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)

Coagulation disorders usually confront the emergency physician as bleeding episodes or as abnormalities of laboratory tests. Bleeding has to be treated aggressively, while pathological coagulation tests should be related to a more differentiated diagnosis at first. The most common causes of acquired coagulation disorders are liver disease, vitamin K deficiency, and disseminated intravascular coagulation (DIC). More rarely, inhibitors, external factors such as drugs or extracorporeal circulation, or other diseases such as amyloidosis are present. Since localized hemorrhage is the most common bleeding source in liver disease, endoscopic and surgical therapeutic measures, respectively, are warranted. Careful and balanced substitution therapy according to laboratory findings should be initiated simultaneously and should consist of fresh frozen plasma (FFP), which contains all components of the coagulation system physiologically balanced. Prothrombin complex concentrates should be used in emergency situations only, keeping their potential hazards in mind. Adequate vitamin K substitution is indicated in liver disease as well as in coagulopathy due to vitamin K deficiency. Management of DIC primarily consists of aggressive treatment of the underlying disease. Substitution therapy is difficult and should be carefully monitored by the adequate laboratory tests. FFP is the adequate source of both procoagulants and inhibitors but may cause certain problems. Heparin therapy can be beneficial but is not recommended generally. Antithrombin III substitution cannot be assumed as established therapy so far. Inhibitors can lead to bleeding, but the most common inhibitor, lupus anticoagulant, rather predisposes to thrombosis. In bleeding patients with inhibitors against single clotting factors, treatment consists of adequate substitution before initiating the diagnostic workup.
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PMID:Management of acquired coagulation disorders in emergency and intensive-care medicine. 871 94

Heparin and heparan sulfate are related glycosaminoglycans which demonstrate high-affinity interactions with a number of proteins, including antithrombin III. The immunogenicity of heparin has been reported previously employing heparin-protein conjugates as immunogens and as antigens in solid-phase assays. Previous studies also demonstrate that anti-heparin antibodies play a role in autoimmune diseases including systemic lupus and anti-phospholipid syndrome and in patients who receive heparin for therapeutic purposes. In the current study, we investigated the expression of monoclonal anti-heparin antibodies in nonimmunized, autoimmune MRL/lpr/lpr++ mice employing a liquid-phase radioimmunoassay. The Kd of monoclonal IgG2b autoantibodies for heparin was approximately 10(-8)M. Anti-heparin antibodies were precipitating, and were not polyreactive. The IgG monoclonal antibodies described in this study represent an immunological instance of a specific, high-affinity heparin-protein interaction.
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PMID:Autoimmune MRL mice express high-affinity IgG2b monoclonal autoantibodies to heparin. 880 43

Repeated fetal loss presents a challenge for both patients and health care professionals. Antiphospholipid syndrome (APS) may account for as much as 10% to 48% of recurrent fetal loss. Suggested pathophysiologic mechanisms of APS in fetal loss include the action of autoantibodies, the lupus anticoagulant, and anticardiolipin antibodies on the endothelial cells, which may lead to platelet aggregation, thrombosis, placental infarcts, and subsequently reduced oxygenation to the fetus. This study explores fetal loss caused by APS, its pathophysiologic features, treatment, and nursing implications. Heparin therapy is presented as a method to prevent intrauterine growth retardation and fetal death. The educational and psychosocial needs of patients receiving this therapy and necessary patient follow-up and coordination of services are reviewed.
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PMID:Prevention of recurrent fetal loss caused by antiphospholipid syndrome. 881 26

