Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This population-based case-control study compared the effect of oral contraceptives (OCs) on hemostatic variables in venous thrombosis patients with the effect on healthy control subjects. A total of 99 premenopausal women aged 15-49 years, who had used OCs at the time of a first, objectively confirmed episode of deep-vein thrombosis, were studied. The median time between occurrence of deep-vein thrombosis and venepuncture was 18 months, and 30 of the 99 women were still using OCs, while 69 had discontinued OC use. In addition, a group of 153 control women (54 of them were OC users and 99 were nonusers) were also studied. The following hemostatic variables were measured: activated thromboplastin time (APTT), factor VII, factor VIII, factor XII, fibrinogen, prothrombin, total antithrombin, normalized activated protein C (n-APC-sr), protein C, protein S, and free protein S. Findings revealed significant effects of OC use on the levels of several clotting factors, with an increase in factors VII and XII and protein C and a decrease in antithrombin, n-APC-sr, and protein S. Less marked effects that were nonsignificant or only significant in either patients or controls were an increase in factor in VIII, fibrinogen, and prothrombin and a decrease in APTT and free protein S. Several of these effects of OCs were more pronounced in former thrombosis patients than in healthy women specifically on factor VII, antithrombin, n-APC-sr, and protein C. In conclusion, former deep-vein thrombosis patients are most vulnerable to the thrombogenic effects of OCs.
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PMID:Hemostatic effects of oral contraceptives in women who developed deep-vein thrombosis while using oral contraceptives. 975 14

Previous reports and reviews indicate differences in effects of second and third generation combined oral contraceptives (COCs) on haemostasis variables. This review analyses directly comparative studies on such effects. From the literature, 17 longitudinal comparative studies with parallel groups were retrieved, containing data on comparisons between COCs containing levonorgestrel (second generation COCs) and COCs containing desogestrel, gestodene or norgestimate (third generation COCs) with 30-35 ug ethinylestradiol. Six or more comparisons were available only for fibrinogen, platelet count, antithrombin III, factor VII, factor VIII and factor X. The comparisons reveal a consistently larger increase in factor VII with the third generation COCs compared to the second generation COCs. The effects on factor VII do not coincide in these comparative studies with effects on factor X and prothrombin, rendering a specific sensitivity of the vitamin K-dependent mechanisms for progestogens unlikely. Fibrinogen effects tend to be different for the different progestogens, suggesting a progestogen-specific dependence. Trends in antithrombin III are towards more reduction for the third generation COCs, but the effects are very minor. The effects on factor V suggest a possible progestogen specificity, which may be relevant to explain the difference in APC-resistance between second and third generation of COCs. In general, direct comparisons of effects of different types of COCs on haemostatic variables are available for only a very few factors, which hampers the drawing of general conclusions with respect to haemostatic consequences.
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PMID:Effects on haemostasis variables by second and third generation combined oral contraceptives: a review of directly comparative studies. 1070 27

To assess the relationship between hemostatic factors and spontaneous abortion, 134 pregnant women presenting to the emergency department were recruited and followed through 22 weeks' gestation. Cases were women experiencing a spontaneous abortion and controls were women who maintained their pregnancy. Fibrinogen, factor VII antigen, activated protein C-sensitivity ratio (APC-SR), protein S, and plasmin-antiplasmin (PAP) were measured. Cases had lower mean levels of fibrinogen and factor VII antigen compared with controls (3.1 g/L vs. 3.7 g/L and 89% of normal vs. 109% of normal, respectively). Regression analyses found that women with fibrinogen levels below 3.0 g/L had a five-fold increased risk of spontaneous abortion (OR = 5.1, 95% CI: 1.8-14.4) and women with factor VII antigen levels below 94% of normal had a threefold increased risk of spontaneous abortion normal (OR = 3.3, 95% CI: 1.2-8.5). Similar mean levels of APC-SR, protein S, and PAP were found in the two groups.
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PMID:Influence of hemostatic factors on spontaneous abortion. 1144 63

