Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A dimorphism in the 3'-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis. We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% CI, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% CI, 1.1 to 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.
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PMID:The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis. 949 5

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

Malignancy is a risk factor for thromboembolism and anti-cancer chemotherapy can increase this risk. Prophylaxis of thrombosis with very-low-dose warfarin given concurrently with chemotherapy has a significantly reduced rate of thromboembolism in a randomized trial in women with stage IV breast cancer. In a group of 32 patients randomized in one center (16 subjects on warfarin and 16 on placebo), we have prospectively studied the plasma levels of: 1. Markers of 'in vivo' clotting activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2] and D-dimer), 2. Factor VII (FVII), and 3. Natural anticoagulants (protein C [PC] and antithrombin [AT]). The aims of this study were: 1. to examine whether laboratory tests predicted those patients who developed thrombosis, and 2. to evaluate the effect of very-low-dose warfarin on hemostatic variables. The patients' hemostatic parameters were evaluated before entry into the study and after starting chemotherapy +/- prophylaxis, before each course for nine courses. Before-treatment results were compared to those of a sex and age-matched non-cancer control group. There was a significant elevation of plasma levels of TAT (p <0.001), F1+2 (p <0.001), D-dimer (p <0.0001) and FVIIa (p <0.05), as well as an increase of FVII proteolysis (p <0.05), whereas plasma PC and AT concentrations were not different from controls. After starting chemotherapy, markers of clotting activation were progressively lower in the group receiving warfarin prophylaxis compared to the group on placebo. Differences between the groups became statistically significant (p <0.01) after the 4th course of chemotherapy. Deep vein thrombosis occurred in two patients in the placebo arm. The results of this study indicate that before therapy, an hypercoagulable state is present in stage IV breast cancer, and after starting chemotherapy, abnormalities of hypercoagulation markers persist, however they are reduced by very-low-dose-warfarin. None of the laboratory variables could predict thrombosis in the single patient.
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PMID:The effect of very-low-dose warfarin on markers of hypercoagulation in metastatic breast cancer: results from a randomized trial. 945 16

Clinically suspected deep vein thrombosis (DVT) or pulmonary thromboembolism (PE) should be initially treated with heparin, and an objective diagnosis obtained. In pregnancy, heparin is usually continued until delivery, following which warfarin is substituted. In the absence of pregnancy, warfarin is substituted and usually continued for 3 months after a first thrombo-embolic event. Low molecular weight heparins are increasingly preferred to unfractionated heparin in non-pregnant patients with acute DVT, because of efficacy when given by daily subcutaneous injection without routine monitoring of coagulation assays, greater efficacy, and lower risks of major bleeding and of mortality. Unfractionated heparin requires monitoring by the APTT (target ratio 1.5-2.5), and warfarin requires monitoring by the International Normalized Ratio (INR) of the prothrombin time (target ratio 2.0-3.0). Graduated elastic compression stockings reduce post-thrombotic leg symptoms after DVT. Secondary prevention is important in future high risk situations.
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PMID:Treatment of venous thrombo-embolism. 948 89

Without prophylaxis, patients subjected to major abdominal surgery have a risk of deep vein thrombosis of approximately 30%, while the rate varies between 40% and 60% in orthopedic surgery. The reasons for this discrepancy are not completely understood. The present study was designed to compare the pre- and postoperative behavior of different coagulation and fibrinolysis parameters in patients undergoing both types of surgery, receiving low molecular weight heparin prophylaxis. Samples were taken before operation and on postoperative days 1, 3, and 7. The following parameters were assessed: prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinopeptide A, tissue plasminogen activator, plasminogen activator inhibitor, plasmin-alpha 2-antiplasmin complexes, and fibrin degradation products. We found a significant increase in the clotting markers postoperatively compared with preoperative values (P < 0.05), both in abdominal and orthopedic surgery, indicating a marked hemostatic activation which remained until postoperative day 7. A significant increase in plasminogen activator inhibitor (P < 0.01) and a decrease in tissue plasminogen activator and plasmin-alpha 2-antiplasmin complexes was also observed early after operation. The plasminogen activator inhibitor activity decreased, while tissue plasminogen activator and plasmin-alpha 2-antiplasmin levels increased significantly on days 3 and 7 (P < 0.05). Fibrin degradation products significantly increased throughout the postoperative period (P < 0.01). Preoperatively, we found higher plasminogen activator inhibitor activity and lower tissue plasminogen activator and plasmin-alpha 2-antiplasmin complexes (P < 0.05) in patients undergoing hip replacement compared with abdominal surgery. Fibrin degradation products were also significantly lower on postoperative day 3 in patients undergoing hip replacement (P < 0.01). We suggest that the lower preoperative fibrinolytic activation observed in patients undergoing orthopedic surgery compared with abdominal surgery might have pathophysiological consequences. Our results also indicate that the hemostatic activation persists beyond the 7th postoperative day despite prophylaxis.
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PMID:Hemostatic markers in surgery: a different fibrinolytic activity may be of pathophysiological significance in orthopedic versus abdominal surgery. 950 66

