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)

A survey is presented of the use of the Oxford type DE(I) II-IX-X concentrate in the treatment of Christmas disease in Oxford from January 1970 to September 1974. 72 different patients were treated with a total of 2436 bottles of this concentrate from 143 different batches (each bottle containing 800-1000 units of factor IX). Although most doses were given for the treatment of minor haemorrhages into joints and muscles, 717 bottles of concentrate were used to treat 11 patients who underwent 14 major surgical operations. No episode of intravascular clotting or pulmonary embolism was seen in any patient receiving the concentrate. A detailed study of the plasma levels of factor V, VIII, total progressive antithrombin, platelets and fibrinogen degradation products was carried out before and after transfusion of type DE(I) concentrate in 14 patients. No significant alteration in those factors was found after the transfusion.
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PMID:A five year experience of the use of factor IX type DE(I) concentrate for the treatment of Christmas disease of Oxford. 120 Dec 27

A case of congenital factor V deficiency is reported. Despite this defect in blood coagulation, the patient had experienced recurrent thrombophlebitis and was referred to us because of deep venous thrombosis of the lower limbs associated with pulmonary embolism. Both functional and immunological assays documented a deficiency of factor V (12 and less than 10%, respectively). The available family members were investigated and the same defect was found in 2 brothers of the propositus, who also suffered from thrombotic diseases (recurrent thrombophlebitis and myocardial infarction). The propositus has been treated with long-term oral anticoagulant therapy, no hemorrhagic complications or thrombotic recurrences being recorded in 2 years' time.
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PMID:Thromboembolic manifestations and congenital factor V deficiency: a family study. 262 Aug 69

The fibrinolytic system comprises a proenzyme, plasminogen, which can be converted to the active enzyme, plasmin, which degrades fibrin. Plasminogen activation is mediated by plasminogen activators, which are classified as either tissue-type plasminogen activators (t-PA) or urokinase-type plasminogen activators (u-PA). Inhibition of the fibrinolytic system may occur at the level of the activators or at the level of generated plasmin. Plasmin has a low substrate specificity, and when circulating freely in the blood it degrades several proteins including fibrinogen, factor V, and factor VIII. Plasma does, however, contain a fast-acting plasmin inhibitor, alpha 2-antiplasmin, which inhibits free plasmin extremely rapidly but which reacts much slower with plasmin bound to fibrin. A "systemic fibrinolytic state" may, however, occur by extensive activation of plasminogen and depletion of alpha 2-antiplasmin. Clot-specific thrombolysis therefore requires plasminogen activation restricted to the vicinity of the fibrin. Two physiological plasminogen activators, t-PA and single-chain u-PA (scu-PA) induce clot-specific thrombolysis, via entirely different mechanisms, however. t-PA is relatively inactive in the absence of fibrin, but fibrin strikingly enhances the activation rate of plasminogen by t-PA. This is explained by an increased affinity of fibrin-bound t-PA for plasminogen and not by alteration of the catalytic rate constant of the enzyme. The high affinity of t-PA for plasminogen in the presence of fibrin thus allows efficient activation on the fibrin clot, while no significant plasminogen activation by t-PA occurs in plasma. scu-PA has a high affinity for plasminogen (Km = 0.3 microM) but a low catalytic rate constant (kcat = 0.02 sec-1). However, scu-PA does not activate plasminogen in plasma in the absence of a fibrin clot, owing to the presence of (a) competitive inhibitor(s). Fibrin-specific thrombolysis appears to be due to the fact that fibrin reverses the competitive inhibition. The thrombolytic efficacy and fibrin specificity of natural and recombinant t-PA has been demonstrated in animal models of pulmonary embolism, venous thrombosis, and coronary artery thrombosis. In all these studies intravenous infusion of t-PA at sufficiently high rates caused efficient thrombolysis in the absence of systemic fibrinolytic activation. The efficacy and relative fibrinogen-sparing effect of t-PA was recently confirmed in three multicenter clinical trials in patients with acute myocardial infarction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular mechanisms of fibrinolysis and their application to fibrin-specific thrombolytic therapy. 355 13

In Sweden, clinicians at the Karolinska Hospital in Stockholm interviewed and took blood samples from 81 women aged 18-52 to examine the incidence of an insufficient response to activated protein C (APC), an increased level of antibodies to anionic phospholipids (Pla), and the presence of the mutation in the factor V gene in women who developed thrombosis while using oral contraceptives (OCs), in OC users who developed thrombosis during other risk situations (pregnancy or delivery, surgery, idiopathic), and in non-users who had a history of thrombosis. Women who had thrombosis during OC use had fewer pregnancies before developing thrombosis (p 0.05) and fewer recurrences after the thrombotic event than women in the other two groups. Non-users had the highest proportion of thrombotic recurrences (26%). Pulmonary embolism occurred more often as a result of the thrombotic event during OC use than during pregnancy, delivery, or surgery (p 0.01). APC resistance occurred in 27% of all women. The normalized ACP (nACP) ratio ranged between 0.41 and 1.48. Women who developed thrombosis during OC use had a significantly lower APC resistance than the other two groups (p 0.05). APC resistance increased as did the recurrence of thrombotic events (14-42%). The mean nACP ratio was highest among women who developed thrombosis during OC use and lowest in non-users (0.94 vs. 0.72). 40% of all women had mutation in the factor V gene. All but one woman was heterozygous. This mutation was present in relatively the same proportion in all three groups. The frequency of mutation was greater than that with laboratory-identified APC resistance in women with a history of thrombosis during OC use (38% vs. 14%; p 0.025). Coagulation and genetic analyses were highly correlated (p = 0.001). Pla were present in all three groups at essentially the same levels. Yet lupus anticoagulant activity was more common in OC users who developed thrombosis during other risk situations than the other two groups (p 0.05). 12% of all women had APC resistance and Pla. These findings show a flexible APC response.
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PMID:Thrombotic risk factors and oral contraception. 766 78