We investigated the effects of ethinylestradiol dose (50, 30 and 20 microg) and progestogen type [desogestrel (DSG), gestodene (GSD), levonorgestrel (LNG) and norgestimate (NGM)] in oral contraceptives on 24 hemostatic variables. In a multicenter, randomized, comparative study, 707 healthy, nonsmoking, nulliparous women were treated for six cycles with one of the seven monophasic oral contraceptives tested. Significantly greater increases in prothrombin fragment 1+2 and factor VII (activity and antigen), were found in the DSG, NGM and GSD groups compared to the LNG group. Similarly, significantly lower levels of protein S (free and total) and increased APC-sr (endogenous thrombin potential based) were found in the same groups compared with the LNG group. In addition, the estradiol dose (50 vs. 30 microg) significantly influenced these parameters. All changes were within the normal range and have not been associated with an increased risk of venous thromboembolic event (VTE). However, raised levels of these variables are associated with prothrombotic states such as pregnancy. The significance of the haemostatic changes found in this study in relation to VTE risk remains to be determined, but results of this study probably cannot explain the differences in risk of VTE between OCs containing different progestogens.
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PMID:The effects of seven monophasic oral contraceptive regimens on hemostatic variables: conclusions from a large randomized multicenter study. 1261 51

Acute myocardial infarction is a very rare event during pregnancy and bears the problem of misdiagnosis. However, about 150 cases have been published worldwide with a preponderance of anterior wall infarcts. With more women delaying childbearing until an older age and increasing prevalence of smoking in young women, it can be expected that all forms of coronary artery disease--including acute myocardial infarction--will be seen more often in the future. Among the causes of coronary artery occlusion in pregnancy are (1) rupture of very small coronary artery plaques triggered by different events, e.g., hypertension; (2) plain coronary artery disease; (3) dissection of coronary arteries; (4) coronary artery spasms with/without arterial thrombosis. Prompt diagnosis and immediate therapy are necessary to lower the high mortality of mother and fetus. The gold standard in the therapy of acute myocardial infarction during pregnancy is immediate coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) with or without stent implantation. Application of thrombolytics (recombinant tissue plasminogen activator [rt-PA], r-PA, streptokinase [SK], urokinase [UK]) has been reported in single patients but should be limited to cases where acute PTCA is not available and where the infarct occurs before the 14th week of pregnancy because of possible embryopathy. If the patient is in the last 10 weeks of pregnancy, anticipation of delivery should be part of the medical planning. Consultation with an obstetrician must be obtained as soon as the patient enters the hospital. Besides bleeding complications, venous thrombosis with pulmonary embolism is among the most common causes of death during pregnancy. Pregnancy-related changes in physiology - increase in the resistance to flow from the lower extremities to the heart - and congenital coagulation abnormalities are most important to be recognized. This leads to the fact that superficial and deep venous thromboses occur more often in pregnancy than in the nonpregnant state. Among the coagulation abnormalities found in pregnancy are hypercoagulability (increased levels of fibrinogen, factor VII, factor VIII, factor X), decreased fibrinolytic activity due to an increased level of plasminogen activator inhibitor, increased adhesion and aggregation of platelets, decreased level of protein C and of the APC (activated protein C) ratio. Individual risks factors justifying diagnostic screening include contraception, smoking, immobilization, infection, adiposity, placental insufficiency, and a family history of thrombosis. It is even more important to establish/rule out the diagnosis of thrombosis in pregnancy than in the nonpregnant state, because the use of anticoagulants carries certain risks during pregnancy. Doppler vein studies should be used for diagnosis. If necessary, venography may be used with shielding of the maternal abdomen. Therapy consists of subcutaneous application of heparin, compression, and early mobilization. Alternatively, especially for long-term management, treatment with low molecular weight heparins is feasible. Thrombolytic treatment is contraindicated in most cases due to the high risk of bleeding complications. However, the application of thrombolytics can be contemplated in single cases after careful consideration of the pros and cons. Most cases of pulmonary embolism should also be handled conservatively with heparin. Only in massive pulmonary embolism with severe hemodynamic compromise, thrombolytic treatment is indicated. To guide future therapy in the patients, it is necessary to establish the lifetime risk of recurrent events by determining: APC resistance, prothrombin mutation 20210 A, homocysteine, AT III, protein C and S, antiphospholipid antibodies, and anticardiolipin antibodies.
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PMID:[Myocardial infarction and thromboembolism during pregnancy]. 1275 75

