Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association of thrombosis with antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) could be due to their interference with natural phospholipid dependent anticoagulant mechanisms. We studied antigenic protein C (APC), functional protein C (FPC), free protein S (FPS), protein S bound to C4 binding protein (C4bp-S), antithrombin III (ATIII), as well as IgG and IgM anticardiolipin antibodies (aCL) in 38 patients with SLE with a history of thromboses and 70 patients with SLE without such history. We found a high frequency of deficiencies of natural anticoagulants in both groups of patients with SLE but, because of patient selection, we could not determine the actual prevalence of these defects. Patients having had a venous thrombosis in the previous year had low C4bp-S more frequently than patients with older or no thromboses. When we divided our patients with SLE into those who had a definite, probable, questionable or no antiphospholipid syndrome (aPS) we found the frequency of C4bp-S deficiency to be significantly higher in those with definite aPS than in those without aPS. Intermediate proportions were found in patients with probable and questionable aPS. The levels of C4bp-S decreased as the levels of aCL, particularly IgG, increased. Stepwise discriminant analysis of natural anticoagulants selected deficiencies of C4bp-S and FPC with increased ATIII as a set of variables with highest predictive power for classification of patients with and without aPS. Thus, deficiencies of natural anticoagulants may occur frequently in patients with SLE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Natural anticoagulants in systemic lupus erythematosus. Deficiency of protein S bound to C4bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome. 182 65

Patients with recurrent venous thrombosis, or those with thrombosis at a young age (less than 45 years) and a family history of thrombotic disorders, may have an inherited hypercoagulable disorder. The most common disorders are deficiencies of protein S, protein C and antithrombin III, inhibitors of the coagulation cascade. These deficiencies may be found in approximately 10 percent of patients who are under age 45 and have venous thrombosis. Acquired disorders associated with recurrent venous thrombosis include carcinoma and antiphospholipid antibody syndrome. Appropriate anticoagulation can reduce the risk of recurrent thrombosis in patients with inherited and acquired abnormalities.
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PMID:Recurrent venous thrombosis and hypercoagulable states. 183 74

New details have been added to the description of the antiphospholipid antibody syndrome. These include quantitation of risk of stroke; delineation of an associated acute occlusive vasculopathy syndrome, including its pathology; increased awareness of the association of adrenal insufficiency with antiphospholipid antibody; new demonstration of placental pathology in cases of fetal death; and new details on the persistence or transience of antibody in patients with systemic lupus erythematosus. There are several animal models for the antiphospholipid antibody syndrome. Assay standardization and reproducibility issues, more for the lupus anticoagulant than for the enzyme-linked immunosorbent assay for antiphospholipid antibody, remain as important barriers to progress. Antibody characteristics of activity, isotype, and subclass must be considered in assay interpretation; antigen characteristics of fatty acid chain and lipid phase are also important variables. Other circulating proteins may have clinical importance. Several laboratories have commented that antiphospholipid antibody interferes with protein C. A cofactor, apolipoprotein H, enhances binding of some antiphospholipid IgG antibodies. Other phospholipid-binding proteins are known. Isolation, purification, and perhaps cloning of many of these factors should lead to a better understanding of the pathogenesis of the syndrome.
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PMID:Antiphospholipid antibody and antiphospholipid antibody syndrome. 183 43

The clinical and serological findings in 13 patients with myocardial infarction and antiphospholipid antibodies (the 'lupus anticoagulant', antibodies to cardiolipin, antibodies to phosphatidylethanolamine (one patient] seen by our unit and other units from 1984 to 1989, are presented (eight males and five females, ages ranging from 20 to 52 years). Five suffered myocardial infarction before the age of 30; four of these five were in their early 20s. Other risk factors such as excessive smoking (greater than 20 cigarettes a day) (two patients), long-term treatment with steroid (one) and use of oral contraceptives (one) were present. One patient had demonstrated a plasminogen activator deficiency and one a deficiency of protein C. Two patients developed myocardial infarction six to eight weeks after warfarin was discontinued for recurrent deep vein thrombosis. Six patients had SLE as defined by the revised 1982 criteria, three suffered from 'lupus-like' disease, while four patients conformed to a 'primary' antiphospholipid syndrome.
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PMID:Myocardial infarction and antiphospholipid antibodies in SLE and related disorders. 251 55

A 16-year-old boy had recurrent venous thromboses and pulmonary thromboembolism that caused him pulmonary hypertension. He also had livedo reticularis, thrombocytopenia and high titer IgG antiphospholipid (cardiolipin) antibodies. In the absence of clinical and laboratory evidence of SLE, he was considered to have a primary antiphospholipid syndrome. Coagulation studies revealed a functional deficiency of protein C although it was present in normal antigenic amounts. Since both his parents had normal functional and antigenic protein C findings, his deficiency was considered acquired. The reactivity of the anticardiolipin antibodies could be decreased in a dose dependent fashion when preincubated with increasing amounts of thrombomodulin, a protein required for protein C activation at the endothelial cell membrane. This interaction of antiphospholipid antibodies with thrombomodulin may help explain the occurrence of thrombosis in some patients with antiphospholipid antibodies, despite the behavior in vitro of these antibodies as circulating anticoagulants.
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PMID:Acquired protein C deficiency in a patient with primary antiphospholipid syndrome. Relationship to reactivity of anticardiolipin antibody with thrombomodulin. 254 43

