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)

Three cases of post-sinusoidal hepatic blood flow obstruction as the main feature of antiphospholipid syndrome are reported. Clinically, these patients developed jaundice, malaise, ascites and hepatomegaly. Ultrasonography-Doppler and hepatic venography showed small hepatic vein disease in two and partial occlusion in the suprahepatic segment of inferior vena cava in the remaining patient. In all, anticardiolipin antibodies were positive and activated partial thromboplastin time was prolonged. This experience emphasizes that in patients with post sinusoidal portal hypertension, a systematic search for antiphospholipid syndrome must be carried out.
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PMID:[Post sinusoidal obstruction of the hepatic venous flow associated with antiphospholipid syndrome in 3 cases]. 827 13

Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth. Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4% +/- 0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS.
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PMID:Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3. 847 80

We have recently described the in vitro mechanism of action of anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies in patients with the antiphospholipid syndrome. LA antibodies inhibit coagulation reactions in plasma because they appear to recognize the complex of lipid-bound (human) prothrombin, whereas aCL antibodies require beta 2-glycoprotein I (beta 2-GPI) for binding to anionic phospholipids. aCL antibodies can be divided into two subgroups, according to their behaviour in lipid-dependent coagulation reactions: aCL-type A enhances the anti-coagulant effect of beta 2-GPI, whereas aCL-type B does not. In the present study we investigated the effect of purified aCL-type A and B and of LA antibodies on the procoagulant activity of both Ca-ionophore activated platelets and platelet-derived microvesicles, using an assay system with highly purified bovine coagulation factors Xa, Va, and prothrombin from human and bovine origin. In the absence of beta 2-GPI neither type of aCL was able to inhibit the prothrombinase activity of platelets or microvesicles. However, a strong and dose-dependent inhibition of the prothrombinase activity of both platelets and platelet-derived microvesicles was observed within a few minutes, when aCL-type A antibodies were added in combination with beta 2-GPI. This inhibitory effect was dependent also on the concentration of beta 2-GPI. Conversely, no inhibitory effect of aCL-type B antibodies on platelet- (or microvesicle) prothrombinase activity in the presence of beta 2-GPI could be observed. LA antibodies were able to inhibit in a dose-dependent way the procoagulant activity of activated platelets and platelet-derived microvesicles. With two LA preparations this inhibition was only apparent when human prothrombin was used as substrate, while a third preparation exhibited its inhibitory effect both in the presence of human and bovine prothrombin. The data indicate that, in the presence of their respective cofactors beta 2-GPI and prothrombin, aCL and LA antibodies interact with the membrane of activated platelets and platelet-derived microvesicles in a very similar way as previously observed for their interaction with anionic phospholipid surfaces.
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PMID:Effect of antiphospholipid antibodies on procoagulant activity of activated platelets and platelet-derived microvesicles. 813 94

Four cases of adrenal insufficiency due to bilateral adrenal haemorrhage in patients with antiphospholipid syndrome are reported. The 1st patient had repeated episodes of thrombosis on a background of altered general condition; he was examined by computed tomography (CT) which showed enlarged and presumably tumoral adrenal glands; adrenal insufficiency was present and improved under hormone replacement therapy; the thrombotic episodes were attributed to the antiphospholipid antibodies; after a 5-year follow-up the antiphospholipid syndrome remained alone, and further examinations showed progressive adrenal atrophy. The 2nd patient had systemic lupus erythematosus with thrombocytopenia; because of abdominal pain CT was performed, showing bilateral adrenal enlargement; treatment with intravenous pulses of cyclophosphamide and high-dose immunoglobulins combined with corticosteroids failed, and splenectomy was performed disclosing an old adrenal haematoma which was evacuated. The 3rd patient had bilateral and asymmetrical adrenal hypertrophy at CT; subsequently, systemic lupus erythematosus was diagnosed with anti-prothrombinase and anticardiolipin accounting for the initial findings; follow-up examinations showed the formation of pseudocysts in the adrenals; following myocardial infarction the patient died of cerebral haemorrhage, and autopsy confirmed the presence of old, bilateral adrenal haematomas. The 4th patient had recurrent vein thrombosis associated with distal ischaemia, which prompted CT in search of a neoplasia; this examination revealed 2 large adrenal haematomas while anticardiolipin antibodies were found. In patients with antiphospholipid syndrome any functional or morphological abnormality of the adrenals should prompt a search for bilateral adrenal haemorrhage. Conversely, in all cases of adrenal insufficiency a search for antiphospholipid antibodies should be part of all aetiological investigations, and this search should be carried out prior to withdrawing corticosteroids in cases of systemic lupus erythematosus with antiphospholipid antibodies.
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PMID:[Antiphospholipid syndrome. A new cause of bilateral hemorrhage of the adrenal glands. 4 cases]. 851 Nov 42