Two Air Assault Surgical Groups (AASGs) from 16 Close Support Medical Regiment deployed to Kuwait on Operation Telic in February 2003. Each AASG was comprised of a four-table resuscitation facility, a two table FST and a twin-bedded ITU facility. An A+E Consultant and nurse, an experienced radiographer and laboratory technician with two further RGNs and CMTs provided resuscitation support. Each FST had an orthopaedic and a general surgeon, two anaesthetists and eight operating department practitioners. Further equipment consisted of a Polymobil 111 X-ray unit, a Sonosite 180 ultrasound scanner and an ISTAT gas, haematocrit and electrolyte analyser. 100 units of mixed blood were carried by each AASG. Fifty-one surgical procedures were performed on thirty one patients. Twenty one of these patients were Iraqi prisoners of war or civilians. Seventeen wound debridements, five amputations, five laparotomies, four insertions of Denham pins with Thomas splintage for femoral fracture, three external fixations and one axillary artery repair formed the basis of the major cases undertaken. The first field use of activated factor VII by the British Army was successful in the resuscitation of a patient with exsanguinating haemorrhage after an open-book (APC-III) pelvic fracture and a ruptured intrapelvic haematoma. The other cases included eleven manipulations under anaesthetic/application of plaster and four finger terminalisations. Forward military surgery has a continued role to play on the modern fast moving battlefield. 16 Close Support Medical Regiment normally supports 16 Air Assault Brigade with its remit for expeditionary operations and SF support. Its experience on Op Telic should influence planning for future deployment.
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PMID:Forward surgery on Operation Telic--Iraq 2003. 1644 Sep 63

Many reports indicate a hypercoagulative state in diabetes mellitus as result of endothelial damage. Experimental evidence suggests that a metabolic derangement triggers a cascade of biochemical events that lead to vascular dysfunction. The net effect is to convert the endothelium from thromboresistant to thrombogenic surface. In literature, a strong association between type 1 diabetes mellitus (DM1) and celiac disease (CD) has been reported. We do not have information about the hemostatic system in these associated conditions. Our study aims at evaluating whether the presence of CD in a group of DM1 patients is associated with a different expression of some hemostatic factors and with a different manifestation and/or progression of microvascular complications of DM1 in comparison with patients with only diabetes. Ninety-four adult DM1 patients were enrolled in the study and subsequently screened for CD. Anti-endomysial antibodies (EMA) were positive in 13 of 94 DM1 patients (13.8%). CD diagnosis was confirmed by histology and organ culture. The mean age and duration of DM1 of patients also affected by CD were similar to those of only diabetic patients, but the metabolic control and the hemocoagulative parameters were significantly different between the two groups: DM1 patients also affected by CD presented significantly lower concentrations of glycosylated hemoglobin (HbA1c) (P < 0.05), cholesterol (P < 0.001), triglycerides (P < 0.001), factor VII antigen (FVII:ag) (P < 0.005), factor VII coagulant activity (FVII:c) (P < 0.05), and prothrombin degradation fragments (F1+2) (P < 0.001), as well as higher values of activated C protein (APC) (<0.001). No retinal abnormalities and no signs of renal damage were observed in DM1 patients also affected by CD. Our results suggest a potential protective role of CD in the prothrombotic state of DM1.
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PMID:Type 1 diabetes mellitus and celiac disease: endothelial dysfunction. 2195 22

Increasing evidence links blood coagulation proteins with the regulation of acute and chronic inflammatory disease. Of particular interest are vitamin K-dependent proteases, which are generated as a hemostatic response to vascular injury, but can also initiate signal transduction via interactions with vascular receptors. The endothelial cell protein C receptor (EPCR) is a multi-ligand vitamin K-dependent protein receptor for zymogen and activated forms of plasma protein C and factor VII. Although the physiological role of the EPCR-FVII(a) interaction is not well-understood, protein C binding to EPCR facilitates rapid generation of APC in response to excessive thrombin generation, and is a central requirement for the multiple signal-transduction cascades initiated by APC on both vascular endothelial and innate immune cells. Exciting recent studies have highlighted the emerging role of EPCR in modulating the cytoprotective properties of APC in a number of diverse inflammatory disorders. In this review, we describe the structure-function relationships, signal transduction pathways, and cellular interactions that enable EPCR to modulate the anticoagulant and anti-inflammatory properties of its vitamin K-dependent protein ligands, and examine the relevance of EPCR to both thrombotic and inflammation-associated disease.
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PMID:The endothelial cell protein C receptor: cell surface conductor of cytoprotective coagulation factor signaling. 2196 19