Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In todays medicine, anticoagulant drugs like heparin and coumadin derivatives have become indispensable for the treatment of thrombo-embolic diseases. Heparin, consisting of long poly-sulfated polysaccharide chains of variable length and sequences is mostly derived from porcine mucosa. Its bioavailability by other than the parenteral way of administration is almost negligible. Therefore, with only few exceptions, it is almost exclusively applied in hospitalized patients (short-term therapy) or to bridge 2 phases of treatment with oral anticoagulant drugs. Today, besides the conventional high-molecular weight heparins, new fractionated heparins are gaining more and more attention. They offer the advantage of a more reliable resorption from the subcutaneous tissue and thus warrant reliable plasma levels. In many recent randomized trials of deep vein thrombosis and pulmonary embolism, those fractionated heparins have proven to successfully substitute for intravenously applied, aPTT-controlled unfractionated heparin. It remains however open, whether this also translates into the prevention of arterial thrombo-embolic diseases. Heparin may not pass through the placental barrier nor into the milk and is regarded non-teratogenic. Therefore, it may be regarded the ideal anticoagulant for pregnant women and lactating mothers. Those women, however, still carry the heparin-associated risk of bleeding and osteoporosis. In comparison: Coumadin derivatives interfere with the carboxylation of the clotting factors II, VII, IX, and X as well as proteins C and S. By inhibiting the synthesis of these proteins they shift the haemostatic balance to a lower level. In addition, they are almost completely bioavailable by the enteral pathway. They are, therefore, regarded the drugs of choice for long-term anticoagulant therapy in patients at particular thromboembolic risk. For their therapeutic range, being extremely narrow, meticulous drug monitoring by repeated INR-measurements as well as a reliable compliance of the patient to drug intake and dietary restrictions are mandatory to exclude phases with over- or under-anticoagulation. Above all, coumadin therapy is characterized by numerous drug interactions. Thus, whenever the basal medication is changed, for whatever reason, more intense care must be laid to drug monitoring, and the intervals for INR determinations must transiently be shortened. Coumadin derivatives do pass through the placental barrier and in minor amounts also into the milk of breast feeding mothers. Furthermore, they are highly teratogenic. If taken during pregnancy, malformations of the central nervous system are reported to occur in some 10% to 30% of the infants. Thus during pregnancy and in the lactation period, coumadin therapy should be avoided. Bleeding episodes of different severity are the most frequent adverse effects of anticoagulant therapy, no matter whether heparin or coumadin is given. There is a direct relation between the intensity of anticoagulant therapy and the frequency of bleeds. Luckily, most bleeding episodes do not create major therapeutic problems. In case of severe bleeds, however, the anticoagulant therapy must immediately be suspended. In case of coumadin therapy the immediate administration of 4 packs of PPSB (prothrombin-complex-concentrates) or FFP (fresh-frozen-plasma) with concomitant low doses of heparin is additionally advised. Allopecia diffusa, urticartia and allergic reactions are known side effects of anticoagulant therapy. Patients on long-term heparin may also suffer from severe osteoporosis. On the other hand, heparin treatment raises the hazzards of a HAT-Syndrome (heparin-associated thrombocytopenia) (estimated frequency 0.01% to 0.1% of treated patients), giving rise to severe and life-threatening thrombo-embolic side effects predominantly in the arterial tree. In these cases, heparin must be suspended despite those severe thrombo-embolic episodes.
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PMID:-Anticoagulant drugs-. 864 76