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

In 70-80% of cases, pulmonary embolism is the consequence of lower extremity deep vein thrombosis. It has been demonstrated that the most common coagulation defect predisposing to venous thrombosis, resistance to activated protein C (APC), is not associated with an increased risk for pulmonary embolism, but the evidence was based on a functional assay to diagnose APC resistance and no information about concomitant deep vein thrombosis was provided. The aim of our study was to evaluate the prevalence of factor V:Q506, the gene mutation responsible for APC resistance, in patients with symptomatic non-fatal pulmonary embolism, whether or not associated with deep vein thrombosis. Patients with uncomplicated deep vein thrombosis and healthy controls were investigated as comparison groups. The overall prevalence of factor V:Q506 in 106 patients with pulmonary embolism was 12.3%, lower than that found in 106 patients with deep vein thrombosis (22.6%, OR 0.5, 95% CI 0.2-1.0) but significantly higher than that found in 212 healthy subjects taken as controls (2.8%, OR 4.8, 95% CI 1.8-13.0). In the 41 patients with isolated pulmonary embolism, i.e., without the presence of deep vein thrombosis, the prevalence was 4.9%, similar to that in controls (OR 1.8, 95% CI 0.3-9.6), while in the remaining 65 patients with pulmonary embolism associated with deep vein thrombosis the prevalence was significantly higher (16.9%, OR 5.5, 95% CI 2.0-15.8). In conclusion, the prevalence of factor V:Q506 is high in patients with pulmonary embolism associated with deep vein thrombosis, whereas in patients with isolated pulmonary embolism it is similar to that found in control subjects. This intriguing finding is of difficult interpretation and needs confirmation by further studies.
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PMID:Low prevalence of factor V:Q506 in 41 patients with isolated pulmonary embolism. 1073 2

Studies conducted in the first three decades after discovery of a link between venous thromboembolism and oral contraceptive users showed a relative risk of first thrombosis during oral contraceptive use of 2.9 (95% CI 0.5-17). In recent studies in which the sub-50 micrograms ethinyl estrodiol containing pills were investigated comparing current users with non-users, the RR is 3.8 for non-fatal deep VTE and 2.7 for superficial VTE, deep VTE and pulmonary embolism (PE) together and 2.1 for fatal VT and PE together. The association is attributed to the estrogenic component and not related to duration of pill use. The risk disappears once the pill has been stopped, and it is not elevated among past users. Smoking does not appear to be risk factor for VTE; obesity and varicose veins are, at the most, weak risk factors. Since a causal relationship between OC use and VTE is tempting, clues for unraveling the mechanism were sought in the hemostatic system. Studies of the coagulation system found changes in the activation of coagulation and fibrinolytic compartments, but within the normal range. An epidemiologic study showed that the risk of VTE among women using OCs is 30-fold increased by the presence of a mutation of factor V, called Factor V Leiden (5% prevalence in the Caucasian population). Selective screening for the mutated factor V should be limited to women with a personal or family history of VTE. Four epidemiologic studies showed a two-fold increase in risk of VTE with the use of OCs containing third-generation progestins (gestodene and desogestrel), relative to second-generations products (levonorgestrel). Biases cannot devaluate the conclusion that the increased risk of VTE in especially first-time and younger users of third-generation OCs is highly likely. The clinical consequence is therefore that second-generation OCs are the first choice in prescription to first-time users.
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PMID:Oral contraceptives and thrombotic disease: risk of venous thromboembolism. 919 74

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

We investigated the influence of the ABO blood group in the observed prevalences of the recently described factor V R506Q and factor II G20210A mutations in a thrombotic population. We determined the ABO blood group in a sample of 178 unselected patients (aged 17-83 years), diagnosed at our center with deep vein thrombosis or pulmonary embolism. The results of this study show a high prevalence of thrombosis in the non-O blood group. In the general population, the prevalence as a fraction of the O blood group was 2.69 (confidence interval 1.90-3.82). Of the factor V R506Q carriers (n = 28), only one had O group blood and 27 of 28 were non-O (24 A, one B and two AB). However, within the group of factor II G20210A carriers (n = 17), seven had O, nine A and one B type blood. The prevalence of the factor V R506Q mutation within the O blood group was 2.4% (one of 42), significantly lower than in the A group (23.3%, 24 of 103; P = 0.002), or in the overall non-O group (19.9%, 27 of 136; P = 0.006). This prevalence was similar to that observed previously in the non-thrombotic population in our area (3.5%; P = 0.9). We analyzed the clotting activity of factor VIII and we found higher levels in the non-O group (1.78+/-0.61 U/ml) than in the O blood group (1.30+/-0.51 U/ ml; P < 0.0001). We speculate that factor Va in individuals with the factor V Leiden mutation could interact with the high levels of factor VIII clotting activity as a necessary cofactor.
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PMID:The O blood group protects against venous thromboembolism in individuals with the factor V Leiden but not the prothrombin (factor II G20210A) mutation. 1045 23

With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46 v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.
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PMID:Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden). 1055 90


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