Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischaemic heart disease is the biggest single cause of excess mortality in winter, accounting for approximately half of all the excess deaths. Most of these deaths take place hours or a day or two after exposure to cold suggesting that some result from thrombosis starting during or shortly after cold exposure, although some can result from immediate reflex effects of cold, and some can occur in association with respiratory deaths which are delayed many days after cold weather. Changes in blood composition observed in the cold that may explain the rapid thrombotic deaths include increased red cell count, plasma cholesterol, and plasma fibrinogen, which are all thrombogenic. The protective protein C does not increase significantly. British data suggests that cold housing particularly affects respiratory mortality in winter, and outdoor cold exposures mortality from arterial thrombosis. A Europe-wide survey is now being run as part of the EC- funded project "Eurowinter" to assess such factors.
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PMID:Cardiovascular mortality in winter. 890 Aug 26

In the UK, the Committee for Safety of Medicines (CSM) issued a warning in October 1995 about the possible increased risk of nonfatal deep venous thrombosis (DVT) among users of oral contraceptives (OCs) containing the third generation progestogens, desogestrel and gestodene. Subsequent media coverage increased the number of consultations and enquiries about these OCs. CSM had concluded that, overall, the third generation OCs are safe. CSM recommended their continued use. Nevertheless, many women stopped using them and induced abortions increased by 11%. In April 1996, the Committee for Proprietary Medicinal Products issued a more cautious statement about the OCs and called for further evaluation. Chance, confounding, and bias may account for the increased risk observed in the studies in question. Yet, it is possible that these OCs may increase the risk of DVT. The increased risk may be offset by a reduced risk of acute myocardial infarction. Physicians need to conduct careful and thorough counseling and to allow the patient to be involved and to take responsibility in making a decision about OC use. They should document all counseling with a note that the patient understands and accepts the increased risk of DVT. They should not prescribe the third generation OCs to women with any of the absolute contraindications to OC use (ischemic heart disease, hypertension, atherogenic lipid disorders, focal or crescendo migraine, cigarette smoking, transient ischemic attacks, past cerebral/subarachnoid hemorrhage, history of vascular thrombosis, prothrombotic abnormalities [e.g., Factor V Leiden], conditions predisposing to thrombosis [e.g., systemic lupus erythematosus], and obesity. Women who are intolerant of second generation OCs may prefer third generation OCs. Physicians should selectively screen women with a family history of a first-degree relative younger than 45 with thromboembolism for Factor V Leiden. They should also screen for protein C, protein S, and antithrombin III deficiency and for acquired antiphospholipid antibodies.
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PMID:Oral contraceptives and the risk of DVT. 898 64

To investigate whether resistance to activated protein C (APC resistance) because of a mutation in the factor V gene (factor V Leiden) leads to a decrease in life expectancy, we analyzed overall and cause-specific mortality in 171 parents whose offspring carried this mutation. Compared with the Dutch general population, and after adjustment for age, sex, and calendar period, we found no excess deaths in the parents (standardized mortality ratio [SMR], 1.0; 95% confidence interval [CI], 0.8 to 1.2). The cause-specific SMR for malignant neoplasms (1.0; 95% CI, 0.6 to 1.4), diseases of the circulatory system (1.0; 95% CI, 0.7 to 1.4), and cerebrovascular disease (1.0; 95% CI, 0.4 to 1.9) also did not differ from unity. The SMRs for diseases of the respiratory system (1.4; 95% CI, 0.6 to 2.6) and for ischemic heart diseases (1.1; 95% CI, 0.7 to 1.7) were slightly increased. Under the age of 45 years, there was a ninefold increase of dying from ischemic heart disease. Thromboembolic complications were mentioned only once (venous embolism or thrombosis) as an underlying ("primary") cause of death (SMR, 2.3; 95% CI, 0.1 to 13.0) and three times (pulmonary embolisms) as a contributing ("secondary") cause of death (SMR, 1.5; 95% CI, 0.3 to 4.4). We conclude that there is no major effect of APC resistance on life expectancy. Therefore, long-term anticoagulation in carriers of factor V Leiden, on the basis of the carrier state alone, is not indicated.
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PMID:Mortality and causes of death in families with the factor V Leiden mutation (resistance to activated protein C). 905 17

