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 first generation high-dose ( 80 mcg estrogen) oral contraceptives (OCs) were associated with an increased risk of deep venous thrombosis (DVT). So manufacturers removed the high-dose OCs and first replaced them with OCs with 50 mcg estrogen, resulting in a lower incidence of thromboembolic events (40 vs. 20/100,000 users). When they introduced an even lower dose OC (30 mcg estrogen), the incidence fell further (about 8/100,000 users). Yet, women using the lowest-dose OCs still have DVT more often than do control women. Life-style, age, and smoking may be confounding factors, however. It is not clear whether loss of endogenous ovarian steroid production or the effects of the orally administered contraceptive steroids cause significant changes in hemostatic factors (antithrombin III, protein S, protein C, plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor 1, histidine-rich glycoprotein, and VII, VIII, X, XII coagulation factors) during OC use. These changes tend to be within normal ranges. There is some doubt that these changes have any clinical significance. In nonsmokers, increased activity of anticoagulant factors and fibrinolytic factors counteract the effects on coagulation factors. Progestin-only OCs appear to affect hemostasis but have not increased the risk of thrombosis. There are considerable differences between people in pharmacokinetics and pharmacodynamics of contraceptive steroids. These differences may account for the increased risk of thromboembolic events in some people. Further research should identify methods of individualizing the dose of contraceptive steroids for a single patient. It should also explore the close interrelationship between hemostasis and lipid metabolism, carbohydrate metabolism, and hypertension in the development of cardiovascular disease in OC users. Providers should discourage women with a past history of DVT from using hormonal contraception.
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PMID:Coagulation and anticoagulation effects of contraceptive steroids. 817 1

We present a 57-year-old man with end-stage renal failure due to chronic glomerulonephritis, who had been on hemodialysis for 13.5 years and had suffered from recurrent painful swelling of the left leg for 4.7 years. A diagnosis of deep venous thrombosis was made by the phlebography. Coagulation studies showed decreased protein C activity despite a normal protein C antigen level. None of his relatives had decreased protein C activity, and the levels of the other coagulation factors synthesized by the liver were all normal. Accordingly, the patient was diagnosed as having acquired type II protein C deficiency.
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PMID:Acquired type II protein C deficiency in a long-term hemodialysis patient. 819 Jan 90

The case of an adult patient with moderately severe protein C deficiency (antigen 16%, activity 12%) is reported. Both parents had protein C levels compatible with heterozygous deficiency. Unlike other reported cases of severe protein C deficiency in adults, the onset of thrombotic symptoms occurred at 1 month of age; however, a symptom-free period until age 17 followed. Replacement therapy with a monoclonal antibody purified protein C concentrate was carried out during the initiation of oral anticoagulation after a course of i.v. heparin for deep vein thrombosis. The administration of the concentrate allowed maintenance of protein C above 50% until a stable therapeutic anticoagulation level could be obtained. This was reached within a short time, thus allowing safe administration of a loading dose of warfarin. We conclude that this approach to the prevention of skin necrosis seems more rapid and safer than previous schedules of oral anticoagulation in protein C-deficient patients.
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PMID:Replacement therapy with a purified protein C concentrate during initiation of oral anticoagulation in severe protein C congenital deficiency. 823 28

The present overview describes the mode of action of direct and indirect anticoagulants. Furthermore it presents well-accepted and potential indications for the different anticoagulants as concomitant treatment during thrombolysis of deep vein thrombosis, pulmonary embolism and myocardial infarction. The new antithrombotics dermatansulfate, hirudine, synthetic peptide thrombin inhibitors, activated protein C, inhibitors of glycoprotein IIb/IIIa are reviewed. Many small and large studies on the thrombolytic treatment of myocardial infarction demonstrate the benefit of simultaneous application of heparins.
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PMID:[Anticoagulation in thrombolytic therapy: importance and future perspectives]. 833 24

In a 14-years old girl, suffering from deep venous thrombosis protein C deficiency (activity: 55-58%) was diagnosed. Following rethrombosis oral anticoagulant therapy (OAT) with Phenprocoumon (Marcumar) was started. To find the required dosage for OAT the concentrations of prothrombin fragment (F1+2; < 0.5 nM/l) and fibrin monomers (< 2.5 mg/l) were measured. With this procedure an unusually high thromboplastin time (40-45%) was found to be safe.
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PMID:[Prevention of thrombosis in protein C deficiency]. 833 42

