Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
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Most people who experience venous thrombosis have normal hemostasis. Some people have inherited deficiencies of protein C, protein S, and antithrombin iii. They tend to have deep venous thrombosis which increases their risk for pulmonary emboli. Some acquired disorders which predisposes people to thrombosis include defective fibrinolysis which often occurs after surgery or infection, Trousseau's syndrome (excessive coagulant activity linked with adenocarcinoma), and lupus anticoagulant which is an immunoglobulin G or M antibody directed against negatively charged phospholipids. Hormones and probably not a dilution effect reduces free and bound protein S levels during pregnancy. Functional protein S activity is still 40-50% below normal levels 1-3 days after delivery. This decrease appears to protect against bleeding but does have venous thrombosis and pulmonary emboli during pregnancy as side effects. Non-oral-contraceptive (OC) users have greatly higher protein S levels than do OC users (28.6 mcg/ml vs. 24.3 mcg/ml; p.005) which gives more credence to the belief that hormones are responsible for the fall in protein S activity during pregnancy. OCs reduce free and total protein S levels almost 20%. Smoking may even further reduce these levels in women during pregnancy and who use Ocs. Women who have had venous thrombosis should not use OCs. Physicians should also consider family history especially age of affected family member, severity of thrombotic episodes, and the clinical setting. They should look for an underlying abnormality in patients who develop thrombosis while using OCs. If thrombosis develops during pregnancy, physicians should call for a venogram, venous duplex scanning, and, if required, invasive tests. The most sensible treatment is intravenous heparin for 5-7 days then therapeutic doses of heparin. Heparin therapy should stop before delivery and be reinstituted shortly thereafter and continued throughout the postpartum period. Physicians should take extra precautions when performing surgery on an OC user.
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PMID:Recent advances in understanding clotting and evaluating patients with recurrent thrombosis. 141 44

A recent cross sectional study on symptomatic acute deep vein thrombosis at the National University Hospital (NUH) in Singapore found a frequency rate of 0.79 per 1000 patient admissions. A total of 39 patients were accrued over 18 months, 36 with deep vein thrombosis alone and three complicated by pulmonary embolism. No sex or ethnic predilection was observed in this cohort of hospitalised patients. Twenty-eight (71.8%) patients were 40 years or older. Majority (89.7%) of patients had at least two predisposing factors. While prolonged bedrest and operative procedures featured equally frequently in patients above and below 40 years, neoplasms were predominantly associated with the former and protein C or S deficiency primarily with the latter. The exhaustive laboratory confirmation of an inherent thrombotic tendency is recommended only for patients below 40 years of age.
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PMID:Acute deep vein thrombosis in hospital practice. 141 82

Of 67 patients with acute deep vein thrombosis of the lower extremity (DVT), 43 patients were treated by venous thrombectomy and 24 patients were managed by conservative treatment. The clinical effect of thrombectomy was evaluated by analyzing follow-up results in the 2 groups. The cumulative incidences of pigmentation and stasis ulcer at the 5th year were 2.7% and 0% respectively in the thrombectomy group, and 24.3% and 10% respectively in the conservative treatment group. Pigmentation and stasis ulcer were significantly more frequent in the conservative treatment group (p < 0.01). It is concluded that venous thrombectomy is superior to conservative treatment to prevent late postthrombotic sequelae. Protein C, protein S and plasminogen were assayed in 40 DVT patients to determine the incidence of hypercoagulable state in DVT. Congenital deficiency or abnormality were found in 15 patients (37.5%). In such DVT patients with thrombophilia anticoagulant prophylaxis should be continued to decrease a risk of rethrombosis.
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PMID:[The treatment of choice in deep vein thrombosis of the lower extremity]. 147 Jan 17