A common mutation in coagulation factor V gene gives rise to factor V Leiden, which is resistant to the proteolytic activity of activated protein C. This mutation is known to be a major inherited risk factor for venous thrombosis. In order to investigate the possible pathogenetic role of factor V Leiden in coronary thrombosis, we screened patients with acute ischemic heart disease for this genetic mutation. We conducted a case-control study on 114 unrelated patients referred to the Cardiology Department of a University Hospital for coronary angiography. Fifty-three case patients with myocardial infarction or unstable angina were compared with 61 control patients seen for a different coronary syndrome or for stable angina pectoris. The two groups did not differ with respect to the well established risk factors for ischemic heart disease. For each patient genomic DNA was extracted from whole blood by standard techniques; the DNA region carrying the mutation was amplified by polymerase chain reaction, and the allele-specific restriction digestion was used in order to detect the mutation itself. The frequency of factor V Leiden was 0.028 among cases and 0.008 among controls (p = 0.5). According to the data presented, factor V Leiden cannot be considered as a risk factor for acute coronary events.
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PMID:Factor V Leiden in patients with acute coronary syndromes. 1052 20

Three patients of ischemic heart disease associated with protein C deficiency are reported. Although delayed diagnosis of protein C deficiency resulted in the failure of repeated interventions, coronary artery bypass grafting performed after making the correct diagnosis has led to satisfactory mid-term results under strict anticoagulation therapy. The level of protein C should be measured more frequently in the field of ischemic heart disease and earlier diagnosis of its deficiency should be made, because measurement of protein C does not cost much.
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PMID:Ischemic heart disease associated with protein C deficiency. 1157 50

We have previously reported that plasma fibrin D-dimer (a marker of turnover of cross-linked fibrin) showed a strong and independent association with incident ischaemic heart disease (IHD) in the Caerphilly Study cohort of 1,998 men aged 49-65. To establish the specificity of this finding, we assayed plasma samples from this cohort with a more specific assay for fibrin D-dimer: this showed an association with incident IHD which was at least as strong and independent as that for the original assay (odds ratio, OR for top fifth compared to bottom fifth 3.79; 95% CI 1.77-8.10; p < 0.0001). To establish potential causes of the increased fibrin turnover, we also assayed several potential markers of coagulation activation or thrombotic tendency (prothrombin fragment F1+2, thrombin-antithrombin complexes, factor VIIc, activated partial thromboplastin time [APTT] and activated protein C resistance): none of these variables were associated with incident IHD in this cohort. We suggest that further studies are required to establish the causes of increased cross-linked fibrin turnover, which is associated with incident IHD in the general population when measured by a specific assay.
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PMID:Fibrin D-dimer, markers of coagulation activation and the risk of major ischaemic heart disease in the caerphilly study. 1158 14

Thrombomodulin (TM) is a vascular endothelial cell (EC) receptor that is a cofactor for thrombin-mediated activation of the anticoagulant protein C. The extracellular NH(2)-terminal domain of TM has homology to C-type lectins that are involved in immune regulation. Using transgenic mice that lack this structure (TM(LeD/LeD)), we show that the lectin-like domain of TM interferes with polymorphonuclear leukocyte (PMN) adhesion to ECs by intercellular adhesion molecule 1-dependent and -independent pathways through the suppression of extracellular signal-regulated kinase (ERK)(1/2) activation. TM(LeD/LeD) mice have reduced survival after endotoxin exposure, accumulate more PMNs in their lungs, and develop larger infarcts after myocardial ischemia/reperfusion. The recombinant lectin-like domain of TM suppresses PMN adhesion to ECs, diminishes cytokine-induced increase in nuclear factor kappaB and activation of ERK(1/2), and rescues ECs from serum starvation, findings that may explain why plasma levels of soluble TM are inversely correlated with cardiovascular disease. These data suggest that TM has antiinflammatory properties in addition to its role in coagulation and fibrinolysis.
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PMID:The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways. 1220 72