Anticoagulant-induced skin reactions appear as allergic or necrotic responses to vitamin K antagonists or heparins. Cutaneous allergy has been reported with danaparoid sodium and flush reactions have been seen with hirudins. The pathogenesis of the reactions differs between drugs. Generally, they occur between days 3 to 10 after the start of treatment, but may also occur later. In patients experiencing necrosis with a vitamin K antagonist, concomitant protein C deficiency, protein S deficiency or lupus anticoagulant has been described, whereas the precise mechanism of the other reactions is unknown. In patients with allergic reactions to heparins, cutaneous tests may help to identify alternative anticoagulants. Such a test cannot be performed in patients with skin necrosis. In patients with heparin-induced skin reactions danaparoid sodium may be used after negative intracutaneous testing in some patients and a hirudin may be used without testing in all patients. Heparin-induced skin necrosis has been reported to be mediated by immunologic mechanisms and to be associated with a high frequency of heparin-induced thrombocytopenia type II. Surgical excision of the necrosis may be required. If further anticoagulation is indicated in any patient, extreme caution has to be taken when restarting oral anticoagulants. Because a large number of anticoagulants available today, safe treatment of all patients experiencing anticoagulant-induced skin reactions is feasible.
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PMID:Cutaneous reactions to anticoagulants. Recognition and management. 1170 6

Antiphospholipid antibodies (aPL) are autoantibodies that are associated with recurrent reproductive failure and thrombotic disease. There are two well-characterised aPL, lupus anticoagulant and anticardiolipin antibodies. aPL were originally thought to bind to negatively-charged phospholipids but it is now clear that the title aPL is a misnomer and that the antigens for these autoantibodies are actually phospholipid-binding proteins. Chief amongst these phospholipid-binding proteins are prothrombin and beta(2) glycoprotein I. This review concentrates on the role of beta(2) glycoprotein I in the reproductive failure caused by aPL. Exactly how aPL cause reproductive failure remains unknown but there is emerging evidence that the antibodies may have several different adverse effects on trophoblasts. There is also evidence questioning the traditional hypothesis that fetal demise is secondary to thrombosis of the utero-placental circulation. Heparin is commonly used to treat pregnant women with aPL but if these antibodies do not cause fetal demise primarily by a thrombotic mechanism a question must be raised over the role of heparin. However, heparin binds to many proteins including beta(2) glycoprotein I and it is possible that the reported beneficial effects of heparin in aPL-affected pregnancies may be due to the ability of heparin to prevent the interaction of aPL and beta(2) glycoprotein I.
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PMID:Antiphospholipid antibodies: biological basis and prospects for treatment. 1238 42

Although significant bone mass loss is rare during pregnancy, some situations may increase the risk of symptomatic osteoporosis. Heparin may be necessary for a number of pregnant women with systemic lupus erythematosus and antiphospholipid syndrome. The osteopenic effect of heparin is low even during pregnancy, and recent data point to a more favourable profile of low-molecular-weight heparins as compared with unfractionated heparin. Lactation results in a significant increase of calcium demands and may be a higher risk period for women at risk for osteoporosis.
Lupus 2002
PMID:Heparin and osteoporosis during pregnancy: 2002 update. 1241 68

Heparin has been conventionally used as an anticoagulant for medical and surgical indications. Because factor Xa is an essential component of the prothrombinase complex and leads to the generation of thrombin, its inhibition has become a focus of newer antithrombotic drug development. The in vitro anticoagulant profile of DX-9065a, a synthetic direct factor Xa inhibitor, was studied using activated clotting time assay, thrombelastography, and global clotting tests, such as prothrombin time (PT), activated partial thromboplastin time (aPTT), diluted aPTT, Heptest, Heptest-HI, dilute Russell's viper venom time (dRVVT), thrombin time, ecarin clotting time, and amidolytic anti-Xa assay. In addition, the effect of DX-9065a on platelet aggregation and inhibition of thrombin generation markers (FPA, F1+2, and TAT) were studied. The pharmacokinetic and pharmacodynamic profiles of DX-9065a were also studied in a non-human primate (Macaca mulatta) model. DX-9065a produced a concentration-dependent increase in the Hemochron celite ACT and HemoTec ACT. Clotting times of 538 +/- 19 and 401 +/- 12, respectively, were reached at a concentration of 25 microg/mL signifying that DX-9065a may be useful in interventional cardiological procedures. DX-9065a prolonged the r-time on thrombelastography. DX-9065a did not show any effect on adenosine diphosphate (ADP)-, collagen-, epinephrine-, and arachidonic acid-induced platelet aggregation at concentrations up to 10 microgram/mL. DX-9065a exhibited a concentration-dependent prolongation of the PT, aPTT, diluted aPTT, Heptest, dRVVT, and reached the clotting times of 51.6, 132, 193, 47.9, 129.9 seconds, respectively, at a final concentration of 12.5 microgram/mL; compared to a control value of 10.6, 30.2, 41.9, 14, 32.2 seconds, respectively. DX-9065a did not affect the ecarin clotting time and thrombin time at concentrations up to 12.5 microgram/mL. Because DX-9065a prolonged the dRVVT, this may impact diagnostic screening of patients with systemic lupus erythematosus.
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PMID:Global anticoagulant effects of a synthetic anti-factor Xa inhibitor (DX-9065a): implications for interventional use. 1264 18

