Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated partial thromboplastin time may be prolonged as the result of either of two different autoimmune complications of chronic lymphocytic leukemia: the development of antiphospholipid antibodies, such as lupus anticoagulant or anticardiolipin antibodies, or anti-factor VIII inhibitors, such as acquired hemophilia A. In the rare simultaneous occurrence of both inhibitors, differential diagnosis of a prolonged activated partial thromboplastin time poses a number of problems during laboratory work-up, due to mutual interference of the commonly performed tests. Only careful clinical follow-up can disclose the significance of the laboratory findings. We report the case of concurrent antiphospholipid antibodies (lupus anticoagulant positivity, anticardiolipin antibodies; IgM 3880 MPL/mL and IgG 265 GPL/mL) and anti-factor VIII antibodies (46.8 Bethesda Units) in a patient with chronic B-cell lymphocytic leukemia who had prolonged activated partial thromboplastin time (78.8 s). The relationship between lymphoproliferative and antiphospholipid syndrome, laboratory work-up in the case of the association of antiphospholipid and anti-factor VIII antibodies, and related problems that occur during clinical management of the patient are also discussed.
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PMID:[The antiphospholipid syndrome during chronic lymphatic leukemia. An association with anti-factor VIII antibodies]. 1052 24

Prothrombin time (PT) is routinely used to monitor oral anticoagulant treatment in patients with the antiphospholipid antibody syndrome (APS). The fact that PT is a phospholipid (PL)-dependent coagulation test raises the possibility that lupus anticoagulant (LA) might interfere with this test, thus complicating the control of anticoagulant treatment. The effect of 6 affinity-purified preparations of anti- (a)beta2-glycoprotein I (GPI) antibodies with LA activity on the PT was tested. Instead of prolonging PT as expected, the abeta2-GPI antibodies reduced the PT of both normal plasma and anticoagulated plasma by a mean of 2.4 seconds and 5.6 seconds, respectively. This effect was also observed using other 5 commercially available preparations of thromboplastin. The abeta2-GPI-mediated reduction in PT was dose-dependent and was lost upon removal of beta2-GPI. The failure of abeta2-GPI antibodies to express LA activity in PT was found to depend on the fact that calcium ions were added together with PL at the beginning of the assay. In fact, modification of the standard diluted Russell viper venom time (dRVVT) test by adding calcium ions together with PL resulted in a loss of abeta2-GPI anticoagulant activity. The procoagulant effect was not as evident in an assay that used stimulated monocytes as a source of thromboplastin. These results show that abeta2-GPI antibodies exhibit an 'in vitro' procoagulant effect in PT and an anticoagulant effect in dRVVT only when the interaction with their antigen and PL occurs in the absence of calcium ions.
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PMID:Procoagulant effect of anti-beta2-glycoprotein I antibodies with lupus anticoagulant activity. 1057 96

The occurrence of erythema multiforme (EM) in patients with lupus erythematosus (LE) has been described previously as a coincidental association. In contrast, LE with EM-like lesions and a peculiar immunological pattern, including positive rheumatoid factor, antinuclear antibodies and a serum antibody against an extract of human tissues recently recognized as similar to Ro (SSA), constitutes an established entity named Rowell's syndrome. We describe a woman with LE and long-standing widespread vesiculobullous and necrotic haemorrhagic EM-like lesions in combination with Ro (SSA) and scl-70 antibodies and the typical laboratory findings of the antiphospholipid syndrome (APS), namely lupus anticoagulant, anticardiolipin antibodies and prolonged activated partial thromboplastin time. This case could conceivably be consistent with a diagnosis of Rowell's syndrome, if the latter is regarded as a clinicopathological spectrum. However, the coexistence of LE, persistent EM-like disease and incomplete APS may also fulfil the diagnostic criteria for the 'multiple autoimmune syndromes'. We speculate that the laboratory markers of APS play a pivotal part in such an unusual clinical presentation.
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PMID:Lupus erythematosus with antiphospholipid syndrome and erythema multiforme-like lesions. 1058 25