Activated protein C resistance is the most frequent cause of thrombophilia. It is found in 20% of patients with an episode of deep vein thrombosis (DVT) and its prevalence in caucasian population is between 3-7%. Activated protein C resistance is secondary to an Arg 506 to Gln mutation of factor V (factor V Leiden). The relative risk of DVT for heterozygotes is 5 to 10, and for homozygotes 50 to 100. There is a 2- to 4-fold increase risk of recurrences in patients bearing the factor V Leiden mutation after a first episode of DVT. Recently a new mutation in the prothrombin gene (20210 G/A) was found to increase the relative risk of DVT by 2 to 4. Finally we also reviewed the association between DVT and hyperhomocysteinemia that is associated with a 2-fold increase risk of DVT.
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PMID:[New causes of inherited thrombophilia]. 951 43

Colloid solutions have been developed and used over the past 70 years as expanders of the intravascular space, based on an understanding of Starling's law. Increasing osmotic pressure with colloidal products has remained an attractive theoretical premise for volume resuscitation. Indeed, colloids have been shown to increase osmotic pressure in clinical practice; however, the effects are short-lived. Lower molecular weight colloids exert a larger initial osmotic effect, but are rapidly cleared from the circulation. Larger molecules exert a smaller osmotic pressure that is sustained longer. The main drawback to colloid therapy lies in pathological states with endothelial injury and capillary leak, precisely the clinical scenario where colloids are commonly given. The colloid solution may leak into the interstitium and remain there exerting an osmotic gradient, pulling additional water into the interstitium. There are 4 general types of colloid products available for clinical use. Albumin is the predominant plasma protein and remains the standard against which other colloids are compared. Albumin, pooled from human donors, is in short supply and remains expensive. Dextrans have been used to prevent deep venous thrombosis and to lower blood viscosity during surgery. Hetastarch has been widely used as a plasma volume expander. It provides equivalent plasma volume expansion to albumin, but has been shown to alter clotting parameters in studies (prolonging the activated partial thromboplastin time and prothrombin time). Although severe coagulopathies have been reported in sporadic cases, hetastarch has not been shown to increase postoperative bleeding compared with albumin therapy, even in large doses (3 L/day). Despite some theoretical advantages compared with crystalloid therapy, colloid administration has not been shown to decrease the risk of acute lung injury or to improve survival. Specific indications for colloid products include hypoproteinaemic or malnourished states, patients who require plasma volume expansion who are unable to tolerate larger amounts of fluid, orthopaedic and reconstructive procedures requiring prevention of thrombus formation and leukapheresis.
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PMID:Colloid volume expanders. Problems, pitfalls and possibilities. 958 60

A polymorphism, C-->T677, in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified as a cause of mild hyperhomocysteinemia, a risk factor for venous thrombosis. We have investigated the frequency of the TT genotype in 277 consecutive patients with confirmed deep venous thrombosis and 431 healthy subjects. The TT MTHFR genotype was more frequent in patients than in controls (25.6% vs. 18.1%; p = 0.016). The risk of thrombosis among carriers of this genotype was significantly increased [odds ratio: 1.6 (95% CI: 1.1-2.3)]. The estimated risk associated with the TT genotype was 2.0 (95% CI: 1.3-3.1) in subjects with (n = 122), and 1.3 (95% CI: 0.8-2.0) in those without (n = 155) predisposing (hereditary, acquired or circumstantial) risk factors for venous thrombosis. Factor V Leiden and prothrombin G-->A20210 are known risk factors for venous thrombosis. After stratification for FV Leiden and prothrombin A20210 mutations, a significant association was also observed. After adjustment for sex, FV Leiden and prothrombin A20210 mutation, the estimated risk of venous thrombosis among carriers of the TT MTHFR genotype was 1.7 (95% CI: 1.2-2.6). The TT MTHFR genotype is independently associated with venous thrombosis, mainly among individuals with a high risk profile.
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PMID:The methylenetetrahydrofolate reductase TT677 genotype is associated with venous thrombosis independently of the coexistence of the FV Leiden and the prothrombin A20210 mutation. 960 18

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


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