Plasma levels of selected coagulation and fibrinolytic parameters (activated partial thromboplastin time, prothrombin time, fibrinogen, antithrombin III, protein C, thrombin-anti-thrombin III complexes (TAT), plasminogen activator inhibitor-1 (PAI-1), plasminogen, alpha 2-plasmin inhibitor) were evaluated in 90 patients with clinical suspicion of pulmonary embolism (PE). Plasma levels of fibrinogen, PAI-1 and TAT were significantly higher in patients than in controls (p < 0.01): evaluation of TAT displayed a sensitivity of 96.1% and specificity of 30.8%, and positive and negative predictive values of 64.5 and 85.7%, respectively. The number of nonperfused lung segments correlated directly with TAT levels (p < 0.01) and inversely with arterial pO2 values (p < 0.01). No significant difference was found in the other parameters between patients and controls. Our results suggest that the finding of normal TAT plasma levels can help to exclude PE in patients with clinically suspected PE.
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PMID:Thrombin-antithrombin III complexes as an additional diagnostic aid in pulmonary embolism. 869 74

The diagnosis of thromboembolic diseases is still difficult to establish before the occurrence of the pathological event, although it is now known that they are the result of a progressive alteration of the cardiovascular system. Introduction of new diagnostic tools for the evaluation of the thromboresistance capacity of the body or for the measurement of molecular markers allows the testing of the body defenses against thrombosis which is becoming a routine clinical diagnosis. Antithrombin III (AT III), protein C, protein S, and parameters of fibrinolysis have been recognized to be very important anticoagulant proteins and regulators of thrombin formation and thrombus extension. Furthermore, a normal factor V is necessary for the normal function of the protein C pathway. The presence of a factor V mutation leads to the activated protein C resistance syndrome. However, the major incidence of thrombotic events concerns the overall population. It has been epidemiologically related to the existence of risk factors producing blood activation, which progressively saturates the body's thromboresistance. This period is clinically silent for a long time. The new molecular markers recently introduced can show the existence of a preclinical state of blood activation at the plasma level (fibrinopeptide A, thrombin-antithrombin complexes, modified antithrombin III, fragments 1 + 2 of prothrombin, D-dimer) or at the platelet level (B-thromboglobulin, platelet factor 4, and thrombospondin), and promising developments concern the endothelial level (soluble thrombomodulin). The most universally used blood activation test is the D-dimer assay. This analyte has become very popular in past years for its high sensitivity, its long half-life, and its easy detection directly on citrated plasma. Its negative predictive value (in deep venous thrombosis or pulmonary embolism) as well as its use for monitoring of thrombotic risk in the post-operative period have been well documented clinically. New investigations are initiated to find analytes reflecting endothelial damage, an early platelet activation, or the involvement of blood cells (mainly monocytes and neutrophils) in abnormal processes. It also becomes possible to evaluate directly pathological causes inducing blood activation, such as the presence of antiphospholipid antibodies or other autoimmune antibodies.
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PMID:Thromboembolic diseases: biochemical mechanisms and new possibilities of biological diagnosis. 880 28

The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin, a low molecular weight heparin, with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis (DVT). Patients were included if they had deep venous thrombosis distal to inguinal ligament and were randomised either before, if it was considered necessary, or after phlebographic verification of the diagnosis. There was no pre-inclusion treatment with unfractionated heparin. One hundred and twenty patients received dalteparin, administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the first or second day, and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range (2 < INR < 3) on two consecutive days. Control phlebograms were taken within 4 days, thereafter. There were no significant differences between the two initial treatment groups in improvements in Marder score. Two major bleeding events occurred in the UFH group versus none in the dalteparin group. One patient in each group experienced clinically significant pulmonary embolism. During a mean follow-up period of 6.9 +/- 1.5 months, recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group. These results confirm those of a previous study on dalteparin in the initial treatment of DVT, and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament. The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH. Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised, studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted.
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PMID:Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. 886 30

