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 combined presence of anti-phospholipid (PL) Ab, including lupus anticoagulants (LAC) and/or anticardiolipin Ab (aCL), and thrombosis is recognized as the antiphospholipid syndrome (APS). LAC are detected as an inhibitory effect on PL-restricted in vitro blood coagulation tests, and are comprised mainly of Ab against beta(2) glycoprotein I and prothrombin (PT). Recently, anti-PT Ab (aPT) were found to be associated with thrombosis by some investigators, although this is not confirmed by others. Considering that aPT are heterogeneous in patients and that PT is converted into thrombin, we hypothesize that certain aPT in patients may bind to thrombin, and that some of such anti-thrombin Ab may interfere with thrombin-antithrombin (AT) interaction and thus reduce the AT inactivation of thrombin. To test this hypothesis, we searched for anti-thrombin Ab in APS patients and then studied those found for their effects on the AT inactivation of thrombin. The results revealed that most, but not all, aPT-positive patient plasma samples contained anti-thrombin Ab. To study the functional significance of these Ab, we identified six patient-derived mAb that bound to both PT and thrombin. Of these mAb, three could reduce the AT inactivation of thrombin, whereas others had minimal effect. These findings indicate that some aPT in patients react with thrombin, and that some of such anti-thrombin Ab could inhibit feedback regulation of thrombin. Because the latter anti-thrombin Ab are likely to promote clotting, it will be important to develop specific assays for such Ab and study their roles in thrombosis in APS patients.
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PMID:Identification of anti-thrombin antibodies in the antiphospholipid syndrome that interfere with the inactivation of thrombin by antithrombin. 1173 42

Chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be an extreme variant of pulmonary thromboembolism. The underlying mechanisms for the failure of thrombus resolution are still unclear. In looking for inherited thrombophilia, an association with a lupus anticoagulant has been described repeatedly, and single cases of anticoagulant deficiencies (ie, antithrombin [AT], protein C, and protein S) have been reported. We describe a young patient with type I AT deficiency, the heterozygous prothrombin G20210A mutation, and unilateral chronic thromboembolic pulmonary disease presenting after a single thrombotic event. Pulmonary vascular patency was restored successfully by surgical pulmonary thromboendarterectomy. This case is unique because unilateral CTEPH is extremely uncommon, and it illustrates the severe clinical sequelae of the cosegregation of inherited thrombophilic defects.
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PMID:Unilateral chronic thromboembolic pulmonary disease associated with combined inherited thrombophilia. 1179 66

Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombosis and recurrent miscarriage. We assessed levels of coagulation activation markers and aPL during normal pregnancy and in women with the antiphospholipid syndrome (aPS). Fluctuations in aPL levels were observed in all patients with aPS. No particular pattern of antibody positivity, or fluctuation in aPL level, was associated with poor pregnancy outcome. A significant increase was observed in levels of factor Xlla (FXIIa; P < 0.001), factor VIIa (FVIIa, P < 0.001), thrombin antithrombin complexes (TAT; P < 0.001), prothrombin fragment F1.2 (F1.2; P < 0.001) and D-dimer (DD; P < 0.05) during normal pregnancy. Factor VIIa, TAT, F1.2 and DD increased significantly before 20 weeks gestation, while a statistically significant increase in FXIIa levels was first detected between weeks 20 and 30 of gestation. In pregnant women with aPS, increases in FXIIa were similar to those in normal pregnancy, but increased FVIIa levels were not observed until after 30 weeks gestation. Similar to normal pregnancy, increased levels of TAT and F1.2 were detected in aPS pregnancies before 20 weeks gestation, but increased DD were not observed until after week 20. Surprisingly, women with aPS receiving low molecular weight heparin prophylaxis had significantly higher (P = 0.02) levels of TAT (median 8.6; interquartile range (IQR) 6.5-20.8) between weeks 20 and 30 of gestation compared to the normal pregnant population (median 5.9; IQR 4.7-7.9), thus indicating increased thrombin generation in women with aPS in mid-pregnancy.
Lupus 2002
PMID:Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal and heparin-treated antiphospholipid syndrome pregnancies. 1189 13