Antiphospholipid syndrome is characterized by the presence of high titers of anti-beta(2)-glycoprotein I (beta(2)GPI) antibodies, lupus anticoagulant associated with thromboembolic phenomena, thrombocytopenia and recurrent fetal loss. Single-chain Fv (scFv) were prepared from four anti-beta(2)GPI mAb, CAM, CAL, CAR and 2C4C2, and one anti-ssDNA. All five scFv showed the same antigen binding properties as the original mAb. Replacement of the pathogenic CAM V(H) domain with the non-pathogenic CAL V(H) or anti-ssDNA V(H) decreased the binding affinity of the scFv to beta(2)GPI and completely abrogated the anticoagulant activity. Exchanging the CAM V(H) with anti-DNA V(H) resulted in a shift from anti-beta(2)GPI to anti-ssDNA binding of the scFv. Replacement of the CAM V(L) with CAL V(L) did not affect the binding and activity. BALB/c mice were immunized with the anti-beta(2)GPI scFv, and the scFv resulting from the substitution of the heavy (H) and light (L) chains. The mice which were immunized with CAM, 2C4C2 and CAR scFv developed clinical manifestations of experimental anti-phospholipid syndrome. Elevated titers of mouse anti-cardiolipin (aCL), anti-beta(2)GPI, associated with lupus anticoagulant activity, thrombocytopenia, prolonged activated partial thromboplastin time and a high percentage of fetal resorptions were detected, in the CAM scFv group and in the scFv composed of CAM V(H) groups. High titers of aCL, anti-beta(2)GPI, anti-ss/dsDNA and anti-histone associated with lupus findings were observed in the sera of the 2C4C2 scFv-immunized mice. Immunization with CAL scFv did not lead to any clinical findings. The current study shows that scFv of pathogenic antibodies are capable of inducing the same clinical manifestations as the whole antibody molecule upon active immunization. Replacement of H/L chains point to the importance of the V(H) domains in the pathogenic potential of anti-beta(2)GPI.
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PMID:Characteristics and pathogenic role of anti-beta2-glycoprotein I single-chain Fv domains: induction of experimental antiphospholipid syndrome. 1059 Feb 57

Pregnancy has been widely recognized as a predisposing risk factor for deep vein thrombosis (DVT). However, it still remains unclear why pregnant women without a history of familial thrombophilia or antiphospholipid syndrome (APS) have a higher incidence of DVT and pulmonary embolism (PE) during pregnancy and puerperium. We examined the activated protein C (APC) system in healthy pregnant women and in patients with the onset of DVT during puerperium. Sixty unselected Japanese pregnant women without a past or family history of thrombosis or APS and 3 Japanese women with DVT during puerperium were evaluated. Endogenous thrombin potential-ratio (ETP-r) was measured by determination of thrombin-alpha2-macroglobulin complexes in thromboplastin-activated patient plasma. APC sensitivity ratio (APC-sr) was calculated by the determination of ETP-r in patient plasma in the presence and absence of APC (final concentration [conc.] 5.9 nM) to evaluate the functional APC anticoagulant activity. Mean APC-sr was significantly increased at 30 weeks' gestation (2.35 +/- 0.72) and remained high during puerperium compared with the mean APC-sr in nonpregnant women (1.15 +/- 0.63). Mean APC-sr in patients with DVT at the onset was significantly higher (3.57 +/- 0.54) than mean APC-sr during puerperium was, indicating that the sensitivity to APC was reduced in the ETP-based assay. These data suggest a significant reduction in the functional sensitivity to APC associated with an increased risk of venous thrombosis during pregnancy.
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PMID:Detection of decreased response to activated protein C during pregnancy by an endogenous thrombin potential-based assay. 1062 9

Recurrent thrombosis is a common complication of various rheumatic disorders and is part of the definition of antiphospholipid syndrome. We report three cases of recurrent venous thrombosis due not only to antiphospholipid syndrome with a normal activated partial thromboplastin time but also to resistance to activated protein C caused by the factor V Leiden mutation. These three cases confirm that thrombotic disease is frequently multifactorial and suggest that resistance to activated protein C should be looked for routinely in patients with suggestive clinical manifestations, particularly when standard clotting tests are normal.
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PMID:Antiphospholipid syndrome and factor V Leiden. Three cases with recurrent venous thrombosis. 1076 7