Deep venous thrombosis and pulmonary embolism are relatively frequent occurrences in pregnancy and the postpartum period. The diagnosis of deep venous thrombosis and pulmonary embolism requires accurate objective tests because clinical diagnosis is unreliable. Procedures that expose the fetus to ionizing radiation must sometimes be performed to make an accurate diagnosis; current evidence suggests that the adverse effects to the fetus associated with such procedures are minimal. Heparin is the anticoagulant of choice during pregnancy and is used for both the treatment and prevention of venous thrombosis and pulmonary embolism. Patients with deficiencies of antithrombin III, protein C, or protein S as well as patients with antiphospholipid antibodies are at increased risk for thrombotic complications and require particular vigilance during pregnancy.
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PMID:Deep venous thrombosis and pulmonary embolism in pregnancy. 147 24

The overall incidence per year of deep vein thrombosis is about one per thousand, but may be much higher in the presence of certain clinical risk factors such as advanced age, immobilization, surgical procedures, pregnancy, puerperium, use of oral contraceptive agents and malignancy. Moreover, homocystinuria, nephrotic syndrome, systemic lupus erythematosus and hematological disorders such as paroxysmal nocturnal hemoglobinuria or myeloproliferative syndromes predispose to thrombotic disease. Evaluation of the patient with thromboembolism should include detailed history, clinical examination and laboratory investigation to exclude these secondary thrombophilic states. Primary or hereditary thrombophilia is suspected mainly in patients suffering from (venous) thromboembolism at an early age (< 45 years), especially if recurrent and/or familial thrombosis is present. Hereditary thrombophilia may be due to deficiency of antithrombin III, protein C, protein S or plasminogen, some other defects being less well-established prethrombotic risk factors. These currently recognized primary prethrombotic molecular defects are found in 10 to 30% of patients with idiopathic thromboembolism. In the majority of cases the cause of thrombosis remains unknown.
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PMID:[Evaluating the origin of thrombophilia: indications and implementation]. 148 83

During a 3-year period we studied 393 adult patients (382 of whom were unrelated) with a history of acute venous thromboembolism. A congenital deficiency state known to predispose to thrombosis was found in 27.2%. Of these, most were due to deficiencies of protein C (9.2%), protein S (7.6%), antithrombin III (5%) or to increased plasma PAI-1 concentration (3.1%) which, in the absence of any known factor that predisposes towards thrombosis, results in a diminished fibrinolytic activity. There was a characteristic pattern between the age of onset (mean 34 years) of thrombosis and individual protein deficiency. Thrombosis appeared spontaneously in 73% of cases with recurrence in 80%. In contrast, in the remaining unrelated patients, 138 (35.1%) in whom venous thromboembolism was secondary and occurred at a mean age of 43 years, and in the other 140 (35.6%) who suffered thromboembolism spontaneously at a later age (mean age 55), there was no permanent protein deficiency state or alteration in fibrinolytic activity and thrombosis recurrence was lower (53.6% and 20.7% respectively). Of the 393 patients, deep vein thrombosis was the most common manifestation; however, in congenital thrombophilia, thrombosis of visceral vessels and Raynaud's syndrome (6%) were also detected.
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PMID:Congenital thrombophilia among patients with venous thromboembolism. 148 96

Hereditary deficiency of protein C, protein S or antithrombin III has been associated with an increased incidence of venous thrombosis or pulmonary embolism. The relationship between these deficiencies and the development of arterial thrombosis is a matter of current investigation. We retrospectively studied the occurrence of arterial thrombosis in 92 symptomatic patients belonging to a group of 160 with a confirmed diagnosis of hereditary deficiency of one of the physiologic clotting inhibitors. Seventeen of them experienced at least one arterial thrombotic event. This indicates that about one out of five of the symptomatic patients had experienced arterial thrombosis. The control group consisted of 92 sex and age matched (+/- 5 years) patients with no clotting deficiency who had experienced in the same period at least one episode of deep vein thrombosis or pulmonary embolism. Only one of them had developed arterial thrombosis. Ischemic stroke, myocardial infarction, upper and lower limb arterial thrombosis, and mesenteric artery occlusion occurred regardless of the type of defect taken into account; mean age of about 37.05 +/- 23 years (mean +/- SD). In some cases, arterial thrombosis was fatal. The overall number of venous thrombotic events in the 92 symptomatic patients of this study was much higher than that of arterial thrombosis, with a ratio of 24 to 1. The use of long-term anticoagulant therapy in our group of patients seemed to be able to prevent recurrences of both arterial and venous thrombosis.
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PMID:Occurrence of arterial thrombosis in a cohort of patients with hereditary deficiency of clotting inhibitors. 153 14