A 37-year-old woman in acute right heart failure had experienced systemic venous thromboses for 17 years, five miscarriages and repeated pulmonary emboli. For the last 7 years she had been treated symptomatically for pulmonary hypertension. The platelet count was 62,000/microliters, thromboplastin time under phenprocoumon was 22%, partial thromboplastin time was 72 s. Despite anticoagulation with phenprocoumon and heparin (7,500 IU two times daily subcutaneously) new pulmonary emboli occurred and platelet count fell to 12,000/microliters. An increased titre for anticardiolipin antibodies (IgG > 320 GPL U/l, IgM 8 MPL U/l), antinuclear (1:640) and anti-ds-DNA antibodies (> 200 IU/ml) with simultaneous complement consumption suggested secondary antiphospholipid syndrome associated with lupus erythematodes. Treatment with prednisolone (150 mg/d), immunoglobulins (20 mg/d intravenously for 5 days) and heparin (25,000 IU/24 h intravenously) achieved an increase in platelet count to 200,000/microliters within 10 days, but fell again when the prednisolone dose was reduced, recovering under azathioprine, 150 mg/d. Four weeks later the patient died of renewed acute right heart failure.
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PMID:[Pulmonary thromboembolism in antiphospholipid syndrome]. 851 8

Antiphospholipid (aPL) antibodies are associated with thrombosis, recurrent abortions and thrombocytopenia. Studies to determine the mechanisms of action of these antibodies have been hindered by their heterogeneity and limited availability of techniques to isolate and characterize subgroups of the antibodies. We report a new phospholipid affinity chromatography method which enables separation of antiphospholipid positive sera into more than one antibody subpopulation. Sera from five patients with complications of the antiphospholipid syndrome (APS) were studied. Each serum was applied to chromatography columns prepared by coating polystyrene beads (diameter 100 A) with phosphatidylserine (PS) or cardiolipin (CL). A linear salt gradient (0.03-1.0 M NaCl) was used for elution. Eluates were analyzed for phospholipid binding and for inhibition of the prothrombin-thrombin conversion reaction. Each sample yielded two to three peaks for CL and PS affinity columns. Molarities at which peaks were eluted differed between samples. For individual samples, molarities at which peaks were eluted differed between CL and PS columns. These data suggest that aPL antibodies are heterogenous, with differences existing between patients and even within single serum samples. Subpopulations differed in their avidities for CL and PS but generally all had prothrombinase inhibitory activity.
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PMID:Demonstration of antiphospholipid antibody heterogeneity by phospholipid column chromatography and salt gradient elution techniques. 852 22

Activated protein C (APC) resistance is usually associated with a single DNA mutation predicting replacement of Arg506 by Gln in factor V (FV). Studies using synthetic peptides suggest that FV residues 493-506 provide factor Xa (FXa) and protein S binding sites. Biochemical studies were performed to test the hypothesis that the Arg506Gln FV mutation causes APC resistance and to define the nature of the resistance of Gln506-FVa to APC. Purified Gln506-FV conveyed APC resistance to FV-deficient plasma in APTT and FXa-1-stage assays. Purified Gln506-FVa, generated either by thrombin or by FXa, was resistant to APC. Nonetheless, Gln506-FVa was not completely resistant to APC since it was inactivated by APC approximately 10-fold slower than normal Arg506-FVa, probably due to cleavage at Arg306. This reduced but significant susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance, especially for heterozygotes, is a relatively moderate risk factor for venous thrombosis. Cardiolipin promotes APC anticoagulant activity better than FXa coagulant activity, and antibodies from some antiphospholipid antibody syndrome patients downregulate APC activity. Thus, acquired APC resistance may contribute to pathogenesis of thrombosis in the antiphospholipid antibody syndrome.
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PMID:Activated protein C resistance: molecular mechanisms. 857 3