Little is known about the pattern of Deep Vein Thrombosis in Saudi Arabia. Over 4 year period, 62 cases with strong evidence of venous thrombosis were studied in King Abdulaziz University and King Fahad Hospitals to learn the pattern of deep vein thrombosis in Jeddah, Western Saudi Arabia. There were 32 females and 30 males. The mean age of the group was 36.0 years (range 6-90 years). One or more risk factors was/were detected in 40 patients. Among these 14 factors, age more than 50 years, obesity, vasculitis, malignancy and postpartum were the common factors encountered. In other 22 patients, no risk factor was found. However, extensive laboratory search diagnosed 9 rare disorders out of these 22 cases. Antithrombin III, protein C, protein S deficiencies in 5, 2, 1 patients, consecutively. The last patient had significantly shortened PTT. The other 13 (21.0%) patients were considered real idiopathic DVT. Extremities were involved in 54 patients compared to only 8 cases with inferior vena cava or visceral thrombosis. The upper limb was affected in only 10 patients unlike the lower limb which was more commonly affected n = 37.
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PMID:Pattern of deep venous thrombosis in Jeddah area, western Saudi Arabia. 837 13

The alterations of the laboratory assays described for heparin monitoring in low molecular weight and unfractionated heparin prophylaxis groups did not correlate with the clinical outcome. Current laboratory techniques failed to detect an increased need for a higher dose of unfractionated or low molecular weight heparin to prevent DVT in these high-risk patients. The parameters commonly associated with thrombosis, that is, decreases in protein C and AT III were correlated with an increased incidence of DVT, but there was no difference in the assay values between the low molecular weight heparin and unfractionated heparin groups. Fibrinolysis activation is known to be associated with surgery; however, our data suggest an additional activation due to low molecular weight heparin compared with the unfractionated heparin group. Most interestingly, elevated PAI levels appear to correlate with thrombosis.
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PMID:Postoperative monitoring of low molecular weight heparin prophylaxis in high-risk patients. 839 35

A patient with recurrent deep vein thrombosis and heterozygous type II deficiency, characterized by reduced protein C activity in both amidolytic and clotting functional assays, was investigated by direct sequencing of PCR fragments derived from the coding portion of the protein C gene. AG (8856) to A transition was noted in the patient which was not present in healthy controls. This mutation is predicted to cause the substitution of Ser for Gly 381, an evolutionari'y conserved residue in the substrate binding pocket of serine-proteases (Gly 216, chymotrypsin numbering). A computer model of the structure of the serine-protease domain indicates that the properties of the altered protein C molecule can be explained on the basis of steric hindrance between the substituted serine and the substrate arginine side chains.
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PMID:Symptomatic type II protein C deficiency caused by a missense mutation (Gly 381-->Ser) in the substrate-binding pocket. 839 32

Heterozygosity for a G-->C mutation converting the highly conserved Gln184 (CAG) to His (CAC) was identified at the last nucleotide of exon 7 of the protein C gene in two family members with deep vein thrombosis. As the nucleotide is a part of the 5 splice site of intron G, it was examined how the mutation affected splicing of protein C pre-mRNA. Relevant protein C cDNA fragments were amplified with polymerase chain reaction after reverse transcription of ectopic mRNA from peripheral blood lymphocytes. Southern blot analysis and nucleotide sequencing of these fragments showed a fragment (A) corresponding to correctly spliced mRNA originating from the normal allele and a fragment (B) corresponding to a truncated mRNA lacking exon 7, originating from the mutant allele. A third fragment (C) lacking exons 7 and 8 was identified in both affected and unaffected family members, as well as in normal controls. Analysis of human liver protein C mRNA indicated that the ectopic lymphocyte mRNA was qualitatively representative for the tissue-specific mRNA. In conclusion, evidence is provided showing that the mutation abolishes formation of correctly spliced mRNA. This agrees with the observation that the mutation results in a type 1 protein C deficiency.
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PMID:Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis. 840 Feb 92

Progress in the management of medical disorders of pregnancy has occurred in many areas. Only salient features are reviewed. The pathophysiology of maternal hyperglycemia in diabetes and its effects on the fetus are explored. Antiphospholipid antibodies, implicated in adverse pregnancy sequelae, come under closer scrutiny in terms of management and correlation with outcome. Studies defining a need for a strict diet for optimal neonatal outcome are presented regarding maternal phenylketonuria. Coagulopathies including protein C deficiency and deep venous thrombosis are reviewed for their impact on pregnancy. Uncommon disorders including cerebrovascular accidents, ureteric obstruction, and myocardial infarction are discussed in relation to management and outcome in pregnancy.
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PMID:Maternal disease and injury in pregnancy. 842 32


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