Levels of fibrinogen, von Willebrand factor, d-dimer, antithrombin III, protein C, plasminogen, and plasminogen activator inhibitor were measured in 62 men and 37 women with ischemic heart disease before and after 20-min venous occlusion. Women compared with men had higher baseline levels of fibrinogen (4.046-/+0.1785 and 3.584-/+0.1591 g/l, respectively, p=0.021), von Willebrand factor (122.1-/+9.31 and 99.5-/+6.16%, respectively, p=0.035), plasminogen activator inhibitor (4.8-/+0.31 and 2.9-/+0.27 IU/l, respectively, p=0.009). Levels of antithrombin III, protein C, and plasminogen in women were higher than in men both at baseline (108.5-/+1.65 and 100.7-/+1.60 %, p=0.001; 129.1-/+2.91 and 107.2-/+3.79%, p=0.001; 113.6-/+2.13 and 104.1-/+1.89%; p=0.001, respectively) and after venous occlusion. There were no gender differences in dynamics of parameters of hemostasis during venous occlusion. Multifactorial regression analysis showed that gender was independently (of age, duration of hypertension, smoking, body mass index, and total cholesterol level) related to only antithrombin III and protein C levels.
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PMID:[Gender differences in the state of the system of hemostasis in patients with ischemic heart disease]. 1249 45

Hyperactivity of coagulation factor VIII (fVIII) marks hypercoagulation. FVIII enhances activity of factor IX and their combination activates factor X, which is of primary importance in prothrombin transformation into thrombin, on the phospholipid membrane. The activity of fVIII was studied in 28 patients (26 women, 2 men, mean age 49.6 +/- 7.8 years) with Sneddon's syndrome (SS). SS manifests clinically similarly to primary antiphospholipid syndrome (PAS). The leading of them are ischemic disorders of cerebral circulation (IDCC) and advanced livedo present in all the examinees. Hyperactivity of fVIII was registered in 21 (75%) of 28 patients. Most of thrombosis-related symptoms occurred more frequently in patients with high than normal activity of fVIII: ischemic strokes (91% vs 57%, p > 0.05), repeated strokes (71% vs 0%, p = 0.0014), transient IDCC (76% vs 57%, p > 0.05), vascular dementia (43% vs 0%, p > 0.05), ischemic heart disease (43% vs 0%, p > 0.05), thickening of heart valves according to echocardiography (91% vs 57%, p > 0.05), peripheral venous thromboses (24% vs 0%, p > 0.05). In high fVIII activity cardiolipin antibodies occurred more rarely (24% vs 43%, p > 0.05) but lupus anticoagulant was seen more often (47% vs 14%, p > 0.05). High fVIII activity was in 8 of 12 aPL-negative patients. It is demonstrated that elevated fVIII activity is an essential mechanism of thrombosis development in SS. The cause of this enhanced activity is suggested to be special aPL in interaction with which fVIII becomes insensitive to inactivation with protein C. The activity of protein C was normal in all the cases.
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PMID:[Clotting factor VIII in Sneddon syndrome]. 1459 91

Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess phospholipid or platelets. Paradoxically, a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In critically ill patients, administering RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate iron, folate, and cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis, platelet transfusions are often important in managing patients who are bleeding or at risk of bleeding with thrombocytopenia or impaired platelet function. Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important, platelet transfusions are generally contraindicated if the underlying disorder is TTP or type II HIT, because platelet transfusion in these settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when bleeding arises from malfunction, consumption, or underproduction of plasma coagulation proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct clotting factor deficiencies, particularly coagulopathies that are attributable to multiple clotting factor deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic abnormalities from severe liver dysfunction; extensive surgery, trauma, or bleeding; excessive warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated protein C reduces mortality from severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease, as do fibrinogen and platelet levels. Because of its anticoagulant effect, however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa use must take into account bleeding risks.
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PMID:Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. 1471 Jun 93


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