Hereditary prothrombotic states of clinical importance include factor V Leiden, the prothrombin 20210A mutation, deficiencies of protein C, protein S, or antithrombin, sickle cell disease, and hyperhomocysteinemia. Major acquired prothrombotic states include cancer, myeloproliferative disorders, the antiphospholipid syndrome, and heparin-induced thrombocytopenia. Because most of the hereditary prothrombic states are not established risk factors for arterial thrombosis, routine laboratory testing in most patients with ischemic stroke should be limited to complete blood count, lupus anticoagulant, anticardiolipin antibodies, and plasma total homocysteine. Additional testing for factor V Leiden, prothrombin 20210A, antithrombin, protein C, and protein S may be indicated for patients under the age of 50 or those with paradoxical cerebral embolism. The treatment of acute ischemic stroke in patients with prothrombotic states is similar to that in patients without an identifiable prothrombotic condition, and may include antiplatelet agents, anticoagulants, or thrombolytic therapy in patients who otherwise meet eligibility criteria. The potential benefit of chronic anticoagulation therapy for the primary or secondary prevention of stroke in patients with prothrombotic states has not been addressed in controlled clinical trials. Specific therapeutic approaches for the prevention of stroke are established for patients with sickle cell disease, myeloproliferative disorders, and heparin-induced thrombocytopenia, and are under investigation for hyperhomocysteinemia and the antiphospholipid syndrome.
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PMID:Prothrombotic States that Predispose to Stroke. 1235 68

Inherited and acquired thrombophilias have been associated with recurrent pregnancy loss. Over recent years our ability to detect protein and genetic abnormalities responsible for thrombotic tendency has improved. We are now left with the task of deciphering which of these thrombophilias carries an increased risk for recurrent pregnancy loss. Acquired thrombophilias including lupus anticoagulant and anticardiolipin antibodies have been linked to recurrent pregnancy loss. However the evidence for the role of inherited thrombophilias such as, heterozygosity for the factor V Leiden, prothrombin G20210A mutation, the methylenetetrahydrofolate reductase (C677T MTHFR) mutation, as well as deficiencies of antithrombin, protein C and protein S is less clear. The methods for diagnosis and the evidence for their associations are discussed in this paper. Treatment modalities independent of those needed to prevent thrombotic events in pregnancy have generally not been studied. Given the present available data, there is insufficient evidence to include inherited thrombophilias in the initial evaluation of RPL. It is important to look for other, more common, causes of recurrent miscarriage in the evaluation of these patients.
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PMID:Thrombophilias and recurrent miscarriage. 1236 98

Anti-beta -glycoprotein I antibody (abetaGPI) has been recognized in raising the risk of cerebral ischemia in patients with antiphospholipid antibody syndrome (APS), especially by protein C (PC) axis perturbation. Although a high potential is also seen in non-APS patients, the mechanism is substantially unknown. In the present study, we examined the effect of abetaGPI on PC and antithrombin-III (AT-III) activity in non-APS patients with non-cardiac cerebral ischemia (NCCI). A total of 111 NCCI patients and 30 healthy controls were enrolled. They were free of APS manifestation, and their anticardiolipin antibody and lupus anticoagulant tests were within normal range. There were 14.4% patients found to have an abnormal increase of blood abetaGPI. The PC, AT-III, albumin, aminotransferases, creatinine, prothrombin time and activated partial thromboplastin time did not differ between our patients and controls, or patients with or without increased abetaGPI. However, a marked decrease of the PC/AT-III ratio was found in patients with increased abetaGPI. The correlation between PC and AT-III activity was highly significant in patients with an increase of abetaGPI (P = 0.001), only marginal in controls (P = 0.042), and was insignificant in patients with a normal abetaGPI (P = 0.277). The abetaGPI did not correlate to PC or AT-III activity in either patients or controls. These findings suggest that high PC/AT-III coupling may relate to NCCI in non-APS patients associated with an increase of abetaGPI. This coupling effect seems not to be caused by abetaGPI directly.
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PMID:A perturbation of antithrombin-III and protein C coupling associates with an increase of anti-beta2-glycoprotein I antibody in non-antiphospholipid antibody syndrome cerebral ischemia. 1244 9

In order to analyze the incidence of thrombophilia in southern Taiwan, we studied the prevalence of antithrombin (AT), protein C (PC), and protein S (PS) deficiencies, the prevalence of factor V Leiden mutation, and the presence of acquired lupus anticoagulant (LA) and anticardiolipin antibody (ACA) in 56 patients < or =65 years old with deep venous thrombosis (DVT). Of 56 patients, 30 were male, 26 female, and the mean age of the patients was 43 years (18-65 years). None had factor V mutation or activated PC resistance; 21 patients (37.5%) showed abnormal results: 4 (7.1%) had AT deficiencies, 6 (10.7%) PC deficiencies, 6 (10.7%) PS deficiencies, 2 (3.6%) a combined PC and PS deficiency, and 3 (5.4%) LA and ACA. Only PC and PS deficiencies were significantly associated with increased risk for the development of thrombosis with an odds ratio of 4.2 (95% confidence interval: 1.2-15.0, P=0.018) and 8.1 (95% confidence interval: 1.6-40.6, P=0.003), respectively. We concluded that the prevalence of heritable thrombophilia (34.0%) in Taiwan is higher than that in Western countries, but that it is lower than previously reported in Hong Kong and Taiwan. We attribute this to selection bias.
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PMID:Incidence of thrombophilia detected in southern Taiwanese patients with venous thrombosis. 1260 91