The primary antiphospholipid syndrome is a disorder which is characterized by: arterial and/or venous thrombosis, thrombocytopenia, recurrent fetal loss and high plasma levels of antiphospholipid antibodies. Valvular involvement is associated with arterial thrombosis and the most frequent manifestation is regurgitation. We report the case of a young male with primary antiphospholipid syndrome and previous cerebrovascular thrombosis hospitalized for subacute myocardial infarction. Coronary angiography revealed right and left anterior descendent coronary artery stenosis, the latter being successfully recanalized by direct percutaneous transluminal coronary angioplasty. Transthoracic echocardiography demonstrated aortic valve involvement with predominant regurgitation and transesophageal echocardiography detected valve excrescences on the aortic leaflets. Laboratory study demonstrated thrombocytopenia, prolonged activated partial thromboplastin time and high titers of anticardiolipin antibodies. Oral anticoagulation therapy was started. Thrombotic events have not recurred after three months of follow-up.
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PMID:[Antiphospholipid syndrome with myocardial infarction and aortic valve involvement]. 1108 11

The case was a 29 year old female who has suffered from systemic lupus erythematosus (SLE) since 15 years of age. The activity of SLE was low, and she took prednisolone orally. Her first pregnancy failed after 14 weeks. In the second pregnancy, she had thrombocytopenia, prolonged activated partial thromboplastin time (APTT), positive lupus anticoagulant (LAC) and thus was diagnosed with antiphospholipid antibody syndrome (APS). Combination therapy with steroids and aspirin was started, and she underwent treatment of double filtration plasmapheresis (DFPP) in the early stage of pregnancy. Her platelet count increased, and the value of APTT has normalized with DFPP treatment. She delivered successfully on the 32nd week of pregnancy. We think that DFPP is an effective and safe treatment in patients with an LAC positive pregnancy.
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PMID:Successful delivery in a pregnant woman with lupus anticoagulant positive systemic lupus erythematosus treated with double filtration plasmapheresis. 1125 5

The antiphospholipid syndrome has rarely been described in patients with autoimmune hepatitis. Two cases with type I autoimmune hepatitis and antiphospholipid syndrome are presented. The first case is that of a 53-year-old Caucasian female with a history of arterial thrombosis and fetal loss who was submitted to clinical and laboratory testing due to persistent transaminasaemia and was found to have autoimmune hepatitis. Antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) were positive. The second case is that of a 31-year-old Caucasian woman with a history of autoimmune hepatitis who was submitted to laboratory testing due to a second-trimester fetal death, revealing an increased activated partial thromboplastin time and positive antiphospholipid antibodies. In conclusion, secondary antiphospholipid syndrome may accompany autoimmune hepatitis.
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PMID:Autoimmune hepatitis associated with the antiphospholipid syndrome. 1139 42

The association between antiphospholipid antibodies and an increased risk of thrombosis in antiphospholipid syndrome (aPS) patients is probably caused by numerous mechanisms, including the effects of antibodies to phospholipid-binding proteins such as beta(2)-glycoprotein I and prothrombin. In this study, we investigated the inhibition of tissue factor pathway inhibitor (TFPI) in 33 patients with primary antiphospholipid syndrome (PAPS). TFPI was measured in PAPS patients using an amidolytic assay, dependent on the generation of activated factor X (Fxa), and this was compared with 55 healthy subjects. Functional levels of TFPI (mean +/- SD) were significantly lower in PAPS patients (0.89 +/- 0.37 U/ml) than the control group (1.05 +/- 0.15 U/ml) (P = 0.02). The difference was caused by a subset of five patients who had TFPI levels below the lower 99% confidence interval of the normal reference range, representing increased FXa generation in the assay system. IgG fractions were isolated from these five patients and five control subjects, then incorporated into normal plasma to measure FXa generation in the TFPI assay system. FXa generation was increased when polyclonal rabbit anti-human TFPI IgG (P < 0.0001) or PAPS IgG (P = 0.0001) were added to normal plasma, demonstrating inhibition of TFPI. The apparent anti-TFPI activity demonstrated in the five subjects with PAPS in this study may represent a significant new mechanism for thrombosis in patients with aPS, as it implies that increased tissue factor FVIIa-mediated thrombin generation might occur.
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PMID:Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome. 1152 59


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