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)

We have attempted to establish a systematic pathogenetic analysis of thrombophilia by including assays of antithrombin III(AT III), protein C(PC), protein S(PS), fibrinogen, plasminogen and heparin cofactor II by both functional and immunological methods as well as detecting lupus anticoagulants. Such a comprehensive scheme was instrumental in systematically identifying and confirming the pathogenesis of 164 cases which otherwise would have escaped detection since 1994 in our laboratory (Kyushu University Hospital). The analysis was conducted on 485 consecutive patients with venous thrombosis, arterial thrombosis and disorders in which small vessel thrombosis were implicated. Hundred and sixty four patients, (40% of the examined patients), were found to have low activities of PS, PC, ATIII etc. Among them, seventy five patients(46%) had low PS activity, and twenty nine(18%) had low PC activity. Genetic analyses performed on specimens with low PS/PC activities resulted in the confirmation of 24 genetic abnormalities. Such genetic abnormalities, however, does not solely lead to the pathogenesis of thromboses. We have found that some genetic polymorphisms, such as PS Tokushima, factor XII 46C allele, were also additional risk factors for thromboses.
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PMID:[Genetic polymorphism and risk of thromboses]. 1130 10

Forty female patients with either primary anti-phospholipid syndrome (n = 26) or systemic lupus erythematosus (anti-phospholipid syndrome positive) (n = 14) were investigated for levels of factor XII, the presence of lupus anticoagulant and antibodies to cardiolipin, beta 2-glycoprotein I and factor XII. Twenty-one patients had a history of recurrent fetal loss (> 2, mean = 2.6). Lupus anticoagulant positivity showed a weak association with recurrent fetal loss (odds ratio = 1.1). While there was no association between the presence of antibodies to cardiolipin or beta 2-glycoprotein I with recurrent fetal loss, antibodies to factor XII showed a strong and statistically significant association (odds ratio = 5.4, P = 0.025).
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PMID:Antibodies to factor XII and recurrent fetal loss in patients with the anti-phospholipid syndrome. 1138 Apr 30

Hereditary plasma prekallikrein (PK) deficiency was diagnosed in a 71-year-old man with an 8-year history of osteomyelofibrosis. PK deficiency was suspected in view of a severely prolonged activated partial thromboplastin time (aPTT) that nearly normalized following prolonged preincubation (10 min) of patient plasma with kaolin-inosithin reagent. Hereditary PK deficiency was demonstrated by very low PK values in the propositus (PK clotting activity 5%, PK amidolytic activity 5%, PK antigen 2% of normal plasma, respectively) and half normal PK values in his children. Normalization of a severely increased aPTT (>120 s) after prolonged preincubation with aPTT reagent occurred in plasma deficient in PK but not in plasma deficient in factor XII (FXII), high-molecular-weight kininogen (HK), factor XI (FXI), factor IX, factor VIII, Passovoy trait plasma or plasma containing lupus anticoagulant. Autoactivation of FXII in PK-deficient plasma in the presence of kaolin paralleled the normalization of aPTT. Addition of OT-2, a monoclonal antibody inhibiting activated FXII, prevented the normalization of aPTT. We conclude that the normalization of a severely prolonged aPTT upon increased preincubation time (PIT), characteristic of PK deficiency, is due to FXII autoactivation.
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PMID:Prekallikrein deficiency: the characteristic normalization of the severely prolonged aPTT following increased preincubation time is due to autoactivation of factor XII. 1209 Oct 43

Although rheumatological diagnosis often includes an assessment of antiphospholipid (aPL) antibodies, the significance of other prothrombotic factors has not been established in thrombotic patients who are not afflicted with either arteriosclerosis or vasculitis syndrome. We have observed both the presence of antiphospholipid antibodies and a reduction of factor XII in such patients. Our results identified both lupus anticoagulant-positive (50%) and anticardiolipin antibody-positive (58%) patients. In addition, 83% of patients showed factor XII antigen level reduction. Furthermore, 70% of aPL-positive thrombotic patients showed factor XII antigen level reduction. Only two cases had antiphospholipid antibody alone, and 4/12 showed just factor XII antigen reduction. Recently, it has been reported that the presence of antiphospholipid antibodies induces factor XII reduction, and that anti-factor XII autoantibody can be detected in thrombotic patients. However, our results indicate that there are smaller factor XII reductions in non-thrombotic controls who are positive for antiphospholipid antibodies. Furthermore, anti-factor XII autoantibody was not detected in patients with decreased factor XII levels. Kindred research suggested that in two patients there was a genetic component to factor XII reduction. We concluded that the presence of both antiphospholipid antibodies and reduced serum factor XII was observed in most thrombotic patients from our rheumatology clinic. It is therefore possible to consider that the coexistence of these prothrombotic factors can contribute to the onset of thrombosis.
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PMID:Reduction of factor XII in antiphospholipid antibody-positive patients with thrombotic events in the rheumatology clinic. 1260 17