An inherited deficiency of protein C, a recognized hypercoagulable state, may cause a clinically significant deep venous thrombosis. Only some persons with a deficiency of protein C experience thrombosis, and almost always the thrombotic event occurs in the venous circulation. Warfarin-induced skin necrosis, a rare event observed in some patients soon after treatment with warfarin is begun, is believed to be another manifestation of this deficiency. We describe a young woman whose basal functional and antigenic levels of protein C were about 45% and who experienced both deep venous thrombosis and warfarin-induced skin necrosis in a clinically severe course. Evidence for lupus anticoagulants was present, with prolonged activated partial thromboplastin time that was corrected when lysed platelets were added, prolonged Russell's viper venom time, anticardiolipin antibodies, and other laboratory evidence. Lupus anticoagulants are associated also with a significant incidence of thrombosis, including arterial thrombosis, and this patient developed concurrently arterial thrombosis. The combined effects of protein C deficiency and lupus anticoagulants, exacerbated by other potentially thrombogenic conditions, are believed responsible for the severe thrombotic events experienced by this patient.
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PMID:Concurrent protein C deficiency and lupus anticoagulants. 156 44

The haemostatic parameters were studied within 14 days of acute myocardial infarction (AMI) in 103 patients randomly allocated into a group receiving low-dose heparin or into a group treated without anticoagulants. Patients with isotopic evidence of deep vein thrombosis were excluded from the analysis. An important formation of thrombin-antithrombin III complex (TAT) in the plasma was detected in the early stage of the disease. It was accompanied by an activation of plasma intrinsic fibrinolysis (IF), an elevation of fibrinogen and its degradation products (FDP) and a reduction of extrinsic plasma fibrinolytic activity (EF) together with normal levels of factor X, antithrombin III (AT III), protein C and alpha-2-antiplasmin. Sequentially studies periods of the disease revealed a diminution of TAT complex concentration in the plasma on the seventh day of AMI together with a rise of the both plasma fibrinolytic activities (IF, EF) as well as an elevation of fibrinogen and its degradation products, returning to the initial values on the 14 day of AMI. In the patients treated with heparin the augmentation of TAT complex in the plasma was prolonged until the fifth day of AMI. Moreover, heparin administration was connected with significantly higher levels of AT III and protein C along with a lower concentration of factor X and FDP on the seventh day of the disease. The fluctuation of fibrinolytic activities (IF, EF) in the plasma was heparin-independent. The present results indicate that low-dose heparin treatment modulates the plasmatic fluctuation of TAT complex as well as factor X, AT III and protein C levels in patients with acute myocardial infarction.
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PMID:Fluctuation of thrombin-antithrombin III complex in patients with acute myocardial infarction: influence of low-dose heparin administration. 169 24

To determine the etiology of the increased incidence of postoperative deep venous thrombosis (DVT) in patients with carcinoma of the colon, serum levels of protein C were measured preoperatively in 65 patients with colorectal adenocarcinoma. Noninvasive lower-extremity Doppler studies were performed on all patients prior to discharge to assess patency of the deep veins. Six patients (9%) were found to have DVT. The protein C level was considered elevated if it was greater than 125% of control values and reduced if less than 75% of control values. The development of DVT was found to be independent of the serum carcinoembryonic antigen, albumin, total protein, hemoglobin, hematocrit, platelet count, prothrombin time, partial thromboplastin time, and the patient's age and percentage of ideal body weight. There was an inverse relationship between the protein C level (p less than 0.001), Dukes stage of the tumor (p less than 0.001), and the development of DVT. Linear regression analysis revealed that only the tumor stage and the protein C level could be used to predict the development of DVT. The data show that for these patients with colorectal malignancy, the development of DVT may be related to decreased levels of protein C.
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PMID:Protein C activity, stage of disease, and vascular thrombosis in colon carcinoma. 173 77


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