Intracranial surgery is often complicated by thromboembolic events including the life-threatening pulmonary embolism. After head trauma and in patients with brain tumors disseminated intravascular coagulation (DIC) can occur, characterized by the triggering of the coagulation cascade and the depletion of coagulation factors which ultimately leads to bleeding. The identification of patients at high risk as well as the early diagnosis of hemostatic problems uses routine laboratory parameters such as partial thromboplastin time and prothrombin time reflecting the intrinsic and the extrinsic pathway of the coagulation respectively. Thrombin antithrombin III complexes (TAT) and prothrombin fragment 1 + 2 (F1 + 2) are further indicators of an activation of the coagulation whereas fibrinogen degradation products (FDP) refer to the fibrinolytic system. The basic principles of coagulation and fibrinolysis are summarized as well as the changes of laboratory parameters accompanying DIC, hypercoagulability and hyperfibrinolysis.
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PMID:What the neurosurgeon needs to know about the coagulation system. 898 62

The selection of a prophylaxis regimen and its implementation have been influenced considerably by the decreased duration of hospital stays and the pressures of cost containment. The purpose of the present study was to determine the rate of symptomatic pulmonary embolism both before and after discharge, the number of days required to achieve an adequate level of anticoagulation, and the complications associated with the use of low-dose warfarin after total hip arthroplasty. Between 1987 and 1993, 1099 primary and revision total hip arthroplasties were performed in 940 patients who received low-dose warfarin for prophylaxis against thromboembolic disease. The average duration of prophylaxis was fifteen days (range, one to twenty-nine days). The target level of anticoagulation (as indicated by a prothrombin time of fourteen to seventeen seconds) was achieved an average of three days (range, one to sixteen days) after the operation. The level of anticoagulation was lower than the target range at the time of discharge after 257 total hip arthroplasties (23.4 per cent), and the target level was never achieved during the period of hospitalization after fifty-four such procedures (4.9 per cent). Twelve total hip arthroplasties were associated with a symptomatic pulmonary embolism; the over-all prevalence of this complication therefore was 1.1 per cent (95 per cent confidence interval, 0.4 to 1.9 per cent). Four pulmonary emboli were diagnosed before discharge and eight, after discharge. A fatal pulmonary embolism occurred after one procedure (0.1 per cent). Patients who had a history of symptomatic venous thromboembolic disease had a significantly increased risk of symptomatic pulmonary embolism after total hip arthroplasty (p = 0.001, Fisher exact test). A major bleeding episode occurred after thirty-two total hip arthroplasties (2.9 per cent). Patients who had a prothrombin time of more than seventeen seconds had a significantly increased risk of hematoma formation (p = 0.003, chi-square analysis). Prophylaxis with low-dose warfarin is safe and effective for the prevention of pulmonary embolism after total hip arthroplasty.
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PMID:The efficacy of prophylaxis with low-dose warfarin for prevention of pulmonary embolism following total hip arthroplasty. 907 May 18

Antibodies against phospholipid-binding plasma proteins, such as beta2-glycoprotein I (beta2-GPI) and prothrombin, are associated with thromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases. We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids (cardiolipin), to phospholipid-binding plasma proteins beta2-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis. The antibodies were measured in stored serum samples from 265 cases of deep venous thrombosis of the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls. The study subjects were middle-aged men participating in a cancer prevention trial of alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified from nationwide Hospital Discharge Register. The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies. As adjusted for body mass index, number of daily cigarettes and history of chronic bronchitis, myocardial infarction and heart failure at baseline, the odds ratio per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0). The seven highest individual optical density-unit values of antiprothrombin antibodies were all confined to subjects with thromboembolic episodes. In conclusion, the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of deep venous thrombosis and pulmonary embolism and could be involved in the development of the thrombotic processes.
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PMID:High antibody levels to prothrombin imply a risk of deep venous thrombosis and pulmonary embolism in middle-aged men--a nested case-control study. 936 81