A 38 year-old man with a 12-year history of noninsulin-dependent diabetes mellitus with rapidly progressive diabetic complications presented with microangiopathic hemolytic anemia and thrombocytopenia. He had no disorders that could induce microangiopathic hemolytic anemia other than diabetic microangiopathy. In addition, there was a significant negative correlation between serum lactate dehydrogenase levels and peripheral platelet counts, which suggested that the hemolysis and thrombocytopenia occurred through the same mechanism. Activated partial thromboplastin time was slightly prolonged, and lupus anticoagulant and antiphospholipid immunoglobulin G antibodies were positive. Both the hemolysis and the thrombocytopenia spontaneously improved after the initiation of hemodialysis. This is a unique case of diabetic microangiopathic hemolytic anemia and thrombocytopenia in which antiphospholipid syndrome also may be involved.
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PMID:Case report: diabetic microangiopathic hemolytic anemia and thrombocytopenia with antiphospholipid syndrome. 861 92

To avoid wasting healthcare resources through overinvestigation in otherwise healthy people, it is important to remember that antiphospholipid antibodies (ie, lupus anticoagulant and anticardiolipin antibody) often do not signify clinical disease. However, when features of the antiphospholipid syndrome (APS) are also present, serious thrombosis may be expected. Exactly how these antibodies alter hemostasis to induce a hypercoagulable state remains unclear. Activated partial thromboplastin time may not be a reliable screening test in a minority of patients with lupus anticoagulant and is not useful in screening for anticardiolipin antibodies. When APS is strongly suspected on clinical grounds, definitive tests (ie, enzyme-linked immunosorbent assay for IgG, IgA, and IgM anticardiolipin antibodies and the dilute Russell's viper venom time test) followed by confirmatory tests (eg, for lupus anticoagulant) should be ordered. Patients with APS are at high risk for recurrent thrombosis, but questions about optimal clinical management remain unresolved. High-intensity or lifelong anticoagulation therapy should be considered in some cases. Low-molecular-weight heparin may ultimately prove to be the treatment of choice in pregnant APS patients.
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PMID:The antiphospholipid syndrome: when does the presence of antiphospholipid antibodies require therapy? 866 25

Antiphospholipid antibodies, including anticardiolipin antibodies (ACA), are strongly associated with recurrent thrombosis in patients with the antiphospholipid syndrome (APS). To date, reports about the binding specificities of ACA and their role(s) in causing and/or sustaining thrombosis in APS are conflicting and controversial. The plasmas of patients with APS, usually containing a mixture of autoantibodies, vary in binding specificity for different phospholipids/cofactors and vary in in vitro lupus anticoagulant activity. Although in vivo assays that allow assessment of the pathogenic procoagulant activity of patient autoantibodies have recently been developed, the complex nature of the mixed species prevented determination of the particular species responsible for in vivo thrombosis. We have generated two human IgG monoclonal ACA from an APS patient with recurrent thrombosis. Both bound to cardiolipin in the presence of 10% bovine serum, but not in its absence, and both were reactive against phosphatidic acid, but were nonreactive against purified human beta-2 glycoprotein 1, DNA, heparan sulfate, or four other test antigens. Both monoclonal autoantibodies lacked lupus anticoagulant activity and did not inhibit prothrombinase activity. Remarkably, one of the monoclonal antibodies has thrombogenic properties when tested in an in vivo mouse model. This finding provides the first direct evidence that a particular antiphospholipid antibody specificity may contribute to in vivo thrombosis.
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PMID:A monoclonal IgG anticardiolipin antibody from a patient with the antiphospholipid syndrome is thrombogenic in mice. 871 Sep 18


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