The role of paradoxical embolism through patent foramen ovale as a mechanism of cryptogenic stroke is controversial. If a venous source of emboli is relevant, prothrombotic states should be associated with patent foramen ovale and cryptogenic stroke. We assessed the occurrence of several prothrombotic states (factor V Leiden, prothrombin G20210A, deficiencies in protein S, protein C and antithrombin, lupus anticoagulant, anticardiolipin antibodies, elevated factor VIII, resistance to activated protein C) and classical risk factors for venous thrombosis in 57 adult patients with cryptogenic stroke and patent foramen ovale and in 104 matched controls. Prothrombotic states [odds ratio (OR) 2.8; 95% confidence interval (CI), 1.2-6.5; P = 0.021], migraine with aura (OR 4.4; 95% CI 1.8-10.8; P = 0.001) and classical risk factors for venous thrombosis (OR 2.5; 95% CI 1.1-5.7; P = 0.037) were independent risk factors for cryptogenic stroke. In particular factor V Leiden or prothrombin G20210A associated with cryptogenic stroke (P = 0.022) whereas other coagulation abnormalities did not (P = 0.140). Among the patients with prothrombotic states, Valsalva manoeuvre was common at onset of stroke. Our results support the possibility of paradoxical embolism behind strokes in patients with patent foramen ovale.
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PMID:Factor V Leiden and prothrombin gene mutation may predispose to paradoxical embolism in subjects with patent foramen ovale. 1269 49

Arterial hypercoagulability can lead to cerebrovascular disease. Common causes of venous thromboembolism, including factor V Leiden, the prothrombin 20210 mutation, deficiencies of proteins C and S, and antithrombin deficiency are not likely to be associated with stroke. Rather, polymorphisms in fibrinogen, the factor XIII gene, and platelet glycoproteins are congenital abnormalities that have been associated with stroke. Similarly, the acquired conditions, lupus anticoagulants, and heparin-induced thrombocytopenia have a strong association with cerebrovascular disease. This article reviews arterial hypercoagulability as a cause of stroke in adults and identifies an appropriate hypercoagulability workup for patients with idiopathic stroke.
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PMID:Hypercoagulability as a cause of stroke in adults. 1291 52

The influence of anticoagulation components of hemostasis system and lupus anticoagulants (LA) upon the course of multiple sclerosis (MS) was studied. 57 patients with MS diagnosed according to McDonald's criteria (McDonald WI et al., 2001) were examined: 19 males and 38 females aged 16-62 (mean age 36.8 +/- 11.2 yrs) with 1-25 yrs history of MS (mean duration 8.1 +/- 5.7 yrs). 42 patients suffered from relapsing-remitting MS, 17 patients were affected by secondary progressive MS. The degree of neurological deficit was estimated in remission according to Expanded Disability Status Scale (EDSS), mean score was 3.8 +/- 1.7. The progression of MS was estimated as EDSS score per year ratio. In patients with relapsing-remitting MS the mean number of exacerbations per year was calculated. The following laboratory findings were evaluated: thrombin clotting time, antithrombin-III activity, plasminogen reserve by the level of streptokinase-induced euglobulin fibrinolysis, protein C activity, factor Va resistance to activated protein C, lupus anticoagulants (LA). It was revealed that LA could worsen relapsing-remitting MS: in LA-positive patients there were 1.41 +/- 0.69 exacerbations per year and progression score reached 0.82 +/- 0.30, whereas in LA-negative patients the figures were 0.74 +/- 0.58 (p < 0.001) and 0.48 +/- 0.33 (p < 0.01) respectively. All the patients showed decrease of protein C activity (p < 0.001) with no relation to LA activity or factor Va resistance to activated protein C. Normal level of plasminogen and antithrombin-III activity was supposed to be the marker of benign variant of MS. The course of MS was mild in patients with high antithrombin-III activity even if they were hypercoagulative--this suggests neuroprotective activity of antithrombin-III which may relate not only to its anticoagulation effect.
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PMID:[The role of hemostasis system in the pathogenesis and course of multiple sclerosis]. 1293 32


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