The most compelling association between pregnancy loss and autoimmune phenomena has been with the presence of antiphospholipid antibodies (APA)--lupus anticoagulant and anticardiolipin antibody. The 'antiphospholipid antibody syndrome' has been described in women with a history of recurrent pregnancy loss or thrombosis with positive APA or lupus anticoagulant on two occasions. Although several treatments have been advocated, heparin and aspirin treatment is emerging as the treatment of choice for the APA syndrome associated with recurrent pregnancy loss. The rationale for prescribing aspirin in cases of recurrent reproductive failure associated with APA seropositivity is that aspirin may counter APA-mediated hypercoagulability in the choriodecidual space, a situation which if left unaddressed would traumatize the trophoblast and compromise feto-maternal exchange. Heparin on the other hand, through preventing APA from interfering with syncytialization of the early cytotrophoblast and by countering APA interference with phospholipid-decidual reactions that are vital to early implantation, might potentially promote both early implantation and subsequent placentation.
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PMID:Low molecular weight heparin in immunological recurrent abortion--the incredible cure. 1268 92

Venous thromboembolism is a common and potentially fatal disease. If properly used, anticoagulation therapy is effective in preventing recurrence of venous thromboembolism and in improving survival. Symptomatic patients with an objective diagnosis of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) should receive immediate systemic heparin anticoagulation at dosages sufficient to rapidly prolong the activated partial thromboplastin time into the laboratory-specific therapeutic range; this range corresponds to a plasma heparin concentration of 0.2 to 0.4 IU/ml (as measured by protamine sulfate titration), or 0.3 to 0.7 anti-Xa IU/ml. An oral vitamin K antagonist (e.g. warfarin) should be started within 24 hours after starting heparin; the starting dose should be the estimated patient-specific daily dose with no loading dose. Heparin and warfarin anticoagulation should be overlapped for at least 4 to 5 days and until the international normalized ratio (INR) is within the therapeutic range (2.0 to 3.0) on 2 measurements made at least 24 hours apart. The duration of warfarin anticoagulation should be individualized based on the respective risks of venous thromboembolism recurrence and anticoagulant-related bleeding. In general, warfarin should be continued for at least 3 months, and longer for patients with recurrent or idiopathic venous thromboembolism, malignant neoplasm, neurologic disease with extremity paresis, obesity, or laboratory evidence of a lupus anticoagulant/anticardiolipin antibody, homozygous carrier or combined heterozygous carrier for the factor V R506Q (Leiden) and prothrombin G20210A mutations, and possibly deficiency of either antithrombin, protein C, or protein S. Low molecular weight heparin (LMWH) is effective and well tolerated as acute therapy for patients with DVT or stable PE, and does not require laboratory monitoring or dose adjustment. Outpatient LMWH therapy is also well tolerated and cost effective for most patients with DVT, and possibly for selected patients with PE.
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PMID:Current management of acute symptomatic deep vein thrombosis. 1472 51

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


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