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)

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

We compared 1-stage clot-based, chromogenic, and immunoassay methods for measuring factor VIII in plasma with a focus on the measurement of elevated levels of factor VIII. The chromogenic assay showed the best interassay imprecision for factor VIII levels near 150 IU/dL. The best correlation was between the 1-stage clot-based and chromogenic factor VIII assays (r2 = 0.934), and the lowest correlation was between the 1-stage clot-based and antigenic factor VIII assays (r2 = 0.821). The presence of heparin, low-molecular-weight heparin, lepirudin, or lupus inhibitors in the sample resulted in major interference in the 1-stage clot-based assay but not the chromogenic or antigenic factor VIII assays. Overall, the chromogenic factor VIII activity assay was the optimal method, showing good precision, the best overall correlation with other assays, and no interference from heparin, low-molecular-weight heparin, lepirudin, or lupus inhibitors.
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PMID:Comparison of three methods for measuring factor VIII levels in plasma. 1286 70

To better understand potentially reversible causes of idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, and an apparent association of IIH with polycystic-ovary syndrome (PCOS), we assessed associations of IIH with coagulation disorders and with PCOS in 38 women with well-documented IIH. Fifteen women were found to have PCOS; 14 of them were obese, with a body-mass index (BMI) greater than 30 kg/m(2), and 10 were extremely obese (BMI > or = 40). Factor VIII concentration was high (>150%) in 9 of 38 (24%) IIH cases, compared with 0 of 40 healthy adults controls (P(f) =.0009). Familial aggregation of high concentrations of factor VIII, associated with thrombophilia, was documented in all 5 of the 9 high-level factor VIII probands' families who were sampled. Activated partial thromboplastin time (APTT) was prolonged (> or =31.5 seconds) in 10 of 38 (26%) IIH cases, compared with 1 of 32 (3%) controls (P(f) =.009) and, in 4 of these cases, was accompanied by the lupus anticoagulant. Plasminogen activator inhibitor activity (PAI-Fx) was high (>21.1 U/mL) in 9 of 38 cases (24%), compared with 1 of 40 controls (3%) (P(f) =.006). Lipoprotein A was high (> or =35 mg/dL) in 13 of 37 cases (35%), compared with 5 of 40 controls (13%) (P(f) =.03). IIH cases did not differ (P >.05) from controls for homocysteine, proteins C and S, free S, antithrombin III, ACLAs IgG and IgM, dilute Russell's viper venom time, Factor XI, factor V Leiden G1691A, G20210A prothrombin, C677T MTHFR, plasminogen activator inhibitor 4G/5G, or platelet glycoprotein PL A1A2 mutations. Exogenous estrogens (n = 23), clomiphene (n = 1), or pregnancy (n = 4) accompanied the first appearance of IIH in 28 women. PCOS and coagulation disorders, often augmented by exogenous estrogens or pregnancy, are associated with IIH.
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PMID:Idiopathic intracranial hypertension: associations with coagulation disorders and polycystic-ovary syndrome. 1287 84

Acquired haemophilia or factor VIII (FVIII) deficiency, caused by FVIII inhibitor antibodies, is a very rare condition that commonly results in severe haemorrhagic complications. We report a case of acquired haemophilia presenting with a left calfnontraumatic haematoma. The patient was also found to have lupus anticoagulant (LAC). The simultaneous presence of LAC and FVIII inhibitor is exceedingly rare. The differentiation between these two conditions is crucial, because both result in a prolongation of the activated partial thromboplastin time test, which does not correct when mixed with the plasma of a normal control; however, the clinical manifestations range from thrombosis in the presence of LAC to massive haemorrhage with FVIII inhibitors.
Lupus 2003
PMID:Coexistence of lupus anticoagulant and acquired haemophilia in a patient with monoclonal gammopathy of unknown significance. 1466 3

The acquired inhibitors of blood clotting-factors are immunoglobulins that directly inhibit clotting factors or accelerate their clearance from circulation. The majority of inhibitors are directed against factor VIII, which arises spontaneously in healthy elderly, postpartum women, patients with autoimmune disorders or malignancy, and those with various underlying disorders. The most common initial symptom is bleeding into the skin or muscles spontaneously or caused by minor trauma, which sometimes extends to cause severe anemia. Those with acquired hemophilia may not receive a first consultation by a hematologist, resulting in delayed laboratory diagnosis. The activated partial thromboplastin time (APTT) of the hemophilia patient's plasma is prolonged, and is not corrected by mixing with normal plasma for 2 hours. The mixing test provides suggestive evidence of a factor VIII inhibitor, but can not distinguish lupus anticoagulant. Although the factor VIII activity of plasma is remarkably low, the activities of other intrinsic clotting factors can also be reduced apparently in the one-stage assay. A quantitative inhibitor measurement assay is required to confirm that the inhibitor acts specifically on factor VIII.
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PMID:[Coagulopathy with autoantibodies to blood-clotting factors: overview and laboratory diagnosis]. 1502 24