Presence of beta 2 Glycoprotein I (beta 2GPI), in addition to phospholipids, is an absolute requirement for binding APA. This binding is frequently observed with beta 2GPI coated alone, however many APA react only with beta 2GPI complexed to phospholipids, but not with phospholipids alone. We demonstrate that a subgroup of rabbit polyclonal antibodies to human beta 2GPI binds to this protein only when it is coated on a solid surface, but not if it is in solution. In addition, beta 2GPI present in goat serum is strongly fixed by the coated phospholipids and the complexes formed bind as well APA as the rabbit antibodies to beta 2GPI. The diluent used for testing APA, has a strong incidence on APA's reactivity as it can be a source of beta 2GPI. Antibody binding to beta 2GPI, Prothrombin, Protein S, and Annexin V, coated in the presence or in the absence of phospholipids, was tested in 55 patients with the antiphospholipid syndrome. The strongest binding of antibodies was observed in 39 plasma to a mixture of phospholipids and purified human beta 2GPI, however 17 samples also presented a significant reactivity to beta 2GPI alone. Nine plasmas contained antibodies to Prothrombin, 4 to Protein S, 3 to Annexin V, and 1 to Protein C. We conclude that most of the APA are directed to a complex of beta 2GPI and phospholipids although in some patients antibodies to beta 2GPI alone or to other phospholipid binding proteins are present.
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PMID:Standardization of immunoassays for antiphospholipid antibodies with beta 2GPI and role of other phospholipid cofactors. 752 66

The unusual case of a boy with a stroke occurring at three years of age, transient reduction in protein C activity and high concentrations of antiphospholipid antibodies (APA) is described. APA or Lupus Anticoagulant (LA) were found in 7 of 11 relatives studied out of three different generations. In addition, antigenic Factor (F) XII deficiencies or borderline values were found in the propositus and 2 relatives. Evidence for F. XII inhibitors was found in the propositus, one of his brothers and both of his parents. Whether F. XII inhibitors in patients with APA and/or LA are pathophysiologically relevant in vivo or if they are only an in vitro phenomenon remains to be elucidated. It is reasonable to believe that the main laboratory pathology (APA and/or LA activity) in antiphospholipid syndrome is related to the clinical picture of a hypercoagulable state. There is evidence from the literature that deficiency or inhibition of F. XII might contribute to a prothrombotic state through impairment of the fibrinolytic system. There is also evidence that APA are able to reduce protein C activation. From a clinical point of view, it seems that hypercoagulability in our patient was controlled by low-dose aspirin therapy (75 mg/d). In conclusion, this case seems to support the idea of a genetic predisposition for the development of APA and/or LA. The related disturbances of the coagulatory, anticoagulatory and fibrinolytic systems might contribute in different ways to the prothrombotic state seen in patients with "antiphospholipid syndrome", eventually resulting in possible venous thrombosis or arterial thrombosis with corresponding ischaemic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Childhood stroke at three years of age with transient protein C deficiency, familial antiphospholipid antibodies and F. XII deficiency--a family study. 777 Jan 25

We report the occurrence of livedo reticularis in a patient with symptomatic hereditary type 1 protein C deficiency. Antithrombin III deficiency and the antiphospholipid syndrome may also be associated with livedo reticularis, and we suggest that a thrombophilia screen may be a useful investigation in a patient with otherwise unexplained livedo, particularly if there is a personal or family history of thromboembolism.
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PMID:Livedo reticularis associated with hereditary protein C deficiency and recurrent thromboembolism. 788 69

Results obtained in three patients with juvenile ischemic stroke and criteria of primary antiphospholipid syndrome is reported. These patients are selected out from a series of 12 patients with 18-mounts follow-up. Lupic anticoagulant and anticardiolipin antibodies were found in two of three patients and one patient show anticardiolipin antibodies with negative lupic anticoagulant. All others coagulation proteins examined (antithrombin III, plasminogen, protein C and protein S) were normal. We conclude that antiphospholipid antibodies are associated with increase risk of thrombosis. Therefore should be systematically investigated in juvenile ischemic stroke of unknown aetiology.
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PMID:[Primary antiphospholipid syndrome in juvenile ischemic stroke]. 824 Aug 35

The skin is often the presenting organ for thrombotic disorders. Purpura fulminans, with its widespread cutaneous necrosis, may be the result of severe infection, of an inherited or acquired disorder of the protein C procoagulant pathway, or of unknown causes (the idiopathic form). Recurrent venous or arterial thrombosis and the associated skin findings at an early age may be clues to an inherited disorder of protein C, protein S, or antithrombin III. Livedo reticularis, leg ulcerations, and hemorrhagic purpura may suggest the antiphospholipid antibody syndrome.
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PMID:Clotting and thrombotic disorders of the skin in children. 837 73


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