Acquired deficiency of the PC pathway occurs in disseminated intravascular coagulation and possibly other diseases such as those associated with a lupus anticoagulant.
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PMID:Coumarin necrosis, neonatal purpura fulminans, and protein C deficiency. 296 8

Plasma samples from nineteen patients with well characterized lupus anticoagulants (LA) were evaluated using a series of test systems. An ELISA was used to determine if the plasmas contained antiphospholipid antibodies (APA); fifteen of nineteen LA plasmas contained APA, with five exhibiting IgG only, two exhibiting IgM, and eight plasmas containing both IgG and IgM. Anti-phosphatidyl serine (PS) was the predominant IgG specificity and all IgM APA-containing plasmas reacted with phosphatidyl inositol (PI). An ELISA was developed to determine if LA plasmas contained immunoglobulin which would associate with cultured human umbilical cord vein-derived endothelial cells (HUV); ten of nineteen plasmas contained endothelium associated immunoglobulin (EAI). There was significant concordance between the occurrence of EAI and IgM anti-PI. The occurrence of EAI or APA, either singly or in combination, did not correlate with a past history of thrombosis. Patient plasmas were incubated with HUV and examined for effects on HUV prostacyclin (PGI2) secretion; six plasmas significantly stimulated PGI2 secretion and one plasma was inhibitory. Finally, plasma levels of free and total antigenic protein S were determined by EID. Five plasmas contained significantly reduced levels of free antigenic protein S, and total antigenic protein S was reduced in ten plasmas. Patient histories were examined for evidence of thrombotic episodes; six patients had a history of either arterial or venous thrombosis, with five of these six patients having drug-induced LA. Thus, unlike previous studies, drug-induced LA were associated with thrombosis.
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PMID:Evaluation of lupus anticoagulants: antiphospholipid antibodies, endothelium associated immunoglobulin, endothelial prostacyclin secretion, and antigenic protein S levels. 297 88


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