Thrombophilia is characterized by clinical tendency to thrombosis or molecular abnomalities of hemostasis that predisposes to thromboembolic disease. Hereditary thrombophilia may be due to antithrombin deficiency, or protein C or protein S deficiency. More recently, other molecular abnormalities have been described: activated protein C resistance due to factor V Leiden, G 20210 A polymorphism on the prothrombin gene, increased factor VIII plasma levels or hyperhomocysteinemia. Acquired thrombophilia is frequently associated with the antiphospholipid syndrome characterized by thrombosis and presence of lupus anticoagulant or phospholipid-binding antibodies. In some cases, no molecular abnormality is found despite recurrent thrombosis observed in patient and his/her family. This situation can be considered as clinical thrombophilia.
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PMID:[Definition of thrombophilia]. 1502 78

Coagulopathy is a life-threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell-free dialysis technique, on the blood coagulation of cirrhotic patients. From February 2002 to July 2002, nine patients--five males (55.5%) and four females (44.4%), age 47-70 yr (median 56)--underwent 12 courses (4-7 sessions each) of MARS. Patients were treated for the following indications: six (66.6%) acute-on-chronic hepatic failure, three (33.3%) intractable pruritus. Platelet count, prothrombin time (PT), international standardized ratio and thromboelastography were measured before and after each MARS session. Coagulation factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand, lupus anticoagulant, protein C, protein S, antithrombin III, plasminogen, alpha 2 antiplasmin, D-dimer, fibrin monomers, complement, and C(1) inactivator were measured before and at the end of each MARS treatment. We found a statistically significant difference (p < 0.05) in the platelet count, PT, all the thromboelastograph variables (reaction and constant time, alpha angle, and maximal amplitude), factor VIII, von Willebrand, and D-dimer, when measured before and after MARS. Previous reports have shown amelioration of blood coagulation following MARS treatments. However, we document that MARS induces coagulopathy through a platelet-mediated mechanism, whereby platelet may be mechanically destroyed during the passage of blood through the filters and lines. An alternative postulated mechanism is an immune-mediated platelet disruption - coagulopathy.
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PMID:Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system. 1523 11

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

A new prothrombin-based activated protein C resistance (APC-R) test is described. In this method, the patient sample is prediluted in a plasma depleted of factor V (FV). A reagent containing APC and a specific activator of FV is added. After an incubation period, clotting is initiated by the addition of the FV-dependent prothrombin activator Noscarin. We analyzed 703 samples from patients undergoing thrombophilia screening. By using a predefined cutoff ratio of 2.5, 100% sensitivity and specificity for the detection of a factor V Leiden (FVL) mutation was found. With a cutoff ratio of 1.2, a complete but narrow distinction of FVL heterozygous (n = 192) and FVL homozygous samples (n = 27) was determined. No interference by the international normalized ratio, activated partial thromboplastin time (aPTT), protein S activity, fibrinogen and factor VIII (FVIII) levels, or lupus anticoagulant ratio was detected. The new prothrombin-based APC-R assay provides improved distinction of FV wild-type and FVL carriers compared with the aPTT-based method. By the use of an FV-dependent prothrombin activator, the assay is not influenced by FVIII concentration or lupus anticoagulants.
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PMID:Improved distinction of factor V wild-type and factor V Leiden using a novel prothrombin-based activated protein C resistance assay. 1553 75

We describe a patient with non-Hodgkin's lymphoma who developed a lupus anticoagulant (LA) detectable by activated partial thromboplastin time (APTT), dilute Russell's viper venom time (DRVVT) and kaolin clotting time (KCT). IgM anticardiolipin antibodies (ACA) were elevated. At a later admission, and following treatment for the lymphoma, routine coagulation screening showed an elevated prothrombin time (PT) without correction in mixing tests using a recombinant thromboplastin. Routine APTT was below the reference range and ACA levels were normal. Raw data for one-stage factor assays demonstrated the presence of an inhibitor. Analysis for LA was undertaken by DRVVT, KCT, activated seven lupus anticoagulant assay, Taipan snake venom time, platelet neutralisation procedures (PNP), Ecarin time and PT using rabbit brain thromboplastin. The results revealed a LA capable of prolonging the clotting times of the PNPs and PT using recombinant thromboplastin, but that was corrected using Ecarin venom, modified PNP and brain thromboplastin. The antibody also demonstrated the lupus anticoagulant co-factor effect. The factor VIII: C was markedly raised which may have masked the LA in the APTT. The changing laboratory profile over time demonstrates the effects of LA heterogeneity and variations in sensitivity and specificity of assays for the detection of antiphospholipid antibodies.
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PMID:Alteration in the laboratory profile of a lupus anticoagulant in a patient with non-Hodgkin's lymphoma. 1559 3


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