Antibodies to factor XII (FXIIabs) have been demonstrated in some patients with the anti-phospholipid syndrome (APS). The presence of these antibodies were shown to lead to statistically significantly reduced levels of FXII (p = 0.02). In an extension to this study forty female patients with either primary APS (n = 26) or systemic lupus erythematosus (APS positive) (n = 14) were investigated for levels of factor XII, the presence of lupus anticoagulant and antibodies to cardiolipin, beta 2-glycoprotein I and factor XII. Twenty one of the forty patients had a history of foetal loss (> 2, mean = 2.6). Lupus anticoagulant positivity showed a weak association with foetal loss (odds ratio = 1.1). While there was no association between the presence of antibodies to cardiolipin or beta 2-glycoprotein I with foetal loss, antibodies to factor XII showed a strong and statistically significant association (odds ratio = 5.4, p = 0.025).
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PMID:Antibodies to factor XII: a possible predictive marker for recurrent foetal loss. 1263 2

Disturbances of the embryo-maternal interaction, i.e. impaired implantation, are seen in only a minor fraction of couples. These malfunctions become evident as recurrent spontaneous abortions (RSA), or repetitive implantation failure (RIF) in cases with IVF or ICSI procedures. The antiphospholipid syndrome (APL) is the only consensus-defined syndrome associated with RSA (anticardiolipin antibodies and/or lupus anticoagulant plus clinical symptoms). Since antiphospholipid antibodies directly interfere with hemostasis (increased coagulation), heparin is an established treatment option in these cases resulting in unequivocal benefits. There is no defined antibody syndrome in RIF even if it may be assumed that it exists. Conclusive evidence for a benefit of heparin (and aspirin) in this situation is lacking as well. However, the majority of investigations including our own experience indicate that anticoagulation may be useful. Besides the extensively studied anticardiolipin antibodies, other - by far less thoroughly investigated - antiphospholid antibodies have been described. So far it is unclear if heparin may exert positive effects in women carrying these antibodies. Autoreactive immune processes may also become apparent by the emergence of further antibodies, such as antinuclear (ANA), thyreoglobulin (TGA) and thyreoperoxidase antibodies (TPO) etc. However, there is no established definition of a syndrome associated with these antibodies, TGA and TPO probably being the most relevant. - Most studies in this area including our own experience indicate that heparin may be a useful. The detection or autoantibodies per se is probably not of pathophysiological relevance if there is no ongoing pathological activation of the immune system. However, an acute autoimmune response associated with irregular antibodies may represent the pathophysiological basis of a reproductive autoimmune failure syndrome. In these cases, immune-equilibrating interventions appear to be more appropriate than heparin therapy. - Coagulation disorders, namely thrombophilia, are a frequent cause of RSA and probably RIF as well, the most relevant being antithrombin deficiency, Factor V Leiden and prothrombin mutations. Deficiencies of protein S, protein C and factor XII and XIII are of minor importance. There is a varying degree of evidence for a benefit of heparin/aspirin in these syndromes. Heparin not only reduces the abortion rate but also lowers the risk for developmental retardation, premature birth and preeclampsia. - The effects of heparin are not restricted to anticoagulation. It is directly or indirectly (e.g. via heparan sulfate proteoglycans or heparin-binding EGF) involved in the adhesion of the blastocyst to the endometrial epithelium and the subsequent invasion. Actually, prolonged heparin treatment (14 days) resulted in an increased pregnancy rate in our patient population. Shorter courses of heparin where not effective.
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PMID:Effectivity of heparin in assisted reproduction. 1521 Apr 1

Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition, there was a reduction of factor XII during the treatment. It is possible to assume in the TC group and, to a lesser extent, also in the NTC group that endothelial cells liberate PAI-1 in the vascular lumen, which causes hypofibrinolysis. In addition, an excess of factor VIII is activated by endothelial dysfunction with subsequent activation of the coagulation cascade as shown by increased F1+2 and fibrinogen. ACA-IgM, in turn, is capable of interfering with the system of protein C, a potent anticoagulant factor that inactivates cofactors Va and VIIIa. They also induce the expression of procoagulant factors on the surface of the endothelial cells. In conclusion, the hypercoagulable state caused by alterations of coagulation and fibrinolytic factors is a cause of vascular access dysfunction and thrombosis of other vessels.
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PMID:Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk factors for thrombosis in hemodialysis patients. 1549 Apr 19

Coagulation screening using prothrombin time (PT) and activated partial thromboplastin time (APTT) is widely used. We performed an audit of coagulation screening in an Irish teaching hospital. We analysed PT and/or APTT results received during normal working hours during a 1-week period in our hospital. Abnormal results due to anticoagulants were excluded from further study. In samples with PT longer than 15.5 s and/or APTT longer than 42 s, we proceeded to 1: 1 mixing studies if the PT was prolonged and 1: 1 mixing studies, factor XII assay and lupus screen if the APTT was prolonged. We also obtained referral source for all samples and clinical details for abnormal samples. Six hundred and seventy-one coagulation requests were received during the study period. Three hundred and eighteen of 671 (47.4%) coagulation requests were for monitoring of anticoagulation. Three hundred and fifty-three of 671 (52.6%) requests were for coagulation screening rather than anticoagulant monitoring. In the coagulation screens received, PT was prolonged in 19 of 353 (5.4%). PT was longer than 20 s in four of 353 cases (1.1%). APTT was prolonged in 19 of 353 (5.4%). APTT was longer than 50 s in four of 353 (1.1%). No patients with abnormal PT or APTT had any bleeding sequelae during the study period. Unregulated coagulation screening has a low yield of abnormal results; the majority of these abnormal results show mild prolongation of PT or APTT with no evidence that they are associated with an increased bleeding risk.
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PMID:An assessment of the utility of unselected coagulation screening in general hospital practice. 2124 44

The pathogenesis of venous and arterial thrombosis is complex and multifaceted, entailing a multitude of risk factors, which only marginally overlap between the two vessels districts. Along with conventional and universally recognized risk factors, thrombosis might also develop as a consequence of unusual, atypical, unsuspected and even paradoxical conditions. Although the term "paradoxical embolism" is typically used to identify an embolization process that originates from the low-pressure venous system and may generate ischemic stroke or peripheral arterial occlusion through a cardiac or pulmonary shunt, there are additional clinical circumstances whereby the risk of thrombosis is surprising, unpredicted or even neglected. In this article we thereby analyze the prevalence, as well as the pathogenesis, of thrombosis associated with apparently paradoxical triggers such as during factor replacement therapy in haemophiliacs or in patients with von Willebrand disease; in patients with inherited clotting factor deficiencies especially involving factor XII, factor VII, fibrinogen; or in those with a prolonged activated partial thromboplastin time for the presence of lupus anticoagulant.
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PMID:Paradoxical thrombosis part 1: factor replacement therapy, inherited clotting factor deficiencies and prolonged APTT. 2264 22

The first case report describes an extremely prolonged activated partial thromboplastin time (APTT) in a patient with no history of increased bleeding tendency. Heparin use was excluded. The APTT mixing study combined with the medical history suggests a deficiency in one of the non-essential coagulation factors. This was confirmed by factor XII activity of <1%. The second case report describes a prolonged APTT in a patient with no history of increased bleeding tendency. The negative bleeding tendency in combination with a failure of the mixing study to correct the coagulation assay results suggests a factor inhibitor, most probably lupus anticoagulant. Indeed, the lupus anticoagulant was positive and the anti-cardiolipin antibody titre was also positive. Aberrations in the process of haemostasis can be efficiently screened using a platelet count, an APTT, a PT and a thorough physical examination combined with a thorough medical history taking. Common causes of prolonged PT and/or APTT are the use of oral anticoagulants or heparin, vitamin K deficiency and liver disease. Other causes include coagulation factor deficiencies, coagulation factor inhibitors and diffuse intravascular coagulation.
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PMID:[Investigation of coagulation time: PT and APTT]. 2291 38


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