The authors used an antithrombotic agent (Nadroparin Calcium) with anti-Xa effect in their experiments to prevent thromboembolic complications in the model of endoprosthetic replacement of the hip joint in mongrel dogs. 10 experimental animals (Group I.) were given doses of 100 A Xa ICU/kg/bwt of Nadroparin Calcium subcutaneously 4 hours prior to the operation and also once a day until the 3rd postoperative day; between the 4th and 10th postoperative days doses of 150 A Xa ICU/kg/bwt Nadroparin Calcium were given. The 10 control animals (Group II.) did not receive anticoagulant treatment. In both groups platelet count, activated partial thromboplastin times (APTT), prothrombin and fibrinogen levels as well as activated factor X inhibition (F Xa) were measured prior to surgery and also until the 14th postoperative day. No changes in APTT and prothrombin levels were detected during the experiment, however platelet count and fibrinogen levels as well as the extent of F Xa inhibition showed significant and different changes in groups I. and II. The Group I. which had received thromboembolic prophylaxis did not develop deep venous thrombosis or pulmonary embolism, but the control group did. Based on their investigations, the authors concluded that they had been able to achieve F Xa inhibition by giving the above mentioned doses of Nadroparin Calcium which was enough to prevent thromboembolic complications in their model experiment of implanting hip endoprosthesis.
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PMID:Efficacy of prevention of thromboembolic complications with LMW-heparin in experiment. 940

Tissue injury during hip surgery results in the activation of the haemostatic system. The aim of this study was to detect markers of haemostatic activity, i.e. prothrombin fragment 1 and 2 (F1+2), thrombin-antithrombin (TAT) complexes, fibrin degradation products (FbDP), and soluble fibrin monomers (SF), preoperatively, and on days 1, 7 and 35 in plasma of patients undergoing total hip arthroplasty. The study was part of a multicentre study in which the patients were randomized to receive a subcutaneous injection of low molecular weight heparin (LMWH, dalteparin, Fragmin) once daily for 5 weeks or placebo following a 1-week LMWH treatment (once daily). Bilateral phlebography was performed between days 33 and 35 or before if patients had clinical symptoms of deep vein thrombosis. A lung scan was performed in patients with clinical symptoms of pulmonary embolism. Levels of the markers were significantly increased on day 35 in the patients receiving LMWH for 7 days compared to patients receiving LMWH for 35 days. In patients receiving LMWH for 5 weeks, levels of FbDP and SF were significantly higher during the entire study period, but TAT and F1+2 were normalized on day 35. The markers were increased two to five times on the 1st postoperative day in patients with diagnosed venous thromboembolism.
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PMID:Postoperative activation of the haemostatic system--influence of prolonged thromboprophylaxis in patients undergoing total hip arthroplasty. 969 Apr 80

Thromboembolic episodes are common events and affect approximately one in 1,000 persons annually. Pulmonary embolism alone accounts for 50,000 to 100,000 deaths per year in the United States with > 50% of those being elderly persons. Resistance to activated protein C is the most common inherited disorder associated with hereditary thrombophilia. A missense mutation has been identified in the gene coding for coagulation factor V (codon 506) which renders this procoagulant factor resistant to inactivation by activated protein C resulting in an increased risk for venous thrombosis. Recently, a second polymorphism was identified in the prothrombin gene (factor II) which is also associated with increased risk for venous thrombosis. Because of the high prevalence of these two mutations in the general population as well as in specific patient populations, the ability readily to detect these two mutations must be feasible. In this study, we evaluated 303 patients for the prothrombin mutatin (G20210A) which were previously tested for the factor V mutation using established polymerase chain reaction-mediated restriction fragment length polymorphism assays. In these patients, 30 (9.9%) were found to be heterozygous for the factor V Leiden mutation with no homozygous mutants identified. Twenty individuals (6.6%) were heterozygous for the prothrombin G20210A mutation, and we identified two individuals (0.66%) who were homozygous for the 20210A allele. Of the total 303 individuals screened, two were double heterozygotes for both the factor V Leiden and the prothrombin gene mutations. We also describe a multiplex polymerase chain reaction-mediated restriction fragment length polymorphism assay for detecting both mutations in a single-tube double-enzyme digestion reaction making identification of these two mutations easily achievable.
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PMID:Rapid multiplex analysis for the factor V Leiden and prothrombin G20210A mutations associated with hereditary thrombophilia. 978 36


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